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Office of Neuroscience Research > Resources and Facilities > WUSTL Neuroscience Publications for the week > Weekly Neuroscience Publications - Archives > Neuroscience Publications Archive - November 2017

Neuroscience Publications Archive - November 2017

Weekly Scopus Report: 

November 27, 2017

 

November 20, 2017

 

November 13, 2017

 

November 6, 2017



November 27, 2017

1) 

De Maria, A., Zhao, H., Bassnett, S.
Expression of potassium-dependent sodium-calcium exchanger in the murine lens
(2018) Experimental Eye Research, 167, pp. 18-24. 

DOI: 10.1016/j.exer.2017.11.002


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660S. Euclid Ave, Campus Box 8096, St. Louis, MO, United States
b Department of Biology, Johns Hopkins University, Baltimore, MD, United States


Abstract
Loss of intracellular calcium homeostasis may contribute to the opacification of lens tissue during cortical cataract formation. In healthy lenses, the concentration of intracellular calcium is maintained at levels far below electrochemical equilibrium but the identity of the calcium extrusion mechanism in lens fiber cells has remained elusive. Previous studies focused on the role of plasma membrane calcium ATPases and sodium-calcium exchangers. Here, we examined the expression of mRNA transcripts encoding potassium-dependent sodium-calcium exchangers (Nckx's, encoded by the Slc24 gene family) in the mouse lens. The most abundant of the five Slc24 family members was Slc24a4 (Nckx4). Notably, Slc24a4 was the only family member with increased expression in fiber cells. Using an antibody raised against recombinant mouse Nckx4, we showed that the protein is expressed strongly in the outer cortical fibers, consistent with results of in situ hybridization experiments and earlier mass spectrometry analysis. To test the role of Nckx4 directly, we generated mice in which Slc24a4 was deleted conditionally in lens tissue. In conditional knockout animals, the level of Nckx4 protein was reduced to background levels without a discernible effect on lens growth or transparency. Thus, despite its relative abundance in the lens, Nckx4 does not appear to have an indispensable role in the maintenance of lens clarity. © 2017 Elsevier Ltd


Document Type: Article
Source: Scopus

 

2) 

Jeong, A., Nakagawa, J.A., Wong, M.
Predictors of Drug-Resistant Epilepsy in Tuberous Sclerosis Complex
(2017) Journal of Child Neurology, 32 (14), pp. 1092-1098. 

DOI: 10.1177/0883073817737446


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Tuberous Sclerosis Alliance, Silver Spring, MD, United States
c Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Utilizing the multicenter TSC (tuberous sclerosis complex) Natural History Database including 2034 subjects, this study aimed to identify predictors of drug-resistant epilepsy in TSC. Basic epilepsy data were available for 1965 individuals in the database. Supplemental data were further collected from 1546 of these subjects through directed site queries, addressing additional epilepsy characteristics including the presence of drug-resistant epilepsy, therapies trialed, and outcomes of specific therapies. Epilepsy was reported in 86.4% of individuals with TSC. Infantile spasms were reported in 45.2% of individuals and focal seizures were reported in 84.4% of individuals. In those with focal epilepsy, drug resistance was reported in 59.6%, with focal seizure onset prior to age 1 year (odds ratio [OR] 1.9, confidence interval [CI] 1.4-2.5, P <.001), infantile spasms (OR 2.0, CI 1.5-2.5, P < 0.001), and infantile spasms incompletely responsive to therapy (OR 47.6, CI 6.7-333.3, P < 0.001) being associated with an increased likelihood of drug resistance. © 2017, © The Author(s) 2017.


Author Keywords
epilepsy;  infantile spasms;  refractory;  seizures;  tuberous sclerosis complex


Document Type: Article
Source: Scopus

 

3) 

Rietschel, L., Streit, F., Zhu, G., McAloney, K., Frank, J., Couvy-Duchesne, B., Witt, S.H., Binz, T.M., Bolton, J.L., Hayward, C., Direk, N., Anderson, A., Huffman, J., Wilson, J.F., Campbell, H., Rudan, I., Wright, A., Hastie, N., Wild, S.H., Velders, F.P., Hofman, A., Uitterlinden, A.G., Lahti, J., Räikkönen, K., Kajantie, E., Widen, E., Palotie, A., Eriksson, J.G., Kaakinen, M., Järvelin, M.-R., Timpson, N.J., Davey Smith, G., Ring, S.M., Evans, D.M., St Pourcain, B., Tanaka, T., Milaneschi, Y., Bandinelli, S., Ferrucci, L., Van Der Harst, P., Rosmalen, J.G., Bakker, S.J., Verweij, N., Dullaart, R.P., Mahajan, A., Lindgren, C.M., Morris, A., Lind, L., Ingelsson, E., Anderson, L.N., Pennell, C.E., Lye, S.J., Matthews, S.G., Eriksson, J., Mellstrom, D., Ohlsson, C., Price, J.F., Strachan, M.W., Reynolds, R.M., Tiemeier, H., Ripke, S., Mattheisen, M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T.M., Andlauer, T.F., Bacanu, S.-A., Bækvad-Hansen, M., Beekman, A.T., Bennett, D.A., Berger, K., Bigdeli, T.B., Bybjerg-Grauholm, J., Byrne, E.M., Cai, N., Castelao, E., Clarke, T.-K., Coleman, J.R., Consortium, C., Craddock, N., Dannlowski, U., Davies, G., Davies, G., De Geus, E.J.C., De Jager, P., Deary, I.J., Degenhardt, F., Dunn, E.C., Ehli, E.A., Eley, T.C., Escott-Price, V., Esko, T., Finucane, H.K., Gill, M., Gordon, S.D., Grove, J., Hall, L.S., Hansen, T.F., Søholm Hansen, C., Heath, A.C., Henders, A.K., Herms, S., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.-J., Hougaard, D., Huang, H., Ising, M., Jansen, R., Jorgenson, E., Kloiber, S., Knowles, J.A., Kretzschmar, W.W., Krogh, J., Kutalik, Z., Lang, M., Lewis, G., Li, Y., MacIntyre, D.J., Madden, P.A., Marchine, J., Mbarek, H., McGuffin, P., Mehta, D., Metspalu, A., Middeldorp, C.M., Mihailov, E., Milani, L., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nordentoft, M., Nyholt, D.R., O'Donovan, M.C., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Paciga, S.A., Pedersen, C.Bø., Pedersen, M.G., Pedersen, N.L., Pergadia, M.L., Peterson, R.E., Pettersson, E., Peyrot, W.J., Porteous, D.J., Posthuma, D., Potash, J.B., Quiroz, J.A., Rice, J.P., Riley, B.P., Rivera, M., Ruderfer, D.M., Saeed Mirza, S., Schoevers, R., Shen, L., Shi, J., Sigurdsson, E., Sinnamon, G.C., Smit, J.H., Smith, D.J., Stephansson, H., Steinberg, S., Strohmaier, J., Tansey, K.E., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Treutlein, J., Trzaskowski, M., Umbricht, D., Van Der Auwera, S., Van Grootheest, G., Van Hemert, A.M., Viktorin, A., Völzke, H., Wang, Y., Webb, B.T., Weissman, M.M., Wellmann, J., Willemsen, G., Xi, H.S., Baune, B.T., Blackwood, D.H.R., Boomsma, D.I., Børglum, A.D., Buttenschøn, H.N., Cichon, S., Domenici, E., Flint, J., Grabe, H.J., Hamilton, S.P., Kendler, K.S., Li, Q.S., Lucae, S., Magnusson, P.K., McIntosh, A.M., Mors, O., Bo Mortensen, P., Müller-Myhsok, B., Penninx, B.W., Perlis, R.H., Preisig, M., Schaefer, C., Smoller, J.W., Stephansson, K., Uher, R., Werge, T., Winslow, A.R., Breen, G., Levinson, D.F., Lewis, C.M., Wray, N.R., Sullivan, P.F., McGrath, J., Hickie, I.B., Hansell, N.K., Wright, M.J., Gillespie, N.A., Forstner, A.J., Schulze, T.G., Wüst, S., Nöthen, M.M., Baumgartner, M.R., Walker, B.R., Crawford, A.A., Colodro-Conde, L., Medland, S.E., Martin, N.G., Rietschel, M.
Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes
(2017) Scientific Reports, 7 (1), art. no. 15351, . 

DOI: 10.1038/s41598-017-11852-3


a University Hospital of Child and Adolescent Psychiatry and Psychotherapy, Research Department, University of Bern, Bern, Switzerland
b SRH University Heidelberg, Academy for Psychotherapy, Heidelberg, Germany
c Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
d Genetics and Computational Biology Department, QIMR Berghofer Medical Research, Brisbane, Australia
e Queensland Brain Institute, University of Queensland Australia, Brisbane, Australia
f Zurich Institute of Forensic Medicine, Centre for Forensic Hair Analysis, University of Zurich, Zurich, Switzerland
g Queensland Centre for Mental Health Research, Park Centre for Mental Health, Wacol, Australia
h National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
i Brain and Mind Centre, University of Sydney, Sydney, Australia
j Centre for Advanced Imaging, University of Queensland, Brisbane, Australia
k Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States
l Institute of Human Genetics, University of Bonn, Bonn, Germany
m Life and Brain Center, Department of Genomics, University of Bonn, Bonn, Germany
n Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
o Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland
p Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, United States
q Institute of Psychiatric Phenomics and Genomics (IPPG), Medical Center of the University of Munich, Campus Innenstadt, Munich, DE, Germany
r Human Genetics Branch, NIMH Division of Intramural Research Programs, Bethesda, United States
s Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Goettingen, DE, Germany
t Institute of Experimental Psychology, University of Regensburg, Regensburg, Germany
u British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
v Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
w MRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
x Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands
y Psychiatry, Dokuz Eylul University School of Medicine, Izmir, TR, Turkey
z Centre for Population Health Sciences, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
aa Internal Medicine, Erasmus MC, Rotterdam, NL, Netherlands
ab Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland
ac National Institute for Health and Welfare, Helsinki, Finland
ad Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
ae Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland
af Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
ag Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland
ah Folkhalsan Research Centre, Helsinki, Finland
ai Vasa Central Hospital Finland, Vasa, Finland
aj Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland
ak Department of Children and Yond People and Families, National Institute for Health and Elfare, Oulu, Finland
al Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, Imperial College London, London, United Kingdom
am Unit of Primary Care, Oulu University Hospital, Oulu, Finland
an MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
ao School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
ap Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, MD, United States
aq Department of Psychiatry, VU University Medical Center/GGZ Ingest, Amsterdam, Netherlands
ar Geriatric Unit, ASF, Florence, Italy
as University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands
at University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands
au Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, Netherlands
av University of Groningen, University Medical Center Groningen, Interdisciplinary Center for Psychiatric Epidemiology, Groningen, Netherlands
aw University of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, Netherlands
ax Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
ay Department of Medical Sciences, Uppsala University Sweden, Uppsala, Sweden
az Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
ba School of Women's and Infant's Health, University of Western Australia, Crawley, Australia
bb Department of Physiology, University of Toronto, Toronto, ON, Canada
bc Center for Bone and Arthritis Research, Institute of Medicin, University of Gothenburg, Gothenburg, Sweden
bd Child and Adolescent Psychiatry, Erasmus MC, Rotterdam, Netherlands
be Psychiatry, Erasmus MC, Rotterdam, Netherlands
bf Medical and Population Genetics, Broad Institute, Cambridge, United States
bg Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, United States
bh Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany
bi Department of Biomedicine, Aarhus University, Aarhus, Denmark
bj ISEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark
bk ISPYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark
bl Dept of Biological Psychology, VU University Amsterdam, Amsterdam, Netherlands
bm Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom
bn Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark
bo IPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark
bp Discipline of Psychiatry, University of Adelaide, Adelaide, Australia
bq Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
br Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
bs Department of Psychiatry, Virginia Commonwealth University, Richmond, United States
bt Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
bu Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, United States
bv Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, United Kingdom
bw Human Genetics, Wellcome Trust Sanger Institute, Cambridge, United Kingdom
bx Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland
by MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, United Kingdom
bz University of Oxford, Oxford, United Kingdom
ca Psychological Medicine, Cardiff University, Cardiff, United Kingdom
cb Department of Psychiatry, University of Marburg, Marburg, Germany
cc Department of Psychiatry, University of Münster, Münster, Germany
cd Avera Institute for Human Genetics, Sioux Falls, United States
ce Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom
cf EMGO+ Institute, VU University Medical Center, Amsterdam, Netherlands
cg Neurology, Brigham and Women's Hospital, Boston, United States
ch Stanley Center for Psychiatric Research, Broad Institute, Cambridge, United States
ci Department of Psychiatry, Massachusetts General Hospital, Boston, United States
cj Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, United States
ck Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom
cl Division of Endocrinology, Children's Hospital Boston, Boston, United States
cm Department of Genetics, Harvard Medical School, Boston, United States
cn Estonian Genome Center, University of Tartu, Tartu, Estonia
co Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, United States
cp Department of Mathematics, Massachusetts Institute of Technology, Cambridge, United States
cq Department of Psychiatry, Trinity College Dublin, Dublin, Ireland
cr Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
cs Bioinformatics Research Centre (BiRC), Aarhus University, Aarhus, Denmark
ct Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom
cu Danish Headache Centre, Department of Neurology, Rigshospitalet Glostrup, Glostrup, Denmark
cv Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Capital Region of Denmark, Roskilde, Denmark
cw IPSYCH, Lundbeck Foundation Initiative for Psychiatric Research, Copenhagen, Denmark
cx Department of Psychiatry, Washington University in Saint Louis School of Medicine, Saint Louis, United States
cy Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Germany
cz Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland
da Department of Medicine, Harvard Medical School, Boston, United States
db Max Planck Institute of Psychiatry, Munich, Germany
dc Division of Research, Kaiser Permanente Northern California, Oakland, United States
dd Centre for Addiction and Mental Health, Toronto, Canada
de Department of Psychiatry, University of Toronto, Toronto, Canada
df Psychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, United States
dg Department of Endocrinology at Herlev University Hospital, University of Copenhagen, Copenhagen, Denmark
dh Swiss Institute of Bioinformatics, Lausanne, Switzerland
di Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland
dj Division of Psychiatry, University College London, London, United Kingdom
dk Mental Health NHS 24, Glasgow, United Kingdom
dl Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
dm Statistics, University of Oxford, Oxford, United Kingdom
dn EMGO+ Institute for Health and Care Research, Amsterdam, Netherlands
do School of Psychology and Counseling, Queensland University of Technology, Brisbane, Australia
dp Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
dq Estonian Biocentre, Tartu, Estonia
dr Institute for Molecular Biology, University of Queensland, Brisbane, Australia
ds Medical Genetics, University of British Columbia, Vancouver, Canada
dt Statistics, University of British Columbia, Vancouver, Canada
du DZHK German Centre for Cardiovascular Research, Partner Site Greifswald, University Medicine, Greifswald, Germany
dv Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
dw Mental Health Centre Copenhagen, Copenhagen Universtity Hospital, Copenhagen, Denmark
dx Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
dy MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom
dz Humus, Reykjavik, Iceland
ea Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Groton, United States
eb Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
ec Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, United States
ed Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
ee Medical Genetics Section, CGEM, University of Edinburgh, Edinburgh, United Kingdom
ef Complex Trait Genetics, VU University Amsterdam, Amsterdam, Netherlands
eg Clinical Genetics, VU University Medical Center, Amsterdam, Netherlands
eh Psychiatry, University of Iowa, Iowa City, United States
ei Solid, Boston, GT, United States
ej Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, University of Granada, Granada, Spain
ek Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States
el Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
em Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, United States
en Faculty of Medicine, Department of Psychiatry, University of Iceland, Reykjavik, Iceland
eo School of Medicine and Dentistry, James Cook University, Townsville, Australia
ep Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom
eq DeCODE Genetics/Amgen, Reykjavik, Iceland
er College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom
es Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
et IPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark
eu KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
ev Department of Psychiatry, University of California, San Diego, United States
ew Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
ex Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery and Translational Medicine Area, Roche Innovation Center Basel, Basel, Switzerland
ey Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
ez Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands
fa Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, United States
fb Psychiatry, Columbia University College of Physicians, New York, United States
fc Division of Epidemiology, New York State Psychiatric Institute, New York, United States
fd Computational Sciences Center of Emphasis, Pfizer Global Research and Development, Cambridge, United States
fe Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark
ff Institute of Neuroscience and Medicine (INM), Research Center Juelich, Juelich, Germany
fg Department of Biomedicine, University of Basel, Basel, CH, Switzerland
fh Division of Medical Genetics, University of Basel, Basel, CH, Switzerland
fi Centre for Integrative Biology, Università degli Studi di Trento, Trento, Italy
fj Psychiatry, University of California Los Angeles, Los Angeles, United States
fk Psychiatry, Kaiser Permanente Northern California, San Francisco, United States
fl Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, United States
fm Psychosis Research Unit, Aarhus University Hospital Risskov, Aarhus, Denmark
fn Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
fo Psychiatry, Harvard Medical School, Boston, United States
fp Psychiatry, Dalhousie University, Halifax, Canada
fq Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
fr Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Cambridge, United States
fs Orphan Disease Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
ft NIHR BRC for Mental Health, King's College London, London, United Kingdom
fu Psychiatry and Behavioral Sciences, Stanford University, Stanford, United States
fv Department of Medical and Molecular Genetics, King's College London, London, United Kingdom
fw Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States
fx Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States


Abstract
Hair cortisol concentration (HCC) is a promising measure of long-Term hypothalamus-pituitary-Adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

4) 

Thompson, R.E., Lake, A., Kenny, P., Saunders, M.N., Sakers, K., Iyer, N.R., Dougherty, J.D., Sakiyama-Elbert, S.E.
Different Mixed Astrocyte Populations Derived from Embryonic Stem Cells Have Variable Neuronal Growth Support Capacities
(2017) Stem Cells and Development, 26 (22), pp. 1597-1611. 

DOI: 10.1089/scd.2017.0121


a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Department of Biomedical Engineering, University of Texas at Austin, 107 West Dean Keeton Street, Austin, TX, United States
c Department of Genetics, Washington University, School of Medicine, St. Louis, MO, United States
d Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United States


Abstract
Central nervous system injury often leads to functional impairment due, in part, to the formation of an inhibitory glial scar following injury that contributes to poor regeneration. Astrocytes are the major cellular components of the glial scar, which has led to the belief that they are primarily inhibitory following injury. Recent work has challenged this by demonstrating that some astrocytes are required for spinal cord regeneration and astrocytic roles in recovery depend on their phenotype. In this work, two mixed populations containing primarily either fibrous or protoplasmic astrocytes were derived from mouse embryonic stem cells (mESCs). Motoneuron and V2a interneuron growth on live cultures, freeze-lysed cultures, or decellularized extracellular matrix (ECM) from astrocytes were assessed. Both neuronal populations were found to extend significantly longer neurites on protoplasmic-derived substrates than fibrous-derived substrates. Interestingly, neurons extended longer neurites on protoplasmic-derived ECM than fibrous-derived ECM. ECM proteins were compared with in vivo astrocyte expression profiles, and it was found that the ESC-derived ECMs were enriched for astrocyte-specific proteins. Further characterization revealed that protoplasmic ECM had significantly higher levels of axon growth promoting proteins, while fibrous ECM had significantly higher levels of proteins that inhibit axon growth. Supporting this observation, knockdown of spondin-1 improved neurite growth on fibrous ECM, while laminin α5 and γ1 knockdown decreased neurite growth on protoplasmic ECM. These methods allow for scalable production of specific astrocyte subtype-containing populations with different neuronal growth support capacities, and can be used for further studies of the functional importance of astrocyte heterogeneity. © Copyright 2017, Mary Ann Liebert, Inc. 2017.


Author Keywords
interneuron;  motor neuron;  spinal cord injury;  tissue engineering


Document Type: Article
Source: Scopus

 

5) 

Padoa-Schioppa, C., Conen, K.E.
Orbitofrontal Cortex: A Neural Circuit for Economic Decisions
(2017) Neuron, 96 (4), pp. 736-754. 

DOI: 10.1016/j.neuron.2017.09.031


a Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
b Department of Economics, Washington University in St. Louis, St. Louis, MO, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Economic choice behavior entails the computation and comparison of subjective values. A central contribution of neuroeconomics has been to show that subjective values are represented explicitly at the neuronal level. With this result at hand, the field has increasingly focused on the difficult question of where in the brain and how exactly subjective values are compared to make a decision. Here, we review a broad range of experimental and theoretical results suggesting that good-based decisions are generated in a neural circuit within the orbitofrontal cortex (OFC). The main lines of evidence supporting this proposal include the fact that goal-directed behavior is specifically disrupted by OFC lesions, the fact that different groups of neurons in this area encode the input and the output of the decision process, the fact that activity fluctuations in each of these cell groups correlate with choice variability, and the fact that these groups of neurons are computationally sufficient to generate decisions. Results from other brain regions are consistent with the idea that good-based decisions take place in OFC and indicate that value signals inform a variety of mental functions. We also contrast the present proposal with other leading models for the neural mechanisms of economic decisions. Finally, we indicate open questions and suggest possible directions for future research. Padoa-Schioppa and Conen review recent advances on the neuronal mechanisms underlying economic choices. They propose that good-based decisions are formed in a neural circuit within the orbitofrontal cortex. © 2017 Elsevier Inc.


Author Keywords
attentional drift-diffusion model;  decision neuroscience;  distributed-consensus model;  economic choice;  goal-directed behavior;  good-based model;  neuroeconomics;  prefrontal cortex;  subjective value;  value-based decision


Document Type: Review
Source: Scopus

6) 

Kraft, A.W., Mitra, A., Bauer, A.Q., Snyder, A.Z., Raichle, M.E., Culver, J.P., Lee, J.-M.
Visual experience sculpts whole-cortex spontaneous infraslow activity patterns through an Arc-dependent mechanism
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (46), pp. E9952-E9961. 

DOI: 10.1073/pnas.1711789114


a Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
d Department of Physics, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Decades of work in experimental animals has established the importance of visual experience during critical periods for the development of normal sensory-evoked responses in the visual cortex. However, much less is known concerning the impact of early visual experience on the systems-level organization of spontaneous activity. Human resting-state fMRI has revealed that infraslow fluctuations in spontaneous activity are organized into stereotyped spatiotemporal patterns across the entire brain. Furthermore, the organization of spontaneous infraslow activity (ISA) is plastic in that it can be modulated by learning and experience, suggesting heightened sensitivity to change during critical periods. Here we used wide-field optical intrinsic signal imaging in mice to examine whole-cortex spontaneous ISA patterns. Using monocular or binocular visual deprivation, we examined the effects of critical period visual experience on the development of ISA correlation and latency patterns within and across cortical resting-state networks. Visual modification with monocular lid suturing reduced correlation between left and right cortices (homotopic correlation) within the visual network, but had little effect on internetwork correlation. In contrast, visual deprivation with binocular lid suturing resulted in increased visual homotopic correlation and increased anti-correlation between the visual network and several extravisual networks, suggesting cross-modal plasticity. These network-level changes were markedly attenuated in mice with genetic deletion of Arc, a gene known to be critical for activity-dependent synaptic plasticity. Taken together, our results suggest that critical period visual experience induces global changes in spontaneous ISA relationships, both within the visual network and across networks, through an Arc-dependent mechanism. © 2017, National Academy of Sciences. All rights reserved.


Author Keywords
Activity-regulated cytoskeleton-associated protein;  Functional connectivity;  Infraslow activity;  Visual critical period


Document Type: Article
Source: Scopus

7) 

Andrew, R.J., Fernandez, C.G., Stanley, M., Jiang, H., Nguyen, P., Rice, R.C., Buggia-Prévot, V., De Rossi, P., Vetrivel, K.S., Lamb, R., Argemi, A., Allaert, E.S., Rathbun, E.M., Krause, S.V., Wagner, S.L., Parent, A.T., Holtzman, D.M., Thinakaran, G.
Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzheimer’s disease
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (45), pp. E9665-E9674. 

