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Analysis Of Novel Caudal Hindbrain Genes Reveals Different Regulatory Logic For Gene Expression In Rhombomere 4 Versus 5/6 In Embryonic Zebrafish, Priyanjali Ghosh, Jennifer M. Maurer, Charles G. Sagerstrom 2018 University of Massachusetts Medical School

Analysis Of Novel Caudal Hindbrain Genes Reveals Different Regulatory Logic For Gene Expression In Rhombomere 4 Versus 5/6 In Embryonic Zebrafish, Priyanjali Ghosh, Jennifer M. Maurer, Charles G. Sagerstrom

Open Access Articles

BACKGROUND: Previous work aimed at understanding the gene regulatory networks (GRNs) governing caudal hindbrain formation identified morphogens such as Retinoic Acid (RA) and Fibroblast growth factors (FGFs), as well as transcription factors like hoxb1b, hoxb1a, hnf1ba, and valentino as being required for rhombomere (r) r4-r6 formation in zebrafish. Considering that the caudal hindbrain is relatively complex - for instance, unique sets of neurons are formed in each rhombomere segment - it is likely that additional essential genes remain to be identified and integrated into the caudal hindbrain GRN.

METHODS: By taking advantage of gene expression data available in the Zebrafish Information Network ...


Inactivation Of The Medial-Prefrontal Cortex Impairs Interval Timing Precision, But Not Timing Accuracy Or Scalar Timing In A Peak-Interval Procedure In Rats, Catalin V. Buhusi, Marcelo B. Reyes, Cody-Aaron Gathers, Sorinel A. Oprisan, Mona Buhusi 2018 Utah State University

Inactivation Of The Medial-Prefrontal Cortex Impairs Interval Timing Precision, But Not Timing Accuracy Or Scalar Timing In A Peak-Interval Procedure In Rats, Catalin V. Buhusi, Marcelo B. Reyes, Cody-Aaron Gathers, Sorinel A. Oprisan, Mona Buhusi

Psychology Faculty Publications

Motor sequence learning, planning and execution of goal-directed behaviors, and decision making rely on accurate time estimation and production of durations in the seconds-to-minutes range. The pathways involved in planning and execution of goal-directed behaviors include cortico-striato-thalamo-cortical circuitry modulated by dopaminergic inputs. A critical feature of interval timing is its scalar property, by which the precision of timing is proportional to the timed duration. We examined the role of medial prefrontal cortex (mPFC) in timing by evaluating the effect of its reversible inactivation on timing accuracy, timing precision and scalar timing. Rats were trained to time two durations in a ...


Als-Associated Missense And Nonsense Tbk1 Mutations Can Both Cause Loss Of Kinase Function, Martina de Majo, Kevin P. Kenna, Robert H. Brown Jr., John E. Landers, Christopher E. Shaw 2018 King's College London

Als-Associated Missense And Nonsense Tbk1 Mutations Can Both Cause Loss Of Kinase Function, Martina De Majo, Kevin P. Kenna, Robert H. Brown Jr., John E. Landers, Christopher E. Shaw

Open Access Articles

Mutations in TANK binding kinase 1 (TBK1) have been linked to amyotrophic lateral sclerosis. Some TBK1 variants are nonsense and are predicted to cause disease through haploinsufficiency; however, many other mutations are missense with unknown functional effects. We exome sequenced 699 familial amyotrophic lateral sclerosis patients and identified 16 TBK1 novel or extremely rare protein-changing variants. We characterized a subset of these: p.G217R, p.R357X, and p.C471Y. Here, we show that the p.R357X and p.G217R both abolish the ability of TBK1 to phosphorylate 2 of its kinase targets, IRF3 and optineurin, and to undergo phosphorylation. They ...


