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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.

October 16, 2017  

1) 

Kafashan, M., Palanca, B.J.A., Ching, S.
Dimensionality reduction impedes the extraction of dynamic functional connectivity states from fMRI recordings of resting wakefulness
(2018) Journal of Neuroscience Methods, 293, pp. 151-161. 

DOI: 10.1016/j.jneumeth.2017.09.013


a Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Department of Neurobiology, Harvard Medical School, Boston, MA, United States
c Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
d Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Background Resting wakefulness is not a unitary state, with evidence accumulating that spontaneous reorganization of brain activity can be assayed through functional magnetic resonance imaging (fMRI). The dynamics of correlated fMRI signals among functionally-related brain regions, termed dynamic functional connectivity (dFC), may represent nonstationarity arising from underlying neural processes. However, given the dimensionality and noise inherent in such recordings, seeming fluctuations in dFC could be due to sampling variability or artifacts. New method Here, we highlight key methodological considerations when evaluating dFC in resting-state fMRI data. Comparison with existing method In particular, we demonstrate how dimensionality reduction of fMRI data, a common practice often involving principal component analysis, may give rise to spurious dFC phenomenology due to its effect of decorrelating the underlying time-series. Conclusion We formalize a dFC assessment that avoids dimensionality reduction and use it to show the existence of at least two FC states in the resting-state. © 2017 Elsevier B.V.


Author Keywords
Dynamic functional connectivity (dFC);  FC state analysis;  Resting-state functional magnetic resonance;  Spatiotemporal analysis


Document Type: Article
Source: Scopus

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2) 

Gross, J.H., Bertrand, M., Hirose, K.
Benign Rolandic epilepsy presenting like paradoxical vocal fold motion
(2017) International Journal of Pediatric Otorhinolaryngology, 102, pp. 154-156. 

DOI: 10.1016/j.ijporl.2017.09.021


a Washington University School of Medicine, Department of Otolaryngology, 660 South Euclid Avenue, Saint Louis, Missouri, United States
b Washington University School of Medicine, Department of Neurology, 660 South Euclid Avenue, Saint Louis, Missouri, United States


Abstract
Paradoxical vocal fold motion (PVFM) is characterized by vocal fold adduction during respiration. Benign Rolandic epilepsy (BRE) is the most common childhood epilepsy and can cause oropharyngolaryngeal or facial manifestations. A 9-year-old male presented with intermittent apnea lasting 30–60 seconds and presumed PVFM. The patient's physical and fiberoptic exam were normal. He was admitted and found to have episodes of oxygen desaturation, neck twitching, and tongue burning. An EEG revealed focal epilepsy. After starting anti-epileptic medications, he had resolution of symptoms. Our patient was eventually diagnosed with BRE, a focal onset epilepsy that can mimic primary otolaryngologic disease. © 2017 Elsevier B.V.


Author Keywords
Apnea;  Children;  Epilepsy;  Laryngeal spasm;  Paradoxical vocal fold motion


Document Type: Article
Source: Scopus

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3) 

Joksimovic, S.M., Eggan, P., Izumi, Y., Joksimovic, S.L., Tesic, V., Dietz, R.M., Orfila, J.E., DiGruccio, M.R., Herson, P.S., Jevtovic-Todorovic, V., Zorumski, C.F., Todorovic, S.M.
The role of T-type calcium channels in the subiculum: to burst or not to burst?
(2017) Journal of Physiology, 595 (19), pp. 6327-6348. Cited 1 time.