DOI: 10.1073/pnas.1708568114


a Department of Neurobiology, University of Chicago, Chicago, IL, United States
b Department of Neurology, University of Chicago, Chicago, IL, United States
c Department of Pathology, University of Chicago, Chicago, IL, United States
d Hope Center for Neurological Disorders, Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
e Knight Alzheimer’s Disease Research Center, Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Neurosciences, University of California, San Diego, San Diego, CA, United States


Abstract
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by pathological brain lesions and a decline in cognitive function. β-Amyloid peptides (Aβ), derived from proteolytic processing of amyloid precursor protein (APP), play a central role in AD pathogenesis. β-Site APP cleaving enzyme 1 (BACE1), the transmembrane aspartyl protease which initiates Aβ production, is axonally transported in neurons and accumulates in dystrophic neurites near cerebral amyloid deposits in AD. BACE1 is modified by S-palmitoylation at four juxtamembrane cysteine residues. S-palmitoylation is a dynamic posttranslational modification that is important for trafficking and function of several synaptic proteins. Here, we investigated the in vivo significance of BACE1 S-palmitoylation through the analysis of knock-in mice with cysteine-to-alanine substitution at the palmitoylated residues (4CA mice). BACE1 expression, as well as processing of APP and other neuronal substrates, was unaltered in 4CA mice despite the lack of BACE1 S-palmitoylation and reduced lipid raft association. Whereas steady-state Aβ levels were similar, synaptic activity-induced endogenous Aβ production was not observed in 4CA mice. Furthermore, we report a significant reduction of cerebral amyloid burden and BACE1 accumulation in dystrophic neurites in the absence of BACE1 S-palmitoylation in mouse models of AD amyloidosis. Studies in cultured neurons suggest that S-palmitoylation is required for dendritic spine localization and axonal targeting of BACE1. Finally, the lack of BACE1 S-palmitoylation mitigates cognitive deficits in 5XFAD mice. Using transgenic mouse models, these results demonstrate that intrinsic posttranslational S-palmitoylation of BACE1 has a significant impact on amyloid pathogenesis and the consequent cognitive decline. © 2017, National Academy of Sciences. All rights reserved.


Author Keywords
5XFAD;  Axonal transport;  Dystrophic neurite;  Neurodegeneration;  PDAPP


Document Type: Article
Source: Scopus

 

8) 

Kolesnikov, A.V., Orban, T., Jin, H., Brooks, C., Hofmann, L., Dong, Z., Sokolov, M., Palczewski, K., Kefalov, V.J.
Dephosphorylation by protein phosphatase 2A regulates visual pigment regeneration and the dark adaptation of mammalian photoreceptors
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (45), pp. E9675-E9684. 

DOI: 10.1073/pnas.1712405114


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
b Department of Pharmacology, Case Western Reserve University, Cleveland, OH, United States
c Department of Ophthalmology, West Virginia University, Morgantown, WV, United States
d Department of Medical Devices, Polgenix, Inc., Cleveland, OH, United States


Abstract
Resetting of G-protein–coupled receptors (GPCRs) from their active state back to their biologically inert ground state is an integral part of GPCR signaling. This “on–off” GPCR cycle is regulated by reversible phosphorylation. Retinal rod and cone photoreceptors arguably represent the best-understood example of such GPCR signaling. Their visual pigments (opsins) are activated by light, transduce the signal, and are then inactivated by a GPCR kinase and arrestin. Although pigment inactivation by phosphorylation is well understood, the enzyme(s) responsible for pigment dephosphorylation and the functional significance of this reaction remain unknown. Here, we show that protein phosphatase 2A (PP2A) acts as opsin phosphatase in both rods and cones. Elimination of PP2A substantially slows pigment dephosphorylation, visual chromophore recycling, and ultimately photoreceptor dark adaptation. These findings demonstrate that visual pigment dephosphorylation regulates the dark adaptation of photoreceptors and provide insights into the role of this reaction in GPCR signaling. © 2017, National Academy of Sciences. All rights reserved.


Author Keywords
Dark adaptation;  GPCRs;  Photoreceptors;  PP2A;  Visual cycle


Document Type: Article
Source: Scopus

9) 

Dhar, R., Rajajee, V., Caulfield, A.F., Maas, M.B., James, M.L., Kumar, A.B., Figueroa, S.A., McDonagh, D., Ardelt, A.
The state of neurocritical care fellowship training and attitudes toward accreditation and certification: A survey of neurocritical care fellowship program directors
(2017) Frontiers in Neurology, 8 (NOV), art. no. 548, . 

DOI: 10.3389/fneur.2017.00548


a Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Neurology, University of Michigan, Ann Arbor, MI, United States
c Department of Neurosurgery, University of Michigan, Ann Arbor, MI, United States
d Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
e Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
f Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
g Department of Neurology, Duke University Medical Center, Durham, NC, United States
h Department of Anesthesiology, Duke University Medical Center, Durham, NC, United States
i Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States
j Department of Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
k Department of Neurological Surgery, University of Texas Southwestern, Dallas, TX, United States
l Department of Neurology, University of Texas Southwestern, Dallas, TX, United States
m Department of Anesthesia and Pain Management, University of Texas Southwestern, Dallas, TX, United States
n Department of Neurology (Neurosurgery), University of Chicago, Chicago, IL, United States
o Department of Surgery (Neurosurgery), University of Chicago, Chicago, IL, United States


Abstract
Neurocritical care as a recognized and distinct subspecialty of critical care has grown remarkably since its inception in the 1980s. As of 2016, there were 61 fellowship training programs accredited by the United Council for Neurologic Subspecialties (UCNS) in the USA and more than 1,000 UCNS-certified neurointensivists from diverse medical backgrounds. In late 2015, the Program Accreditation, Physician Certification, and Fellowship Training (PACT) Committee of the Neurocritical Care Society (NCS) was convened to promote and support excellence in the training and certification of neurointensivists. One of the first tasks of the committee was to survey neurocritical care fellowship training program directors to ascertain the current state of fellowship training and attitudes regarding transition to Accreditation Council for Graduate Medical Education (ACGME) accreditation of training programs and American Board of Medical Specialties (ABMS) certification of physicians. First, the survey revealed significant heterogeneities in the manner of neurocritical care training and a lack of consistency in requirements for fellow procedural competency. Second, although a majority of the 33 respondents indicated that a move toward ACGME accreditation/ABMS certification would facilitate further growth and mainstreaming of training in neurocritical care, many programs do not currently meet administrative requirements and do not receive the level of institutional support that would be needed for such a transition. In summary, the results revealed that there is an opportunity for future harmonization of training standards and that a transition to ACGME accreditation/ABMS certification is preferred. While the results reflect the opinions of more than half of the survey respondents, they represent only a small sample of neurointensivists. © 2017 Dhar, Rajajee, Finley Caulfield, Maas, James, Kumar, Figueroa, McDonagh and Ardelt.


Author Keywords
Accreditation;  Certification;  Fellowship;  Neurocritical care;  Training


Document Type: Article
Source: Scopus

10) 

Küry, S., van Woerden, G.M., Besnard, T., Proietti Onori, M., Latypova, X., Towne, M.C., Cho, M.T., Prescott, T.E., Ploeg, M.A., Sanders, S., Stessman, H.A.F., Pujol, A., Distel, B., Robak, L.A., Bernstein, J.A., Denommé-Pichon, A.-S., Lesca, G., Sellars, E.A., Berg, J., Carré, W., Busk, ØL., van Bon, B.W.M., Waugh, J.L., Deardorff, M., Hoganson, G.E., Bosanko, K.B., Johnson, D.S., Dabir, T., Holla, ØL., Sarkar, A., Tveten, K., de Bellescize, J., Braathen, G.J., Terhal, P.A., Grange, D.K., van Haeringen, A., Lam, C., Mirzaa, G., Burton, J., Bhoj, E.J., Douglas, J., Santani, A.B., Nesbitt, A.I., Helbig, K.L., Andrews, M.V., Begtrup, A., Tang, S., van Gassen, K.L.I., Juusola, J., Foss, K., Enns, G.M., Moog, U., Hinderhofer, K., Paramasivam, N., Lincoln, S., Kusako, B.H., Lindenbaum, P., Charpentier, E., Nowak, C.B., Cherot, E., Simonet, T., Ruivenkamp, C.A.L., Hahn, S., Brownstein, C.A., Xia, F., Schmitt, S., Deb, W., Bonneau, D., Nizon, M., Quinquis, D., Chelly, J., Rudolf, G., Sanlaville, D., Parent, P., Gilbert-Dussardier, B., Toutain, A., Sutton, V.R., Thies, J., Peart-Vissers, L.E.L.M., Boisseau, P., Vincent, M., Grabrucker, A.M., Dubourg, C., Undiagnosed Diseases Network, Tan, W.-H., Verbeek, N.E., Granzow, M., Santen, G.W.E., Shendure, J., Isidor, B., Pasquier, L., Redon, R., Yang, Y., State, M.W., Kleefstra, T., Cogné, B., GEM HUGO, Deciphering Developmental Disorders Study, Petrovski, S., Retterer, K., Eichler, E.E., Rosenfeld, J.A., Agrawal, P.B., Bézieau, S., Odent, S., Elgersma, Y., Mercier, S.
De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability
(2017) American journal of human genetics, 101 (5), pp. 768-788. 

DOI: 10.1016/j.ajhg.2017.10.003


a CHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France. Electronic address: sebastien.kury@chu-nantes.fr
b Department of Neuroscience, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands; ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands
c CHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France
d Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Gene Discovery Core, The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA
e GeneDx, Gaithersburg, MD 20877, USA
f Department of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway
g Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA
h Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Department of Pharmacology, Creighton University Medical School, Omaha, NE 68178, USA
i Neurometabolic Diseases Laboratory, IDIBELL, Gran Via, 199, L'Hospitalet de Llobregat, 08908 Barcelona, and CIBERER U759, Center for Biomedical Research on Rare Diseases, 08908 Barcelona, Spain; Catalan Institution of Research and Advanced Studies (ICREA), 08010 Barcelona, Spain
j Department of Neuroscience, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands; ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands; Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, the Netherlands
k Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
l Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
m CHU Angers, Département de Biochimie et Génétique, 49933 Angers Cedex 9, France; UMR INSERM 1083 - CNRS 6015, 49933 Angers Cedex 9, France
n Service de génétique, Centre de Référence des Anomalies du Développement, Hospices Civils de Lyon, 69288 Lyon, France; INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, 69675 Bron, France
o Section of Genetics and Metabolism, Arkansas Children's Hospital, Little Rock, AR 72202, USA
p Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital & Medical School, Dundee DD1 9SY, UK
q Laboratoire de Génétique Moléculaire & Génomique, CHU de Rennes, 35033 Rennes, France
r Department of Human Genetics, Nijmegen Center for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, the Netherlands
s Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA
t Department of Pediatrics, Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
u Department of Pediatrics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA
v Sheffield Children's Hospital, Western Bank, Sheffield S10 2TH, UK
w Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK
x Nottingham Regional Genetics Service, City Hospital Campus, Nottingham University Hospitals NHS Trust, The Gables, Hucknall Road, Nottingham NG5 1PB, UK
y Epilepsy, Sleep and Pediatric Neurophysiology Department, Hospices Civils, Lyon, 69677 Bron, France
z Department of Genetics, University Medical Center Utrecht, Utrecht 3584 EA, the Netherlands
aa Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO 63110, USA
ab Department of Clinical Genetics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, the Netherlands
ac Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital, Seattle, WA 98105, USA
ad Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital, Seattle, WA 98105, USA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA
ae Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
af Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA
ag Division of Genomic Diagnostics, Department of Path and Lab Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Path and Lab Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-4238, USA
ah Division of Genomic Diagnostics, Department of Path and Lab Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
ai Division of Clinical Genomics, Ambry Genetics, 15 Argonaut, Aliso Viejo, CA 92656, USA; Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
aj Division of Clinical Genomics, Ambry Genetics, 15 Argonaut, Aliso Viejo, CA 92656, USA
ak Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA
al Institute of Human Genetics, University Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany
am Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany and Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
an INSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France; CHU Nantes, l'institut du thorax, 44093 Nantes, France
ao Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics, Houston, TX 77030, USA
ap Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, 67091 Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 67000 Strasbourg, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, 67404 Illkirch, France
aq Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 67000 Strasbourg, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, 67404 Illkirch, France; Service of Neurology, University Hospital of Strasbourg, Hospital of Hautepierre, 1 avenue Molière, 67098 Strasbourg Cedex, France
ar CHRU Brest, Génétique médicale, 29609 Brest, France
as CHU Poitiers, Service de Génétique, BP577, 86021 Poitiers, France; EA 3808 Université Poitiers, France
at CHU Tours, Service de Génétique, 2 Boulevard Tonnellé, 37044 Tours, France
au Baylor Genetics, Houston, TX 77030, USA
av Division of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA 98105, USA
aw Department of Biological Sciences, University of Limerick, Limerick V94 T9PX, Ireland; Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland
ax Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA
ay CHU Rennes, Service de Génétique Clinique, CNRS UMR6290, Université Rennes1, 35203 Rennes, France
az Réseau de génétique et génomique médicale - Hôpitaux Universitaires du Grand Ouest, CHU Rennes, Service de Génétique Clinique, 35203 Rennes, France
ba Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK
bb Department of Medicine, The University of Melbourne, Austin Health and Royal Melbourne Hospital, Melbourne, VIC 3010, Australia
bc Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Gene Discovery Core, The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Newborn Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA
bd CHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France; CRCINA, Inserm, Université d'Angers, Université de Nantes, 44000 Nantes, France


Abstract
Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathway. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.


Author Keywords
AMPAR;  CAMK2;  CAMK2A;  CAMK2B;  de novo mutations;  intellectual disability;  NMDAR;  synaptic plasticity


Document Type: Article
Source: Scopus

11) 

Hamdan, F.F., Myers, C.T., Cossette, P., Lemay, P., Spiegelman, D., Laporte, A.D., Nassif, C., Diallo, O., Monlong, J., Cadieux-Dion, M., Dobrzeniecka, S., Meloche, C., Retterer, K., Cho, M.T., Rosenfeld, J.A., Bi, W., Massicotte, C., Miguet, M., Brunga, L., Regan, B.M., Mo, K., Tam, C., Schneider, A., Hollingsworth, G., Deciphering Developmental Disorders Study, FitzPatrick, D.R., Donaldson, A., Canham, N., Blair, E., Kerr, B., Fry, A.E., Thomas, R.H., Shelagh, J., Hurst, J.A., Brittain, H., Blyth, M., Lebel, R.R., Gerkes, E.H., Davis-Keppen, L., Stein, Q., Chung, W.K., Dorison, S.J., Benke, P.J., Fassi, E., Corsten-Janssen, N., Kamsteeg, E.-J., Mau-Them, F.T., Bruel, A.-L., Verloes, A., Õunap, K., Wojcik, M.H., Albert, D.V.F., Venkateswaran, S., Ware, T., Jones, D., Liu, Y.-C., Mohammad, S.S., Bizargity, P., Bacino, C.A., Leuzzi, V., Martinelli, S., Dallapiccola, B., Tartaglia, M., Blumkin, L., Wierenga, K.J., Purcarin, G., O'Byrne, J.J., Stockler, S., Lehman, A., Keren, B., Nougues, M.-C., Mignot, C., Auvin, S., Nava, C., Hiatt, S.M., Bebin, M., Shao, Y., Scaglia, F., Lalani, S.R., Frye, R.E., Jarjour, I.T., Jacques, S., Boucher, R.-M., Riou, E., Srour, M., Carmant, L., Lortie, A., Major, P., Diadori, P., Dubeau, F., D'Anjou, G., Bourque, G., Berkovic, S.F., Sadleir, L.G., Campeau, P.M., Kibar, Z., Lafrenière, R.G., Girard, S.L., Mercimek-Mahmutoglu, S., Boelman, C., Rouleau, G.A., Scheffer, I.E., Mefford, H.C., Andrade, D.M., Rossignol, E., Minassian, B.A., Michaud, J.L.
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies
(2017) American journal of human genetics, 101 (5), pp. 664-685. 

DOI: 10.1016/j.ajhg.2017.09.008


a Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada
b Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA 98195, USA
c Centre Hospitalier de l'Université de Montréal Research Center, Montreal, QC H2X 0A9, Canada; Department of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada
d Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A2B4, Canada
e McGill University and Genome Quebec Innovation Center, Montreal, QC H3A 1A4, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada
f Centre Hospitalier de l'Université de Montréal Research Center, Montreal, QC H2X 0A9, Canada; Center for Pediatric Genomic Medicine, Children's Mercy Kansas City, Kansas City, MO 64108, USA; Department of Pathology and Laboratory Medicine, Children's Mercy Kansas City, Kansas City, MO 64108, USA
g Centre Hospitalier de l'Université de Montréal Research Center, Montreal, QC H2X 0A9, Canada
h GeneDx, Gaithersburg, MD 20877, USA
i Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
j Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Baylor College of Medicine, Houston, TX 77021, USA
k Program in Genetics and Genome Biology, Division of Neurology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON M5G 0A4, Canada
l Division of Neurology, Epilepsy Genetics Program, Krembil Neuroscience Centre, Toronto Western Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada
m Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia
n Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
o MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK
p Clinical Genetics Service, University Hospitals Bristol NHS Foundation Trust, St. Michael's Hospital, St. Michael's Hill, Bristol BS2 8DT, UK
q North West Thames Regional Genetics Service, London North West Healthcare NHS Trust, Northwick Park Hospital, Watford Road, Harrow HA1 3UJ, UK
r Oxford Centre for Genomic Medicine, ACE building Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7HE, UK
s Manchester Centre for Genomic Medicine, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK
t Institute of Medical Genetics, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK
u MRC Centre for Neuropsychiatric Genetics & Genomics, Hadyn Ellis Building, Cathays, Cardiff University, Cardiff CF24 4HQ, UK
v West of Scotland Regional Genetics Service, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK
w North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London WC1N 3JH, UK
x Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Department of Clinical Genetics, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK
y Department of Pediatrics, Section of Medical Genetics, SUNY Upstate Medical University, Syracuse, NY 13210, USA
z University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, the Netherlands
aa University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57117, USA
ab Augustana-Sanford Genetic Counseling Graduate Program, Sioux Falls, SD 57197, USA
ac Departments of Medicine and Pediatrics, Columbia University Medical Center, New York, NY 10032, USA
ad Baptist Hospital, Miami, FL 33176 USA
ae Joe DiMaggio Children's Hospital, Hollywood, FL 33021, USA
af Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA
ag Department of Human Genetics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands
ah Centre de Génétique des Anomalies du Développement, Centre Hospitalier Universitaire de Dijon, 21000 Dijon, France; Équipe INSERM 1231, Génétique des Anomalies du Développement, Université de Bourgogne, 21000 Dijon, France
ai Genetics Department, Assistance Publique - Hôpitaux de Paris, Robert-Debré University Hospital, 75000 Paris, France
aj Department of Clinical Genetics, United Laboratories, Tartu University Hospital and Institute of Clinical Medicine, University of Tartu, Tartu 51014, Estonia
ak Division of Genetics and Genomics and Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
al Nationwide Children's Hospital and Ohio State University, Department of Pediatrics, Division of Neurology, Columbus, OH 43205, USA
am Division of Neurology, Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada
an University of Tasmania, Royal Hobart Hospital, Department of Paediatrics, Hobart, TAS 7000, Australia
ao School of Medicine, University of Tasmania, Hobart, TAS 7000, Australia
ap Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia
aq Children's Hospital at Westmead Clinical School, University of Sydney, Westmead, NSW 2145, Australia
ar Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA
as Dipartimento di Pediatria e di Neuropsichiatria Infantile, Università La Sapienza, 00185 Rome, Italy
at Dipartimento di Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, 00161 Rome, Italy
au Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy
av Metabolic Neurogenetic Clinic and Pediatric Movement Disorders Clinic, Wolfson Medical Center, Holon 5822012, Israel
aw University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
ax University of British Columbia, BC Children's Hospital, Vancouver, BC V6H 3N1, Canada
ay Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada
az Département de Génétique, Centre de Référence des Déficiences Intellectuelles de Causes Rares, Groupe de Recherche Clinique "Déficiences Intellectuelles et Autisme," Université Pierre et Marie Curie, Hôpital de la Pitié-Salpêtrière, Paris 75013, France; Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), UMRS 1127, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle Épinière, Paris 75013, France
ba Assistance Publique - Hôpitaux de Paris, Hôpital d'Enfants Armand Trousseau, Service de Neuropédiatrie, Paris 75012, France
bb Université Paris Diderot, Sorbonne Paris Cité, INSERM UMR 1141, Paris 75019, France; Assistance Publique - Hôpitaux de Paris, Hôpital Robert Debré, Service de Neurologie Pédiatrique, Paris 75019, France
bc HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA
bd Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
be Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Arkansas Children's Research Institute, Little Rock, AR 72205, USA
bf Texas Children's Hospital and Baylor College of Medicine, Houston, TX 77030, USA
bg Centre Hospitalier Rouyn-Noranda, Rouyn-Noranda, QC J9X 2B2, Canada
bh Division of Neurology, Centre Hospitalier Universitaire de Québec, Quebec, QC G1V 4G2, Canada
bi Department of Pediatrics, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
bj Department of Pediatrics, McGill University, Montreal, QC H3A 1A4, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 1A4, Canada
bk Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada; Department of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada
bl Department of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada
bm Department of Pediatrics and Child Health, University of Otago, Wellington 9016, New Zealand
bn Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada
bo Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada; Department of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada
bp Centre Hospitalier de l'Université de Montréal Research Center, Montreal, QC H2X 0A9, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Département des Sciences Fondamentales, Université du Québec à Chicoutimi, Chicoutimi, QC G7H 2B1, Canada
bq Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
br Division of Neurology, BC Children's Hospital, Vancouver, BC V6H 3N1, Canada
bs Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia; Department of Pediatrics, University of Melbourne Royal Children's Hospital, Parkville, VIC 3052, Australia; Florey Institute of Neuroscience and Mental Health, Melbourne, VIC 3084, Australia
bt Program in Genetics and Genome Biology, Division of Neurology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON M5G 0A4, Canada; Division of Child Neurology, Department of Pediatrics, University of Texas Southwestern, Dallas, TX 75390, USA


Abstract
Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. We sought to identify additional subjects with DNMs in these genes by performing targeted sequencing in another series of individuals with DEE and by mining various sequencing datasets. We also performed meta-analyses to document enrichment of DNMs in candidate genes by leveraging our WGS dataset with those of several DEE and ID series. By combining these strategies, we were able to provide a causal link between DEE and the following genes: NTRK2, GABRB2, CLTC, DHDDS, NUS1, RAB11A, GABBR2, and SNAP25. Overall, we established a molecular diagnosis in 63/197 (32%) individuals in our WGS series. The main cause of DEE in these individuals was de novo point mutations (53/63 solved cases), followed by inherited mutations (6/63 solved cases) and de novo CNVs (4/63 solved cases). De novo missense variants explained a larger proportion of individuals in our series than in other series that were primarily ascertained because of ID. Moreover, these DNMs were more frequently recurrent than those identified in ID series. These observations indicate that the genetic landscape of DEE might be different from that of ID without epilepsy. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.


Author Keywords
CLTC;  DHDDS;  epileptic encephalopathy;  GABBR2;  GABRB2;  NTRK2;  NUS1;  RAB11;  SNAP25


Document Type: Article
Source: Scopus

 

12) 

Evanoff, A.B., Quan, T., Dufault, C., Awad, M., Bierut, L.J.
Physicians-in-training are not prepared to prescribe medical marijuana
(2017) Drug and Alcohol Dependence, 180, pp. 151-155. 

DOI: 10.1016/j.drugalcdep.2017.08.010


a Medical Education, Washington University School of Medicine, St. Louis, MO, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United States
d Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Background While medical marijuana use is legal in more than half of U.S. states, evidence is limited about the preparation of physicians-in-training to prescribe medical marijuana. We asked whether current medical school and graduate medical educational training prepare physicians to prescribe medical marijuana. Methods We conducted a national survey of U.S. medical school curriculum deans, a similar survey of residents and fellows at Washington University in St. Louis, and a query of the Association of American Medical Colleges (AAMC) Curriculum Inventory database for keywords associated with medical marijuana. Results Surveys were obtained from 101 curriculum deans, and 258 residents and fellows. 145 schools were included in the curriculum search. The majority of deans (66.7%) reported that their graduates were not at all prepared to prescribe medical marijuana, and 25.0% reported that their graduates were not at all prepared to answer questions about medical marijuana. The vast majority of residents and fellows (89.5%) felt not at all prepared to prescribe medical marijuana, while 35.3% felt not at all prepared to answer questions, and 84.9% reported receiving no education in medical school or residency on medical marijuana. Finally, only 9% of medical school curriculums document in the AAMC Curriculum Inventory database content on medical marijuana. Conclusions Our study highlights a fundamental mismatch between the state-level legalization of medical marijuana and the lack of preparation of physicians-in-training to prescribe it. With even more states on the cusp of legalizing medical marijuana, physician training should adapt to encompass this new reality of medical practice. © 2017 Elsevier B.V.


