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Office of Neuroscience Research > Resources and Facilities > WUSTL Neuroscience Publications for the week

WUSTL Neuroscience Publications for the week

 

The publications below include authors at Washington University and were identified by Scopus search.  These are the most current publications.  For previous lists, visit the WUSTL Neuroscience publications archive.

February 12, 2018 

1) 

Li, Z.a , Mazzoni, P.b , Song, S.c , Qian, N.d
A single, continuously applied control policy for modeling reaching movements with and without perturbation
(2018) Neural Computation, 30 (2), pp. 397-427. 


a Department of Biomedical Engineering, Center for Brain-Inspired Computing Research, Tsinghua University, Beijing, China
b Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
c Department of Biological Engineering, Center for Brain-Inspired Computing Research, Tsinghua University, Beijing, China
d Department of Neuroscience and Department of Physiology and Cellular Biophysics, Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, United States


Abstract
It has been debated whether kinematic features, such as the number of peaks or decomposed submovements in a velocity profile, indicate the number of discrete motor impulses or result from a continuous control process. The debate is particularly relevant for tasks involving target perturbation, which can alter movement kinematics. To simulate such tasks, finite-horizon models require two preset movement durations to compute two control policies before and after the perturbation. Another model employs infinite- and finite-horizon formulations to determine, respectively, movement durations and control policies, which are updated every time step. We adopted an infinite-horizon optimal feedback control model that, unlike previous approaches, does not preset movement durations or use multiple control policies. It contains both controldependent and independent noises in system dynamics, state-dependent and independent noises in sensory feedbacks, and different delays and noise levels for visual and proprioceptive feedbacks. We analytically derived an optimal solution that can be applied continuously to move an effector toward a target regardless of whether, when, or where the target jumps. This single policy produces different numbers of peaks and "submovements" in velocity profiles for different conditions and trials. Movements that are slower or perturbed later appear to have more submovements. The model is also consistent with the observation that subjects can perform the perturbation task even without detecting the target jump or seeing their hands during reaching. Finally, because the model incorporates Weber's law via a state representation relative to the target, it explainswhy initial and terminal visual feedback are, respectively, less and more effective in improving end-point accuracy. Our work suggests that the number of peaks or submovements in a velocity profile does not necessarily reflect the number of motor impulses and that the difference between initial and terminal feedback does not necessarily imply a transition between open- and closed-loop strategies. © 2018 Massachusetts Institute of Technology.


Document Type: Letter
Source: Scopus

 

2) 

Micalizzi, L.a b c , Marceau, K.d , Brick, L.A.e f , Palmer, R.H.g , Todorov, A.A.h i , Heath, A.C.h i , Evans, A.j , Knopik, V.S.d e f
Inhibitory control in siblings discordant for exposure to maternal smoking during pregnancy
(2018) Developmental Psychology, 54 (2), pp. 199-208. 


a Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, United States
b Department of Psychiatry and Human Behavior, Center for Alcohol and Addiction Studies, United States
c Department of Behavioral and Social Sciences, Brown University, United States
d Department of Human Development and Family Studies, Purdue University, United States
e Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, United States
f Department of Psychiatry and Human Behavior, Brown University, United States
g Department of Psychology, Emory University, United States
h Midwest Alcoholism Research Center, Family and Population Research Center, United States
i Department of Psychiatry, Washington University School of Medicine, United States
j Memorial Hospital, Warren Alpert Medical School, Brown University, United States


Abstract
Maternal smoking during pregnancy (SDP) has been linked to poorer offspring executive function across development, but SDP does not occur independent of other familial risk factors. As such, poor and inconsistent control for potential confounds, notably shared familial (i.e., genetic and environmental) confounds, preclude concluding causal effects of SDP on child outcomes. We examined the withinfamily association between SDP and one component of executive function, inhibitory control, in a sample of families (N=173) specifically selected for sibling pairs discordant for exposure to SDP. Thus, the present study examines if the SDP-inhibitory control association withstands rigorous control for potential child and familial confounds. 79% of the variation in child inhibitory control was attributable to within-family differences and 21% was attributable to differences between families, indicating that the variability in inhibitory control was primarily a function of differences between siblings rather than differences across families. Further, the association between SDP and inhibitory control was fully attenuated when confounds were considered. These findings suggest that co-occurring vulnerabilities act as more salient risk factors for poorer child inhibitory control than SDP and may serve as effective targets of interventions seeking to improve children's inhibitory control in families with nicotine dependent mothers. © 2017 American Psychological Association.