DOI: 10.1113/JP274565


a Department of Anesthesiology, University of Colorado, School of Medicine, Aurora, CO, United States
b Department of Psychiatry & Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St Louis, MO, United States
c Department of Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California, Davis, CA, United States


Abstract
Key points: Pharmacological, molecular and genetic data indicate a prominent role of low-voltage-activated T-type calcium channels (T-channels) in the firing activity of both pyramidal and inhibitory interneurons in the subiculum. Pharmacological inhibition of T-channels switched burst firing with lower depolarizing stimuli to regular spiking, and fully abolished hyperpolarization-induced burst firing. Our molecular studies showed that CaV3.1 is the most abundantly expressed isoform of T-channels in the rat subiculum. Consistent with this finding, both regular-spiking and burst firing patterns were profoundly depressed in the mouse with global deletion of CaV3.1 isoform of T-channels. Selective inhibition of T-channels and global deletion of CaV3.1 channels completely suppressed development of long-term potentiation (LTP) in the CA1–subiculum, but not in the CA3–CA1 pathway. Abstract: Several studies suggest that voltage-gated calcium currents are involved in generating high frequency burst firing in the subiculum, but the exact nature of these currents remains unknown. Here, we used selective pharmacology, molecular and genetic approaches to implicate Cav3.1-containing T-channels in subicular burst firing, in contrast to several previous reports discounting T-channels as major contributors to subicular neuron physiology. Furthermore, pharmacological antagonism of T-channels, as well as global deletion of CaV3.1 isoform, completely suppressed development of long-term potentiation (LTP) in the CA1–subiculum, but not in the CA3–CA1 pathway. Our results indicate that excitability and synaptic plasticity of subicular neurons relies heavily on T-channels. Hence, T-channels may be a promising new drug target for different cognitive deficits. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society


Author Keywords
calcium;  hippocampus;  low-threshold-activated


Document Type: Article
Source: Scopus

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4) 

Rogers, C.E.
Here/In This Issue and There/Abstract Thinking: Does This Answer Your Question?
(2017) Journal of the American Academy of Child and Adolescent Psychiatry, 56 (10), pp. 801-802. 

DOI: 10.1016/j.jaac.2017.08.007


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


Document Type: Article
Source: Scopus

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5) 

Sun, W., Marongelli, E.N., Watkins, P.V., Barbour, D.L.
Decoding sound level in the marmoset primary auditory cortex
(2017) Journal of Neurophysiology, 118 (4), pp. 2024-2033. 

DOI: 10.1152/jn.00670.2016


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


Abstract
Neurons that respond favorably to a particular sound level have been observed throughout the central auditory system, becoming steadily more common at higher processing areas. One theory about the role of these level-tuned or nonmonotonic neurons is the level-invariant encoding of sounds. To investigate this theory, we simulated various subpopulations of neurons by drawing from real primary auditory cortex (A1) neuron responses and surveyed their performance in forming different sound level representations. Pure nonmonotonic subpopulations did not provide the best level-invariant decoding; instead, mixtures of monotonic and nonmonotonic neurons provided the most accurate decoding. For level-fidelity decoding, the inclusion of nonmonotonic neurons slightly improved or did not change decoding accuracy until they constituted a high proportion. These results indicate that nonmonotonic neurons fill an encoding role complementary to, rather than alternate to, monotonic neurons. NEW & NOTEWORTHY Neurons with nonmonotonic rate-level functions are unique to the central auditory system. These level-tuned neurons have been proposed to account for invariant sound perception across sound levels. Through systematic simulations based on real neuron responses, this study shows that neuron populations perform sound encoding optimally when containing both monotonic and nonmonotonic neurons. The results indicate that instead of working independently, nonmonotonic neurons complement the function of monotonic neurons in different sound-encoding contexts. © 2017 the American Physiological Society.


Author Keywords
Auditory cortex;  Neural coding;  Nonmonotonic;  Primate;  Sound pressure level encoding


Document Type: Article
Source: Scopus

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6) 

Wright, N.C., Wessel, R.
Network activity influences the subthreshold and spiking visual responses of pyramidal neurons in the three-layer turtle cortex
(2017) Journal of Neurophysiology, 118 (4), pp. 2142-2155. 