Author Keywords
Cannabis;  Marijuana;  Medical education


Document Type: Article
Source: Scopus

13) 

Zhou, Y., Yang, H., Cui, J., Lingle, C.J.
Threading the biophysics of mammalian Slo1 channels onto structures of an invertebrate Slo1 channel
(2017) Journal of General Physiology, 149 (11), pp. 985-1007. 

DOI: 10.1085/jgp.201711845


a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
c Department of Biochemistry, Duke University School of Medicine, Durham, NC, United States


Abstract
For those interested in the machinery of ion channel gating, the Ca2+ and voltage-activated BK K+ channel provides a compelling topic for investigation, by virtue of its dual allosteric regulation by both voltage and intracellular Ca2+ and because its large-single channel conductance facilitates detailed kinetic analysis. Over the years, biophysical analyses have illuminated details of the allosteric regulation of BK channels and revealed insights into the mechanism of BK gating, e.g., inner cavity size and accessibility and voltage sensor-pore coupling. Now the publication of two structures of an Aplysia californica BK channel-one liganded and one metal free-promises to reinvigorate functional studies and interpretation of biophysical results. The new structures confirm some of the previous functional inferences but also suggest new perspectives regarding cooperativity between Ca2+-binding sites and the relationship between voltage- and Ca2+-dependent gating. Here we consider the extent to which the two structures explain previous functional data on pore-domain properties, voltage-sensor motions, and divalent cation binding and activation of the channel. © 2017 Zhou et al.


Document Type: Review
Source: Scopus

 

14) 

Stephens, R.J., Ablordeppey, E., Drewry, A.M., Palmer, C., Wessman, B.T., Mohr, N.M., Roberts, B.W., Liang, S.Y., Kollef, M.H., Fuller, B.M.
Analgosedation Practices and the Impact of Sedation Depth on Clinical Outcomes Among Patients Requiring Mechanical Ventilation in the ED: A Cohort Study
(2017) Chest, 152 (5), pp. 963-971. 

DOI: 10.1016/j.chest.2017.05.041


a Washington University School of Medicine in St. Louis, St. Louis, MO, United States
b Departments of Emergency Medicine and Anesthesiology, Division of Critical Care, Washington School of Medicine in St. Louis, St. Louis, MO, United States
c Departments of Medicine and Emergency Medicine, Division of Infectious Diseases, Washington School of Medicine in St. Louis, St. Louis, MO, United States
d Department of Medicine, Division of Pulmonary and Critical Care Medicine, Washington School of Medicine in St. Louis, St. Louis, MO, United States
e Department of Anesthesiology, Division of Critical Care Medicine, Washington School of Medicine in St. Louis, St. Louis, MO, United States
f Departments of Emergency Medicine and Anesthesiology, Division of Critical Care Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States
g Department of Emergency Medicine, Cooper University Hospital, Camden, NJ, United States


Abstract
Background Analgesia and sedation are cornerstone therapies for mechanically ventilated patients. Despite data showing that early deep sedation in the ICU influences outcome, this has not been investigated in the ED. Therefore, ED-based sedation practices, and their influence on outcome, remain incompletely defined. This study's objectives were to describe ED sedation practices in mechanically ventilated patients and to test the hypothesis that ED sedation depth is associated with worse outcomes. Methods This was a cohort study of a prospectively compiled ED registry of adult mechanically ventilated patients at a single academic medical center. Hospital mortality was the primary outcome and hospital-, ICU-, and ventilator-free days were secondary outcomes. A backward stepwise multivariable logistic regression model evaluated the primary outcome as a function of ED sedation depth. Sedation depth was assessed with the Richmond Agitation-Sedation Scale (RASS). Results Four hundred fourteen patients were studied. In the ED, 354 patients (85.5%) received fentanyl, 254 (61.3%) received midazolam, and 194 (46.9%) received propofol. Deep sedation was observed in 244 patients (64.0%). After adjusting for confounders, a deeper ED RASS was associated with mortality (adjusted OR, 0.77; 95% CI, 0.63-0.94). Conclusions Early deep sedation is common in mechanically ventilated ED patients and is associated with worse mortality. These data suggest that ED-based sedation is a modifiable variable that could be targeted to improve outcome. © 2017 American College of Chest Physicians


Author Keywords
ED;  mechanical ventilation;  sedation depth


Document Type: Article
Source: Scopus

15) 

Andersen, A.M., Pietrzak, R.H., Kranzler, H.R., Ma, L., Zhou, H., Liu, X., Kramer, J., Kuperman, S., Edenberg, H.J., Nurnberger, J.I., Jr, Rice, J.P., Tischfield, J.A., Goate, A., Foroud, T.M., Meyers, J.L., Porjesz, B., Dick, D.M., Hesselbrock, V., Boerwinkle, E., Southwick, S.M., Krystal, J.H., Weissman, M.M., Levinson, D.F., Potash, J.B., Gelernter, J., Han, S.
Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence
(2017) JAMA psychiatry, 74 (11), pp. 1153-1160. 

DOI: 10.1001/jamapsychiatry.2017.2269


a Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City
b US Department of Veterans Affairs (VA) National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven
c Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
d Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia
e Mental Illness, Research, Education and Clinical Center of Veterans Integrated Service Network 4, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania
f Department of Animal and Avian Sciences, University of Maryland, College Park
g Human Genetics Center, University of Texas Health Science Center at Houston
h Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis
i Department of Psychiatry, Indiana University School of Medicine, Indianapolis
j Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri
k Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway
l Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York
m Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis
n Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn
o Departments of Psychology and Human and Molecular Genetics, Virginia Commonwealth University, Richmond
p Department of Psychiatry, University of Connecticut School of Medicine, Farmington
q Division of Epidemiology, New York State Psychiatric Institute, New York
r Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, New York
s Columbia University, Mailman School of Public Health, New York, New York
t Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California
u Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City
v now with the Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland


Abstract
Importance: Major depressive disorder (MDD) and alcohol dependence (AD) are heritable disorders with significant public health burdens, and they are frequently comorbid. Common genetic factors that influence the co-occurrence of MDD and AD have been sought in family, twin, and adoption studies, and results to date have been promising but inconclusive.

Objective: To examine whether AD and MDD overlap genetically, using a polygenic score approach.

Design, Settings, and Participants: Association analyses were conducted between MDD polygenic risk score (PRS) and AD case-control status in European ancestry samples from 4 independent genome-wide association study (GWAS) data sets: the Collaborative Study on the Genetics of Alcoholism (COGA); the Study of Addiction, Genetics, and Environment (SAGE); the Yale-Penn genetic study of substance dependence; and the National Health and Resilience in Veterans Study (NHRVS). Results from a meta-analysis of MDD (9240 patients with MDD and 9519 controls) from the Psychiatric Genomics Consortium were applied to calculate PRS at thresholds from P < .05 to P ≤ .99 in each AD GWAS data set.

Main Outcomes and Measures: Association between MDD PRS and AD.

Results: Participants analyzed included 788 cases (548 [69.5%] men; mean [SD] age, 38.2 [10.8] years) and 522 controls (151 [28.9.%] men; age [SD], 43.9 [11.6] years) from COGA; 631 cases (333 [52.8%] men; age [SD], 35.0 [7.7] years) and 756 controls (260 [34.4%] male; age [SD] 36.1 [7.7] years) from SAGE; 2135 cases (1375 [64.4%] men; age [SD], 39.4 [11.5] years) and 350 controls (126 [36.0%] men; age [SD], 43.5 [13.9] years) from Yale-Penn; and 317 cases (295 [93.1%] men; age [SD], 59.1 [13.1] years) and 1719 controls (1545 [89.9%] men; age [SD], 64.5 [13.3] years) from NHRVS. Higher MDD PRS was associated with a significantly increased risk of AD in all samples (COGA: best P = 1.7 × 10-6, R2 = 0.026; SAGE: best P = .001, R2 = 0.01; Yale-Penn: best P = .035, R2 = 0.0018; and NHRVS: best P = .004, R2 = 0.0074), with stronger evidence for association after meta-analysis of the 4 samples (best P = 3.3 × 10-9). In analyses adjusted for MDD status in 3 AD GWAS data sets, similar patterns of association were observed (COGA: best P = 7.6 × 10-6, R2 = 0.023; Yale-Penn: best P = .08, R2 = 0.0013; and NHRVS: best P = .006, R2 = 0.0072). After recalculating MDD PRS using MDD GWAS data sets without comorbid MDD-AD cases, significant evidence was observed for an association between the MDD PRS and AD in the meta-analysis of 3 GWAS AD samples without MDD cases (best P = .007).

Conclusions and Relevance: These results suggest that shared genetic susceptibility contributes modestly to MDD and AD comorbidity. Individuals with elevated polygenic risk for MDD may also be at risk for AD.


Document Type: Article
Source: Scopus

 

16) 

Curley, K.C., O'Neil, B.J., Naunheim, R., Wright, D.W.
Intracranial Pathology (CT+) in Emergency Department Patients With High GCS and High Standard Assessment of Concussion (SAC) Scores
(2017) Journal of Head Trauma Rehabilitation, . Article in Press. 

DOI: 10.1097/HTR.0000000000000355


Iatrikos Research and Development Strategies, LLC, Tampa, Florida (Dr Curley); Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland (Dr Curley); Department of Emergency Medicine, School of Medicine, Wayne State University, Detroit, Michigan (Dr O'Neil); Department of Emergency Medicine, Washington University School of Medicine, St Louis, Missouri (Dr Naunheim); and Department of Emergency Medicine, Emory University School of Medicine, and Grady Memorial Hospital, Atlanta, Georgia (Dr Wright).


Abstract
Objective: To demonstrate that a subpopulation of patients with mild/moderate traumatic brain injury (TBI) had intracranial pathology despite having a Glasgow Coma Scale (GCS) score of 15 and a Standardized Assessment of Concussion (SAC) score of 25 or higher. Setting: A network of 11 US emergency departments (ED) enrolling patients in a multisite study of TBI. Participants: Men and women between the ages of 18 and 85 years admitted to a participating ED having sustained a closed head injury within the prior 72 hours and a GCS score of 13 to 15 at the time of enrollment. Design: Prospective observational study. Main Measures: GCS, SAC, computed tomography (CT) positive or negative for intracranial pathology, Marshall scoring of CT scans. Results: Of 191 patients with intracranial pathology (CT+) and having a SAC score recorded, 24% (46/191) had a SAC score in the normal range (≥25) as well as a GCS score of 15. All causes of CT+ brain injury were present in both SAC groups. Conclusion: A normal GCS score and a SAC score do not exclude the possibility of significant intracranial injury. © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Author Keywords
assessment;  brain bleed;  concussion;  CT;  neurocognitive testing;  TBI;  traumatic hematoma


Document Type: Article in Press
Source: Scopus

 

 

17) 

Gaffrey, M.S., Barch, D.M., Bogdan, R., Farris, K., Petersen, S.E., Luby, J.L.
Amygdala Reward Reactivity Mediates the Association Between Preschool Stress Response and Depression Severity
(2017) Biological Psychiatry, . Article in Press. 

DOI: 10.1016/j.biopsych.2017.08.020


a Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri
b Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, Missouri
c Department of Radiology, Washington University in St. Louis, St. Louis, Missouri


Abstract
Background: Research in adolescents and adults has suggested that altered neural processing of reward following early life adversity is a highly promising depressive intermediate phenotype. However, very little is known about how stress response, neural processing of reward, and depression are related in very young children. The present study examined the concurrent associations between cortisol response following a stressor, functional brain activity to reward, and depression severity in children 4 to 6 years old. Methods: Medication-naïve children 4 to 6 years old (N = 52) participated in a study using functional magnetic resonance imaging to assess neural reactivity to reward, including gain, loss, and neutral outcomes. Parent-reported child depression severity and child cortisol response following stress were also measured. Results: Greater caudate and medial prefrontal cortex reactivity to gain outcomes and increased amygdala reactivity to salient (i.e., both gain and loss) outcomes were observed. Higher total cortisol output following a stressor was associated with increased depression severity and reduced amygdala reactivity to salient outcomes. Amygdala reactivity was also inversely associated with depression severity and was found to mediate the relationship between cortisol output and depression severity. Conclusions: Results suggest that altered neural processing of reward is already related to increased cortisol output and depression severity in preschoolers. These results also demonstrate an important role for amygdala function as a mediator of this relationship at a very early age. Our results further underscore early childhood as an important developmental period for understanding the neurobiological correlates of early stress and increased risk for depression. © 2017 Society of Biological Psychiatry.


Author Keywords
Amygdala;  Depression;  Development;  FMRI;  Reward processing;  Stress


Document Type: Article in Press
Source: Scopus

November 20, 2017

1) 

Gebara, M.A., Kasckow, J., Smagula, S.F., DiNapoli, E.A., Karp, J.F., Lenze, E.J., Mulsant, B.H., Reynolds, C.F., III
The role of late life depressive symptoms on the trajectories of insomnia symptoms during antidepressant treatment
(2018) Journal of Psychiatric Research, 96, pp. 162-166. 

DOI: 10.1016/j.jpsychires.2017.10.013


a VISN 4 Mental Illness Research, Education and Clinical Center (MIRECC), VA Pittsburgh Health Care System, Pittsburgh, PA, United States
b Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
c Beckley Health Care System, Behavioral Health, Beckley, WV, United States
d Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
e Department of Psychiatry, University of Toronto, Toronto, Canada


Abstract
Objective Sleep disturbances are common in late life depression; however, changes in insomnia symptoms during antidepressant treatment need to be characterized further. The objective of this study was two-fold: 1) to describe longitudinal trajectories of insomnia symptoms in older adults receiving antidepressant treatment and 2) to examine whether baseline depressive symptoms were associated with trajectories of sleep over time. Methods Data was obtained from 680 older adults (aged ≥ 60) with major depression who participated in one of two protocolized open-label antidepressant treatment clinical trials (Maintenance Therapies in Late Life Depression [MTLD-3]; Incomplete Response in Late Life Depression: Getting to Remission [IRL-GRey]). Depression (total score minus sleep items) and sleep (sum of sleep items) outcomes were derived from the Hamilton Depression Rating Scale in the MLTD-3 and Montgomery-Asberg Depression Rating Scale in the IRL-GRey. Results Both datasets identified 5 possible trajectories of insomnia symptoms with about half of the older adults having clinically significant baseline sleep disturbances and minimal improvement following a course of antidepressant treatment (i.e., sub-optimal sleep trajectory). Furthermore, across both datasets, worse baseline depression severity was associated with sub-optimal sleep trajectories. Conclusion In older adults receiving antidepressant treatment, those with clinically significant baseline sleep disturbances and greater depression severity may require adjunctive sleep-focused treatment to ameliorate sleep symptoms. © 2017 Elsevier Ltd


Author Keywords
Aging;  Antidepressant treatment;  Depression;  Sleep trajectories


Document Type: Article
Source: Scopus

 

2) 

Liu, S., Jiao, J., Lu, T.J., Xu, F., Pickard, B.G., Genin, G.M.
Arabidopsis Leaf Trichomes as Acoustic Antennae
(2017) Biophysical Journal, 113 (9), pp. 2068-2076. 

DOI: 10.1016/j.bpj.2017.07.035


a Biomedical Engineering and Biomechanics Center (BEBC), School of Life Sciences, Xi'an Jiaotong University, Xi'an, China
b Ministry of Education Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
c Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, Missouri, United States
d Gladys Levis Allen Laboratory of Plant Sensory Physiology, Biology Department, Washington University in St. Louis, St. Louis, Missouri, United States
e NSF Center for Engineering MechanoBiology, Washington University in St. Louis, St. Louis, Missouri, United States
f Ministry of Education Key Laboratory for Multifunction Materials and Structures (LMMS), Xi'an Jiaotong University, Xi'an, China


Abstract
The much studied plant Arabidopsis thaliana has been reported recently to react to the sounds of caterpillars of Pieris rapae chewing on its leaves by promoting synthesis of toxins that can deter herbivory. Identifying participating receptor cells—potential “ears”—of Arabidopsis is critical to understanding and harnessing this response. Motivated in part by other recent observations that Arabidopsis trichomes (hair cells) respond to mechanical stimuli such as pressing or brushing by initiating potential signaling factors in themselves and in the neighboring skirt of cells, we analyzed the vibrational responses of Arabidopsis trichomes to test the hypothesis that trichomes can respond acoustically to vibrations associated with feeding caterpillars. We found that these trichomes have vibrational modes in the frequency range of the sounds of feeding caterpillars, encouraging further experimentation to determine whether trichomes serve as mechanical antennae. © 2017 Biophysical Society


Document Type: Article
Source: Scopus

 

3) 

Ogilvie, M.P., Few, J.W., Jr., Semersky, A.J., Kulick, N.T., Vorisek, M.K.
What Neurotoxins Have Taught Us About the Brow: The Reintroduction and Review of the Transpalpebral Browpexy
(2017) Aesthetic Plastic Surgery, pp. 1-11. Article in Press. 

DOI: 10.1007/s00266-017-0988-7


a The Few Institute for Aesthetic Plastic Surgery, Chicago, IL, United States
b Division of Plastic Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL, United States
c Division of Plastic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
d University of North Carolina, Chapel Hill, NC, United States
e Northwestern University, Evanston, IL, United States
f Washington University, Saint Louis, MO, United States
g Division of Plastic and Reconstructive Surgery, Christ Medical Center, Advocate Medical Group, Oak Lawn, IL, United States


Abstract
Introduction: The use of neuromodulators has grown substantially in our society, particularly in the temporary treatment of brow ptosis. This study revisits the use of the transpalpebral browpexy for upper face and brow rejuvenation in the context of what has been learned from neuromodulators. Methods: A retrospective review of 97 subjects was conducted who had transpalpebral browpexy performed for lateral brow ptosis. Qualitative degree of brow elevation after the procedure was determined by examining before and after photographs for each patient. Results: Out of 97 patients, 95 (98%) experienced aesthetically optimal brow elevation for their respective gender. Two patients required surgical revision, both of which experienced extenuating circumstances. Two patients experienced edema and one patient experienced periodic eruptions of chalazia along the upper eyelid. Conclusion: Transpalpebral browpexy is a reliable, minimally invasive surgical procedure that effectively emulates the results of neuromodulator injections for a much longer period of time. While it cannot replace traditional brow-lifting techniques, transpalpebral browpexy does have solid indications with proven long-lasting results, which can be effective in a significant portion of patients with brow ptosis. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. © 2017 Springer Science+Business Media, LLC and International Society of Aesthetic Plastic Surgery


Author Keywords
Brow lift;  Browpexy;  Coronal brow lift;  Endoscopic brow lift;  Neuromodulator;  Neurotoxin;  Open brow lift;  Pretrichial brow lift;  Transpalpebral browpexy


Document Type: Article in Press
Source: Scopus

 

4) 

Hoseini, M.S., Pobst, J., Wright, N., Clawson, W., Shew, W., Wessel, R.
Induced cortical oscillations in turtle cortex are coherent at the mesoscale of population activity, but not at the microscale of the membrane potential of neurons
(2017) Journal of Neurophysiology, 118 (5), pp. 2579-2591. 

DOI: 10.1152/jn.00375.2017


a Department of Physics, Washington University, Saint Louis, MO, United States
b Department of Electrical Engineering, University of Arkansas, Fayetteville, AR, United States
c Department of Physics, University of Arkansas, Fayetteville, AR, United States


Abstract
Bursts of oscillatory neural activity have been hypothesized to be a core mechanism by which remote brain regions can communicate. Such a hypothesis raises the question to what extent oscillations are coherent across spatially distant neural populations. To address this question, we obtained local field potential (LFP) and membrane potential recordings from the visual cortex of turtle in response to visual stimulation of the retina. The time-frequency analysis of these recordings revealed pronounced bursts of oscillatory neural activity and a large trial-to-trial variability in the spectral and temporal properties of the observed oscillations. First, local bursts of oscillations varied from trial to trial in both burst duration and peak frequency. Second, oscillations of a given recording site were not autocoherent; i.e., the phase did not progress linearly in time. Third, LFP oscillations at spatially separate locations within the visual cortex were more phase coherent in the presence of visual stimulation than during ongoing activity. In contrast, the membrane potential oscillations from pairs of simultaneously recorded pyramidal neurons showed smaller phase coherence, which did not change when switching from black screen to visual stimulation. In conclusion, neuronal oscillations at distant locations in visual cortex are coherent at the mesoscale of population activity, but coherence is largely absent at the microscale of the membrane potential of neurons. NEW & NOTEWORTHY Coherent oscillatory neural activity has long been hypothesized as a potential mechanism for communication across locations in the brain. In this study we confirm the existence of coherent oscillations at the mesoscale of integrated cortical population activity. However, at the microscopic level of neurons, we find no evidence for coherence among oscillatory membrane potential fluctuations. These results raise questions about the applicability of the communication through coherence hypothesis to the level of the membrane potential. © 2017 the American Physiological Society.


Author Keywords
Coherent oscillations;  Local field potential;  Membrane potential;  Microelectrode array;  Visual cortex


Document Type: Article
Source: Scopus

 

5) 

Forte, L.A., Gramlich, M.W., Klyachko, V.A.
Activity-dependence of synaptic vesicle dynamics
(2017) Journal of Neuroscience, 37 (44), pp. 10597-10610. 

DOI: 10.1523/JNEUROSCI.0383-17.2017


Department of Cell Biology and Physiology, Department of Biomedical Engineering, Washington University, St. Louis, MO, United States


Abstract
The proper function of synapses relies on efficient recycling of synaptic vesicles. The small size of synaptic boutons has hampered efforts to define the dynamical states of vesicles during recycling. Moreover, whether vesicle motion during recycling is regulated by neural activity remains largely unknown. We combined nanoscale-resolution tracking of individual synaptic vesicles in cultured hippocampal neurons from rats of both sexes with advanced motion analyses to demonstrate that the majority of recently endocytosed vesicles undergo sequences of transient dynamical states including epochs of directed, diffusional, and stalled motion. We observed that vesicle motion is modulated in an activity-dependent manner, with dynamical changes apparent in ~20% of observed boutons. Within this subpopulation of boutons, 35% of observed vesicles exhibited acceleration and 65% exhibited deceleration, accompanied by corresponding changes in directed motion. Individual vesicles observed in the remaining ~80% of boutons did not exhibit apparent dynamical changes in response to stimulation. More quantitative transient motion analyses revealed that the overall reduction of vesicle mobility, and specifically of the directed motion component, is the predominant activity-evoked change across the entire bouton population. Activity-dependent modulation of vesicle mobility may represent an important mechanism controlling vesicle availability and neurotransmitter release. © 2017 the authors.


Author Keywords
Activity-dependence;  Presynaptic function;  Single-particle tracking;  Synaptic vesicle;  Vesicle recycling


Document Type: Article
Source: Scopus

 

6) 

Hoseini, M.S., Pobst, J., Wright, N.C., Clawson, W., Shew, W., Wessel, R.
The turtle visual system mediates a complex spatiotemporal transformation of visual stimuli into cortical activity
(2017) Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology, pp. 1-15. Article in Press. 