Metabolic And Vascular Imaging Biomarkers In Down Syndrome Provide Unique Insights Into Brain Aging And Alzheimer Disease Pathogenesis, Elizabeth Head, David K. Powell, Frederick A. Schmitt 2018 University of Kentucky

Metabolic And Vascular Imaging Biomarkers In Down Syndrome Provide Unique Insights Into Brain Aging And Alzheimer Disease Pathogenesis, Elizabeth Head, David K. Powell, Frederick A. Schmitt

Pharmacology and Nutritional Sciences Faculty Publications

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD). Neuropathology consistent with AD is present by 40 years of age and dementia may develop up to a decade later. In this review, we describe metabolic and vascular neuroimaging studies in DS that suggest these functional changes are a key feature of aging, linked to cognitive decline and AD in this vulnerable cohort. FDG-PET imaging in DS suggests systematic reductions in glucose metabolism in posterior cingulate and parietotemporal cortex. Magentic resonance spectroscopy studies show consistent decreases in neuronal health and increased myoinositol, suggesting inflammation. There are ...


A Rationally Engineered Capsid Variant Of Aav9 For Systemic Cns-Directed And Peripheral Tissue-Detargeted Gene Delivery In Neonates, Dan Wang, Shaoyong Li, Dominic J. Gessler, Jun Xie, Li Zhong, Jia Li, Karen Tran, Kim Van Vliet, Lingzhi Ren, Qin Su, Ran He, Jason E. Goetzmann, Terence R. Flotte, Mavis Agbandje-McKenna, Guangping Gao 2018 University of Massachusetts Medical School

A Rationally Engineered Capsid Variant Of Aav9 For Systemic Cns-Directed And Peripheral Tissue-Detargeted Gene Delivery In Neonates, Dan Wang, Shaoyong Li, Dominic J. Gessler, Jun Xie, Li Zhong, Jia Li, Karen Tran, Kim Van Vliet, Lingzhi Ren, Qin Su, Ran He, Jason E. Goetzmann, Terence R. Flotte, Mavis Agbandje-Mckenna, Guangping Gao

Open Access Articles

Adeno-associated virus (AAV) has provided the gene therapy field with the most powerful in vivo gene delivery vector to realize safe, efficacious, and sustainable therapeutic gene expression. Because many clinically relevant properties of AAV-based vectors are governed by the capsid, much research effort has been devoted to the development of AAV capsids for desired features. Here, we combine AAV capsid discovery from nature and rational engineering to report an AAV9 capsid variant, designated as AAV9.HR, which retains AAV9's capability to traverse the blood-brain barrier and transduce neurons. This variant shows reduced transduction in peripheral tissues when delivered through ...


Dopaminergic Medication Decreases Motor Impulsivity On The Go/No-Go Task In Parkinson's Disease, Xue Qing Yang 2018 The University of Western Ontario

Dopaminergic Medication Decreases Motor Impulsivity On The Go/No-Go Task In Parkinson's Disease, Xue Qing Yang

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is characterized by resting tremor, rigidity, and bradykinesia. Dopaminergic medications treat motor symptoms, but have complex effects on cognition, including impulse control. Impulsivity is multifaceted in nature. Motor impulsivity involves inability to withhold prepotent, automatic responses whereas cognitive impulsivity refers to increased risk-taking and reward-seeking. We anticipated that dopaminergic therapy would decrease motor impulsivity. We employed the Go/No-go paradigm to assess motor impulsivity. PD patients were tested on and off their dopaminergic medication. PD patients on medication had a significantly higher proportion of Go Timeouts (i.e., Go responses not completed by the 750 millisecond ...


Activity-Induced Regulation Of Synaptic Strength Through The Chromatin Reader L3mbtl1, Wenjie Mao, Anna C. Salzberg, Motokazu Uchigashima, Yuto Hasegawa, Hanno Hock, Masahiko Watanabe, Schahram Akbarian, Yuka Imamura. Kawasawa, Kensuke Futai 2018 University of Massachusetts Medical School

Activity-Induced Regulation Of Synaptic Strength Through The Chromatin Reader L3mbtl1, Wenjie Mao, Anna C. Salzberg, Motokazu Uchigashima, Yuto Hasegawa, Hanno Hock, Masahiko Watanabe, Schahram Akbarian, Yuka Imamura. Kawasawa, Kensuke Futai