DOI: 10.1152/jn.00340.2017


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


Abstract
A primary goal of systems neuroscience is to understand cortical function, typically by studying spontaneous and stimulus-modulated cortical activity. Mounting evidence suggests a strong and complex relationship exists between the ongoing and stimulus-modulated cortical state. To date, most work in this area has been based on spiking in populations of neurons. While advantageous in many respects, this approach is limited in scope: it records the activity of a minority of neurons and gives no direct indication of the underlying subthreshold dynamics. Membrane potential recordings can fill these gaps in our understanding, but stable recordings are difficult to obtain in vivo. Here, we recorded subthreshold cortical visual responses in the ex vivo turtle eye-attached whole brain preparation, which is ideally suited for such a study. We found that, in the absence of visual stimulation, the network was “synchronous”; neurons displayed net-work-mediated transitions between hyperpolarized (Down) and depo-larized (Up) membrane potential states. The prevalence of these slow-wave transitions varied across turtles and recording sessions. Visual stimulation evoked similar Up states, which were on average larger and less reliable when the ongoing state was more synchronous. Responses were muted when immediately preceded by large, spontaneous Up states. Evoked spiking was sparse, highly variable across trials, and mediated by concerted synaptic inputs that were, in general, only very weakly correlated with inputs to nearby neurons. Together, these results highlight the multiplexed influence of the cortical network on the spontaneous and sensory-evoked activity of individual cortical neurons. NEW & NOTEWORTHY Most studies of cortical activity focus on spikes. Subthreshold membrane potential recordings can provide complementary insight, but stable recordings are difficult to obtain in vivo. Here, we recorded the membrane potentials of cortical neurons during ongoing and visually evoked activity. We observed a strong relationship between network and single-neuron evoked activity spanning multiple temporal scales. The membrane potential perspective of cortical dynamics thus highlights the influence of intrinsic network properties on visual processing. © 2017 the American Physiological Society.


Author Keywords
Cortex;  Membrane potential;  Network state;  Vision


Document Type: Article
Source: Scopus

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7) 

Duncan, R.P., McNeely, M.E., Earhart, G.M.
Maximum Step Length Test Performance in People with Parkinson Disease: A Cross-sectional Study
(2017) Journal of Neurologic Physical Therapy, 41 (4), pp. 215-221. 

DOI: 10.1097/NPT.0000000000000201


a Program in Physical Therapy, Washington University, School of Medicine, 4444 Forest Park Blvd, Saint Louis, MO, United States
b Department of Neurology, Washington University, School of Medicine, Saint Louis, MO, United States
c Department of Neuroscience, Washington University, School of Medicine, Saint Louis, MO, United States


Abstract
Background and Purpose: The Maximum Step Length Test (MSLT), a measure of one's capacity to produce a large step, has been studied in older adults, but not in people with Parkinson disease (PD). We characterized performance and construct validity of the MSLT in PD. Methods: Forty participants (mean age: 65.12 ± 8.20 years; 45% female) with idiopathic PD completed the MSLT while "OFF" and "ON" anti-PD medication. Construct validity was investigated by examining relationships between MSLT and measures of motor performance. The following measures were collected: Mini-Balance Evaluation Systems Test (Mini-BESTest), Activities-specific Balance Confidence (ABC) scale, gait velocity, 6-minute walk test (6MWT), Movement Disorder Society-Unified Parkinson Disease Rating Scale subsection III (MDS-UPDRS III), and Timed Up and Go (TUG) test. A repeated-measures analysis of variance tested for main effects of medication and stepping direction and the interaction between the 2. Pearson or Spearman correlations were used to assess the relationships between MSLT and motor performance measures (α = 0.05). Results: Regardless of medication status, participants stepped further in the forward direction compared with the backward and lateral directions (P < 0.001). Participants increased MSLT performance when ON-medication compared with OFF-medication (P = 0.004). Regardless of medication status, MSLT was moderately to strongly related to Mini-BESTest, TUG, and 6MWT. Discussion and Conclusions: People with PD stepped furthest in the forward direction when performing the MSLT. Increased MSLT performance was observed in the ON-medication state compared with OFF-medication; however, the small increase may not be clinically meaningful. Given the relationships between the MSLT and the Mini-BESTest, 6MWT, and TUG, MSLT performance appears to be associated with balance and gait hypokinesia in people with PD. Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A186). © 2017 Academy of Neurologic Physical Therapy, APTA.