DOI: 10.1007/s00359-017-1219-z


a Department of Physics, Washington University, St. Louis, MO, United States
b Department of Electrical Engineering, University of Arkansas, Fayetteville, AR, United States
c Department of Physics, University of Arkansas, Fayetteville, AR, United States


Abstract
The three-layered visual cortex of turtle is characterized by extensive intracortical axonal projections and receives non-retinotopic axonal projections from lateral geniculate nucleus. What spatiotemporal transformation of visual stimuli into cortical activity arises from such tangle of malleable cortical inputs and intracortical connections? To address this question, we obtained band-pass filtered extracellular recordings of neural activity in turtle dorsal cortex during visual stimulation of the retina. We discovered important spatial and temporal features of stimulus-modulated cortical local field potential (LFP) recordings. Spatial receptive fields span large areas of the visual field, have an intricate internal structure, and lack directional tuning. The receptive field structure varies across recording sites in a distant-dependent manner. Such composite spatial organization of stimulus-modulated cortical activity is accompanied by an equally multifaceted temporal organization. Cortical visual responses are delayed, persistent, and oscillatory. Further, prior cortical activity contributes globally to adaptation in turtle visual cortex. In conclusion, these results demonstrate convoluted spatiotemporal transformations of visual stimuli into stimulus-modulated cortical activity that, at present, largely evade computational frameworks. © 2017 Springer-Verlag GmbH Germany


Author Keywords
Oscillation;  Persistent activity;  Receptive field;  Turtle;  Visual cortex


Document Type: Article in Press
Source: Scopus

 

7) 

Pati, S., McClain, L., Moura, L., Fan, Y., Westover, M.B.
Accuracy of Limited-Montage Electroencephalography in Monitoring Postanoxic Comatose Patients
(2017) Clinical EEG and Neuroscience, 48 (6), pp. 422-427. 

DOI: 10.1177/1550059417715389


a Department of Neurology, Massachusetts General Hospital, Boston, MA, United States
b Department of Neurology, University of Alabama, Birmingham Hospital, 1719 6th Avenue South, CIRC 312, Birmingham, AL, United States
c Department of Neurology, Washington University, St Louis, MO, United States


Abstract
Background. Continuous EEG (cEEG) monitoring may help to identify the small percentage of adults with hypoxic-ischemic encephalopathy (HIE) who will regain consciousness if allowed sufficient time. However, the limited yield in this population has led some to question the cost-effectiveness cEEG monitoring in this population. We hypothesized that limited-montage cEEG could provide essentially the same neurophysiologic information at lower cost. In this proof of concept study, we aim to demonstrate the potentials of limited channel EEG in prognostication in postanoxic patients. Methods. We retrospectively reviewed cEEG data from cases monitored at our institution with conventional 21-channel EEG over a 6-month period. Twenty-eight cases were identified in which patients with HIE underwent cEEG for at least 24 hours. Gold-standard findings were determined by conventional visual analysis of the full cEEG, and 2 independent electroencephalographers scored the same data using only limited-montage (4-channel) views. The sensitivity and specificity of limited-montage cEEG review were compared with conventional analysis. We also compared the relative costs of conventional and limited-montage EEG. Results. Using 4-channel limited montage cEEG, reviewers were able to classify accurately background continuity (in 88%), background amplitude (in 81%), maximum background frequency (in 70%), periodic epileptiform discharges, including a seizure (in 92%) and sporadic discharges (in 91%). All epileptiform features were detected with greater than 90% sensitivity and specificity. Eye movement artifact seen over bifrontal electrodes gave false positive detections of periodic epileptiform discharges in 31% of cases. Conclusions. Limited-channel continuous EEG monitoring can provide meaningful electrophysiological data that can be used for prognostication in postanoxic comatose patients. Limited channel EEG can be a cost-effective alternative to conventional EEG monitoring in post-anoxic comatose patients. © EEG and Clinical Neuroscience Society (ECNS) 2017.


Author Keywords
cardiac arrest;  coma;  continuous EEG;  cost-effectiveness;  hypoxic-ischemic encephalopathy


Document Type: Article
Source: Scopus

 

8) 

Grucza, R.A., Krueger, R.F., Agrawal, A., Plunk, A.D., Krauss, M.J., Bongu, J., Cavazos-Rehg, P.A., Bierut, L.J.
Declines in prevalence of adolescent substance use disorders and delinquent behaviors in the USA: a unitary trend?
(2017) Psychological Medicine, pp. 1-12. Article in Press. 

DOI: 10.1017/S0033291717002999


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
b Department of Psychology, University of Minnesota, Minneapolis, MN, USA
c Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA, USA


Abstract
Background: Downward trends in a number of adolescent risk behaviors including violence, crime, and drug use have been observed in the USA in recent years. It is unknown whether these are separate trends or whether they might relate to a general reduction in propensity to engage in such behaviors. Our objectives were to quantify trends in substance use disorders (SUDs) and delinquent behaviors over the 2003–2014 period and to determine whether they might reflect a single trend in an Externalizing-like trait. Methods: We analyzed data from 12 to 17 year old participants from the National Survey on Drug Use and Health, a representative survey of the household dwelling population of the USA, across the 2003–2014 period (N = 210 599). Outcomes included past-year prevalence of six categories of substance use disorder and six categories of delinquent behavior. Results: Trend analysis suggested a net decline of 49% in mean number of SUDs and a 34% decline in delinquent behaviors over the 12-year period. Item Response Theory models were consistent with the interpretation that declines in each set of outcomes could be attributed to changes in mean levels of a latent, Externalizing-like trait. Conclusions: Our findings suggest that declines in SUDs and some delinquent behaviors reflect a single trend related to an Externalizing-like trait. Identifying the factors contributing to this trend may facilitate continued improvement across a spectrum of adolescent risk behaviors. Copyright © Cambridge University Press 2017


Author Keywords
Epidemiology;  juvenile delinquency;  structural models;  substance use disorder;  trends


Document Type: Article in Press
Source: Scopus

 

9) 

Garcia, M., Edmiston, C., Marinov, R., Vail, A., Gruev, V.
Bio-inspired color-polarization imager for real-time in situ imaging
(2017) Optica, 4 (10), art. no. 302203, pp. 1263-1271. 

DOI: 10.1364/OPTICA.4.001263


a Washington University in St. Louis, Department of Computer Science and Engineering, St. Louis, MO, United States
b University of Illinois at Urbana-Champaign, Department of Electrical and Computer Engineering, Urbana, IL, United States
c Washington University in St. Louis, Institute of Materials Science and Engineering, St. Louis, MO, United States
d University of Cambridge, Department of Zoology, Cambridge, United Kingdom
e University of Illinois at Urbana-Champaign, Beckman Institute for Advanced Science and Technology, Urbana, IL, United States


Abstract
Nature has a large repertoire of animals that take advantage of naturally abundant polarization phenomena. Among them, the mantis shrimp possesses one of the most advanced and elegant visual systems nature has developed, capable of high polarization sensitivity and hyperspectral imaging. Here, we demonstrate that by shifting the design paradigm away from the conventional paths adopted in the imaging and vision sensor fields and instead functionally mimicking the visual system of the mantis shrimp, we have developed a single-chip, low-power, high-resolution color-polarization imaging system. Our bio-inspired imager captures co-registered color and polarization information in real time with high resolution by monolithically integrating nanowire polarization filters with vertically stacked photodetectors. These photodetectors capture three different spectral channels per pixel by exploiting wavelength-dependent depth absorption of photons. Our bio-inspired imager comprises 1280 by 720 pixels with a dynamic range of 62 dB and a maximum signal-to-noise ratio of 48 dB. The quantum efficiency is above 30% over the entire visible spectrum, while achieving high polarization extinction ratios of 40 on each spectral channel. This technology is enabling underwater imaging studies of marine species, which exploit both color and polarization information, as well as applications in biomedical fields. © 2017 Optical Society of America.


Document Type: Article
Source: Scopus

 

10) 

Hsiang, J.-C., Johnson, K.P., Madisen, L., Zeng, H., Kerschensteiner, D.
Local processing in neurites of VGluT3-expressing amacrine cells differentially organizes visual information
(2017) eLife, 6, art. no. e31307, . 

DOI: 10.7554/eLife.31307


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States
b Washington University School of Medicine, Saint Louis, United States
c Allen Institute for Brain Science, Seattle, United States
d Department of Neuroscience, Washington University School of Medicine, Saint Louis, United States
e Department of Biomedical Engineering, Washington University School of Medicine, Saint Louis, United States
f Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, United States


Abstract
Neurons receive synaptic inputs on extensive neurite arbors. How information is organized across arbors and how local processing in neurites contributes to circuit function is mostly unknown. Here, we used two-photon Ca2+ imaging to study visual processing in VGluT3-expressing amacrine cells (VG3-ACs) in the mouse retina. Contrast preferences (ON vs. OFF) varied across VG3-AC arbors depending on the laminar position of neurites, with ON responses preferring larger stimuli than OFFresponses. Although arbors of neighboring cells overlap extensively, imaging population activity revealed continuous topographic maps of visual space in the VG3-AC plexus. All VG3-AC neurites responded strongly to object motion, but remained silent during global image motion. Thus, VG3-AC arbors limit vertical and lateral integration of contrast and location information, respectively. We propose that this local processing enables the dense VG3-AC plexus to contribute precise object motion signals to diverse targets without distorting targetspecific contrast preferences and spatial receptive fields. © Hsiang et al.


Document Type: Article
Source: Scopus

 

11) 

Der-Ghazarian, T.S., Call, T., Scott, S.N., Dai, K., Brunwasser, S.J., Noudali, S.N., Pentkowski, N.S., Neisewander, J.L.
Effects of a 5-HT1B receptor agonist on locomotion and reinstatement of cocaine-conditioned place preference after abstinence from repeated injections in mice
(2017) Frontiers in Systems Neuroscience, 11, art. no. 73, . 

DOI: 10.3389/fnsys.2017.00073


a School of Life Sciences, Arizona State University, Tempe, AZ, United States
b Allen Institute for Brain Science, Seattle, WA, United States
c Medical School, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychology, University of New Mexico, Albuquerque, NM, United States


Abstract
5-HT1B receptors (5-HT1BRs) modulate behavioral effects of cocaine. Here we examined the effects of the 5-HT1BR agonist 5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1Hpyrrolo[ 3,2-b]pyridine (CP94253) on spontaneous and cocaine-induced locomotion and on cocaine-primed reinstatement of conditioned place preference (CPP) in male mice given daily repeated injections of either saline or cocaine (15 mg/kg, IP) for 20 days. In the locomotor activity experiment, testing occurred both 1 and 20 days after the final injection. In the CPP experiment, mice underwent conditioning procedures while receiving the last of their daily injections, which were given either during or ≤2 h after CPP procedures. The CPP procedural timeline consisted of baseline preference testing (days 12-13 of the chronic regimen), conditioning (days 14-19, 2 daily 30-min sessions separated by 5 h), CPP test (day 21), extinction (days 22-34; no injections), CPP extinction test (day 35), and reinstatement test (day 36). Mice that had not extinguished received additional extinction sessions prior to reinstatement testing on day 42. On test days, mice were pretreated with either saline or CP94253 (10 mg/kg, IP). Testing began 30 min later, immediately after mice were primed with either saline or cocaine (5 mg/kg for locomotion; 15 mg/kg for reinstatement). We found that CP94253 increased spontaneous locomotion in mice receiving repeated injections of either saline or cocaine when tested 1 day after the last injection, but had no effect on spontaneous locomotion after 20 days abstinence from repeated injections. Surprisingly, cocaine-induced locomotion was sensitized regardless of whether the mice had received repeated saline or cocaine. CP94253 attenuated expression of the sensitized locomotion after 20 days abstinence. A control experiment in noninjected, drug-naïve mice showed that CP94253 had no effect on spontaneous or cocaineinduced locomotion. Mice reinstated cocaine-CPP when given a cocaine prime, and CP94253 pretreatment attenuated cocaine reinstatement. The findings suggest that stress from repeated saline injections and/or co-housing with cocaine-injected mice may cross-sensitize with cocaine effects on locomotion and that CP94253 attenuates these effects, as well as reinstatement of cocaine-CPP. This study supports the idea that 5-HT1BR agonists may be useful anti-cocaine medications. © 2017 Der-Ghazarian, Call, Scott, Dai, Brunwasser, Noudali, Pentkowski and Neisewander.


Author Keywords
Addiction;  CP94253;  Place conditioning;  Sensitization;  Serotonin;  Withdrawal


Document Type: Article
Source: Scopus

 

12) 

Palanca, B.J.A., Avidan, M.S., Mashour, G.A.
Human neural correlates of sevoflurane-induced unconsciousness
(2017) British Journal of Anaesthesia, 119 (4), pp. 573-582. 

DOI: 10.1093/bja/aex244


a Division of Biology and Biomedical Sciences, United States
b Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
c Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
d Department of Anesthesiology, Center for Consciousness Science, Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI, United States


Abstract
Sevoflurane, a volatile anaesthetic agent well-tolerated for inhalation induction, provides a useful opportunity to elucidate the processes whereby halogenated ethers disrupt consciousness and cognition. Multiple molecular targets of sevoflurane have been identified, complementing imaging and electrophysiologic markers for the mechanistically obscure progression from wakefulness to unconsciousness. Recent investigations have more precisely detailed scalp EEG activity during this transition, with practical clinical implications. The relative timing of scalp potentials in frontal and parietal EEG signals suggests that sevoflurane might perturb the propagation of neural information between underlying cortical regions. Spatially distributed brain activity during general anaesthesia has been further investigated with positron emission tomography (PET) and resting-state functional magnetic resonance imaging (fMRI). Combined EEG and PET investigations have identified changes in cerebral blood flow and metabolic activity in frontal, parietal, and thalamic regions during sevoflurane-induced loss of consciousness. More recent fMRI investigations have revealed that sevoflurane weakens the signal correlations among brain regions that share functionality and specialization during wakefulness. In particular, two such resting-state networks have shown progressive breakdown in intracortical and thalamocortical connectivity with increasing anaesthetic concentrations: the Default Mode Network (introspection and episodic memory) and the Ventral Attention Network (orienting of attention to salient feature of the external world). These data support the hypotheses that perturbations in temporally correlated activity across brain regions contribute to the transition between states of sevoflurane sedation and general anaesthesia. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.


Author Keywords
anaesthetic mechanisms;  electroencephalography;  functional neuroimaging;  general anaesthesia


Document Type: Review
Source: Scopus

 

13) 

Baranger, D.A.A., Margolis, S., Hariri, A.R., Bogdan, R.
An earlier time of scan is associated with greater threat-related amygdala reactivity
(2017) Social Cognitive and Affective Neuroscience, 12 (8), pp. 1272-1283. 

DOI: 10.1093/scan/nsx057


a BRAIN Laboratory, Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
b Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, United States
c Laboratory of NeuroGenetics, Department of Psychology and Neuroscience, Duke University, Durham, NC, United States


Abstract
Time-dependent variability in mood and anxiety suggest that related neural phenotypes, such as threat-related amygdala reactivity, may also follow a diurnal pattern. Here, using data from 1,043 young adult volunteers, we found that threatrelated amygdala reactivity was negatively coupled with time of day, an effect which was stronger in the left hemisphere (β=-0.1083, p-fdr=0.0012). This effect was moderated by subjective sleep quality (β=-0.0715, p-fdr=0.0387); participants who reported average and poor sleep quality had relatively increased left amygdala reactivity in the morning. Bootstrapped simulations suggest that similar cross-sectional samples with at least 300 participants would be able to detect associations between amygdala reactivity and time of scan. In control analyses, we found no associations between time and V1 activation. Our results provide initial evidence that threat-related amygdala reactivity may vary diurnally, and that this effect is potentiated among individuals with average to low sleep quality. More broadly, our results suggest that considering time of scan in study design or modeling time of scan in analyses, as well as collecting additional measures of circadian variation, may be useful for understanding threat-related neural phenotypes and their associations with behavior, such as fear conditioning, mood and anxiety symptoms, and related phenotypes. © The Author (2017).


Author Keywords
Amygdala;  Anxiety;  Diurnal;  Sleep;  Time


Document Type: Article
Source: Scopus

 

14) 

Peyrot, W.J., Van der Auwera, S., Milaneschi, Y., Dolan, C.V., Madden, P.A.F., Sullivan, P.F., Strohmaier, J., Ripke, S., Rietschel, M., Nivard, M.G., Mullins, N., Montgomery, G.W., Henders, A.K., Heat, A.C., Fisher, H.L., Dunn, E.C., Byrne, E.M., Air, T.A., Baune, B.T., Breen, G., Levinson, D.F., Lewis, C.M., Martin, N.G., Nelson, E.N., Boomsma, D.I., Grabe, H.J., Wray, N.R., Penninx, B.W.J.H.
Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium
(2017) Biological Psychiatry, . Article in Press. 

DOI: 10.1016/j.biopsych.2017.09.009


a Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands
b Department of Biological Psychology, VU University Medical Center, Amsterdam, the Netherlands
c Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
d Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
e Department of Psychiatry and Psychotherapy, Charite´-Universitätsmedizin, Berlin, Germany
f Department of Psychiatry, Washington University Medical School, St. Louis, Missouri
g Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
h Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts
i Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
j Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California
k Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
l Queensland Brain Institute, University of Queensland, Brisbane, Australia
m Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
n Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Australia
o Discipline of Psychiatry, University of Adelaide, Adelaide, Australia


Abstract
Background: The heterogeneity of genetic effects on major depressive disorder (MDD) may be partly attributable to moderation of genetic effects by environment, such as exposure to childhood trauma (CT). Indeed, previous findings in two independent cohorts showed evidence for interaction between polygenic risk scores (PRSs) and CT, albeit in opposing directions. This study aims to meta-analyze MDD-PRS × CT interaction results across these two and other cohorts, while applying more accurate PRSs based on a larger discovery sample. Methods: Data were combined from 3024 MDD cases and 2741 control subjects from nine cohorts contributing to the MDD Working Group of the Psychiatric Genomics Consortium. MDD-PRS were based on a discovery sample of ~110,000 independent individuals. CT was assessed as exposure to sexual or physical abuse during childhood. In a subset of 1957 cases and 2002 control subjects, a more detailed five-domain measure additionally included emotional abuse, physical neglect, and emotional neglect. Results: MDD was associated with the MDD-PRS (odds ratio [OR] = 1.24, p = 3.6 × 10-5, R 2 = 1.18%) and with CT (OR = 2.63, p = 3.5 × 10-18 and OR = 2.62, p = 1.4 ×10-5 for the two- and five-domain measures, respectively). No interaction was found between MDD-PRS and the two-domain and five-domain CT measure (OR = 1.00, p = .89 and OR = 1.05, p = .66). Conclusions: No meta-analytic evidence for interaction between MDD-PRS and CT was found. This suggests that the previously reported interaction effects, although both statistically significant, can best be interpreted as chance findings. Further research is required, but this study suggests that the genetic heterogeneity of MDD is not attributable to genome-wide moderation of genetic effects by CT. © 2017 Society of Biological Psychiatry.


Author Keywords
Childhood trauma;  Depression;  Genetics;  Interaction;  Meta-analysis;  Polygenic risk


Document Type: Article in Press
Source: Scopus

 

15) 

Camacho-Soto, A., Warden, M.N., Searles Nielsen, S., Salter, A., Brody, D.L., Prather, H., Racette, B.A.
Traumatic brain injury in the prodromal period of Parkinson's disease: A large epidemiological study using medicare data
(2017) Annals of Neurology, . Article in Press. 

DOI: 10.1002/ana.25074


a Washington University School of Medicine, Department of NeurologySt. Louis, MO
b Washington University in St. Louis, Division of BiostatisticsSt. Louis, MO
c Washington University School of Medicine, Department of Orthopedic SurgerySt. Louis, MO
d University of the Witwatersrand, School of Public Health, Faculty of Health SciencesJohannesburg, South Africa


Abstract
Objective: Studies suggest a greater risk of Parkinson's disease (PD) after traumatic brain injury (TBI), but it is possible that the risk of TBI is greater in the prodromal period of PD. We aimed to examine the time-to-TBI in PD patients in their prodromal period compared to population-based controls. Methods: We identified 89,790 incident PD cases and 118,095 comparable controls aged>65 years in 2009 using Medicare claims data. Using data from the preceding 5 years, we compared time-to-TBI in PD patients in their prodromal period to controls. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for TBI in a Cox regression, while adjusting for age, sex, race/ethnicity, modified Charlson comorbidity index, smoking, and alcohol use. Results: Risk of TBI was greater in PD patients in their prodromal period across all age and sex groups, with HRs consistently increasing with proximity to PD diagnosis. HRs ranged from 1.64 (95% CI, 1.52, 1.77) 5 years preceding diagnosis to 3.93 (95% CI, 3.74, 4.13) in the year before. The interaction between PD, TBI, and time was primarily observed for TBI attributed to falls. Motor dysfunction and cognitive impairment, suggested by corresponding International Classification of Diseases, Ninth Revision codes, partially mediated the PD-TBI association. Interpretation: There is a strong association between PD and a recent TBI in the prodromal period of PD. This association strengthens as PD diagnosis approaches and may be a result of undetected nonmotor and motor symptoms, but confirmation will be required. © 2017 American Neurological Association.


Document Type: Article in Press
Source: Scopus

 

16) 

Johnson, K.J., Schwartzbaum, J., Kruchko, C., Scheurer, M.E., Lau, C.C., Woehrer, A., Hainfellner, J.A., Wiemels, J.
Brain tumor epidemiology in the era of precision medicine: The 2017 Brain Tumor Epidemiology Consortium meeting report
(2017) Clinical Neuropathology, 36 (6), pp. 255-262. 

DOI: 10.5414/NP301066


a Brown School Master of Public Health Program, Washington University, St. Louis, MO, United States
b Division of Epidemiology, College of Public Health, Ohio State University, Columbus, OH, United States
c Central Brain Tumor Registry of the United States, Hinsdale, IL, United States
d Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX, United States
e Division of Hematology-Oncology, Connecticut Children's Medical Center, Hartford, CT, United States
f The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
g Institute of Neurology, Medical University of Vienna, Austria
h Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, United States


Abstract
The Brain Tumor Epidemiology Consortium (BTEC) is an international consortium that aims to advance the development of multicenter and interdisciplinary collaborations that focus on research related to the etiology, outcomes, and prevention of brain tumors. The 18th annual BTEC meeting was held in Banff, AB, Canada, on June 27-29, 2017. The meeting focused on the intersection between epidemiology and precision medicine, that is, the use of molecular indicators of risk, early disease and prognosis or precision epidemiology. While traditional epidemiologic approaches group large numbers of participants for statistical power, precision epidemiology is founded on the uniqueness and biology of individual disease characteristics. With this in mind, plenary speakers described the molecular heterogeneity of adult and pediatric brain tumors and how those characteristics are currently being used to guide therapy and etiologic research. Rare subtypes and novel mechanisms for recruitment of individuals for research on brain tumors were discussed along with concepts and methodology related to biological and etiologic heterogeneity. The incorporation of relevant molecular classifiers into population registries was emphasized for its role in future research endeavors, ensuring the accessibility of such tools for researchers and clinicians seeking to improve the lives of individuals with brain tumors and those at risk. The next BTEC meeting will be held in Copenhagen, Denmark, in June 2018. © 2017 Dustri-Verlag Dr. K. Feistle.


Author Keywords
Brain tumors;  Cancer;  Epidemiology;  Precision medicine


Document Type: Article
Source: Scopus

 

17) 

Xiong, W.
The art of psychopharmacology: Avoiding medication changes and slowing down
(2017) Current Psychiatry, 16 (11), pp. 46-47. 


Department of Psychiatry, Washington University, St. Louis, MO, United States


Document Type: Article
Source: Scopus

 

18) 

Cadet, J.L., Gold, M.
Methamphetamine-induced psychosis: Who says all drug use is reversible?
(2017) Current Psychiatry, 16 (11), pp. 14-20. 


a Molecular Neuropsychiatry Research Branch, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, United States
b Psychiatry Washington University, School of Medicine, St. Louis, MO, United States
c Scientific Advisory Boards, RiverMend Health, Atlanta, GA, United States


Document Type: Article
Source: Scopus

 

19) 

Shirani, H., Appelqvist, H., Bäck, M., Klingstedt, T., Cairns, N.J., Nilsson, K.P.R.
Synthesis of Thiophene-Based Optical Ligands That Selectively Detect Tau Pathology in Alzheimer's Disease
(2017) Chemistry - A European Journal, . Article in Press. 