Author Keywords
Sibling comparison;  Behavioral genetics;  Executive function;  Inhibitory control;  Maternal smoking during pregnancy


Document Type: Article
Source: Scopus

 

3) 

Sylvester, C.M.
Brain Games to Reduce Anxiety in High-Risk Children
(2018) Journal of the American Academy of Child and Adolescent Psychiatry, 57 (2), pp. 86-95. 


Washington University School of Medicine, St. Louis, United States


Document Type: Editorial
Source: Scopus

 

4) 

Lewis, E.M.A., Kroll, K.L.
Development and disease in a dish: The epigenetics of neurodevelopmental disorders
(2018) Epigenomics, 10 (2), pp. 219-231. 


Department of Developmental Biology, Washington University School of Medicine, 660 S Euclid Avenue, Saint Louis, MO, United States


Abstract
Human neurodevelopmental disorders (NDDs) involve mutations in hundreds of individual genes, with over-representation in genes encoding proteins that alter chromatin structure to modulate gene expression. Here, we highlight efforts to model these NDDs through in vitro differentiation of patient-specific induced pluripotent stem cells into neurons. We discuss how epigenetic regulation controls normal cortical development, how mutations in several classes of epigenetic regulators contribute to NDDs, and approaches for modeling cortical development and function using both directed differentiation and formation of cerebral organoids. We explore successful applications of these models to study both syndromic and nonsyndromic NDDs and to define convergent mechanisms, addressing both the potential and challenges of using this approach to define cellular and molecular mechanisms that underlie NDDs. © 2018 Future Medicine Ltd.


Author Keywords
autism spectrum disorder;  cerebral cortex;  cerebral organoid;  chromatin;  epigenetic;  genetics;  in vitro differentiation;  induced pluripotent stem cell;  neurodevelopmental disorder;  neuron


Document Type: Review
Source: Scopus

 

5) 

Shin, D.J.a , Germann, A.L.a , Johnson, A.D.a , Forman, S.A.c , Steinbach, J.H.a b , Akk, G.a b
Propofol is an allosteric agonist with multiple binding sites on concatemeric ternary GABAA receptors
(2018) Molecular Pharmacology, 93 (2), pp. 178-189. 


a Department of Anesthesiology, Washington University, School of Medicine, Campus Box 8054, 660 S. Euclid Avenue, St. Louis, MO, United States
b Taylor Family Institute for Innovative Psychiatric Research, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States


Abstract
GABAA receptors can be directly activated and potentiated by the intravenous anesthetic propofol. Previous photolabeling, modeling, and functional data have identified two binding domains through which propofol acts on the GABAA receptor. These domains are defined by the β(M286) residue at the β"+"-α"-" interface in the transmembrane region and the β(Y143) residue near the β"-" surface in the junction between the extracellular and transmembrane domains. In the ternary receptor, there are predicted to be two copies of each class of sites, for a total of four sites per receptor. We used β2α 1 γ2L and β2α1 concatemeric constructs to determine the functional effects of the β(Y143W) and β(M286W) mutations to gain insight into the number of functional binding sites for propofol and the energetic contributions stemming from propofol binding to the individual sites. A mutation of each of the four sites affected the response to propofol, indicating that each of the four sites is functional in the wild-type receptor. The mutations mainly impaired stabilization of the open state by propofol, i.e., reduced gating efficacy. The effects were similar for mutations at either site and were largely additive and independent of the presence of other Y143W or M286W mutations in the receptor. The two classes of sites appeared to differ in affinity for propofol, with the site affected by M286W having about a 2-fold higher affinity. Our analysis indicates there may be one or two additional functionally equivalent binding sites for propofol, other than those modified by substitutions at β(Y143) and β(M286). Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.


Document Type: Article
Source: Scopus

 

6) 

Reiersen, A.M.
New Evidence of Genetic Overlap Between Atypical Sensory Reactivity and Autistic Traits: Implications for Future Research
(2018) Journal of the American Academy of Child and Adolescent Psychiatry, 57 (2), pp. 86-95. 