Author Keywords
balance;  gait;  human movement system;  outcome measure


Document Type: Conference Paper
Source: Scopus

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8) 

Moore, A.M.
Commentary on Management of Atraumatic Posterior Interosseous Nerve Palsy
(2017) Journal of Hand Surgery, 42 (10), pp. 831-832. 

DOI: 10.1016/j.jhsa.2017.07.027


Chief of the Section of Hand Surgery, Program Director of the Hand Fellowship, Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, MO, United States


Document Type: Note
Source: Scopus

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9) 

Blum, K., Badgaiyan, R.D., Dunston, G.M., Baron, D., Modestino, E.J., McLaughlin, T., Steinberg, B., Gold, M.S., Gondré-Lewis, M.C.
The DRD2 Taq1A A1 Allele May Magnify the Risk of Alzheimer’s in Aging African-Americans
(2017) Molecular Neurobiology, pp. 1-11. Article in Press. 

DOI: 10.1007/s12035-017-0758-1


a Department of Psychiatry & McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United States
b Department of Psychiatry and Behavioral Sciences, Keck Medicine University of Southern California, Los Angeles, CA, United States
c Division of Applied Clinical Research & Education, Dominion Diagnostics, LLC, North Kingstown, RI, United States
d Department of Neurogenetics, Igene, LLC, Austin, TX, United States
e Division of Reward Deficiency Syndrome and Addiction Therapy, Nupathways, Inc., Innsbrook, MO, United States
f Department of Clinical Neurology, Path Foundation, New York, NY, United States
g Division of Neuroscience Based Addiction Therapy, The Shores Treatment & Recovery Center, Port Saint Lucie, FL, United States
h Eötvös Loránd University, Institute of Psychology, Budapest, Hungary
i Department of Psychiatry and Behavioral Health, Richmond University Medical Center, 355 Bard Avenue, Staten Island, NY, United States
j NeuroPsychoSocial Genomics Core, National Human Genome Center, Howard University, Washington, DC, United States
k Department of Psychology, Curry College, Milton, MA, United States
l Center for Psychiatric Medicine, North Andover, MA, United States
m Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
n Developmental Neuropsychopharmacology Laboratory, Department of Anatomy, Howard University College of Medicine, Washington, DC, United States
o Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC, United States


Abstract
Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys cognitive skills and the ability to perform the simplest tasks. More than 5 million Americans are afflicted with Alzheimer’s; a disorder which ranks third, just behind heart disease and cancer, as a cause of death for older people. With no real cure and in spite of enormous efforts worldwide, the disease remains a mystery in terms of treatment. Importantly, African-Americans are two times as likely as Whites to develop late-onset Alzheimer’s disease and less likely to receive timely diagnosis and treatment. Dopamine function is linked to normal cognition and memory and carriers of the DRD2 Taq1A A1 allele have significant loss of D2 receptor density in the brain. Recent research has shown that A1 carriers have worse memory performance during long-term memory (LTM) updating, compared to non-carriers or A2-carriers. A1carriers also show less blood oxygen level-dependent (BOLD) activation in the left caudate nucleus which is important for LTM updating. This latter effect was only seen in older adults, suggesting magnification of genetic effects on brain functioning in the elderly. Moreover, the frequency of the A1 allele is 0.40 in African-Americans, with an approximate prevalence of the DRD2 A1 allele in 50% of an African-American subset of individuals. This is higher than what is found in a non-screened American population (≤ 28%) for reward deficiency syndrome (RDS) behaviors. Based on DRD2 known genetic polymorphisms, we hypothesize that the DRD2 Taq1A A1 allele magnifies the risk of Alzheimer’s in aging African-Americans. Research linking this high risk for Alzheimer’s in the African-American population, with DRD2/ANKK1-TaqIA polymorphism and neurocognitive deficits related to LTM, could pave the way for novel, targeted pro-dopamine homeostatic treatment. © 2017 Springer Science+Business Media, LLC