DOI: 10.1002/chem.201703846


a Division of Chemistry Department of Physics, Chemistry and Biology Linko¨ping University 581 83 Linko¨ping Sweden
b Department of Pathology and Immunology Washington University School of Medicine St. Louis, Missouri USA


Abstract
The accumulation of protein aggregates is associated with many devastating neurodegenerative diseases and the development of molecular ligands able to detect these pathological hallmarks is essential. Here, the synthesis of thiophene based optical ligands, denoted bi-thiophene-vinyl-benzothiazoles (bTVBTs) that can be utilized for selective assignment of tau aggregates in brain tissue with Alzheimer's disease (AD) pathology is reported. The ability of the ligands to selectively distinguish tau deposits from the other AD associated pathological hallmark, senile plaques consisting of aggregated amyloid-β (Aβ) peptide, was reduced when the chemical composition of the ligands was altered, verifying that specific molecular interactions between the ligands and the aggregates are necessary for the selective detection of tau deposits. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between aggregated proteinaceous species consisting of different proteins. In addition, the bTVBT scaffold might be utilized to create powerful practical research tools for studying the underlying molecular events of tau aggregation and for creating novel agents for clinical imaging of tau pathology in AD. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


Author Keywords
Alzheimer's disease;  Amyloid-beta;  Fluorescent ligands;  Protein aggregates;  Tau aggregates


Document Type: Article in Press
Source: Scopus

 

20) 

Doulgerakis, M., Eggebrecht, A., Culver, J., Dehghani, H.
Towards real-time functional human brain imaging with diffuse optical tomography
(2017) Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 10412, art. no. 1041209, . 

DOI: 10.1117/12.2285983


a School of Computer Science, University of Birmingham, Birmingham, United Kingdom
b Department of Radiology, Washington University School of MedicineMO, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
d Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States


Abstract
A framework for efficient formulation of the inverse model in diffuse optical tomography, incorporating parallel computing is proposed. Based on 24 subjects, a tenfold speed increase and a hundredfold memory efficiency is reported, whilst maintaining reconstruction quality. © 2017 OSA-SPIE.


Document Type: Conference Paper
Source: Scopus

 

21) 

Vellimana, A.K., Zhou, M.-L., Singh, I., Aum, D.J., Nelson, J.W., Harris, G.R., Athiraman, U., Han, B.H., Zipfel, G.J.
Minocycline protects against delayed cerebral ischemia after subarachnoid hemorrhage via matrix metalloproteinase-9 inhibition
(2017) Annals of Clinical and Translational Neurology, . Article in Press. 

DOI: 10.1002/acn3.492


a Department of Neurological Surgery Washington University School of Medicine St. Louis, Missouri
b Department of Neurosurgery Jinling Hospital School of Medicine Nanjing University Nanjing, Jiangsu Province China
c Department of Anesthesiology Washington University School of Medicine St. Louis, Missouri
d Department of Pharmacology A.T. Still University of Health Sciences Kirksville College of Osteopathic Medicine Kirksville, Missouri


Abstract
Objective: Delayed cerebral ischemia (DCI) is an independent risk factor for poor outcome after aneurysmal subarachnoid hemorrhage (SAH) and is multifactorial in etiology. While prior studies have suggested a role for matrix metalloproteinase-9 (MMP-9) in early brain injury after SAH, its contribution to the pathophysiology of DCI is unclear. Methods: In the first experiment, wild-type (WT) and MMP-9-/- mice were subjected to sham or endovascular perforation SAH surgery. In separate experiments, WT and MMP-9-/-mice were administered vehicle or minocycline either pre- or post-SAH. All mice underwent assessment of multiple components of DCI including vasospasm, neurobehavioral function, and microvessel thrombosis. In another experiment, rabbits were subjected to sham or cisterna magna injection SAH surgery, and administered vehicle or minocycline followed by vasospasm assessment. Results: MMP-9 expression and activity was increased after SAH. Genetic (MMP-9-/- mice) and pharmacological (pre-SAH minocycline administration) inhibition of MMP-9 resulted in decreased vasospasm and neurobehavioral deficits. A therapeutically feasible strategy of post-SAH administration of minocycline resulted in attenuation of multiple components of DCI. Minocycline administration to MMP-9-/- mice did not yield additional protection. Consistent with experiments in mice, both pre- and post-SAH administration of minocycline attenuated SAH-induced vasospasm in rabbits. Interpretation: MMP-9 is a key player in the pathogenesis of DCI. The consistent attenuation of multiple components of DCI with both pre- and post-SAH administration of minocycline across different species and experimental models of SAH, combined with the excellent safety profile of minocycline in humans suggest that a clinical trial in SAH patients is warranted. © 2017 American Neurological Association.


Document Type: Article in Press
Source: Scopus

 

22) 

Browne, L.R., Schwartz, H., Ahmad, F.A., Wallendorf, M., Kuppermann, N., Lerner, E.B., Leonard, J.C.
Interobserver Agreement in Pediatric Cervical Spine Injury Assessment Between Prehospital and Emergency Department Providers
(2017) Academic Emergency Medicine, . Article in Press. 

DOI: 10.1111/acem.13312


a Department of Pediatrics and Emergency Medicine Medical College of Wisconsin (LRB, EBL) Madison, WI
b Department of Pediatrics University of Cincinnati College of Medicine (HS) Cincinnati, OH
c Department Pediatrics Washington University School of Medicine in St. Louis St. Louis, MO
d Department of Biostatistics Washington University School of Medicine in St. Louis St. Louis, MO
e Department of Emergency Medicine and Pediatrics University of California Davis School of Medicine Sacramento, CA
f Nationwide Children's Hospital and The Ohio State University College of Medicine Columbus, OH


Abstract
Background: Investigators have derived cervical spine injury (CSI) decision support tools from physician observations. There is a need to demonstrate that prehospital emergency medical services (EMS) providers can use these tools to appropriately determine the need for spinal motion restrictions and make field disposition decisions. Objectives: The objective was to determine the interobserver agreement between EMS and emergency department (ED) providers for CSI risk assessment variables and overall gestalt for CSI in children after blunt trauma. Methods: This was a planned, substudy of a four-site, prospective cohort of children &#60; 18 years transported by EMS to pediatric EDs for evaluation of CSI after blunt trauma. Inclusion criteria were trauma team activation and/or EMS-initiated spinal motion restriction. Exclusion criteria were penetrating trauma, transfer to another facility for definitive care, state custody, or substantial language barrier. For each eligible child, the transporting EMS provider and treating ED provider independently recorded their clinical assessment for CSI. This included mechanism of injury and patient history and physical examination findings. We assessed each paired variable for interobserver agreement between EMS and ED provider using kappa (κ) analysis. We considered variables with κ lower confidence interval values ≥0.4 to have moderate or better agreement. Results: We obtained 1,372 paired observations for 29 variables. After finding prevalence and observer bias were adjusted for, all variables achieved moderate to better agreement including eight variables previously shown to be independently associated with CSI in children: diving mechanism, high-risk motor vehicle collision, altered mental status, focal neurologic findings, neck pain, torticollis, substantial torso injury, and predisposing medical condition. EMS and ED providers, however, showed less than moderate agreement for their overall gestalt for CSI in children. Of note, both EMS and ED providers did not assess for neck pain, inability to move the neck, and/or cervical spine tenderness in more than 10% of study patients. Conclusions: Emergency medical services and ED providers achieved at least moderate agreement in the assessment of CSI risk factors in children after blunt trauma. However, EMS and ED providers did not achieve moderate agreement on gestalt for CSI and some risk factors went unassessed by providers. These findings support the development of a pediatric CSI risk assessment tool for EMS and ED providers to reduce interventions for those children at very low risk for CSIs while still identifying all children with injury. © 2017 Society for Academic Emergency Medicine.


Document Type: Article in Press
Source: Scopus

November 13, 2017

1) 

Rustichini, A., Conen, K.E., Cai, X., Padoa-Schioppa, C.
Optimal coding and neuronal adaptation in economic decisions
(2017) Nature Communications, 8 (1), art. no. 1208, . 

DOI: 10.1038/s41467-017-01373-y


a Department of Economics, University of Minnesota, 1925 4th Street South 4-101, Minneapolis, MN, United States
b Department of Neuroscience, Washington University in St Louis, 660 South Euclid Avenue, St Louis, MO, United States
c Department of Economics, Washington University in St Louis, St Louis, MO, United States
d Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, United States
e NYU Shanghai, 1555 Century Ave, Pudong New District, Shanghai, China


Abstract
During economic decisions, offer value cells in orbitofrontal cortex (OFC) encode the values of offered goods. Furthermore, their tuning functions adapt to the range of values available in any given context. A fundamental and open question is whether range adaptation is behaviorally advantageous. Here we present a theory of optimal coding for economic decisions. We propose that the representation of offer values is optimal if it ensures maximal expected payoff. In this framework, we examine offer value cells in non-human primates. We show that their responses are quasi-linear even when optimal tuning functions are highly non-linear. Most importantly, we demonstrate that for linear tuning functions range adaptation maximizes the expected payoff. Thus value coding in OFC is functionally rigid (linear tuning) but parametrically plastic (range adaptation with optimal gain). Importantly, the benefit of range adaptation outweighs the cost of functional rigidity. While generally suboptimal, linear tuning may facilitate transitive choices. © 2017 The Author(s).


Document Type: Article
Source: Scopus

2) 

Johnson, R.E., Tien, N.-W., Shen, N., Pearson, J.T., Soto, F., Kerschensteiner, D.
Homeostatic plasticity shapes the visual system's first synapse
(2017) Nature Communications, 8 (1), art. no. 1220, . 

DOI: 10.1038/s41467-017-01332-7


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, MO, United States
b Graduate Program in Neuroscience, Washington University School of Medicine, Saint Louis, MO, United States
c Graduate Program in Developmental, Regenerative and Stem Cell Biology, Washington University School of Medicine, Saint Louis, MO, United States
d Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO, United States
e Department of Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO, United States
f Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO, United States


Abstract
Vision in dim light depends on synapses between rods and rod bipolar cells (RBCs). Here, we find that these synapses exist in multiple configurations, in which single release sites of rods are apposed by one to three postsynaptic densities (PSDs). Single RBCs often form multiple PSDs with one rod; and neighboring RBCs share ~13% of their inputs. Rod-RBC synapses develop while ~7% of RBCs undergo programmed cell death (PCD). Although PCD is common throughout the nervous system, its influences on circuit development and function are not well understood. We generate mice in which ~53 and ~93% of RBCs, respectively, are removed during development. In these mice, dendrites of the remaining RBCs expand in graded fashion independent of light-evoked input. As RBC dendrites expand, they form fewer multi-PSD contacts with rods. Electrophysiological recordings indicate that this homeostatic co-regulation of neurite and synapse development preserves retinal function in dim light. © 2017 The Author(s).


Document Type: Article
Source: Scopus

3) 

Feng, J., Yang, P., Mack, M.R., Dryn, D., Luo, J., Gong, X., Liu, S., Oetjen, L.K., Zholos, A.V., Mei, Z., Yin, S., Kim, B.S., Hu, H.
Sensory TRP channels contribute differentially to skin inflammation and persistent itch
(2017) Nature Communications, 8 (1), art. no. 980, . 

DOI: 10.1038/s41467-017-01056-8


a Department of Anesthesiology, Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO, United States
b Division of Dermatology, Department of Medicine, Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO, United States
c Department of Biophysics, Institute of Biology, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
d College of Pharmacy, South-Central University for Nationalities, Wuhan, China


Abstract
Although both persistent itch and inflammation are commonly associated with allergic contact dermatitis (ACD), it is not known if they are mediated by shared or distinct signaling pathways. Here we show that both TRPA1 and TRPV1 channels are required for generating spontaneous scratching in a mouse model of ACD induced by squaric acid dibutylester (SADBE), a small molecule hapten, through directly promoting the excitability of pruriceptors. TRPV1 but not TRPA1 channels protect the skin inflammation, as genetic ablation of TRPV1 function or pharmacological ablation of TRPV1-positive sensory nerves promotes cutaneous inflammation in the SADBE-induced ACD. Our results demonstrate that persistent itch and inflammation are mediated by distinct cellular and molecular mechanisms in a mouse model of ACD. Identification of distinct roles of TRPA1 and TRPV1 in regulating itch and inflammation may provide new insights into the pathophysiology and treatment of chronic itch and inflammation in ACD patients. © 2017 The Author(s).


Document Type: Article
Source: Scopus

4) 

Gutmann, D.H.
Caddyshack therapeutics: Overcoming glioblastoma adaptation
(2017) Neuro-Oncology, 19 (11), pp. 1429-1431. 

DOI: 10.1093/neuonc/nox096


Department of Neurology, Washington University School of Medicine, Box 8111 660 South Euclid Avenue, St. Louis, MO, United States


Document Type: Article
Source: Scopus

5) 

Nguyen, D.C., Farber, S.J., Skolnick, G.B., Naidoo, S.D., Smyth, M.D., Kane, A.A., Patel, K.B., Woo, A.S.
One hundred consecutive endoscopic repairs of sagittal craniosynostosis: An evolution in care
(2017) Journal of Neurosurgery: Pediatrics, 20 (5), pp. 410-418. 

DOI: 10.3171/2017.5.PEDS16674


a Division of Plastic and Reconstructive Surgery, Department of Surgery, United States
b Division of Pediatric Neurosurgery, Department of Neurosurgery, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, United States
d Division of Plastic and Reconstructive Surgery, Warren Alpert Medical School, Brown University, Providence, RI, United States
e Division of Plastic and Reconstructive Surgery, Washington University, School of Medicine, 660 South Euclid Ave., Northwest Tower, Ste. 1150, St. Louis, MO, United States


Abstract
OBJECTIVE Endoscope-assisted repair of sagittal craniosynostosis was adopted at St. Louis Children’s Hospital in 2006. This study examines the first 100 cases and reviews the outcomes and evolution of patient care protocols at our institution. METHODS The authors performed a retrospective chart review of the first 100 consecutive endoscopic repairs of sagittal craniosynostosis between 2006 and 2014. The data associated with length of hospital stay, blood loss, transfusion rates, operative times, cephalic indices (CIs), complications, and cranial remolding orthosis were reviewed. Measurements were taken from available preoperative and 1-year postoperative 3D reconstructed CT scans. RESULTS The patients’ mean age at surgery was 3.3 ± 1.1 months. Of the 100 patients, 30 were female and 70 were male. The following perioperative data were noted. The mean operative time (± SD) was 77.1 ± 22.2 minutes, the mean estimated blood loss was 34.0 ± 34.8 ml, and the mean length of stay was 1.1 ± 0.4 days; 9% of patients required transfusions; and the mean pre- and postoperative CI values were 69.1 ± 3.8 and 77.7 ± 4.2, respectively. Conversion to open technique was required in 1 case due to presence of a large emissary vein that was difficult to control endoscopically. The mean duration of helmet therapy was 8.0 ± 2.9 months. Parietal osteotomies were eventually excluded from the procedure. CONCLUSIONS The clinical outcomes and improvements in CI seen in our population are similar to those seen at other high-volume centers. Since the inception of endoscope-assisted repair at our institution, the patient care protocol has undergone several significant changes. We have been able to remove less cranium using our “narrow-vertex” suturectomy technique without affecting patient safety or outcome. Patient compliance with helmet therapy and collaborative care with the orthotists remain the most essential aspects of a successful outcome. ©AANS, 2017.


Author Keywords
Craniofacial surgery;  Craniosynostosis;  Endoscopic


Document Type: Article
Source: Scopus

6) 

Leighton, B.L., Crock, L.W.
Case Series of Successful Postoperative Pain Management in Buprenorphine Maintenance Therapy Patients
(2017) Anesthesia and analgesia, 125 (5), pp. 1779-1783. 

DOI: 10.1213/ANE.0000000000002498


From the *Department of Surgery, Garrett Regional Medical Center, Oakland, Maryland; and †Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri


Abstract
Buprenorphine maintenance therapy patients frequently have severe postoperative pain due to buprenorphine-induced hyperalgesia and provider use of opioids with limited efficacy in the presence of buprenorphine. The authors report good-to-excellent pain management in 4 obstetric patients using nonopioid analgesics, regional anesthesia, continuation of buprenorphine, and use of opioids with high μ receptor affinity.


Document Type: Article
Source: Scopus

7) 

Sherry, K.P., Das, R.K., Pappu, R.V., Barrick, D.
Control of transcriptional activity by design of charge patterning in the intrinsically disordered RAM region of the Notch receptor
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (44), pp. E9243-E9252. 

DOI: 10.1073/pnas.1706083114


a T. C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD, United States
b Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
c Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States
d Ra Pharmaceuticals, Cambridge, MA, United States
e GNS Healthcare, Cambridge, MA, United States


Abstract
Intrinsically disordered regions (IDRs) play important roles in proteins that regulate gene expression. A prominent example is the intracellular domain of the Notch receptor (NICD), which regulates the transcription of Notch-responsive genes. The NICD sequence includes an intrinsically disordered RAM region and a conserved ankyrin (ANK) domain. The 111-residue RAM region mediates bivalent interactions of NICD with the transcription factor CSL. Although the sequence of RAM is poorly conserved, the linear patterning of oppositely charged residues shows minimal variation. The conformational properties of polyampholytic IDRs are governed as much by linear charge patterning as by overall charge content. Here, we used sequence design to assess how changing the charge patterning within RAM affects its conformational properties, the affinity of NICD to CSL, and Notch transcriptional activity. Increased segregation of oppositely charged residues leads to linear decreases in the global dimensions of RAM and decreases the affinity of a construct including a C-terminal ANK domain (RAMANK) for CSL. Increasing charge segregation from WT RAM sharply decreases transcriptional activation for all permutants. Activation also decreases for some, but not all, permutants with low charge segregation, although there is considerable variation. Our results suggest that the RAM linker is more than a passive tether, contributing local and/or long-range sequence features that modulate interactions within NICD and with downstream components of the Notch pathway. We propose that sequence features within IDRs have evolved to ensure an optimal balance of sequence-encoded conformational properties, interaction strengths, and cellular activities. © 2017, National Academy of Sciences. All rights reserved.


Author Keywords
Ankyrin repeats;  Intrinsically disordered proteins;  Notch signaling;  Sequence design;  Transcriptional activation


Document Type: Article
Source: Scopus

8) 

Carlson, B.A.
Early life experiences have complex and long-lasting effects on behavior
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (44), pp. 11571-11573. 

DOI: 10.1073/pnas.1716037114


Department of Biology, Washington University in St. Louis, St. Louis, MO, United States


Document Type: Note
Source: Scopus

9) 

Morgan, J.L., Lichtman, J.W.
Digital tissue and what it may reveal about the brain
(2017) BMC Biology, 15 (1), art. no. 101, . 

DOI: 10.1186/s12915-017-0436-9


a Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, Neuroscience, St. Louis, MO, United States
b Harvard University, Department of Molecular and Cellular Biology, Center for Brain Science, Cambridge, MA, United States


Abstract
Imaging as a means of scientific data storage has evolved rapidly over the past century from hand drawings, to photography, to digital images. Only recently can sufficiently large datasets be acquired, stored, and processed such that tissue digitization can actually reveal more than direct observation of tissue. One field where this transformation is occurring is connectomics: the mapping of neural connections in large volumes of digitized brain tissue. © 2017 Morgan et al.


Document Type: Review
Source: Scopus

10) 

Arandjelovic, K., Eyre, H.A., Lenze, E., Singh, A.B., Berk, M., Bousman, C.
The role of depression pharmacogenetic decision support tools in shared decision making
(2017) Journal of Neural Transmission, pp. 1-8. Article in Press. 

DOI: 10.1007/s00702-017-1806-8


a IMPACT SRC, School of Medicine, Deakin University, Geelong, VIC, Australia
b Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia
c Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia
d Innovation Institute, Texas Medical Center, Houston, TX, United States
e Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
f Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, Australia
g Departments of Medical Genetics, Psychiatry, and Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada


Abstract
Patients discontinue antidepressant medications due to lack of knowledge, unrealistic expectations, and/or unacceptable side effects. Shared decision making (SDM) invites patients to play an active role in their treatment and may indirectly improve outcomes through enhanced engagement in care, adherence to treatment, and positive expectancy of medication outcomes. We believe decisional aids, such as pharmacogenetic decision support tools (PDSTs), facilitate SDM in the clinical setting. PDSTs may likewise predict drug tolerance and efficacy, and therefore adherence and effectiveness on an individual-patient level. There are several important ethical considerations to be navigated when integrating PDSTs into clinical practice. The field requires greater empirical research to demonstrate clinical utility, and the mechanisms thereof, as well as exploration of the ethical use of these technologies. © 2017 Springer-Verlag GmbH Austria


Author Keywords
Adherence;  Antidepressants;  Decision support tool;  Pharmacogenetics;  Psychoeducation;  Shared decision making;  Therapeutic alliance


Document Type: Article in Press
Source: Scopus

11) 

Scheid, B., Chakrabartty, S.
Feasibility of hybrid ultrasound-electrical nerve stimulation for electroceuticals
(2017) Proceedings - IEEE International Symposium on Circuits and Systems, art. no. 8050555, . 

DOI: 10.1109/ISCAS.2017.8050555


a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Achieving targeted and efficient neural excitation is one of the major challenges in the design of implantable electroceutical devices. In this study, we explore the potential of using direct-contact ultrasound to localize and enhance the process of electrical current stimulation. The underlying premise of this study is to use ultrasonic pulses to vary the non-linear capacitive element formed by the neural membrane which would result in an ionic charge-pump that would reduce the activation threshold for a subsequent electrical stimulation. We have tested this hypothesis using a phantom experiment where a millimeter-scale ultrasonic crystal was affixed directly to the sciatic nerve of a frog and was driven both by a continuous train and by a 5 ms train of 3 MHz pulses with a monophasic electrical stimulus pulse applied at varying latencies. Compound action potential amplitudes were recorded from the gastrocnemius muscle during dual-mode stimulation, and were compared to baseline amplitudes. The experimental results showed that a downward shift in strength-duration was evident, and that a larger latency between ultrasound and electrical stimulation appeared to produce a larger amplitude with respect to the baseline, while near-simultaneous stimulation showed a suppression of action potential amplitude. © 2017 IEEE.


Document Type: Conference Paper
Source: Scopus

12) 

Mehta, D., Altan, E., Chandak, R., Raman, B., Chakrabartty, S.
Behaving cyborg locusts for standoff chemical sensing
(2017) Proceedings - IEEE International Symposium on Circuits and Systems, art. no. 8050610, . 

DOI: 10.1109/ISCAS.2017.8050610


a Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, United States
b Department of Electrical and Systems Engineering, Washington University in St. Louis, Saint Louis, MO, United States


Abstract
Cyborg insects provide a unique platform to implement autonomous robotics on a large scale. Compared to vertebrates, insect cyborgs can be deployed in swarms and at a significantly lower cost. In this paper, we propose a cyborg sensing platform that leverages the acute olfactory sensing capability of locusts (Schistocerca americana) for standoff detection of target chemicals. Contrary to cyborg sensing technologies that are based on implantable neural devices, the proposed platform relies on extraneous palp tracking which can be measured non-invasively for extended periods of time. In this work, locusts are conditioned (trained) to respond (move their palp) to a specific target odor and the palp movements are measured in real-time using a silver-enhanced infrared reflectance technique. The measured results correlate well with a gold-standard palp tracking method. The efficacy of our platform based on behavioral readout is demonstrated for non-invasive chemical sensing. © 2017 IEEE.


Author Keywords
biosensor;  chemical sensing;  cyborg;  locust;  sniffer;  standoff detection


Document Type: Conference Paper
Source: Scopus

13) 

Giles, G.M., Edwards, D.F., Morrison, M.T., Baum, C., Wolf, T.J.
Screening for Functional Cognition in Postacute Care and the Improving Medicare Post-Acute Care Transformation (IMPACT) Act of 2014
(2017) The American journal of occupational therapy : official publication of the American Occupational Therapy Association, 71 (5), pp. p1-7105090010. 

DOI: 10.5014/ajot.2017.715001


a Gordon Muir Giles, PhD, OTR/L, FAOTA, is Professor, Samuel Merritt University, Oakland, CA, and Director of Neurobehavioral Services, Crestwood Behavioral Health, Inc., Sacramento, CA;
b Dorothy Farrar Edwards, PhD, is Professor, Departments of Kinesiology and Medicine, University of Wisconsin-Madison
c M. Tracy Morrison, OTD, OTR/L, is Chair and Associate Professor, Occupational Therapy, College of Nursing and Health Professions, Arkansas State University, Jonesboro
d Carolyn Baum, PhD, OTR, FAOTA, is Professor, Occupational Therapy, Neurology, and Social Work, Washington University in St. Louis, St. Louis, MO
e Timothy J. Wolf, OTD, PhD, OTR/L, FAOTA, is Associate Professor and Chair, Department of Occupational Therapy, University of Missouri, Columbia,


Abstract
Occupational therapists have a long history of assessing functional cognition, defined as the ability to use and integrate thinking and performance skills to accomplish complex everyday activities. In response to passage of the Improving Medicare Post-Acute Care Transformation (IMPACT) Act of 2014 (Pub. L. 113-185), the American Occupational Therapy Association has been advocating that the Centers for Medicare and Medicaid Services consider functional cognition for inclusion in routine patient assessment in postacute care settings, with important implications for occupational therapy. These efforts have the potential to increase referrals to occupational therapy, emphasize the importance of addressing functional cognition in occupational therapy practice, and support the value of occupational therapy in achieving optimal postacute care outcomes. Copyright © 2017 by the American Occupational Therapy Association, Inc.