Neurobiology Publications and Presentations

Homeostatic synaptic downscaling reduces neuronal excitability by modulating the number of postsynaptic receptors. Histone modifications and the subsequent chromatin remodeling play critical roles in activity-dependent gene expression. Histone modification codes are recognized by chromatin readers that affect gene expression by altering chromatin structure. We show that L3mbtl1 (lethal 3 malignant brain tumor-like 1), a polycomb chromatin reader, is downregulated by neuronal activity and is essential for synaptic response and downscaling. Genome-scale mapping of L3mbtl1 occupancies identified Ctnnb1 as a key gene downstream of L3mbtl1. Importantly, the occupancy of L3mbtl1 on the Ctnnb1 gene was regulated by neuronal activity. L3mbtl1 knockout ...


Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad M. Khan, Alice H. Grant, Anais Martinez, Gully APC Burns, Brendan S. Thatcher, Vishwanath T. Anekonda, Benjamin W. Thompson, Zachary S. Roberts, Daniel H. Moralejo, James E. Blevins 2018 University of Texas at El Paso

Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad M. Khan, Alice H. Grant, Anais Martinez, Gully Apc Burns, Brendan S. Thatcher, Vishwanath T. Anekonda, Benjamin W. Thompson, Zachary S. Roberts, Daniel H. Moralejo, James E. Blevins

Arshad M. Khan, Ph.D.

This article, which includes novel unpublished data along with commentary and analysis,
focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined from
brain tissue to the original locations within the brain that they are derived from using digital atlas
mapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomic
analyses conducted in the mammalian hypothalamus. Following a brief historical overview, we
highlight studies that have mined biochemical and molecular information from the hypothalamus
and then lay out a strategy for how these data can be linked spatially to the mapped locations in a
canonical brain atlas ...


Processing Emotional Expression In The Dance Of A Foreign Culture: Gestural Responses Of Germans And Koreans To Ballet And Korean Dance, Zi Hyun Kim, Hedda Lausberg 2018 German Sport University Cologne

Processing Emotional Expression In The Dance Of A Foreign Culture: Gestural Responses Of Germans And Koreans To Ballet And Korean Dance, Zi Hyun Kim, Hedda Lausberg

Journal of Movement Arts Literacy

Artistic dance differs between cultures with regard to the formal movement repertoire and methods to represent dancer's emotions. The present study explores how differently the spectators perceive the dance scenes of their own and foreign cultures. We showed German and Korean participants sad and happy dance scenes of the French ballet Giselle and Korean dance Sung-Mu. To learn the perceived thoughts and feelings of the participant from the dance scenes, we analyzed the frequency of their hand movements and gestures, which were accompanied by verbal descriptions of the participant's appreciation immediately after observation of the dance stimuli. The ...


When Less Is More: Mindfulness Predicts Adaptive Affective Responding To Rejection Via Reduced Prefrontal Recruitment, Alexandra M. Martelli, David S. Chester, Kirk Warren Brown, Naomi I. Eisenberger, C. Nathan DeWall 2018 Virginia Commonwealth University

When Less Is More: Mindfulness Predicts Adaptive Affective Responding To Rejection Via Reduced Prefrontal Recruitment, Alexandra M. Martelli, David S. Chester, Kirk Warren Brown, Naomi I. Eisenberger, C. Nathan Dewall

Psychology Faculty Publications

Social rejection is a distressing and painful event that many people must cope with on a frequent basis. Mindfulness—defined here as a mental state of receptive attentiveness to internal and external stimuli as they arise, moment-to-moment—may buffer such social distress. However, little research indicates whether mindful individuals adaptively regulate the distress of rejection—or the neural mechanisms underlying this potential capacity. To fill these gaps in the literature, participants reported their trait mindfulness and then completed a social rejection paradigm (Cyberball) while undergoing functional magnetic resonance imaging. Approximately 1 hour after the rejection incident, participants reported their level ...