Washington University School of Medicine, St. Louis, United States


Document Type: Editorial
Source: Scopus

 

7) 

Huang, J.a , Campian, J.L.b , Gujar, A.D.c , Tsien, C.a , Ansstas, G.b , Tran, D.D.b , DeWees, T.A.a , Lockhart, A.C.b , Kim, A.H.c
Final results of a phase I dose-escalation, dose-expansion study of adding disulfiram with or without copper to adjuvant temozolomide for newly diagnosed glioblastoma
(2018) Journal of Neuro-Oncology, pp. 1-7. Article in Press. 


a Department of Radiation Oncology, Center for Advanced Medicine, Washington University School of Medicine, 4921 Parkview Place, Campus Box #8224, St. Louis, MO, United States
b Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, United States
c Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, United States


Abstract
Disulfiram has shown promising activity including proteasome inhibitory properties and synergy with temozolomide in preclinical glioblastoma (GBM) models. In a phase I study for newly diagnosed GBM after chemoradiotherapy, we have previously reported our initial dose-escalation results combining disulfiram with adjuvant temozolomide and established the maximum tolerated dose (MTD) as 500 mg per day. Here we report the final results of the phase I study including an additional dose-expansion cohort of disulfiram with concurrent copper. The phase I study consisted of an initial dose-escalation phase of disulfiram 500–1000 mg daily during adjuvant temozolomide, followed by a dose-expansion phase of disulfiram 500 mg daily with copper 2 mg three times daily. Proteasome inhibition was assessed using fluorometric 20S proteasome assay on peripheral blood cell. A total of 18 patients were enrolled: 7 patients received 500 mg disulfiram, 5 patients received 1000 mg disulfiram, and 6 patients received 500 mg disulfiram with copper. Two dose-limiting toxicities occurred with 1000 mg disulfiram. At disulfiram 500 mg with or without copper, only 1 patient (7%) required dose-reduction during the first month of therapy. Addition of copper to disulfiram did not increase toxicity nor proteasome inhibition. The median progression-free survival was 4.5 months (95% CI 0.8–8.2). The median overall survival (OS) was 14.0 months (95% CI 8.3–19.6), and the 2-year OS was 24%. The MTD of disulfiram at 500 mg daily in combination with adjuvant temozolomide was well tolerated by GBM patients, but 1000 mg daily was not. Toxicity and pharmacodynamic effect of disulfiram were similar with or without concurrent copper. The clinical efficacy appeared to be comparable to historical data. Additional clinical trials to combine disulfiram and copper with chemoradiotherapy or to resensitize recurrent GBM to temozolomide are ongoing. © 2018 Springer Science+Business Media, LLC, part of Springer Nature


Author Keywords
Copper;  Disulfiram;  Glioblastoma;  Phase 1 study;  Proteasome inhibition;  Temozolomide


Document Type: Article in Press
Source: Scopus

 

8) 

Rubin, J.B.a , Finlay, J.L.b
Pediatric low-grade gliomas: A brave new world
(2018) Neuro-Oncology, 20 (2), pp. 149-150. 


a Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine, St Louis, MO, United States
b Nationwide Children's Hospital, Ohio State University, Columbus, OH, United States


Document Type: Editorial
Source: Scopus

 

9) 

Mulvey, B., Dougherty, J.D.
Weaving New Insights for the Genetic Regulation of Human Cognitive Phenotypes
(2018) Cell, 172 (1-2), pp. 10-13. 


Department of Genetics, Department of Psychiatry, the Hope Center of Washington University School of Medicine, St. Louis, MO, United States


Abstract
Psychiatric genetic studies have drawn associations between human cognitive traits and noncoding genomic variants. However, the mechanistic effects of these variants are unclear. By weaving in strands of genomic data from developing human brains, de la Torre-Ubieta et al. tie disease-associated loci to functional enhancers, target genes, and putatively affected cell types. Psychiatric genetic studies have drawn associations between human cognitive traits and noncoding genomic variants. However, the mechanistic effects of these variants are unclear. By weaving in strands of genomic data from developing human brains, de la Torre-Ubieta et al. tie disease-associated loci to functional enhancers, target genes, and putatively affected cell types. © 2017 Elsevier Inc.