Document Type: Article
Source: Scopus

14) 

Smallfield, S., Heckenlaible, C.
Effectiveness of Occupational Therapy Interventions to Enhance Occupational Performance for Adults With Alzheimer's Disease and Related Major Neurocognitive Disorders: A Systematic Review
(2017) The American journal of occupational therapy : official publication of the American Occupational Therapy Association, 71 (5), pp. p1-7105180010. Cited 1 time.

DOI: 10.5014/ajot.2017.024752


a Stacy Smallfield, DrOT, OTR/L, BCG, FAOTA, is Assistant Director, Entry-Level Doctoral Program, and Associate Professor of Occupational Therapy and Medicine, Washington University School of Medicine, St. Louis, MO;
b Cindy Heckenlaible, MS, OTR/L, is Inpatient/Outpatient Occupational Therapist, Avera Sacred Heart Hospital, Yankton, SD. At the time of the review, she was Graduate Student, Department of Occupational Therapy, University of South Dakota, Vermillion


Abstract
OBJECTIVE: The purpose of this systematic review was to describe the evidence for the effectiveness of interventions designed to establish, modify, and maintain occupations for adults with Alzheimer's disease (AD) and related neurocognitive disorders.

METHOD: Titles and abstracts of 2,597 articles were reviewed, of which 256 were retrieved for full review and 52 met inclusion criteria. U.S. Preventive Services Task Force levels of certainty and grade definitions were used to describe the strength of evidence.

RESULTS: Articles were categorized into five themes: occupation-based, sleep, cognitive, physical exercise, and multicomponent interventions. Strong evidence supports the benefits of occupation-based interventions, physical exercise, and error-reduction learning.

CONCLUSION: Occupational therapy practitioners should integrate daily occupations, physical exercise, and error-reduction techniques into the daily routine of adults with AD to enhance occupational performance and delay functional decline. Future research should focus on establishing consensus on types and dosage of exercise and cognitive interventions.


Document Type: Review
Source: Scopus

15) 

Barch, D.M.
Resting-state functional connectivity in the human connectome project: Current status and relevance to understanding psychopathology
(2017) Harvard Review of Psychiatry, 25 (5), pp. 209-217. 

DOI: 10.1097/HRP.0000000000000166


Department of Psychological and Brain Sciences, Washington University, St. Louis, United States


Abstract
A key tenet of modern psychiatry is that psychiatric disorders arise from abnormalities in brain circuits that support human behavior. Our ability to examine hypotheses around circuit-level abnormalities in psychiatric disorders has been made possible by advances in human neuroimaging technologies. These advances have provided the basis for recent efforts to develop amore complex understanding of the function of brain circuits in health and of their relationship to behavior—providing, in turn, a foundation for our understanding of how disruptions in such circuits contribute to the development of psychiatric disorders. This review focuses on the use of resting-state functional connectivity MRI to assess brain circuits, on the advances generated by the Human Connectome Project, and on how these advances potentially contribute to understanding neural circuit dysfunction in psychopathology. The review gives particular attention to the methods developed by the Human Connectome Project that may be especially relevant to studies of psychopathology; it outlines some of the key findings about what constitutes a brain region; and it highlights new information about the nature and stability of brain circuits. Some of the Human Connectome Project’s new findings particularly relevant to psychopathology—about neural circuits and their relationships to behavior—are also presented. The review ends by discussing the extension of Human Connectome Project methods across the lifespan and intomanifest illness. Potential treatment implications are also considered. © 2017 President and Fellows of Harvard College.


Author Keywords
Brain;  Functional connectivity;  Network;  Neuroimaging;  Psychopathology


Document Type: Article
Source: Scopus

 

 
 

16) 

Seo, D.-O., Bruchas, M.R.
Polymorphic computation in locus coeruleus networks
(2017) Nature Neuroscience, 20 (11), pp. 1517-1519. 

DOI: 10.1038/nn.4663


a Department of Anesthesiology, Division of Basic Research, Japan
b Departments of Neuroscience and Psychiatry, Division of Biology and Biomedical Sciences, United Kingdom
c Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, United States


Document Type: Short Survey
Source: Scopus

 

November 6, 2017

1) 

Cruitt, P.J., Oltmanns, T.F.
Age-related outcomes associated with personality pathology in later life
(2018) Current Opinion in Psychology, 21, pp. 89-93. 

DOI: 10.1016/j.copsyc.2017.09.013


From the Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Methodological advances enable the latest research on personality pathology in later life to turn toward understanding the role personality pathology plays in age-related outcomes. Despite indications that some features of personality disorders fade in later life, a prevalence rate of approximately 10 percent has been established for adults aged 50 or older. Personality disorder features have been linked to suicidal ideation, poorer physical health, and cognitive decline in later life. Given these associations, the literature on treatment of personality disorders in this age group is surprisingly scant. Future research needs to address this lack in order to provide guidelines for the use of the DSM-5 Alternative Model for Personality Disorders with older adults. © 2017 Elsevier Ltd


Document Type: Review
Source: Scopus

 

2) 

Wang, S., Brettmann, J.B., Nichols, C.G.
Studying structural dynamics of potassium channels by single-molecule FRET
(2018) Methods in Molecular Biology, 1684, pp. 163-180. 

DOI: 10.1007/978-1-4939-7362-0_13


Center for the Investigation of Membrane Excitability Diseases and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Single-molecule FRET (smFRET) can visualize conformational dynamics of individual ion channels in lipid bilayers of defined composition. Dynamic and distance measurements from smFRET, combined with single channel recordings, can provide previously unattainable direct mechanistic insights into ion channel function and modulation. smFRET measurements require site-specific fluorophore labeling between two distinct sites, which is a major challenge for multimeric ion channels. This chapter aims to provide a step-by-step protocol: (1) to design concatemeric constructs with only two cysteine residues within a homotetrameric channel; (2) to express, purify, label, and reconstitute channel proteins; (3) to perform smFRET imaging on channel proteins in liposomes with an objective-based Total Internal Reflection (TIRF) microscope; and finally (4) to analyze the FRET distributions and dynamics that reflect the dynamic conformational transitions of ion channels in membranes. © 2018, Springer Science+Business Media LLC.


Author Keywords
Conformational dynamics;  Fluorophore labeling;  Ion channel;  Membrane protein;  Single-molecule FRET;  TIRF


Document Type: Book Chapter
Source: Scopus

 

3) 

Platt, D.J., Miner, J.J.
Consequences of congenital Zika virus infection
(2017) Current Opinion in Virology, 27, pp. 1-7. 

DOI: 10.1016/j.coviro.2017.09.005


a Department of Medicine, Washington University in St. Louis School of Medicine, Saint Louis, MO, United States
b Department of Molecular Microbiology, Washington University in St. Louis School of Medicine, Saint Louis, MO, United States
c Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, Saint Louis, MO, United States


Abstract
The 2015 Zika virus (ZIKV) epidemic in the Americas led to the discovery that ZIKV causes congenital abnormalities including microcephaly, intrauterine growth restriction, and eye disease that can result in blindness. Studies in animal models and human organoid cultures, together with human epidemiological studies, have shown that ZIKV crosses the placenta and subsequently replicates within fetal tissues including the developing brain. Preferential infection of neural cell precursors causes damage to the developing fetal brain. However, a majority of congenitally infected humans do not develop microcephaly or other overt congenital abnormalities, so longitudinal epidemiological studies are necessary to more completely define the long-term consequences of in utero ZIKV infection. © 2017 Elsevier B.V.


Document Type: Review
Source: Scopus

 

4) 

Harty, B.L., Monk, K.R.
Unwrapping the unappreciated: recent progress in Remak Schwann cell biology
(2017) Current Opinion in Neurobiology, 47, pp. 131-137. 

DOI: 10.1016/j.conb.2017.10.003


a Department of Developmental Biology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University School of Medicine, United States
c Vollum Institute, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR, United States


Abstract
Schwann cells (SCs) are specialized glial cells that myelinate and protect axons in the peripheral nervous system (PNS). Although myelinating SCs are more commonly studied, the PNS also contains a variety of non-myelinating SCs, including but not limited to Remak SCs (RSCs), terminal SCs, enteric glia. Although the field currently lacks many robust tools for interrogating the functions of non-myelinating SCs, recent evidence suggests that, like their myelinating counterparts, non-myelinating SCs are critical for proper PNS function. In this review, we focus specifically on RSCs and highlight recent advances in understanding regulators of RSC development, function, and participation in PNS regeneration. © 2017 Elsevier Ltd


Document Type: Review
Source: Scopus

 

5) 

Dong, P., Guo, C., Huang, S., Ma, M., Liu, Q., Luo, W.
TRPC3 Is Dispensable for β-Alanine Triggered Acute Itch
(2017) Scientific Reports, 7 (1), art. no. 13869, . 

DOI: 10.1038/s41598-017-12770-0


a Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
b Department of Anesthesiology, Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO, United States
c Wuhan University, Wuhan, Hubei, China


Abstract
The detection of pruritic (itchy) stimuli is mediated by a variety of receptors and channels expressed by primary sensory neurons. The G protein-coupled receptor (GPCR) MRGPRD is selectively expressed by a subset of mouse non-peptidergic nociceptors and functions as the molecular receptor for the itch-inducing chemical β-alanine. However, the channels responsible for generating electrical signals downstream of MRGPRD remain unclear. Here, we found that a member of the canonical TRP channel family, TRPC3, is highly expressed in MRGPRD+ non-peptidergic nociceptors, raising the possibility of whether TRPC3 functions as a downstream channel in the MRGPRD signaling pathway. We tested TrpC3 null mice for β-alanine induced itch, and found that these mice exhibit normal responses to β-alanine. At the cellular level, calcium influx triggered by β-alanine is also unchanged in cultured DRG neurons from TrpC3 null mice compared to wild type. Together, our results demonstrate that mouse TrpC3 is dispensable for β-alanine-induced acute itch. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

6) 

Nandi, A., Schättler, H., Ritt, J.T., Ching, S.N.
Fundamental Limits of Forced Asynchronous Spiking with Integrate and Fire Dynamics
(2017) Journal of Mathematical Neuroscience, 7 (1), art. no. 11, . 

DOI: 10.1186/s13408-017-0053-5


a Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Department of Biomedical Engineering, Boston University, Boston, MA, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States


Author Keywords
Selective spiking;  Spike pattern;  Time optimal control


Document Type: Article
Source: Scopus

 

7) 

Du, L., Liu, K., Yao, X., Yan, J., Risacher, S.L., Han, J., Guo, L., Saykin, A.J., Shen, L., Weiner, M.W., Aisen, P., Petersen, R., Jack, C.R., Jagust, W., Trojanowki, J.Q., Toga, A.W., Beckett, L., Green, R.C., Morris, J., Shaw, L.M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M.M., Potter, W., Snyder, P., Schwartz, A., Montine, T., Thomas, R.G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Balasubramanian, A.B., Mason, J., Sim, I., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., Decarli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R.A., Foster, N., Reiman, E.M., Chen, K., Mathis, C., Landau, S., Cairns, N.J., Franklin, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T.M., Potkin, S., Faber, K., Kim, S., Nho, K., Thal, L., Buckholtz, N., Albert, M., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Schneider, L.S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B.M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J.L., Lord, J.L., Mason, S.S., Albers, C.S., Knopman, D., Johnson, K., Doody, R.S., Villanueva-Meyer, J., Pavlik, V., Shibley, V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L.S., Bell, K.L., Ances, B., Carroll, M., Creech, M.L., Franklin, E., Mintun, M.A., Schneider, S., Oliver, A., Marson, D., Geldmacher, D., Love, M.N., Griffith, R., Clark, D., Brockington, J., Roberson, E., Grossman, H., Mitsis, E., Shah, R.C., Detoledo-Morrell, L., Duara, R., Greig-Custo, M.T., Barker, W., Onyike, C., D'Agostino, D., Kielb, S., Sadowski, M., Sheikh, M.O., Ulysse, A., Gaikwad, M., Murali Doraiswamy, P., Petrella, J.R., Borges-Neto, S., Wong, T.Z., Coleman, E., Arnold, S.E., Karlawish, J.H., Wolk, D.A., Clark, C.M., Smith, C.D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Lopez, O.L., Oakley, M.A., Simpson, D.M., Porsteinsson, A.P., Goldstein, B.S., Martin, K., Makino, K.M., Ismail, M.S., Brand, C., Preda, A., Nguyen, D., Womack, K., Mathews, D., Quiceno, M., Levey, A.I., Lah, J.J., Cellar, J.S., Burns, J.M., Swerdlow, R.H., Brooks, W.M., Apostolova, L., Tingus, K., Woo, E., Silverman, D.H.S., Lu, P.H., Bartzokis, G., Graff-Radford, N.R., Parfitt, F., Poki-Walker, K., Farlow, M.R., Marie Hake, A., Matthews, B.R., Brosch, J.R., Herring, S., Van Dyck, C.H., Carson, R.E., MacAvoy, M.G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Robin Hsiung, G.-Y., Mudge, B., Sossi, V., Feldman, H., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Rogers, J., Trost, D., Kertesz, A., Bernick, C., Munic, D., Rogalski, E., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C.-K., Johnson, N., Sadowsky, C., Villena, T., Scott Turner, R., Johnson, K., Reynolds, B., Sperling, R.A., Johnson, K.A., Marshall, G., Yesavage, J., Taylor, J.L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M.N., Belden, C.M., Jacobson, S.A., Sirrel, S.A., Kowall, N., Killiany, R., Budson, A.E., Norbash, A., Lynn Johnson, P., Obisesan, T.O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Decarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T.-Y., Bartha, R., Johnson, S., Asthana, S., Carlsson, C.M., Tariot, P., Burke, A., Milliken, A.M., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D.W., Kataki, M., Kelly, B., Zimmerman, E.A., Celmins, D., Brown, A.D., Pearlson, G.D., Blank, K., Anderson, K., Flashman, L.A., Seltzer, M., Hynes, M.L., Santulli, R.B., Sink, K.M., Gordineer, L., Williamson, J.D., Garg, P., Watkins, F., Ott, B.R., Tremont, G., Daiello, L.A., Salloway, S., Malloy, P., Correia, S., Rosen, H.J., Miller, B.L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S.K., Ekstam Smith, K., Koleva, H., Nam, K.W., Shim, H., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Ashok Raj, B., Fargher, K.
Pattern Discovery in Brain Imaging Genetics via SCCA Modeling with a Generic Non-convex Penalty
(2017) Scientific Reports, 7 (1), art. no. 14052, . 

DOI: 10.1038/s41598-017-13930-y


a School of Automation, Northwestern Polytechnical University, Xi'an, China
b Radiology and Imaging Sciences, Indiana University, School of Medicine, Indianapolis, IN, United States
c University of California, San Francisco, United States
d University of Southern California, Los Angeles, United States
e Mayo Clinic, Rochester, MN, United States
f University of California, Berkeley, Berkeley, United States
g University of Pennsylvania, Philadelphia, United States
h University of California, Davis, Davis, United States
i Brigham and Women's Hospital, Harvard Medical School, Boston, United States
j Washington University St. Louis, St. Louis, United States
k Prevent Alzheimer's Disease, Rockville, United States
l Siemens, Munich, Germany
m Alzheimer's AssociationIL, United States
n University of PittsburghPA, United States
o Cornell University, New York, NY, United States
p Albert Einstein College of Medicine, Yeshiva University, New York, NY, United States
q AD Drug Discovery Foundation, New York, NY, United States
r Acumen PharmaceuticalsCA, United States
s Northwestern UniversityIL, United States
t National Institute of Mental HealthMD, United States
u Brown UniversityRI, United States
v Eli LillyIN, United States
w University of WashingtonWA, United States
x University of California, San Diego, CA, United States
y University of London, London, United Kingdom
z University of California, Los Angeles, CA, United States
aa University of MichiganMI, United States
ab University of UtahUT, United States
ac Banner Alzheimer's InstituteAZ, United States
ad University of California, Irvine, CA, United States
ae National Institute on AgingMD, United States
af Johns Hopkins UniversityMD, United States
ag Richard Frank ConsultingNH, United States
ah Oregon Health and Science UniversityOR, United States
ai Baylor College of MedicineTX, United States
aj Columbia University Medical Center, New York, NY, United States
ak University of Alabama-BirminghamAL, United States
al Mount Sinai School of Medicine, New York, NY, United States
am Rush University Medical Center, Rush UniversityIL, United States
an Wien CenterFL, United States
ao New York University, New York, NY, United States
ap Duke University Medical CenterNC, United States
aq University of KentuckyKY, United States
ar University of Rochester Medical Center, New York, NY, United States
as University of Texas, Southwestern Medical SchoolTX, United States
at Emory UniversityGA, United States
au University of Kansas, Medical CenterKS, United States
av Mayo Clinic, Jacksonville, FL, United States
aw Yale University, School of MedicineCT, United States
ax McGill University, Montreal-Jewish General HospitalQC, Canada
ay Sunnybrook Health SciencesON, Canada
az U.B.C. Clinic for AD and Related DisordersBC, Canada
ba Cognitive Neurology-St. Joseph'sON, Canada
bb Cleveland Clinic, Lou Ruvo Center for Brain HealthOH, United States
bc Premiere Research Inst (Palm Beach Neurology)FL, United States
bd Georgetown University Medical Center, Washington, DC, United States
be Stanford UniversityCA, United States
bf Banner Sun Health Research InstituteAZ, United States
bg Boston UniversityMA, United States
bh Howard University, Washington, DC, United States
bi Case Western Reserve UniversityOH, United States
bj Neurological Care of CNY, New York, NY, United States
bk Parkwood HospitalPA, United States
bl University of WisconsinWI, United States
bm Dent Neurologic Institute, New York, NY, United States
bn Ohio State UniversityOH, United States
bo Albany Medical College, New York, NY, United States
bp Hartford Hospital, Olin Neuropsychiatry Research CenterCT, United States
bq Dartmouth-Hitchcock Medical CenterNH, United States
br Wake Forest University Health SciencesNC, United States
bs Rhode Island HospitalRI, United States
bt Butler HospitalRI, United States
bu Medical University South CarolinaCA, United States
bv Nathan Kline Institute, New York, NY, United States
bw University of Iowa, College of MedicineIA, United States
bx USF Health Byrd Alzheimer's Institute, University of South FloridaFL, United States


Abstract
Brain imaging genetics intends to uncover associations between genetic markers and neuroimaging quantitative traits. Sparse canonical correlation analysis (SCCA) can discover bi-multivariate associations and select relevant features, and is becoming popular in imaging genetic studies. The L1-norm function is not only convex, but also singular at the origin, which is a necessary condition for sparsity. Thus most SCCA methods impose l 1 -norm onto the individual feature or the structure level of features to pursuit corresponding sparsity. However, the l1 -norm penalty over-penalizes large coefficients and may incurs estimation bias. A number of non-convex penalties are proposed to reduce the estimation bias in regression tasks. But using them in SCCA remains largely unexplored. In this paper, we design a unified non-convex SCCA model, based on seven non-convex functions, for unbiased estimation and stable feature selection simultaneously. We also propose an efficient optimization algorithm. The proposed method obtains both higher correlation coefficients and better canonical loading patterns. Specifically, these SCCA methods with non-convex penalties discover a strong association between the APOE e4 rs429358 SNP and the hippocampus region of the brain. They both are Alzheimer's disease related biomarkers, indicating the potential and power of the non-convex methods in brain imaging genetics. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

8) 

Sethe Burgie, E., Bussell, A.N., Lye, S.-H., Wang, T., Hu, W., McLoughlin, K.E., Weber, E.L., Li, H., Vierstra, R.D.
Photosensing and Thermosensing by Phytochrome B Require Both Proximal and Distal Allosteric Features within the Dimeric Photoreceptor
(2017) Scientific Reports, 7 (1), art. no. 13678, . 

DOI: 10.1038/s41598-017-14037-0


a Department of Biology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Genetics, University of Wisconsin-Madison, Madison, WI, United States
c Department of Biology, Brookhaven National Laboratory, Upton, NY, United States
d Van Andel Research Institute, Grand Rapids, MI, United States
e CUNY Advanced Science Research Center, City University of New York, New York, NY, United States


Abstract
Phytochromes (Phys) encompass a diverse collection of bilin-containing photoreceptors that help plants and microorganisms perceive light through photointerconversion between red light (Pr) and far-red light (Pfr)-absorbing states. In addition, Pfr reverts thermally back to Pr via a highly enthalpic process that enables temperature sensation in plants and possibly other organisms. Through domain analysis of the Arabidopsis PhyB isoform assembled recombinantly, coupled with measurements of solution size, photoconversion, and thermal reversion, we identified both proximal and distal features that influence all three metrics. Included are the downstream C-terminal histidine kinase-related domain known to promote dimerization and a conserved patch just upstream of an N-terminal Period/Arnt/Sim (PAS) domain, which upon removal dramatically accelerates thermal reversion. We also discovered that the nature of the bilin strongly influences Pfr stability. Whereas incorporation of the native bilin phytochromobilin into PhyB confers robust Pfr → Pr thermal reversion, that assembled with the cyanobacterial version phycocyanobilin, often used for optogenetics, has a dramatically stabilized Pfr state. Taken together, we conclude that Pfr acquisition and stability are impacted by a collection of opposing allosteric features that inhibit or promote photoconversion and reversion of Pfr back to Pr, thus allowing Phys to dynamically measure light, temperature, and possibly time. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

9) 

Carter, R., Leath, S., Butler-Barnes, S.T., Bryd, C.M., Chavous, T.M., Caldwell, C.H., Jackson, J.S.
Comparing Associations Between Perceived Puberty, Same-Race Friends and Same-Race Peers, and Psychosocial Outcomes Among African American and Caribbean Black Girls
(2017) Journal of Black Psychology, 43 (8), pp. 836-862. 

DOI: 10.1177/0095798417711024


a University of Michigan, Ann Arbor, MI, United States
b Washington University in St. LouisMO, United States
c University of California, Santa Cruz, CA, United States


Abstract
Despite indications that adolescent peer relations is a mediator of associations between early pubertal timing and psychosocial problems, extant studies have not explicitly examined race or ethnic-related variables that shape the peer experiences of early developers. This study compared associations between pubertal timing, same race-friends, same-race peers, and psychosocial outcomes (school bonding, academic grades, externalizing behaviors, and peer deviancy) among a nationally representative sample of African American (n = 412) and Caribbean Black (n = 195) girls aged 13 to 17 years (Mage = 15 years). Results indicated that girls who perceived that their development was early relative to their peers reported better academic grades. Having more same-race friends were associated with school connectedness and fewer externalizing behaviors among girls who perceived that their development was early relative to their peers, whereas late-developing girls felt more bonded to school and engaged in fewer externalizing behaviors when they report fewer same-race friendships. These findings did not vary by ethnic subgroup. Findings suggest race-related variables (in this case number of same-race friends) provide important insight for understanding perceived pubertal timing effects within this population. © 2017, © The Author(s) 2017.