Author Keywords
African Americans;  Alzheimer’s disease;  Dopamine;  DRD2 gene;  Early life stress;  Long-term memory (LTM);  Reward deficiency syndrome


Document Type: Article in Press
Source: Scopus

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10) 

Morley, B.J., Dolan, D.F., Ohlemiller, K.K., Simmons, D.D.
Generation and characterization of α9 and α10 nicotinic acetylcholine receptor subunit knockout mice on a C57BL/6J background
(2017) Frontiers in Neuroscience, 11 (SEP), art. no. 516, . 

DOI: 10.3389/fnins.2017.00516


a Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE, United States
b Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, United States
c Department of Otolaryngology, Washington University, St. Louis, MO, United States
d Department of Biology, Baylor University, Waco, TX, United States


Abstract
We generated constitutive knockout mouse models for the α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits by derivation from conditional knockouts by breeding with CRE deleter mice. We then backcrossed them onto a C57BL/6J genetic background. In this manuscript, we report the generation of the strains and an auditory phenotypic characterization of the constitutive α9 and α10 knockouts and a double α9α10 constitutive knockout. Although the α9 and α10 nAChR subunits are relevant to a number of physiological measures, we chose to characterize the mouse with auditory studies to compare them to existing but different α9 and α10 nAChR knockouts (KOs). Auditory brainstem response (ABR) measurements and distortion product otoacoustic emissions (DPOAEs) showed that all constitutive mouse strains had normal hearing. DPOAEs with contralateral noise (efferent adaptation measurements), however, showed that efferent strength was significantly reduced after deletion of both the α9 and α10 subunits, in comparison to wildtype controls. Animals tested were 3-8 weeks of age and efferent strength was not correlated with age. Confocal studies of single and double constitutive KOs showed that all KOs had abnormal efferent innervation of cochlear hair cells. The morphological results are similar to those obtained in other strains using constitutive deletion of exon 4 of α9 or α10 nAChR. The results of our physiological studies, however, differ from previous auditory studies using a α9 KO generated by deletion of the exon 4 region and backcrossed onto a mixed CBA/CaJ X 129Sv background. © 2017 Morley, Dolan, Ohlemiller and Simmons.


Author Keywords
Auditory brainstem response;  Distortion product otoacoustic emissions;  Efferent strength;  Nicotinic acetylcholine receptor


Document Type: Article
Source: Scopus

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11) 

Klein, R.S.
Dual Blades: The Role of Musashi 1 in Zika Replication and Microcephaly
(2017) Cell Host and Microbe, 22 (1), pp. 9-11. 

DOI: 10.1016/j.chom.2017.06.015


a Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States
c Department of Neuroscience, Washington University School of Medicine, St Louis, MO, United States


Abstract
Infection with Zika virus (ZIKV) during pregnancy may cause severe developmental defects in the human brain via unknown mechanisms. In a recent issue of Science, Chavali et al. (2017) identified a neural progenitor cell (NPC)-specific RNA binding protein that may underlie the high levels of ZIKV replication and apoptosis observed in these cells during congenital infections. Infection with Zika virus (ZIKV) during pregnancy may cause severe developmental defects in the human brain via unknown mechanisms. In a recent issue of Science, Chavali et al. (2017) identified a neural progenitor cell (NPC)-specific RNA binding protein that may underlie the high levels of ZIKV replication and apoptosis observed in these cells during congenital infections. © 2017 Elsevier Inc.