Document Type: Short Survey
Source: Scopus

 

10) 

Harris, J.K.a , Duncan, A.a b , Men, V.a , Shevick, N.c , Krauss, M.J.b , Patricia A. Cavazos-Rehgb
Messengers and messages for tweets that used #thinspo and #fitspo hashtags in 2016
(2018) Preventing Chronic Disease, 15 (1), art. no. 170309, . 


a Brown School, Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychiatry, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
c Washington University in St. Louis, St. Louis, MO, United States


Abstract
Introduction: Twitter is widely used by young adults and is popular for seeking and sharing health information. The hashtags #thinspo and #fitspo provide a way to identify tweets designed to inspire thinness (thin-spiration, thinspo) or fitness (fitspiration, fitspo). However, despite having different purposes, both terms may be associated with content that promotes eating disorders. We sought to 1) examine and compare the characteristics of senders and the content of tweets using these hashtags and 2) identify characteristics associated with engagement with a #thinspo or #fitspo tweet. Methods: In May 2016 we collected 1,035 tweets with #thinspo and #fitspo hashtags by using a constructed week sampling procedure. Using consensus coding, pairs of raters assessed each tweet's topic and associated images and videos. We used descriptive statistics to examine topics and user characteristics and inferential models to determine topics and characteristics associated with retweets, likes, and replies to tweets. Results: Of the 1,035 tweets, 696 (67.2%) were relevant to body image, fitness, food, dieting, or eating disorders. Fitspo tweets came from organizations or businesses, were promotional, and focused on nutrition and exercise, whereas #thinspo tweets came from individuals, focused on thinness and disordered eating behaviors, and contained images of extremely thin women. Rates of retweeting and liking were significantly higher for #thinspo than for #fitspo. Conclusion: Characteristics of messages and messengers differed between #thinspo and #fitspo tweets; #thinspo tweets were used for messages about disordered eating. Public health professionals should consider using the #thinspo hashtag to reach the #thinspo group.


Document Type: Article
Source: Scopus

 

11) 

Stout, S.H.a b , Babulal, G.M.a b , Ma, C.a c , Carr, D.B.d e , Head, D.M.a f , Grant, E.A.a c , Williams, M.M.g , Holtzman, D.M.a b , Fagan, A.M.a b , Morris, J.C.a b h i j , Roe, C.M.a b
Driving cessation over a 24-year period: Dementia severity and cerebrospinal fluid biomarkers
(2018) Alzheimer's and Dementia, . Article in Press. 


a Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
c Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
d Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
e The Rehabilitation Institute of St. Louis, St. Louis, MO, USA
f Department of Psychology and Brain Sciences, Washington University School of Medicine, St. Louis, MO, USA
g VITAS Healthcare, St. Louis, MO, USA
h Department of Occupational Therapy, Washington University School of Medicine, St. Louis, MO, USA
i Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
j Department of Physical Therapy, Washington University School of Medicine, St. Louis, MO, USA


Abstract
Introduction: With 36 million older adult U.S. drivers, safety is a critical concern, particularly among those with dementia. It is unclear at what stage of Alzheimer's disease (AD) older adults stop driving and whether preclinical AD affects driving cessation. Methods: Time to driving cessation was examined based on Clinical Dementia Rating (CDR) and AD cerebrospinal fluid biomarkers. 1795 older adults followed up to 24 years received CDR ratings. A subset (591) had cerebrospinal fluid biomarker measurements and was followed up to 17 years. Differences in CDR and biomarker groups as predictors of time to driving cessation were analyzed using Kaplan-Meier curves and Cox proportional models. Results: Higher CDR scores and more abnormal biomarker measurements predicted a shorter time to driving cessation. Discussion: Higher levels of AD biomarkers, including among individuals with preclinical AD, lead to earlier driving cessation. Negative functional outcomes of preclinical AD show a nonbenign phase of the disease. © 2017 the Alzheimer's Association.


Author Keywords
Aged;  Alzheimer's disease;  Amyloid β;  Biomarker;  Cerebrospinal fluid;  Driving;  Driving cessation;  Older adults;  Preclinical;  Ptau;  Tau


Document Type: Article in Press
Source: Scopus

 

12) 

Gelman, S.J.a , Naser, F.a , Mahieu, N.G.a , McKenzie, L.D.b , Dunn, G.P.c , Chheda, M.G.b d , Patti, G.J.a b
Consumption of NADPH for 2-HG Synthesis Increases Pentose Phosphate Pathway Flux and Sensitizes Cells to Oxidative Stress
(2018) Cell Reports, 22 (2), pp. 512-522. 