Author Keywords
academic grades;  Black adolescents girls;  externalizing;  peer deviancy;  perceived pubertal timing;  school bonding


Document Type: Article
Source: Scopus

 

10) 

Lewczuk, P., Riederer, P., O’Bryant, S.E., Verbeek, M.M., Dubois, B., Visser, P.J., Jellinger, K.A., Engelborghs, S., Ramirez, A., Parnetti, L., Jack, C.R., Jr, Teunissen, C.E., Hampel, H., Lleó, A., Jessen, F., Glodzik, L., de Leon, M.J., Fagan, A.M., Molinuevo, J.L., Jansen, W.J., Winblad, B., Shaw, L.M., Andreasson, U., Otto, M., Mollenhauer, B., Wiltfang, J., Turner, M.R., Zerr, I., Handels, R., Thompson, A.G., Johansson, G., Ermann, N., Trojanowski, J.Q., Karaca, I., Wagner, H., Oeckl, P., van Waalwijk van Doorn, L., Bjerke, M., Kapogiannis, D., Kuiperij, H.B., Farotti, L., Li, Y., Gordon, B.A., Epelbaum, S., Vos, S.J.B., Klijn, C.J.M., Van Nostrand, W.E., Minguillon, C., Schmitz, M., Gallo, C., Lopez Mato, A., Thibaut, F., Lista, S., Alcolea, D., Zetterberg, H., Blennow, K., Kornhuber, J., on Behalf of the Members of the WFSBP Task Force Working on this Topic: Peter Riederer, Carla Gallo, Dimitrios Kapogiannis, Andrea Lopez Mato, Florence Thibaut
Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry
(2017) World Journal of Biological Psychiatry, pp. 1-85. Article in Press. 

DOI: 10.1080/15622975.2017.1375556


a Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
b Department of Neurodegeneration Diagnostics, Medical University of Bialystok, and Department of Biochemical Diagnostics, University Hospital of Bialystok, Bialystok, Poland
c Center of Mental Health, Clinic and Policlinic of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany
d Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA
e Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Nijmegen, The Netherlands
f Department of Laboratory Medicine, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer center, Nijmegen, The Netherlands
g Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Salpêtrièrie Hospital, INSERM UMR-S 975 (ICM), Paris 6 University, Paris, France
h Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands
i Department of Neurology, Alzheimer Centre, Amsterdam Neuroscience VU University Medical Centre, Amsterdam, The Netherlands
j Institute of Clinical Neurobiology, Vienna, Austria
k Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium
l Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium
m Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
n Institute of Human Genetics, University of Bonn, Bonn, Germany
o Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany
p Section of Neurology, Center for Memory Disturbances, Lab of Clinical Neurochemistry, University of Perugia, Perugia, Italy
q Department of Radiology, Mayo Clinic, Rochester, MN, USA
r Neurochemistry Lab and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center Amsterdam, Amsterdam, The Netherlands
s AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l’hôpital, Paris, France
t Department of Neurology, Institut d’Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
u Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, CIBERNED, Spain
v German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany
w Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY, USA
x Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA
y Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA
z Barcelonabeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain
aa Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
ab Karolinska Institutet, Department NVS, Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden
ac Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
ad Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
ae Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
af Department of Neurology, University of Ulm, Ulm, Germany
ag Paracelsus-Elena-Klinik, Kassel and University Medical Center Göttingen, Department of Neurology, Göttingen, Germany
ah Department of Psychiatry & Psychotherapy, University of Göttingen, Göttingen, Germany
ai German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany
aj iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal
ak Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
al Clinical Dementia Centre, Department of Neurology, University Medical School, Göttingen, Germany
am Laboratory of Neurosciences, National Institute on Aging/National Institutes of Health (NIA/NIH) Baltimore, MD, USA
an Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA
ao Department of Neurosurgery, HSC T-12/086 Stony Brook University, New York, NY, USA
ap Departamento de Ciencias Celulares y Moleculares/Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
aq Chair of Psychoneuroimmunoendocrinology, Maimonides University, Buenos Aires, Argentina
ar Department of Psychiatry, University Hospital Cochin-Site Tarnier 89 rue d’Assas, INSERM 894, Faculty of Medicine Paris Descartes, Paris, France
as Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK


Abstract
In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer’s disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders. © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.


Author Keywords
Alzheimer’s disease;  biomarkers;  cerebrospinal fluid;  consensus;  dementia


Document Type: Article in Press
Source: Scopus

 

11) 

Herbert, A.L., Fu, M.-M., Drerup, C.M., Gray, R.S., Harty, B.L., Ackerman, S.D., O'Reilly-Pol, T., Johnson, S.L., Nechiporuk, A.V., Barres, B.A., Monk, K.R.
Dynein/dynactin is necessary for anterograde transport of Mbp mRNA in oligodendrocytes and for myelination in vivo
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (43), pp. E9153-E9162. 

DOI: 10.1073/pnas.1711088114


a Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurobiology, Stanford University School of Medicine, Stanford, CA, United States
c Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR, United States
d Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
e National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
f Department of Pediatrics, Dell Medical School, University of Texas at Austin, Austin, TX, United States
g Vollum Institute, Oregon Health and Science University, Portland, OR, United States
h Institute of Neuroscience, University of Oregon, Eugene, OR, United States


Abstract
Oligodendrocytes in the central nervous system produce myelin, a lipid-rich, multilamellar sheath that surrounds axons and promotes the rapid propagation of action potentials. A critical component of myelin is myelin basic protein (MBP), expression of which requires anterograde mRNA transport followed by local translation at the developing myelin sheath. Although the anterograde motor kinesin KIF1B is involved in mbp mRNA transport in zebrafish, it is not entirely clear how mbp transport is regulated. From a forward genetic screen for myelination defects in zebrafish, we identified a mutation in actr10, which encodes the Arp11 subunit of dynactin, a critical activator of the retrograde motor dynein. Both the actr10 mutation and pharmacological dynein inhibition in zebrafish result in failure to properly distribute mbp mRNA in oligodendrocytes, indicating a paradoxical role for the retrograde dynein/dynactin complex in anterograde mbp mRNA transport. To address the molecular mechanism underlying this observation, we biochemically isolated reporter-tagged Mbp mRNA granules from primary cultured mammalian oligodendrocytes to show that they indeed associate with the retrograde motor complex. Next, we used live-cell imaging to show that acute pharmacological dynein inhibition quickly arrests Mbp mRNA transport in both directions. Chronic pharmacological dynein inhibition also abrogates Mbp mRNA distribution and dramatically decreases MBP protein levels. Thus, these cell culture and whole animal studies demonstrate a role for the retrograde dynein/dynactin motor complex in anterograde mbp mRNA transport and myelination in vivo.


Author Keywords
Dynactin;  Dynein;  MRNA transport;  Myelination;  Oligodendrocytes


Document Type: Article
Source: Scopus

 

12) 

Leyns, C.E.G., Ulrich, J.D., Finn, M.B., Stewart, F.R., Koscal, L.J., Serrano, J.R., Robinson, G.O., Anderson, E., Colonna, M., Holtzman, D.M.
TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (43), pp. 11524-11529. 

DOI: 10.1073/pnas.1710311114


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
c Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) were recently found to increase the risk for developing Alzheimer's disease (AD). In the brain, TREM2 is predominately expressed on microglia, and its association with AD adds to increasing evidence implicating a role for the innate immune system in AD initiation and progression. Thus far, studies have found TREM2 is protective in the response to amyloid pathology while variants leading to a loss of TREM2 function impair microglial signaling and are deleterious. However, the potential role of TREM2 in the context of tau pathology has not yet been characterized. In this study, we crossed Trem2+/+ (T2+/+) and Trem2-/- (T2-/-) mice to the PS19 human tau transgenic line (PS) to investigate whether loss of TREM2 function affected tau pathology, the microglial response to tau pathology, or neurodegeneration. Strikingly, by 9 mo of age, T2-/-PS mice exhibited significantly less brain atrophy as quantified by ventricular enlargement and preserved cortical volume in the entorhinal and piriform regions compared with T2+/+PS mice. However, no TREM2- dependent differences were observed for phosphorylated tau staining or insoluble tau levels. Rather, T2-/-PS mice exhibited significantly reduced microgliosis in the hippocampus and piriform cortex comparedwith T2+/+PS mice. Gene expression analyses and immunostaining revealed microglial activation was significantly attenuated in T2-/- PS mice, and there were lower levels of inflammatory cytokines and astrogliosis. These unexpected findings suggest that impairing microglial TREM2 signaling reduces neuroinflammation and is protective against neurodegeneration in the setting of pure tauopathy.


Author Keywords
Alzheimer's disease;  Neurodegeneration;  Neuroinflammation;  Tau;  TREM2


Document Type: Article
Source: Scopus

 

13) 

Castro, D.C., Berridge, K.C.
Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (43), pp. E9125-E9134. 

DOI: 10.1073/pnas.1705753114


a Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychology, University of Michigan, Ann Arbor, MI, United States


Abstract
Hedonic hotspots are brain sites where particular neurochemical stimulations causally amplify the hedonic impact of sensory rewards, such as "liking" for sweetness. Here, we report the mapping of two hedonic hotspots in cortex, where mu opioid or orexin stimulations enhance the hedonic impact of sucrose taste. One hedonic hotspot was found in anterior orbitofrontal cortex (OFC), and another was found in posterior insula. A suppressive hedonic coldspot was also found in the formof an intervening strip stretching from the posterior OFC through the anterior and middle insula, bracketed by the two cortical hotspots. Opioid/orexin stimulations in either cortical hotspot activated Fos throughout a distributed "hedonic circuit" involving cortical and subcortical structures. Conversely, cortical coldspot stimulation activated circuitry for "hedonic suppression." Finally, food intake was increased by stimulations at several prefrontal cortical sites, indicating that the anatomical substrates in cortex for enhancing the motivation to eat are discriminable from those for hedonic impact.


Author Keywords
Affect;  Affect;  Insula;  Motivation;  Opioid;  Opioid;  Orbitofrontal cortex


Document Type: Article
Source: Scopus

 

14) 

Seugnet, L., Dissel, S., Thimgan, M., Cao, L., Shaw, P.J.
Identification of genes that maintain behavioral and structural plasticity during sleep loss
(2017) Frontiers in Neural Circuits, 11, art. no. 79, . 

DOI: 10.3389/fncir.2017.00079


a Centre de Recherche en Neurosciences de Lyon, U1028/UMR 5292, Team WAKING, Université Claude Bernard Lyon 1, INSERM U1028, CNRS UMR 5292, Lyon, France
b Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
c Department of Biological Sciences, Missouri University of Science and Technology, Rolla, MO, United States


Abstract
Although patients with primary insomnia experience sleep disruption, they are able to maintain normal performance on a variety of cognitive tasks. This observation suggests that insomnia may be a condition where predisposing factors simultaneously increase the risk for insomnia and also mitigate against the deleterious consequences of waking. To gain insight into processes that might regulate sleep and buffer neuronal circuits during sleep loss, we manipulated three genes, fat facet (faf), highwire (hiw) and the GABA receptor Resistance to dieldrin (Rdl), that were differentially modulated in a Drosophila model of insomnia. Our results indicate that increasing faf and decreasing hiw or Rdl within wake-promoting large ventral lateral clock neurons (lLNvs) induces sleep loss. As expected, sleep loss induced by decreasing hiw in the lLNvs results in deficits in short-term memory and increases of synaptic growth. However, sleep loss induced by knocking down Rdl in the lLNvs protects flies from sleep-loss induced deficits in short-term memory and increases in synaptic markers. Surprisingly, decreasing hiw and Rdl within the Mushroom Bodies (MBs) protects against the negative effects of sleep deprivation (SD) as indicated by the absence of a subsequent homeostatic response, or deficits in short-term memory. Together these results indicate that specific genes are able to disrupt sleep and protect against the negative consequences of waking in a circuit dependent manner. © 2017 Hudson.


Author Keywords
Drosophila;  GABA-A receptors;  Homeostasis;  Learning;  Memory;  Plasticity;  Sleep;  Ubiquitin


Document Type: Article
Source: Scopus

 

15) 

Madden, L.K., Hill, M., May, T.L., Human, T., Guanci, M.M., Jacobi, J., Moreda, M.V., Badjatia, N.
The Implementation of Targeted Temperature Management: An Evidence-Based Guideline from the Neurocritical Care Society
(2017) Neurocritical Care, pp. 1-20. Article in Press. 

DOI: 10.1007/s12028-017-0469-5


a University of California Davis, Sacramento, CA, United States
b Riverside Methodist Hospital, Columbus, OH, United States
c Maine Medical Center, Portland, ME, United States
d Barnes Jewish Hospital, Washington University, Saint Louis, MO, United States
e Massachusetts General Hospital, Boston, MA, United States
f Indiana University Health Methodist Hospital, Indianapolis, IN, United States
g Duke Raleigh Hospital, Raleigh, NC, United States
h University of Maryland, Baltimore, MD, United States


Abstract
Background: Targeted temperature management (TTM) is often used in neurocritical care to minimize secondary neurologic injury and improve outcomes. TTM encompasses therapeutic hypothermia, controlled normothermia, and treatment of fever. TTM is best supported by evidence from neonatal hypoxic-ischemic encephalopathy and out-of-hospital cardiac arrest, although it has also been explored in ischemic stroke, traumatic brain injury, and intracranial hemorrhage patients. Critical care clinicians using TTM must select appropriate cooling techniques, provide a reasonable rate of cooling, manage shivering, and ensure adequate patient monitoring among other challenges. Methods: The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacotherapy to form a writing Committee in 2015. The group generated a set of 16 clinical questions relevant to TTM using the PICO format. With the assistance of a research librarian, the Committee undertook a comprehensive literature search with no back date through November 2016 with additional references up to March 2017. Results: The Committee utilized GRADE methodology to adjudicate the quality of evidence as high, moderate, low, or very low based on their confidence that the estimate of effect approximated the true effect. They generated recommendations regarding the implementation of TTM based on this systematic review only after considering the quality of evidence, relative risks and benefits, patient values and preferences, and resource allocation. Conclusion: This guideline is intended for neurocritical care clinicians who have chosen to use TTM in patient care; it is not meant to provide guidance regarding the clinical indications for TTM itself. While there are areas of TTM practice where clear evidence guides strong recommendations, many of the recommendations are conditional, and must be contextualized to individual patient and system needs. © 2017 Springer Science+Business Media, LLC


Author Keywords
Complications;  Controlled normothermia;  Fever treatment;  GRADE methodology;  Guideline;  Hypothermia;  Implementation guideline;  Metabolism;  Normothermia;  Patient management;  Shivering;  Systematic review;  Targeted temperature management;  Therapeutic hypothermia


Document Type: Article in Press
Source: Scopus

 

16) 

Wright, P.W., Brier, L.M., Bauer, A.Q., Baxter, G.A., Kraft, A.W., Reisman, M.D., Bice, A.R., Snyder, A.Z., Lee, J.-M., Culver, J.P.
Functional connectivity structure of cortical calcium dynamics in anesthetized and awake mice
(2017) PLoS ONE, 12 (10), art. no. e0185759, . 

DOI: 10.1371/journal.pone.0185759


a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
d Department of Physics, Washington University in St. Louis, St. Louis, MO, United States
e Department Neurology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI and optical intrinsic signal imaging), which are an indirect and relatively slow report of neural activity, and underlying synaptic electrical and metabolic activity through neurovascular coupling is a topic of ongoing research and debate. As application of resting state functional connectivity measures is extended further into topics such as brain development, aging and disease, the importance of understanding the fundamental physiological basis for functional connectivity will grow. Here we extend functional connectivity analysis from hemodynamic- to calcium-based imaging. Transgenic mice (n = 7) expressing a fluorescent calcium indicator (GCaMP6) driven by the Thy1 promoter in glutamatergic neurons were imaged transcranially in both anesthetized (using ketamine/xylazine) and awake states. Sequential LED illumination (λ = 454, 523, 595, 640nm) enabled concurrent imaging of both GCaMP6 fluorescence emission (corrected for hemoglobin absorption) and hemodynamics. Functional connectivity network maps were constructed for infraslow (0.009–0.08Hz), intermediate (0.08–0.4Hz), and high (0.4–4.0Hz) frequency bands. At infraslow and intermediate frequencies, commonly used in BOLD fMRI and fcOIS studies of functional connectivity and implicated in neurovascular coupling mechanisms, GCaMP6 and HbO2 functional connectivity structures were in high agreement, both qualitatively and also quantitatively through a measure of spatial similarity. The spontaneous dynamics of both contrasts had the highest correlation when the GCaMP6 signal was delayed with a ~0.6–1.5s temporal offset. Within the higher-frequency delta band, sensitive to slow wave sleep oscillations in non-REM sleep and anesthesia, we evaluate the speed with which the connectivity analysis stabilized and found that the functional connectivity maps captured putative network structure within time window lengths as short as 30 seconds. Homotopic GCaMP6 functional connectivity maps at 0.4–4.0Hz in the anesthetized states show a striking correlated and anti-correlated structure along the anterior to posterior axis. This structure is potentially explained in part by observed propagation of delta-band activity from frontal somatomotor regions to visuoparietal areas. During awake imaging, this spatio-temporal quality is altered, and a more complex and detailed functional connectivity structure is observed. The combined calcium/hemoglobin imaging technique described here will enable the dissociation of changes in ionic and hemodynamic functional structure and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke. © 2017 Wright et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Document Type: Article
Source: Scopus

 

17) 

Gomez, A.M., Bruchas, M.R.
A Molecular Code for Imprinting Drug-Cue Associations
(2017) Neuron, 96 (1), pp. 3-5. 

DOI: 10.1016/j.neuron.2017.09.018


a Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States
e Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Previous studies suggest that nuclear histone deacetylase HDAC5 has a dynamic relationship with drug-induced behavioral neuroadaptations. The new work by Taniguchi et al. (2017) suggests that targets of nuclear HDAC5 mediate the behavioral effects of rewarding drugs via regulation of cocaine-associated stimuli. Previous studies suggest that nuclear histone deacetylase HDAC5 has a dynamic relationship with drug-induced behavioral neuroadaptations. The new work by Taniguchi et al. (2017) suggests that targets of nuclear HDAC5 mediate the behavioral effects of rewarding drugs via regulation of cocaine-associated stimuli. © 2017 Elsevier Inc.


Author Keywords
cocaine;  HDAC5;  Npas4;  nucleus accumbens


Document Type: Short Survey
Source: Scopus

 

18) 

Acharya, K.D., Nettles, S.A., Sellers, K.J., Im, D.D., Harling, M., Pattanayak, C., Vardar-Ulu, D., Lichti, C.F., Huang, S., Edwards, D.P., Srivastava, D.P., Denner, L., Tetel, M.J.
The progestin receptor interactome in the female mouse hypothalamus: Interactions with synaptic proteins are isoform specific and ligand dependent
(2017) eNeuro, 4 (5), art. no. e0272-17.2017, . 

DOI: 10.1523/ENEURO.0272-17.2017


a Wellesley College, Wellesley, MA, United States
b Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neurosciences Institute, Institute of Psychiatry, Psychology and Neuroscience, MRC Centre for Neurodevelopmental Disorders, King’s College London, London, United Kingdom
c Quantitative Analysis Institute, Departments of Mathematics and Quantitative Reasoning, Wellesley College, Wellesley, MA, United States
d Chemistry Department, Boston University, Boston, MA, United States
e Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Molecular and Cellular Biology, Department of Pathology and Immunology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States
g Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, United States


Abstract
Progestins bind to the progestin receptor (PR) isoforms, PR-A and PR-B, in brain to influence development, female reproduction, anxiety, and stress. Hormone-activated PRs associate with multiple proteins to form functional complexes. In the present study, proteins from female mouse hypothalamus that associate with PR were isolated using affinity pull-down assays with glutathione S-transferase–tagged mouse PR-A and PR-B. Using complementary proteomics approaches, reverse phase protein array (RPPA) and mass spectrometry, we identified hypothalamic proteins that interact with PR in a ligand-dependent and isoform-specific manner and were confirmed by Western blot. Synaptic proteins, including synapsin-I and synapsin-II, interacted with agonist-bound PR isoforms, suggesting that both isoforms function in synaptic plasticity. In further support, synaptogyrin-III and synapsin-III associated with PR-A and PR-B, respectively. PR also interacted with kinases, including c-Src, mTOR, and MAPK1, confirming phosphorylation as an integral process in rapid effects of PR in the brain. Consistent with a role in transcriptional regulation, PR associated with transcription factors and coactivators in a ligand-specific and isoform-dependent manner. Interestingly, both PR isoforms associated with a key regulator of energy homeostasis, FoxO1, suggesting a novel role for PR in energy metabolism. Because many identified proteins in this PR interactome are synaptic proteins, we tested the hypothesis that progestins function in synaptic plasticity. Indeed, progesterone enhanced synaptic density, by increasing synapsin-I–positive synapses, in rat primary cortical neuronal cultures. This novel combination of RPPA and mass spectrometry allowed identification of PR action in synaptic remodeling and energy homeostasis and reveals unique roles for progestins in brain function and disease. © 2017 Acharya et al.


Author Keywords
Cortex;  Estrogen;  Progesterone;  Proteomics;  Synapse;  Synapsin


Document Type: Article
Source: Scopus

 

19) 

Diringer, M.N., Dhar, R., Zazulia, A.
The authors reply
(2017) Critical Care Medicine, 45 (9), pp. e987-e988. 

DOI: 10.1097/CCM.0000000000002532


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States


Document Type: Letter
Source: Scopus

 

20) 

Middleton, J.W., Simons, D.J., Simmons, J.W., Clark, R.S., Kochanek, P.M., Shoykhet, M.
Long-term deficits in cortical circuit function after asphyxial cardiac arrest and resuscitation in developing rats
(2017) eNeuro, 4 (3), art. no. e0319-16.2017, . 

DOI: 10.1523/ENEURO.0319-16.2017


a Department of Cell Biology and Anatomy, Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, United States
b Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
c Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
d Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
e Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, United States


Abstract
Cardiac arrest is a common cause of global hypoxic-ischemic brain injury. Poor neurologic outcome among cardiac arrest survivors results not only from direct cellular injury but also from subsequent long-term dysfunction of neuronal circuits. Here, we investigated the long-term impact of cardiac arrest during development on the function of cortical layer IV (L4) barrel circuits in the rat primary somatosensory cortex. We used multielectrode single-neuron recordings to examine responses of presumed excitatory L4 barrel neurons to controlled whisker stimuli in adult (8 ± 2-mo-old) rats that had undergone 9 min of asphyxial cardiac arrest and resuscitation during the third postnatal week. Results indicate that responses to deflections of the topographically appropriate principal whisker (PW) are smaller in magnitude in cardiac arrest survivors than in control rats. Responses to adjacent whisker (AW) deflections are similar in magnitude between the two groups. Because of a disproportionate decrease in PW-evoked responses, receptive fields of L4 barrel neurons are less spatially focused in cardiac arrest survivors than in control rats. In addition, spiking activity among L4 barrel neurons is more correlated in cardiac arrest survivors than in controls. Computational modeling demonstrates that experimentally observed disruptions in barrel circuit function after cardiac arrest can emerge from a balanced increase in background excitatory and inhibitory conductances in L4 neurons. Experimental and modeling data together suggest that after a hypoxic-ischemic insult, cortical sensory circuits are less responsive and less spatially tuned. Modulation of these deficits may represent a therapeutic approach to improving neurologic outcome after cardiac arrest. © 2017 Middleton et al.


Author Keywords
Cortex;  Hypoxia;  Ischemia;  Somatosensory;  Synchrony;  Thalamus


Document Type: Article
Source: Scopus

 

21) 

Izumi, Y., Zorumski, C.F.
Neuregulin and dopamine D4 receptors contribute independently to depotentiation of schaffer collateral LTP by temperoammonic path stimulation
(2017) eNeuro, 4 (4), art. no. e0176-17.2017, . 

DOI: 10.1523/ENEURO.0176-17.2017


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
c Taylor Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, United States
d Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Prior studies have found that dopamine (DA), acting at D4 receptors, and neuregulin (NRG), likely acting at ErbB4 receptors, are involved in a form of depotentiation of long-term potentiation (LTP) at Schaffer collateral (SC) synapses in the hippocampus. Furthermore, DA and NRG actions are intertwined in that NRG induces DA release. We previously found that low-frequency stimulation (LFS) of temperoammonic (TA) inputs to area CA1 also depotentiates previously established SC LTP through a complex signaling pathway involving endocannabinoids, GABA, adenosine, and mitogen-activated protein kinases (MAPKs), but not glutamate. In the present studies, we found that TA-induced SC depotentiation in hippocampal slices from Sprague-Dawley albino rats also involves activation of both D4 receptors and NRG-activated ErbB receptors, but that the roles of these two modulator systems are independent with D4 receptor antagonism failing to alter chemical depotentiation by NRG1α. Furthermore, a selective D4 receptor agonist was unable to depotentiate SC LTP when administered alone, suggesting that D4 receptor activation is necessary but not sufficient for TA-induced SC depotentiation. Chemical depotentiation by NRG1α was inhibited by a Pan-ErbB antagonist and by picrotoxin (PTX), an antagonist of GABA-A receptors (GABAARs), indicating that NRG likely promotes SC depotentiation via effects on GABA and interneurons. These findings have implications for understanding the role of DA and NRG in cognitive dysfunction associated with neuropsychiatric illnesses. © 2017 Izumi and Zorumski.


