Neurosciences Commons^™

Sex And Gender Differences In Acute Stroke Care: Metrics, Access To Treatment And Outcome A Territorial Analysis Of The Stroke Code System Of Catalonia, Yolanda Silva, Laura Sánchez-Cirera, Mikel Terceño, Laura Dorado, Adrián Valls, Marina Martínez, Sònia Abilleira, Marta Rubiera, Helena Quesada, Laura Llull, Ana Rodríguez-Campello, Joan Martí-Fàbregas, Laia Seró, Francisco Purroy, Iago Payo, Sònia García, David Cánovas, Jurek Krupinski, Natalia Mas, Ernest Palomeras, Dolores Cocho, Maria Àngels Font, Esther Catena, Elsa Puiggròs, Claudia Pedroza, Gemma Marín, Dolors Carrión, Xavier Costa, Mari Cruz Almendros, Ivan Torres, Carla Colom, John Alejandro Velasquez, Gloria Diaz, Xavier Jiménez, Teresa Subirats, Anna Deulofeu, Verónica Hidalgo, Mercè Salvat-Plana, Natalia Pérez De La Ossa, Catalan Stroke Code And Reperfusion Consortium (Cat-Scr)

Faculty, Staff and Student Publications

INTRODUCTION: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia.

PATIENTS AND METHODS: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy.

RESULTS: A total of 23,371 stroke code activations were …

Vagus Nerve Stimulation Paired With Rehabilitation For Upper Limb Motor Impairment And Function After Chronic Ischemic Stroke: Subgroup Analysis Of The Randomized, Blinded, Pivotal, Vns-Rehab Device Trial, Jesse Dawson, Navzer D Engineer, Steven C Cramer, Steven L Wolf, Rushna Ali, Michael W O'Dell, David Pierce, Cecília N Prudente, Jessica Redgrave, Wuwei Feng, Charles Y Liu, Gerard E Francisco, Benjamin L Brown, Anand Dixit, Jen Alexander, Louis Demark, Vibor Krishna, Steven A Kautz, Arshad Majid, Brent Tarver, Duncan L Turner, Teresa J Kimberley

Faculty, Staff and Student Publications

BACKGROUND: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke.

OBJECTIVE: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury.

METHODS: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS …

Towards Neuromarkers For Tailored Smoking Cessation Treatments, Francesco Versace, Jason D Robinson, Paul M Cinciripini

Faculty, Staff and Student Publications

Vulnerability to compulsive drug use stems from dysregulated activity within the neural networks that underlie reward and executive functions. Empirical evidence suggests that a) attributing high motivational salience to drug-related stimuli leads to compulsive drug seeking and b) cognitive control deficits lead to compulsive drug taking. Noninvasive neuroimaging techniques enable brain activity monitoring during affective and cognitive processing and are paving the way to precision medicine for substance use disorders. Identifying robust neuromarkers of affective and cognitive dysregulation would allow clinicians to personalize treatments by targeting individual psychophysiological vulnerabilities. However, methodological choices have biased the field toward experimental paradigms that …

Preterm Birth Alters The Feeding-Induced Activation Of Akt Signaling In The Muscle Of Neonatal Piglets, Agus Suryawan, Marko Rudar, Jane K Naberhuis, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Postnatal lean mass accretion is commonly reduced in preterm infants. This study investigated mechanisms involved in the blunted feeding-induced activation of Akt in the skeletal muscle of preterm pigs that contributes to lower protein synthesis rates.

METHODS: On day 3 following cesarean section, preterm and term piglets were fasted or fed an enteral meal. Activation of Akt signaling pathways in skeletal muscle was determined.

RESULTS: Akt1 and Akt2, but not Akt3, phosphorylation were lower in the skeletal muscle of preterm than in term pigs (P < 0.05). Activation of Akt-positive regulators, PDK1 and mTORC2, but not FAK, were lower in preterm than in term (P < 0.05). The formation of Akt complexes with GAPDH and Hsp90 and the abundance of Ubl4A were lower in preterm than in term (P < 0.05). The abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN and IP6K1, were higher in preterm than in term pigs (P < 0.05). PP2A activation was inhibited by feeding in term but not in preterm pigs (P < 0.05).