a Department of Chemistry, Washington University, St. Louis, MO, United States
b Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
c Departments of Neurological Surgery and Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Gain-of-function mutations in isocitrate dehydrogenase 1 (IDH1) occur in multiple types of human cancer. Here, we show that these mutations significantly disrupt NADPH homeostasis by consuming NADPH for 2-hydroxyglutarate (2-HG) synthesis. Cells respond to 2-HG synthesis, but not exogenous administration of 2-HG, by increasing pentose phosphate pathway (PPP) flux. We show that 2-HG production competes with reductive biosynthesis and the buffering of oxidative stress, processes that also require NADPH. IDH1 mutants have a decreased capacity to synthesize palmitate and an increased sensitivity to oxidative stress. Our results demonstrate that, even when NADPH is limiting, IDH1 mutants continue to synthesize 2-HG at the expense of other NADPH-requiring pathways that are essential for cell viability. Thus, rather than attempting to decrease 2-HG synthesis in the clinic, the consumption of NADPH by mutant IDH1 may be exploited as a metabolic weakness that sensitizes tumor cells to ionizing radiation, a commonly used anti-cancer therapy. Using liquid chromatography/mass spectrometry (LC/MS) and stable isotope tracing, Gelman et al. find that 2-HG production in cells with IDH1 mutations leads to increased pentose phosphate pathway activity to generate NADPH. Production of 2-HG competes with other NADPH-dependent pathways and sensitizes cells to redox stress. © 2017 The Author(s)


Author Keywords
2-hydroxyglutarate;  cancer metabolism;  LC/MS;  metabolomcis;  pentose phosphate pathway;  redox regulation


Document Type: Article
Source: Scopus
Access Type: Open Access

 

13) 

Stunkel, L.a , Kung, N.H.b , Wilson, B.b , McClelland, C.M.c , Van Stavern, G.P.b
Incidence and causes of overdiagnosis of optic neuritis
(2018) JAMA Ophthalmology, 136 (1), pp. 76-81. 


a Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
b Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S Euclid Ave., St Louis, MO, United States
c Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, United States


Abstract
IMPORTANCE Diagnostic error is an important source of medical error. Overdiagnosis of optic neuritis may prompt unnecessary and costly diagnostic tests, procedures, and treatments. OBJECTIVE To assess the incidence of and characterize factors contributing to overdiagnosis of acute optic neuritis. DESIGN, SETTING, AND PARTICIPANTS In this retrospective clinic-based cross-sectional study of new patient encounters, 122 patients referred for acute optic neuritis at a university-based Midwestern neuro-ophthalmology clinic between January 2014 and October 2016 were studied. Data were analyzed from September 2016 to July 2017. INTERVENTIONS Definite diagnosis was determined by neuro-ophthalmologists. For patients with alterative diagnoses, the Diagnosis Error Evaluation and Research taxonomy tool was applied to categorize the type of diagnostic error. MAIN OUTCOMES AND MEASURES The primary outcomewas the primary type of diagnostic error in patients erroneously diagnosed as having optic neuritis. Secondary outcomes included final diagnosis and interventions undergone prior to referral. RESULTS A total of 122 patients were referred with acute optic neuritis during the study period; 88 (72.1%) were female, and the mean (SD) age was 42.6 (14.0) years. Of these, 49 patients (40.2%; 95%CI, 31.4-49.4) were confirmed to have optic neuritis, and 73 (59.8%; 95%CI, 50.6-68.6) had an alternative diagnosis. The most common alternative diagnoses were headache and eye pain, functional visual loss, and other optic neuropathies, particularly nonarteritic anterior ischemic optic neuropathy. The most common diagnostic error was eliciting or interpreting critical elements of history, which occurred in 24 of 73 patients (33%) with alternative diagnoses. Other common errors included errors weighing or considering alternative diagnoses (23 patients [32%]), errors weighing or interpreting physical examination findings (15 patients [21%]), and misinterpreting diagnostic test results (11 patients [15%]). In patients with alterative diagnoses, 12 (16%) had normal magnetic resonance imaging findings preceding the referral, 12 (16%) had received a lumbar puncture, and 8 (11%) had received unnecessary treatment with intravenous steroids. CONCLUSIONS AND RELEVANCE These data suggest that nearly 60%(95%CI, 50.6-68.6) of patients referred for optic neuritis have an alternative diagnosis, with the most common errors being overreliance on a single item of history and failure to consider alternative diagnoses. Understanding pitfalls leading to overdiagnosis of optic neuritis may improve clinicians' diagnostic process. © 2017 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus

 

14) 

Howes, S.C.a , Geyer, E.A.b , LaFrance, B.c , Zhang, R.d e f , Kellogg, E.H.d e , Westermann, S.g , Rice, L.M.b , Nogales, E.d e h
Structural and functional differences between porcine brain and budding yeast microtubules
(2018) Cell Cycle, pp. 1-10. Article in Press. 


a Biophysics Graduate Group, UC Berkeley, CA 94720, USA
b UT Southwestern Medical Center, Departments of Biophysics and Biochemistry, Dallas, TX 75390, USA
c Molecular and Cell Biology Graduate Program, UC Berkeley, CA 94720, USA
d Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, CA 94720, USA
e Howard Hughes Medical Institute, UC Berkeley, CA 94720-3220, USA
f Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA
g Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria
h Molecular and Cell Biology Department and QB3 Institute, UC Berkeley, CA 94720, USA


Abstract
The cytoskeleton of eukaryotic cells relies on microtubules to perform many essential functions. We have previously shown that, in spite of the overall conservation in sequence and structure of tubulin subunits across species, there are differences between mammalian and budding yeast microtubules with likely functional consequences for the cell. Here we expand our structural and function comparison of yeast and porcine microtubules to show different distribution of protofilament number in microtubules assembled in vitro from these two species. The different geometry at lateral contacts between protofilaments is likely due to a more polar interface in yeast. We also find that yeast tubulin forms longer and less curved oligomers in solution, suggesting stronger tubulin:tubulin interactions along the protofilament. Finally, we observed species-specific plus-end tracking activity for EB proteins: yeast Bim1 tracked yeast but not mammalian MTs, and human EB1 tracked mammalian but not yeast MTs. These findings further demonstrate that subtle sequence differences in tubulin sequence can have significant structural and functional consequences in microtubule structure and behavior. © 2018 Stuart C. Howes, Elisabeth A. Geyerb, Benjamin LaFrance, Rui Zhang, Elizabeth H. Kellogg, Stefan Westermann, Luke M. Rice and Eva Nogales. Published with license by Taylor & Francis.


Author Keywords
Bim1;  budding yeast;  cryo-EM;  EB;  microtubules;  Tubulin


Document Type: Article in Press
Source: Scopus

 

15) 

Rao, S.a , Ghani, M.b , Guo, Z.a , Deming, Y.c , Wang, K.d , Sims, R.e , Mao, C.a , Yao, Y.f , Cruchaga, C.c g , Stephan, D.A.h , Rogaeva, E.b
An APOE-independent cis-eSNP on chromosome 19q13.32 influences tau levels and late-onset Alzheimer's disease risk
(2018) Neurobiology of Aging, . Article in Press. 


a School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China
b Tanz Centre for Research in Neurodegenerative Diseases, and Department of Medicine, University of Toronto, Toronto, Ontario, Canada
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
d Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, USA
e Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK
f Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
g Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA
h Department of Human Genetics, Graduate School of Public Health, Pittsburgh, PA, USA


Abstract
Although multiple susceptibility loci for late-onset Alzheimer's disease (LOAD) have been identified, a large portion of the genetic risk for this disease remains unexplained. LOAD risk may be associated with single-nucleotide polymorphisms responsible for changes in gene expression (eSNPs). To detect eSNPs associated with LOAD, we integrated data from LOAD genome-wide association studies and expression quantitative trait loci using Sherlock (a Bayesian statistical method). We identified a cis-regulatory eSNP (rs2927438) located on chromosome 19q13.32, for which subsequent analyses confirmed the association with both LOAD risk and the expression level of several nearby genes. Importantly, rs2927438 may represent an APOE-independent LOAD eSNP according to the weak linkage disequilibrium of rs2927438 with the 2 polymorphisms (rs7412 and rs429358) defining the APOE-ε2, -ε3, and -ε4 alleles. Furthermore, rs2927438 does not influence chromatin interaction events at the APOE locus or cis-regulation of APOE expression. Further exploratory analysis revealed that rs2927438 is significantly associated with tau levels in the cerebrospinal fluid. Our findings suggest that rs2927438 may confer APOE-independent risk for LOAD. © 2017 Elsevier Inc.