Document Type: Short Survey
Source: Scopus

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12) 

Ren, L., Chang, M.J., Zhang, Z., Dhaka, A., Guo, Z., Cao, Y.-Q.
Quantitative Analysis of Mouse Dural Afferent Neurons Expressing TRPM8, VGLUT3, and NF200
(2017) Headache, . Article in Press. 

DOI: 10.1111/head.13188


a Washington University Pain Center and Department of Anesthesiology, Washington University School of MedicineSt. Louis, MO USA
b Department of Biological Structure, Neurobiology and Behavior Graduate ProgramUniversity of WashingtonSeattle, WA USA


Abstract
Objective: To quantify the abundance of dural afferent neurons expressing transient receptor potential channel melastatin 8 (TRPM8), vesicular glutamate transporter 3 (VGLUT3), and neurofilament 200 (NF200) in adult mice. Background: With the increasing use of mice as a model system to study headache mechanisms, it is important to understand the composition of dural afferent neurons in mice. In a previous study, we have measured the abundance of mouse dural afferent neurons that express neuropeptide calcitonin gene-related peptide as well as two TRP channels TRPV1 and TRPA1, respectively. Here, we conducted quantitative analysis of three other dural afferent subpopulations in adult mice. Methods: We used the fluorescent tracer Fluoro-Gold to retrogradely label dural afferent neurons in adult mice expressing enhanced green fluorescent protein in discrete subpopulations of trigeminal ganglion (TG) neurons. Mechanoreceptors with myelinated fibers were identified by NF200 immunoreactivity. We also conducted Ca2+-imaging experiments to test the overlap between TRPM8 and VGLUT3 expression in mouse primary afferent neurons (PANs). Results: The abundance of TRPM8-expressing neurons in dural afferent neurons was significantly lower than that in total TG neurons. The percentages of dural afferent neurons expressing VGLUT3 and NF200 were comparable to those of total TG neurons, respectively. TRPM8 agonist menthol evoked Ca2+ influx in less than 7% VGLUT3-expressing PANs in adult mice. Conclusions: TG neurons expressing TRPM8, VGLUT3, and NF200 all innervate adult mouse dura. TRPM8 and VGLUT3 are expressed in distinct subpopulations of PANs in adult mice. These results provide an anatomical basis to investigate headache mechanisms in mouse models. © 2017 American Headache Society.


Author Keywords
Dural afferent neurons;  Headache;  Migraine;  NF200;  TRPM8;  VGlut3


Document Type: Article in Press
Source: Scopus

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13) 

Zhu, Z., Gorman, M.J., McKenzie, L.D., Chai, J.N., Hubert, C.G., Prager, B.C., Fernandez, E., Richner, J.M., Zhang, R., Shan, C., Tycksen, E., Wang, X., Shi, P.-Y., Diamond, M.S., Rich, J.N., Chheda, M.G.
Zika virus has oncolytic activity against glioblastoma stem cells
(2017) Journal of Experimental Medicine, 214 (10), pp. 2843-2857. Cited 1 time.

DOI: 10.1084/jem.20171093


a Department of Medicine, Division of Regenerative Medicine, University of California, School of Medicine, San Diego, La Jolla, CA, United States
b Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States
c Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, United States
g The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, United States
h Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, United States
i Department of Pharmacology and Toxicology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, United States
j Genome Technology Access Center, Department of Genetics, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a mouse-adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients. © 2017 Zhu et al.


Document Type: Article
Source: Scopus

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14) 

Lean, R.E., Paul, R.A., Smyser, C.D., Rogers, C.E.
Maternal intelligence quotient (IQ) predicts IQ and language in very preterm children at age 5 years
(2017) Journal of Child Psychology and Psychiatry and Allied Disciplines, . Article in Press. 