Social Experience Affects Decision Making And Learning: Empirical And Computational Analysis, Sungwoo Ahn 2018 East Carolina University

Social Experience Affects Decision Making And Learning: Empirical And Computational Analysis, Sungwoo Ahn

Biology and Medicine Through Mathematics Conference

No abstract provided.


Reflections On Contributing To “Big Discoveries” About The Fly Clock: Our Fortunate Paths As Post-Docs With 2017 Nobel Laureates Jeff Hall, Michael Rosbash, And Mike Young, Kathleen King Siwicki, P. E. Hardin, J. L. Price 2018 Swarthmore College

Reflections On Contributing To “Big Discoveries” About The Fly Clock: Our Fortunate Paths As Post-Docs With 2017 Nobel Laureates Jeff Hall, Michael Rosbash, And Mike Young, Kathleen King Siwicki, P. E. Hardin, J. L. Price

Biology Faculty Works

In the early 1980s Jeff Hall and Michael Rosbash at Brandeis University and Mike Young at Rockefeller University set out to isolate the period (per) gene, which was recovered in a revolutionary genetic screen by Ron Konopka and Seymour Benzer for mutants that altered circadian behavioral rhythms. Over the next 15 years the Hall, Rosbash and Young labs made a series of groundbreaking discoveries that defined the molecular timekeeping mechanism and formed the basis for them being awarded the 2017 Nobel Prize in Physiology or Medicine. Here the authors recount their experiences as post-docs in the Hall, Rosbash and Young ...


Socioeconomic Status And The Brain: Prospects For Neuroscience-Informed Policy, Martha J. Farah 2018 University of Pennsylvania

Socioeconomic Status And The Brain: Prospects For Neuroscience-Informed Policy, Martha J. Farah

Neuroethics Publications

Socioeconomic status (SES) is associated with health (physical and mental) and cognitive ability. Understanding and ameliorating the problems of low SES have long been goals of economics and sociology; in recent years, these have also become goals of neuroscience. However, opinion varies widely on the relevance of neuroscience to SES-related policy. The present article addresses the question of whether and how neuroscience can contribute to the development of social policy concerning poverty and the social and ethical risks inherent in trying. I argue that the neuroscience approach to SES-related policy has been both prematurely celebrated and peremptorily dismissed and that ...


A Fresh Look At Huntingtin Mrna Processing In Huntington's Disease, Lindsay S. Romo, Emily S. Mohn, Neil Aronin 2018 University of Massachusetts Medical School

A Fresh Look At Huntingtin Mrna Processing In Huntington's Disease, Lindsay S. Romo, Emily S. Mohn, Neil Aronin

RNA Therapeutics Institute Publications

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a mutation that expands the polyglutamine (CAG) repeat in exon 1 of the huntingtin (HTT) gene. Wild-type HTT protein interacts with other proteins to protect cells against toxic stimuli, mediate vesicle transport and endocytosis, and modulate synaptic activity. Mutant HTT protein disrupts autophagy, vesicle transport, neurotransmitter signaling, and mitochondrial function. Although many of the activities of wild-type HTT protein and the toxicities of mutant HTT protein are characterized, less is known about the activities of HTT mRNA. Most putative HD therapies aim to target mutant HTT mRNA before it ...


Defining The Radioresponse Of Mossy Cells, Devon Ivy 2018 California State University, San Bernardino

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in ...


Ephrinb3 Modulates Hippocampal Neurogenesis And The Reelin Signaling Pathway In A Pilocarpineinduced Model Of Epilepsy, Tian-Tian Liu, Yi Li, Yi Shu, Bo Xiao, Li Feng 2018 Central South University

Ephrinb3 Modulates Hippocampal Neurogenesis And The Reelin Signaling Pathway In A Pilocarpineinduced Model Of Epilepsy, Tian-Tian Liu, Yi Li, Yi Shu, Bo Xiao, Li Feng

Open Access Articles

EphrinB3 is important in the regulation of cell proliferation, differentiation and migration via cellcell contact, and can activate the reelin pathway during brain development. However, the effect of ephrinB3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrinB3 in pilocarpineinduced status epilepticus (SE) rats was investigated. SYBR Greenbased reverse transcriptionquantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrinB3 and reelin pathway proteins. Immunofluorescence staining of doublecortin (DCX) was utilized to analyze hippocampal neurogenesis ...