CONCLUSIONS: Our results suggest that preterm birth impairs regulatory components involved in Akt activation, …

Commentary On "Mini-Open Intercostal Retroperitoneal Approach For Upper Lumbar Spine Lateral Interbody Fusion", Alexander E Ropper

Faculty, Staff and Students Publications

No abstract provided.

Dual-Target Deep Brain Stimulation For Obsessive-Compulsive Disorder And Tourette Syndrome, Ricardo A Najera, Nicole Provenza, Huy Dang, Kalman A Katlowitz, Alyssa Hertz, Sandesh Reddy, Ben Shofty, Steven T Bellows, Eric A Storch, Wayne K Goodman, Sameer A Sheth

Faculty, Staff and Students Publications

No abstract provided.

Fetal Malrotation With Midgut Volvulus: Prenatal Diagnosis And Planning, Oluyinka O Olutoye, J D Hammond, Jamie Gilley, Ross M Beckman, Marie Bulathsinghala, Sonya S Keswani, Jonathan Davies, Mark V Mazziotti, Roopali Donepudi, Michael A Belfort, Alice King, Pamela M Ketwaroo, Timothy C Lee

Faculty, Staff and Students Publications

Introduction: Malrotation of the intestinal tract is a congenital malformation commonly found either incidentally or after affected individuals develop signs and symptoms of intestinal obstruction. Malrotation is prone to midgut volvulus that can cause intestinal obstruction and lead to ischemia and necrosis requiring emergent surgical intervention. Rare instances of in utero midgut volvulus have been reported in the literature and carry a high mortality given the difficulty in establishing a diagnosis prior to development of signs of intestinal ischemia and necrosis. Advancements in imaging have made it possible to diagnose in utero malrotation earlier, raising the question of optimal timing …

De Novo Variants In Mrtfb Have Gain-Of-Function Activity In Drosophila And Are Associated With A Novel Neurodevelopmental Phenotype With Dysmorphic Features, Jonathan C Andrews, Jung-Wan Mok, Oguz Kanca, Sharayu Jangam, Cynthia Tifft, Ellen F Macnamara, Bianca E Russell, Lee-Kai Wang, Undiagnosed Diseases Network, Stanley F Nelson, Hugo J Bellen, Shinya Yamamoto, May Christine V Malicdan, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Purpose: Myocardin-related transcription factor B (MRTFB) is an important transcriptional regulator, which promotes the activity of an estimated 300 genes but is not known to underlie a Mendelian disorder.

Methods: Probands were identified through the efforts of the Undiagnosed Disease Network. Because the MRTFB protein is highly conserved between vertebrate and invertebrate model organisms, we generated a humanized Drosophila model expressing the human MRTFB protein in the same spatial and temporal pattern as the fly gene. Actin binding assays were used to validate the effect of the variants on MRTFB.

Results: Here, we report 2 pediatric probands with de novo …

Implication Of Chromosomal Microarray Analysis Prior To In-Utero Repair Of Fetal Open Neural Tube Defect, R Zemet, E Krispin, R M Johnson, N R Kumar, L E Westerfield, S Stover, D G Mann, J Castillo, H A Castillo, A A Nassr, M Sanz Cortes, R Donepudi, J Espinoza, W E Whitehead, M A Belfort, A A Shamshirsaz, I B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Objective: In-utero repair of open neural tube defects (ONTD) is an accepted treatment option with demonstrated superior outcome for eligible patients. While current guidelines recommend genetic testing by chromosomal microarray analysis (CMA) when a major congenital anomaly is detected prenatally, the requirement for an in-utero repair, based on the Management of Myelomeningocele Study (MOMS) criteria, is a normal karyotype. In this study, we aimed to evaluate if CMA should be recommended as a prerequisite for in-utero ONTD repair.