Author Keywords
19q13.32;  APOE;  EQTL;  Late-onset Alzheimer's disease;  Tau level


Document Type: Article in Press
Source: Scopus

 

16) 

McDaniel, M.A., Cahill, M.J., Frey, R.F., Rauch, M., Doele, J., Ruvolo, D., Daschbach, M.M.
Individual Differences in Learning Exemplars Versus Abstracting Rules: Associations with Exam Performance in College Science
(2018) Journal of Applied Research in Memory and Cognition, . Article in Press. 


Washington University in St. Louis, United States


Abstract
Students may do well answering exam questions that are similar to examples presented in class. Yet, some of these students perform poorly on exam questions that require applying instructed concepts to a new problem whereas others fare better on such questions. Our hypothesis is that these performance differences reflect, in part, individual differences in learners' tendencies to focus on acquiring the particular exemplars and responses associated with the training exemplars (exemplar learners) versus attempting to abstract underlying regularities reflected in particular exemplars (abstraction learners). Using a web-based learning task developed in previous laboratory research, we differentiated students on this dimension, and then tracked their final exam performances in introductory chemistry courses. Abstraction learners demonstrated advantages over exemplar learners for transfer questions but not for retention questions. The results converge on the idea that individual differences displayed in how learners acquire and represent concepts persist from laboratory concept learning to learning complex concepts in science courses. © 2017 Society for Applied Research in Memory and Cognition.


Author Keywords
Abstraction;  Exemplar learning;  Individual differences;  Retention;  Student outcomes;  Transfer


Document Type: Article in Press
Source: Scopus

 

17) 

Weintraub, S.a b , Besser, L.c , Dodge, H.H.d e , Teylan, M.c , Ferris, S.f , Goldstein, F.C.g , Giordani, B.e , Kramer, J.h , Loewenstein, D.i , Marson, D.a j , Mungas, D.a k , Salmon, D.a l , Welsh-Bohmer, K.a m , Zhou, X.-H.c , Shirk, S.D.a n , Atri, A.a c o p , Kukull, W.A.c , Phelps, C.a q , Morris, J.C.a r
Version 3 of the Alzheimer Disease Centers’ Neuropsychological Test Battery in the Uniform Data Set (UDS)
(2017) Alzheimer Disease and Associated Disorders, . Article in Press. 


a Departments of Psychiatry
b Neurology Northwestern University Feinberg School of Medicine, Cognitive Neurology and Alzheimer’s Disease Center, Chicago, IL
c Department of Epidemiology, National Alzheimer's Coordinating Center, University of Washington, Seattle, WA
d Department of Neurology, Layton Aging and Alzheimer’s Disease Center, Oregon Health & Science University, Portland, OR
e Department of Neurology, Michigan Alzheimer’s Disease Center, University of Michigan, Ann Arbor, MI
f Alzheimer’s Disease Center, New York University, New York, NY
g Department of Neurology, Alzheimer’s Disease Center, Emory University, Atlanta, GA
h Department of Neurology, University of California San Francisco Medical Center, San Francisco, CA
i Department of Psychiatry and Behavioral Sciences, Miller Medical School, Miami, FL
j Department of Psychiatry, Alzheimer’s Disease Center, University of Alabama-Birmingham, Birmingham, AL
k Department of Neurology, University of California-Davis, Sacramento, CA
l Department of Neurosciences, University of California- San Diego Medical School, San Diego, CA
m Department of Psychiatry & Neurology, Duke University, Durham, NC
n Mental Illness Research Education Clinical Center, ENRM Veterans Affairs Hospital, Bedford, MA
o Ray Dolby Brain Health Center
p California Pacific Medical Center, San Francisco, CA
q Advisor to the National Institute on Aging
r Department of Neurology, Washington University School of Medicine, St. Louis, MO