Self-Regulation, Threat Perception, And Inhibitory Control: An Fmri Investigation Of Children With Adhd, Erin Kaseda 2018 Brigham Young University

Self-Regulation, Threat Perception, And Inhibitory Control: An Fmri Investigation Of Children With Adhd, Erin Kaseda

Undergraduate Honors Theses

This thesis examines the role of perceived parental support on adolescents aged 12-19 who have been diagnosed with attention-deficit/hyperactivity disorder (ADHD). Specifically, the study focused on inhibitory control, one form of cognitive executive control often implicated in ADHD, in three ways: first, through the use of a Go/No-Go task during a functional MRI scan of the brain; second, through the use of a neuropsychological cognitive battery using the NIH Toolbox; and third, through a qualitative interview that examined self-control in school and home contexts. Contrary to the initial hypothesis, parental support was found to be negatively correlated with ...


Geometric Analysis Of Synchronization In Neuronal Networks With Global Inhibition And Coupling Delays, Hwayeon Ryu, Sue Ann Campbell 2018 University of Hartford

Geometric Analysis Of Synchronization In Neuronal Networks With Global Inhibition And Coupling Delays, Hwayeon Ryu, Sue Ann Campbell

Biology and Medicine Through Mathematics Conference

No abstract provided.


Examining Motor Unit Stability Of First Dorsal Interosseous (Fdi) And Biceps Brachii (Bb) Muscles In Healthy And Older Adults Using Decomposition-Based Quantitative Electromyography (Dqemg), Igor Angelovski 2018 The University of Western Ontario

Examining Motor Unit Stability Of First Dorsal Interosseous (Fdi) And Biceps Brachii (Bb) Muscles In Healthy And Older Adults Using Decomposition-Based Quantitative Electromyography (Dqemg), Igor Angelovski

Electronic Thesis and Dissertation Repository

Aging of the human neuromuscular system is associated with gradual decline in motor unit (MU) number leading to denervation of muscle fibers and subsequent compensatory reinnervation from surviving MUs. Lower limb muscles exhibit age-related increased MU instability (measured electrophysiologically), however not much is known regarding MU stability of aging upper limb muscles. The purpose of this study was to examine agerelated MU loss in upper limb muscles (first dorsal interosseous [FDI] and biceps brachii [BB]) and the impact on MU stability in younger and older healthy subjects using electrophysiological near fiber analysis from decomposition-based quantitative electromyography (DQEMG). FDI and BB ...


Genetic Activation, Inactivation, And Deletion Reveal A Limited And Nuanced Role For Somatostatin-Containing Basal Forebrain Neurons In Behavioral State Control, Christelle Anaclet, Roberto De Luca, Anne Venner, Olga Malyshevskaya, Michael Lazarus, Elda Arrigoni, Patrick M. Fuller 2018 University of Massachusetts Medical School

Genetic Activation, Inactivation, And Deletion Reveal A Limited And Nuanced Role For Somatostatin-Containing Basal Forebrain Neurons In Behavioral State Control, Christelle Anaclet, Roberto De Luca, Anne Venner, Olga Malyshevskaya, Michael Lazarus, Elda Arrigoni, Patrick M. Fuller

Neurobiology Publications and Presentations

Recent studies have identified an especially important role for basal forebrain GABAergic (BF(VGAT)) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF(VGAT) neurons comprise several neurochemically and anatomically distinct subpopulations, including parvalbumin-containing BF(VGAT) neurons and somatostatin-containing BF(VGAT) neurons (BF(SOM) neurons), and it was recently reported that optogenetic activation of BF(SOM) neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the rest period of the animal. This finding was unexpected given that most BF(SOM) neurons are not NREM sleep active ...


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