Methods: This was a retrospective cohort study of pregnancies complicated by ONTD that underwent laparotomy-assisted fetoscopic repair or open-hysterotomy fetal surgery at …

Imaging Of Pediatric Cardiac Tumors: A Cog Diagnostic Imaging Committee/Spr Oncology Committee White Paper, Cara E Morin, Lindsay M Griffin, Rebecca S Beroukhim, Pablo Caro-Domínguez, Sherwin Chan, Jason N Johnson, Juan C Infante, Christopher Z Lam, Ladonna J Malone, Elizabeth R Tang, Michael D Taylor, James C Wilkinson, Prakash M Masand

Faculty, Staff and Students Publications

Cardiac tumors in children are rare and the majority are benign. The most common cardiac tumor in children is rhabdomyoma, usually associated with tuberous sclerosis complex. Other benign cardiac masses include fibromas, myxomas, hemangiomas, and teratomas. Primary malignant cardiac tumors are exceedingly rare, with the most common pathology being soft tissue sarcomas. This paper provides consensus-based imaging recommendations for the evaluation of patients with cardiac tumors at diagnosis and follow-up, including during and after therapy.

Thirty-Day Outcomes Of Resolute Onyx Stent For Symptomatic Intracranial Stenosis: A Multicenter Propensity Score-Matched Comparison With Stenting Versus Aggressive Medical Management For Preventing Recurrent Stroke In Intracranial Stenosis Trial, Farhan Siddiq, Ravi S Nunna, Jonathan M Beall, Inamullah Khan, Musharaf Khan, Wondwossen G Tekle, Mohamad Ezzeldin, Omar Tanweer, Jan-Karl Burkhardt, Pascal M Jabbour, Stavropoula I Tjoumakaris, Nabeel A Herial, Adnan H Siddiqui, Ramesh Grandhi, Renee L Martin, Adnan I Qureshi, Ameer E Hassan

Faculty, Staff and Students Publications

BACKGROUND: Symptomatic intracranial atherosclerotic disease (sICAD) is estimated to cause 10% of strokes annually in the United States. However, treatment remains a challenge with several different stenting options studied in the past with unfavorable results.

OBJECTIVE: To report the 30-day stroke and/or death rate associated with intracranial stent placement for sICAD using Resolute Onyx Zotarolimus-Eluting Stent (RO-ZES) and provide a comparison with the results of Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial.

METHODS: Prospectively maintained databases across 8 stroke centers were used to identify adult patients treated with RO-ZES for sICAD between January …

Examination Of Parent-Reported Differences In Children’S Daily Screen Use, Sleep, And Sleep Hygiene Behaviors During The School Year And Summer And Their Association With Bmi, Jennette P Moreno, Alexis C Wood, Brooke Reichek, Hafza Dadabhoy, Tom Baranowski, Debbe Thompson, Teresia M O'Connor

Faculty, Staff and Students Publications

OBJECTIVE: The current study examined school-summer differences in children's sleep patterns and sleep hygiene. Cross-sectional relationships with children's sleep, sleep hygiene, and weight status were explored during the school year and summer.

METHODS: Children (5-8 years) and their parents (n = 197 dyads) were recruited from 4 schools in southeastern Texas and via Facebook. Parents reported children's school year and summer sleep, sleep hygiene, and screen media use. Children's body mass index (BMI) was objectively assessed at the beginning and end of the summer. Associations between children's sleep hygiene and screen media use, sleep duration, and weight status were explored. …

Imaging Of Pediatric Calvarial And Skull Base Tumors: A Cog Diagnostic Imaging Committee/Spr Oncology Committee/Asnpr White Paper, Jarunee Intrapiromkul, Pattana Wangaryattawanich, Zoltan Patay, Thierry A G M Huisman, Jason N Wright, Jeremy Y Jones, Raghu Ramakrishnaiah, Rajan Patel, Adam E Goldman-Yassen, Stephen Kralik, Mark Mamlouk, Nilesh K Desai

Faculty, Staff and Students Publications

A standardized imaging protocol for pediatric oncology patients is essential for accurate and efficient imaging, while simultaneously promoting collaborative understanding of pathologies and radiologic assessment of treatment response. The objective of this article is to provide standardized pediatric imaging guidelines and parameters for evaluation of tumors of the pediatric orbit, calvarium, skull base, and temporal bone. This article was drafted based on current scientific literature as well as consensus opinions of imaging experts in collaboration with the Children's Oncology Group Diagnostic Imaging Committee, Society of Pediatric Radiology Oncology Committee, and American Society of Pediatric Neuroradiology.