Abstract
Introduction: The neuropsychological battery of the Uniform Data Set (UDSNB) was implemented in 2005 by the National Institute on Aging (NIA) Alzheimer Disease Centers program to measure cognitive performance in dementia and mild cognitive impairment due to Alzheimer Disease. This paper describes a revision, the UDSNB 3.0. Methods: The Neuropsychology Work Group of the NIA Clinical Task Force recommended revisions through a process of due diligence to address shortcomings of the original battery. The UDSNB 3.0 covers episodic memory, processing speed, executive function, language, and constructional ability. Data from 3602 cognitively normal participants in the National Alzheimer Coordinating Center database were analyzed. Results: Descriptive statistics are presented. Multivariable linear regression analyses demonstrated score differences by age, sex, and education and were also used to create a normative calculator available online. Discussion: The UDSNB 3.0 neuropsychological battery provides a valuable non proprietary resource for conducting research on cognitive aging and dementia. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Author Keywords
cognition;  dementia;  neuropsychological test;  UDS


Document Type: Article in Press
Source: Scopus

 

18) 

Cicero, T.J., Ellis, M.S.
The prescription opioid epidemic: A review of qualitative studies on the progression from initial use to abuse
(2017) Dialogues in Clinical Neuroscience, 19 (3), pp. 259-269. 


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


Abstract
Most research designed to answer the "why" of the prescription opioid epidemic has relied on structured interviews, which rigidly attempt to capture the complex reasons people use opioids. In contrast, this systematic literature review focuses on peer-reviewed studies that have used a qualitative approach to examine the development of an opioid-use disorder from the point of initial exposure. Rather than simply providing a "high," opioids reportedly relieve psychological/emotional problems or provide an escape from life stressors. As use continues, avoidance of withdrawal sickness becomes an overriding concern, with all other benefits playing minor roles in persistent use. These studies indicate that terms used in structured interviews, such as "nontherapeutic use" or variations thereof, poorly capture the complex range of needs opioids satisfy. Both quantitative/structured studies and more qualitative ones, as well as more focused studies, have an important role in better informing prevention and treatment efforts. © 2017 AICH - Servier Research Group.


Author Keywords
Heroin use;  Prescription opioid abuse;  Progression of opioid use disorder;  Qualitative data;  Qualitative review


Document Type: Article
Source: Scopus

 

19) 

Grajales-Reyes, J.G.a e , García-González, A.a f , María-Ríos, J.C.a g , Grajales-Reyes, G.E.a e , Delgado-Vélez, M.a h , Báez-Pagán, C.A.a i , Quesada, O.c , Gómez, C.M.d , Lasalde-Dominicci, J.A.a b h
A Panel of Slow-Channel Syndrome Mice Reveals a Unique Locomotor Behavioral Signature
(2017) Journal of Neuromuscular Diseases, 4 (4), pp. 341-347. 


a Department of Biology, University of Puerto Rico, Río Piedras Campus, PO Box 23360, San Juan, PR, United States
b Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan, PR, United States
c Department of Physical Sciences, University of Puerto Rico, Río Piedras Campus, San Juan, PR, United States
d Department of Neurology, University of Chicago, Chicago, IL, United States
e Washington University School of Medicine in St Louis, Medical ScientistTraining Program (MSTP), MSTP-Box 8226, 660 Euclid Avenue, St. Louis, MO, United States
f University of Massachusetts Medical School, Medical Scientist Training Program (MSTP), 55 Lake Ave North, Worcester, MA, United States
g University of Puerto Rico, Medical Sciences Campus, B. 365067, San Juan, PR, Puerto Rico
h Molecular Sciences Research Center, University of Puerto Rico, 1390 Ponce de León Avenue, San Juan, PR, Puerto Rico
i University of Puerto Rico, Physical Sciences Department, P.O. BOX 23323, San Juan, PR, Puerto Rico


Abstract
Muscle nicotinic acetylcholine receptor (nAChR) mutations can lead to altered channel kinetics and neuromuscular junction degeneration, a neurodegenerative disorder collectively known as slow-channel syndrome (SCS). A multivariate analysis using running wheels was used to generate activity profiles for a variety of SCS models, uncovering unique locomotor patterns for the different nAChR mutants. Particularly, the αL251T and ?L269F mutations exhibit decreased event distance, duration, and velocity over a period of 24 hours. Our approach suggests a robust relationship between the pathophysiology of SCS and locomotor activity. © 2017 - IOS Press and the authors. All rights reserved.


Author Keywords
acetylcholine;  Congenital myasthenia;  locomotor activity;  mice;  motor endplate;  myalgia;  neuromuscular junction (NMJ);  nicotinic acetylcholine receptor (nAChR);  running


Document Type: Article
Source: Scopus