DOI: 10.1111/jcpp.12810


a Department of Psychiatry Washington University School of Medicine St. Louis, MO USA
b Department of Neurology Washington University School of Medicine St. Louis, MO USA
c Department of Radiology Washington University School of Medicine St. Louis, MO USA
d Department of Pediatrics Washington University School of Medicine St. Louis, MO USA


Abstract
Background: Sociodemographic factors are linked to cognitive outcomes in children born very preterm (VPT; ≤30 weeks gestation). The influence of maternal intellectual ability, a heritable trait, is unknown. Also undetermined is the extent to which associations between maternal and child intellectual ability vary according to parenting behaviors that target cognitive stimulation in the home. Methods: At age 5 years, 84 VPT and 38 demographically matched full-term (FT) children underwent neurodevelopmental assessment. Children's intellectual ability was assessed using The Wechsler Preschool Primary Scale of Intelligence-III, and language was assessed with the Clinical Evaluation of Language Fundamentals Preschool-2. The Wechsler Test of Adult Reading estimated maternal intellectual ability. The StimQ-Preschool questionnaire provided a measure of cognitive stimulation in the home. Linear mixed-effects models examined independent effects and interactions between maternal intellectual ability and cognitive stimulation on children's outcomes. Results: After covariate adjustment, maternal intellectual ability was associated with child intellectual (p < .001) and language (p = .002) abilities. Stronger associations were observed in FT mother-child dyads (B = .63, p = .04) than VPT dyads (B = .42, p = .01). Mothers of VPT children reported lower levels of Parental Involvement in Developmental Advance (p = .007) and Parental Verbal Responsiveness (p = .04). Group differences in Parental Involvement in Developmental Advance, but not Parental Verbal Responsivity, persisted after adjusting for social background (p = .03). There was no evidence of an interaction between maternal intellectual ability and Parental Involvement in Developmental Advance (p = .34). Instead, maternal intellectual ability (p < .001) and Parental Involvement in Developmental Advance (p = .05) independently predicted VPT children's outcomes. Conclusions: Maternal intellectual ability is an important trait linked to VPT and FT children's intellectual and language outcomes. Prematurity increases variation in the heritability of intellectual ability and shifts children from the expected range based on maternal ability. Parental involvement in activities that help children master new skills may promote cognitive development in VPT children born to mothers of lower intellectual ability. © 2017 Association for Child and Adolescent Mental Health.


Author Keywords
Environmental influences;  Follow-up studies;  Intelligence;  Maternal factors;  Prematurity


Document Type: Article in Press
Source: Scopus

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15) 

Lee, C., Jones, T.A.
Neuropharmacological targets for drug action in vestibular sensory pathways
(2017) Journal of Audiology and Otology, 21 (3), pp. 125-132. 

DOI: 10.7874/jao.2017.00171


a Department of Otolaryngology, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, 304 Barkley Memorial Center, Lincoln, NE, United States


Abstract
The use of pharmacological agents is often the preferred approach to the management of vestibular dysfunction. In the vestibular sensory pathways, the sensory neuroepithelia are thought to be influenced by a diverse number of neuroactive substances that may act to enhance or inhibit the effect of the primary neurotransmitters [i.e., glutamate (Glu) and acetylcholine (ACh)] or alter their patterns of release. This review summarizes various efforts to identify drug targets including neurotransmitter and neuromodulator receptors in the vestibular sensory pathways. Identifying these receptor targets provides a strategic basis to use specific pharmacological tools to modify receptor function in the treatment and management of debilitating balance disorders. A review of the literature reveals that most investigations of the neuropharmacology of peripheral vestibular function have been performed using in vitro or ex vivo animal preparations rather than studying drug action on the normal intact vestibular system in situ. Such noninvasive approaches could aid the development of more accurate and effective intervention strategies for the treatment of dizziness and vertigo. The current review explores the major neuropharmacological targets for drug action in the vestibular system. © 2017 The Korean Audiological Society and Korean Otological Society.


Author Keywords
Dizziness;  Neuroactive substance;  Peripheral vestibular system;  Vertigo;  Vestibular suppressant


Document Type: Article
Source: Scopus