Author Keywords
Adenosine;  Endocannabinoids;  ErbB;  GABA;  Hippocampus;  Perforant path


Document Type: Article
Source: Scopus

 

22) 

Hamilton, J.G., Waters, E.A.
How are multifactorial beliefs about the role of genetics and behavior in cancer causation associated with cancer risk cognitions and emotions in the US population?
(2017) Psycho-Oncology, . Article in Press. 

DOI: 10.1002/pon.4563


a Department of Psychiatry and Behavioral Sciences Memorial Sloan Kettering Cancer Center New York, NY USA
b Department of Medicine Memorial Sloan Kettering Cancer Center New York, NY USA
c Department of Surgery-Division of Public Health Sciences Washington University in St. Louis St Louis, MO USA


Abstract
Objective: People who believe that cancer has both genetic and behavioral risk factors have more accurate mental models of cancer causation and may be more likely to engage in cancer screening behaviors than people who do not hold such multifactorial causal beliefs. This research explored possible health cognitions and emotions that might produce such differences. Methods: Using nationally representative cross-sectional data from the US Health Information National Trends Survey (N = 2719), we examined whether endorsing a multifactorial model of cancer causation was associated with perceptions of risk and other cancer-related cognitions and affect. Data were analyzed using linear regression with jackknife variance estimation and procedures to account for the complex survey design and weightings. Results: Bivariate and multivariable analyses indicated that people who endorsed multifactorial beliefs about cancer had higher absolute risk perceptions, lower pessimism about cancer prevention, and higher worry about harm from environmental toxins that could be ingested or that emanate from consumer products (Ps < .05). Bivariate analyses indicated that multifactorial beliefs were also associated with higher feelings of risk, but multivariable analyses suggested that this effect was accounted for by the negative affect associated with reporting a family history of cancer. Multifactorial beliefs were not associated with believing that everything causes cancer or that there are too many cancer recommendations to follow (Ps > .05). Conclusion: Holding multifactorial causal beliefs about cancer are associated with a constellation of risk perceptions, health cognitions, and affect that may motivate cancer prevention and detection behavior. © 2017 John Wiley & Sons, Ltd.


Author Keywords
Cancer cognitions, worry;  Genetics;  Multifactorial beliefs;  Oncology;  Risk perception


Document Type: Article in Press
Source: Scopus

 

23) 

Becske, T., Brinjikji, W., Potts, M.B., Kallmes, D.F., Shapiro, M., Moran, C.J., Levy, E.I., McDougall, C.G., Szikora, I., Lanzino, G., Woo, H.H., Lopes, D.K., Siddiqui, A.H., Albuquerque, F.C., Fiorella, D.J., Saatci, I., Cekirge, S.H., Berez, A.L., Cher, D.J., Berentei, Z., Marosfoi, M., Nelson, P.K.
Long-Term Clinical and Angiographic Outcomes Following Pipeline Embolization Device Treatment of Complex Internal Carotid Artery Aneurysms: Five-Year Results of the Pipeline for Uncoilable or Failed Aneurysms Trial
(2017) Neurosurgery, 80 (1), pp. 40-48. 

DOI: 10.1093/neuros/nyw014


a Rochester General Hospital, Rochester, New York
b Mayo Clinic, Rochester, Minn-esota
c Northwestern University Feinberg School of Medicine, Chicago, Illinois
d New York University Langone Medical Center, New York, New York
e Washington University School of Medicine, St. Louis, Missouri
f University of Buffalo, Buffalo, New York
g Barrow Neurological Institute, Phoenix, Arizona
h National Institute of Neurosurgery, Budapest, Hungary
i Brook Hospital, Stony Brook, New York
j Rush University Medical Center, Chicago, Illinois
k Bayindir Hospital, Ankara, Turkey
l Alembic, LLC, Mountain View, California
m Wild Iris Consulting, Palo Alto, California


Abstract
BACKGROUND: Early and mid-term safety and efficacy of aneurysm treatment with the Pipeline Embolization Device (PED) has been well demonstrated in prior studies.

OBJECTIVE: To present 5-yr follow-up for patients treated in the Pipeline for Uncoilable or Failed Aneurysms clinical trial.

METHODS: In our prospective, multicenter trial, 109 complex internal carotid artery (ICA) aneurysms in 107 subjects were treated with the PED. Patients were followed per a standardized protocol at 180 d and 1, 3, and 5 yr. Aneurysm occlusion, in-stent stenosis, modified Rankin Scale scores, and complications were recorded.

RESULTS: The primary endpoint of complete aneurysm occlusion at 180 d (73.6%) was previously reported. Aneurysm occlusion for those patients with angiographic follow-up progressively increased over time to 86.8% (79/91), 93.4% (71/76), and 95.2% (60/63) at 1, 3, and 5 yr, respectively. Six aneurysms (5.7%) were retreated. New serious device-related events at 1, 3, and 5 yr were noted in 1% (1/96), 3.5% (3/85), and 0% (0/81) of subjects. There were 4 (3.7%) reported deaths in our trial. Seventy-eight (96.3%) of 81 patients with 5-yr clinical follow-up had modified Rankin Scale scores ≤2. No delayed neurological deaths or hemorrhagic or ischemic cerebrovascular events were reported beyond 6 mo. No recanalization of a previously occluded aneurysm was observed.

CONCLUSION: Our 5-yr findings demonstrate that PED is a safe and effective treatment for large and giant wide-necked aneurysms of the intracranial ICA, with high rates of complete occlusion and low rates of delayed adverse events.


Author Keywords
Cerebral aneurysm;  Flow diversion;  Pipeline embolization device;  PUFS


Document Type: Article
Source: Scopus

 

24) 

Siegel, J.S., Mitra, A., Laumann, T.O., Seitzman, B.A., Raichle, M., Corbetta, M., Snyder, A.Z.
Data quality influences observed links between functional connectivity and behavior
(2017) Cerebral Cortex, 27 (9), pp. 4492-4502. 

DOI: 10.1093/cercor/bhw253


a Department of Neurology, Washington University School of Medicine, 4525 Scott Ave., Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine at Washington University, St. Louis, MO, United States
c Department of Neuroscience, Washington University School of Medicine at Washington University, St. Louis, MO, United States
d Department of Neuroscience at University of Padua, Padua, Italy


Abstract
A growing field of research explores links between behavioral measures and functional connectivity (FC) assessed using resting-state functional magnetic resonance imaging. Recent studies suggest that measurement of these relationships may be corrupted by head motion artifact. Using data from the Human Connectome Project (HCP), we find that a surprising number of behavioral, demographic, and physiological measures (23 of 122), including fluid intelligence, reading ability, weight, and psychiatric diagnostic scales, correlate with head motion. We demonstrate that "trait" (across-subject) and "state" (across-day, within-subject) effects of motion on FC are remarkably similar in HCP data, suggesting that state effects of motion could potentially mimic trait correlates of behavior. Thus, head motion is a likely source of systematic errors (bias) in the measurement of FC:behavior relationships. Next, we show that data cleaning strategies reduce the influence of head motion and substantially alter previously reported FC:behavior relationship. Our results suggest that spurious relationships mediated by head motion may be widespread in studies linking FC to behavior. © The Author 2016. Published by Oxford University Press. All rights reserved.


Author Keywords
Functional connectivity;  Head motion;  IQ;  Movement;  Resting state


Document Type: Article
Source: Scopus

 

25) 

Iacono, W.G., Heath, A.C., Hewitt, J.K., Neale, M.C., Banich, M.T., Luciana, M.M., Madden, P.A., Barch, D.M., Bjork, J.M.
The utility of twins in developmental cognitive neuroscience research: How twins strengthen the ABCD research design
(2017) Developmental Cognitive Neuroscience, . Article in Press. 

DOI: 10.1016/j.dcn.2017.09.001


a University of Minnesota, United States
b Washington University in St Louis, United States
c University of Colorado Boulder, United States
d Virginia Commonwealth University, United States


Abstract
The ABCD twin study will elucidate the genetic and environmental contributions to a wide range of mental and physical health outcomes in children, including substance use, brain and behavioral development, and their interrelationship. Comparisons within and between monozygotic and dizygotic twin pairs, further powered by multiple assessments, provide information about genetic and environmental contributions to developmental associations, and enable stronger tests of causal hypotheses, than do comparisons involving unrelated children. Thus a sub-study of 800 pairs of same-sex twins was embedded within the overall Adolescent Brain and Cognitive Development (ABCD) design. The ABCD Twin Hub comprises four leading centers for twin research in Minnesota, Colorado, Virginia, and Missouri. Each site is enrolling 200 twin pairs, as well as singletons. The twins are recruited from registries of all twin births in each State during 2006-2008. Singletons at each site are recruited following the same school-based procedures as the rest of the ABCD study. This paper describes the background and rationale for the ABCD twin study, the ascertainment of twin pairs and implementation strategy at each site, and the details of the proposed analytic strategies to quantify genetic and environmental influences and test hypotheses critical to the aims of the ABCD study. © 2017 The Authors.


Author Keywords
Brain function;  Brain structure;  Environment;  Heritability;  Substance use;  Twins


Document Type: Article in Press
Source: Scopus

 

26) 

Lenze, E.J., Barco, P.P., Bland, M.D.
Depression and Functional Impairment: A Pernicious Pairing in Older Adults
(2017) American Journal of Geriatric Psychiatry, . Article in Press. 

DOI: 10.1016/j.jagp.2017.09.028


Department of Psychiatry, Washington University, St Louis, MO


Document Type: Article in Press
Source: Scopus

 

27) 

Cooper, P.E., McClenaghan, C., Chen, X., Stary-Weinzinger, A., Nichols, C.G.
Conserved functional consequences of disease-associated mutations in the slide helix of Kir6.1 and Kir6.2 subunits of the ATP-sensitive potassium channel
(2017) Journal of Biological Chemistry, 292 (42), pp. 17387-17398. 

DOI: 10.1074/jbc.M117.804971


a Department of Cell Biology and Physiology, Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO, United States
b Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, Vienna, Austria


Abstract
Cantu syndrome (CS) is a condition characterized by a range of anatomical defects, including cardiomegaly, hyperflexibility of the joints, hypertrichosis, and craniofacial dysmorphology. CS is associated with multiple missense mutations in the genes encoding the regulatory sulfonylurea receptor 2 (SUR2) subunits of the ATP-sensitive K+ (KATP) channel as well as two mutations (V65M and C176S) in the Kir6.1 (KCNJ8) subunit. Previous analysis of leucine and alanine substitutions at the Val- 65-equivalent site (Val-64) in Kir6.2 indicated no major effects on channel function. In this study, we characterized the effects of both valine-to-methionine and valine-to-leucine substitutions at this position in both Kir6.1 and Kir6.2 using ion flux and patch clamp techniques. We report that methionine substitution, but not leucine substitution, results in increased open state stability and hence significantly reduced ATP sensitivity and a marked increase of channel activity in the intact cell irrespective of the identity of the coassembled SUR subunit. Sulfonylurea inhibitors, such as glibenclamide, are potential therapies for CS. However, as a consequence of the increased open state stability, both Kir6.1(V65M) and Kir6.2(V64M) mutations essentially abolish high-affinity sensitivity to the KATP blocker glibenclamide in both intact cells and excised patches. This raises the possibility that, at least for some CS mutations, sulfonylurea therapy may not prove to be successful and highlights the need for detailed pharmacogenomic analyses of CS mutations. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.


Document Type: Article
Source: Scopus

 

28) 

Doulgerakis, M., Eggebrecht, A., Culver, J., Dehghani, H.
Towards real-time functional human brain imaging with diffuse optical tomography
(2017) Optics InfoBase Conference Papers, Part F61-ECBO 2017, 3 p. 

DOI: 10.1117/12.2285983


a School of Computer Science, University of Birmingham, Birmingham, United Kingdom
b Department of Radiology, Washington University School of MedicineMO, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
d Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States


Abstract
A framework for efficient formulation of the inverse model in diffuse optical tomography, incorporating parallel computing is proposed. Based on 24 subjects, a tenfold speed increase and a hundredfold memory efficiency is reported, whilst maintaining reconstruction quality. © 2017 SPIE-OSA.


Document Type: Conference Paper
Source: Scopus

 

29) 

Li, P., Stewart, R., Butler, A., Gonzalez-Cota, A.L., Harmon, S., Salkoff, L.
GABA-B controls persistent Na+ current and coupled Na+-activated K+ current
(2017) eNeuro, 4 (3), art. no. e0114-17.2017, . 

DOI: 10.1523/ENEURO.0114-17.2017


a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
b Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The GABA-B receptor is densely expressed throughout the brain and has been implicated in many CNS functions and disorders, including addiction, epilepsy, spasticity, schizophrenia, anxiety, cognitive deficits, and depression, as well as various aspects of nervous system development. How one GABA-B receptor is involved in so many aspects of CNS function remains unanswered. Activation of GABA-B receptors is normally thought to produce inhibitory responses in the nervous system, but puzzling contradictory responses exist. Here we report that in rat mitral cells of the olfactory bulb, GABA-B receptor activation inhibits both the persistent sodium current (INaP) and the sodium-activated potassium current (IKNa), which is coupled to it. We find that the primary effect of GABA-B activation is to inhibit INaP, which has the secondary effect of inhibiting IKNa because of its dependence on persistent sodium entry for activation. This can have either a net excitatory or inhibitory effect depending on the balance of INaP/IKNa currents in neurons. In the olfactory bulb, the cell bodies of mitral cells are densely packed with sodium-activated potassium channels. These channels produce a large IKNa which, if constitutively active, would shunt any synaptic potentials traversing the soma before reaching the spike initiation zone. However, GABA-B receptor activation might have the net effect of reducing the IKNa blocking effect, thus enhancing the effectiveness of synaptic potentials. © 2017 Li et al.


Author Keywords
Baclofen;  GABA-B;  Mitral cell;  Olfactory bulb;  Persistent sodium current;  Potassium channel;  Slick;  SLO2


Document Type: Article
Source: Scopus

 

30) 

Samineni, V.K., Grajales-Reyes, J.G., Copits, B.A., O’Brien, D.E., Trigg, S.L., Gomez, A.M., Bruchas, M.R., Gereau, R.W., IV
Divergent modulation of nociception by glutamatergic and GABAergic neuronal subpopulations in the periaqueductal gray
(2017) eNeuro, 4 (2), art. no. e0129-16.2017, . 

DOI: 10.1523/ENEURO.0129-16.2017


a Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
b Washington University School of Medicine, St. Louis, MO, United States
c Division of Biomedical and Biological Sciences Graduate Program in Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
e Washington University School of Medicine, St. Louis, MO, United States


Abstract
The ventrolateral periaqueductal gray (vlPAG) constitutes a major descending pain modulatory system and is a crucial site for opioid-induced analgesia. A number of previous studies have demonstrated that glutamate and GABA play critical opposing roles in nociceptive processing in the vlPAG. It has been suggested that glutamatergic neurotransmission exerts antinociceptive effects, whereas GABAergic neurotransmission exert pronociceptive effects on pain transmission, through descending pathways. The inability to exclusively manipulate subpopulations of neurons in the PAG has prevented direct testing of this hypothesis. Here, we demonstrate the different contributions of genetically defined glutamatergic and GABAergic vlPAG neurons in nociceptive processing by employing cell type-specific chemogenetic approaches in mice. Global chemogenetic manipulation of vlPAG neuronal activity suggests that vlPAG neural circuits exert tonic suppression of nociception, consistent with previous pharmacological and electrophysiological studies. However, selective modulation of GABAergic or glutamatergic neurons demonstrates an inverse regulation of nociceptive behaviors by these cell populations. Selective chemogenetic activation of glutamatergic neurons, or inhibition of GABAergic neurons, in vlPAG suppresses nociception. In contrast, inhibition of glutamatergic neurons, or activation of GABAergic neurons, in vlPAG facilitates nociception. Our findings provide direct experimental support for a model in which excitatory and inhibitory neurons in the PAG bidirectionally modulate nociception. © 2017 Samineni et al.


Author Keywords
Chemogenetics;  Descending modulation;  DREADDs;  PAG;  Pain;  RVM


Document Type: Article
Source: Scopus

 

31) 

Linardon, J., Fairburn, C.G., Fitzsimmons-Craft, E.E., Wilfley, D.E., Brennan, L.
The empirical status of the third-wave behaviour therapies for the treatment of eating disorders: A systematic review
(2017) Clinical Psychology Review, . Article in Press. 

DOI: 10.1016/j.cpr.2017.10.005


a School of Psychology, Australian Catholic University, 115 Victoria Parade/Locked Bag 4115, Melbourne, Victoria 3065, Australia
b Oxford University, Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK
c Department of Psychiatry, Washington University School of Medicine, Mailstop 8134-29-2100, 660 S. Euclid Ave, St. Louis, MO 63110, United States


Abstract
Although third-wave behaviour therapies are being increasingly used for the treatment of eating disorders, their efficacy is largely unknown. This systematic review and meta-analysis aimed to examine the empirical status of these therapies. Twenty-seven studies met full inclusion criteria. Only 13 randomized controlled trials (RCT) were identified, most on binge eating disorder (BED). Pooled within- (pre-post change) and between-groups effect sizes were calculated for the meta-analysis. Large pre-post symptom improvements were observed for all third-wave treatments, including dialectical behaviour therapy (DBT), schema therapy (ST), acceptance and commitment therapy (ACT), mindfulness-based interventions (MBI), and compassion-focused therapy (CFT). Third-wave therapies were not superior to active comparisons generally, or to cognitive-behaviour therapy (CBT) in RCTs. Based on our qualitative synthesis, none of the third-wave therapies meet established criteria for an empirically supported treatment for particular eating disorder subgroups. Until further RCTs demonstrate the efficacy of third-wave therapies for particular eating disorder subgroups, the available data suggest that CBT should retain its status as the recommended treatment approach for bulimia nervosa (BN) and BED, and the front running treatment for anorexia nervosa (AN) in adults, with interpersonal psychotherapy (IPT) considered a strong empirically-supported alternative. © 2017 Elsevier Ltd.


Author Keywords
Cognitive-behaviour therapy;  Eating disorders;  Interpersonal psychotherapy;  Systematic review;  Third-wave therapies


Document Type: Article in Press
Source: Scopus

 

32) 

Hermanstyne, T.O., Granados-Fuentes, D., Mellor, R.L., Herzog, E.D., Nerbonne, J.M.
Acute knockdown of Kv4.1 regulates repetitive firing rates and clock gene expression in the suprachiasmatic nucleus and daily rhythms in locomotor behavior
(2017) eNeuro, 4 (3), art. no. e0377-16.2017, . 

DOI: 10.1523/ENEURO.0377-16.2017


a Departments of Developmental Biology, Internal Medicine Washington University School of Medicine, Washington University, St. LouisMO, United States
b Department of Biology, Washington University, St. Louis, MO, United States


Abstract
Rapidly activating and inactivating A-type K+ currents (Ia) encoded by Kv4.2 and Kv4.3 pore-forming (a) subunits of the Kv4 subfamily are key regulators of neuronal excitability. Previous studies have suggested a role for Kv4.1 a-subunits in regulating the firing properties of mouse suprachiasmatic nucleus (SCN) neurons. To test this, we utilized an RNA-interference strategy to knockdown Kv4.1, acutely and selectively, in the SCN. Current-clamp recordings revealed that the in vivo knockdown of Kv4.1 significantly (p &lt; 0.0001) increased mean ± SEM repetitive firing rates in SCN neurons during the day (6.4 ± 0.5 Hz) and at night (4.3 ± 0.6 Hz), compared with nontargeted shRNA- expressing SCN neurons (day: 3.1 ± 0.5 Hz; night: 1.6 ± 0.3 Hz). Ia was also significantly (p &lt; 0.05) reduced in Kv4.1 -targeted shRNA-expressing SCN neurons (day: 80.3 ±11.8 pA/pF; night: 55.3 ± 7.7 pA/pF). compared with nontargeted shRNA-expressing (day: 121.7 ± 10.2 pA/pF; night: 120.6 ± 16.5 pA/pF) SCN neurons. The magnitude of the effect of Kv4.1 -targeted shRNA expression on firing rates and lA was larger at night. In addition, Kv4.1 –targeted shRNA expression significantly ip &lt; 0.001) increased mean ± SEM nighttime input resistance (Rin; 2256 ±166 Mil), compared to nontargeted shRNA-expressing SCN neurons (1143 ± 93 MΩ). Additional experiments revealed that acute knockdown of Kv4.1 significantly (p &lt; 0.01) shortened, by ~0.5 h, the circadian period of spontaneous electrical activity, clock gene expression and locomotor activity demonstrating a physiological role for Kv4.1-encoded lA channels in regulating circadian rhythms in neuronal excitability and behavior. © 2017 Hermanstyne et al.


Author Keywords
A-type current;  Action potential waveforms;  Kv channels;  Period2;  Repetitive firing properties;  SCN


Document Type: Article
Source: Scopus

 

33) 

Burel, S., Coyan, F.C., Lorenzini, M., Meyer, M.R., Lichti, C.F., Brown, J.H., Loussouarn, G., Charpentier, F., Nerbonne, J.M., Townsend, R.R., Maier, L.S., Marionneau, C.
C-terminal phosphorylation of NaV1.5 impairs FGF13-dependent regulation of channel inactivation
(2017) Journal of Biological Chemistry, 292 (42), pp. 17431-17448. 

DOI: 10.1074/jbc.M117.787788


a Institut du Thorax, INSERM UMR1087, CNRS UMR6291, IRS, Université de Nantes, 8 Quai Moncousu, Nantes Cedex 1, France
b Department of Medicine, Washington University Medical School, St. Louis, MO, United States
c Department of Developmental Biology, Washington University Medical School, St. Louis, MO, United States
d Department of Internal Medicine, Washington University Medical School, St. Louis, MO, United States
e Department of Cell Biology and Physiology, Washington University Medical School, St. Louis, MO, United States
f Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States
g Department of Pharmacology, University of California at San Diego, San Diego, CA, United States
h Department of Internal Medicine II, University Heart Center, University Hospital Regensburg, Regensburg, Germany


Abstract
Voltage-gated Na+ (NaV) channels are key regulators of myocardial excitability, and Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent alterations in NaV1.5 channel inactivation are emerging as a critical determinant of arrhythmias in heart failure. However, the global native phosphorylation pattern of NaV1.5 subunits associated with these arrhythmogenic disorders and the associated channel regulatory defects remain unknown. Here, we undertook phosphoproteomic analyses to identify and quantify in situ the phosphorylation sites in the NaV1.5 proteins purified from adult WT and failing CaMKIIδc-overexpressing (CaMKIIδc-Tg) mouse ventricles. Of 19 native NaV1.5 phosphorylation sites identified, two Cterminal phosphoserines at positions 1938 and 1989 showed increased phosphorylation in the CaMKIIδc-Tg compared with the WT ventricles. We then tested the hypothesis that phosphorylation at these two sites impairs fibroblast growth factor 13 (FGF13)-dependent regulation of NaV1.5 channel inactivation. Whole-cell voltage-clamp analyses in HEK293 cells demonstrated that FGF13 increases NaV1.5 channel availability and decreases late Na+ current, two effects that were abrogated with NaV1.5 mutants mimicking phosphorylation at both sites. Additional co-immunoprecipitation experiments revealed that FGF13 potentiates the binding of calmodulin to NaV1.5 and that phosphomimetic mutations at both sites decrease the interaction of FGF13 and, consequently, of calmodulin with NaV1.5. Together, we have identified two novel native phosphorylation sites in the C terminus of NaV1.5 that impair FGF13-dependent regulation of channel inactivation and may contribute to CaMKIIδc-dependent arrhythmogenic disorders in failing hearts. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.


Document Type: Article
Source: Scopus