Target Cell-Specific Synaptic Dynamics Of Excitatory To Inhibitory Neuron Connections In Supragranular Layers Of Human Neocortex, Mean-Hwan Kim, Cristina Radaelli, Elliot R Thomsen, Deja Monet, Thomas Chartrand, Nikolas L Jorstad, Joseph T Mahoney, Michael J Taormina, Brian Long, Katherine Baker, Trygve E Bakken, Luke Campagnola, Tamara Casper, Michael Clark, Nick Dee, Florence D'Orazi, Clare Gamlin, Brian E Kalmbach, Sara Kebede, Brian R Lee, Lindsay Ng, Jessica Trinh, Charles Cobbs, Ryder P Gwinn, C Dirk Keene, Andrew L Ko, Jeffrey G Ojemann, Daniel L Silbergeld, Staci A Sorensen, Jim Berg, Kimberly A Smith, Philip R Nicovich, Tim Jarsky, Hongkui Zeng, Jonathan T Ting, Boaz P Levi, Ed Lein

Faculty, Staff and Student Publications

Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings, post-hoc fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- …

Alcohol As A Modifiable Risk Factor For Alzheimer’S Disease—Evidence From Experimental Studies, Devaraj V. Chandrashekar, Ross A. Steinberg, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can …

Microrna (Mirna) Complexity In Alzheimer’S Disease (Ad), Walter J. Lukiw

School of Medicine Faculty Publications

AD is a complex, progressive, age-related neurodegenerative disorder representing the most common cause of senile dementia and neurological dysfunction in our elderly domestic population. The widely observed heterogeneity of AD is a reflection of the complexity of the AD process itself and the altered molecular-genetic mechanisms operating in the diseased human brain and CNS. One of the key players in this complex regulation of gene expression in human pathological neurobiology are microRNAs (miRNAs) that, through their actions, shape the transcriptome of brain cells that normally associate with very high rates of genetic activity, gene transcription and messenger RNA (mRNA) generation. …

Lateral Septum As A Melanocortin Downstream Site In Obesity Development, Yuanzhong Xu, Zhiying Jiang, Hongli Li, Jing Cai, Yanyan Jiang, Joshua Otiz-Guzman, Yong Xu, Benjamin R Arenkiel, Qingchun Tong

Faculty, Staff and Students Publications

The melanocortin pathway is well established to be critical for body-weight regulation in both rodents and humans. Despite extensive studies focusing on this pathway, the downstream brain sites that mediate its action are not clear. Here, we found that, among the known paraventricular hypothalamic (PVH) neuron groups, those expressing melanocortin receptors 4 (PVHMc4R) preferably project to the ventral part of the lateral septum (LSv), a brain region known to be involved in emotional behaviors. Photostimulation of PVHMc4R neuron terminals in the LSv reduces feeding and causes aversion, whereas deletion of Mc4Rs or disruption of glutamate release from LSv-projecting PVH neurons …

The Metreleptin Effectiveness And Safety Registry (Measure): Concept, Design And Challenges, Morey W Haymond, David Araújo-Vilar, John Balser, James H Lewis, Ruth Louzado, Carla Musso, Julia Von Schnurbein, Martin Wabitsch

Faculty, Staff and Students Publications

BACKGROUND: Metreleptin, a recombinant analog of human leptin, is an approved therapy, adjunct to diet, to treat the metabolic complications of leptin deficiency in patients with lipodystrophy - a group of rare diseases characterized by a paucity of adipose tissue. MEASuRE (Metreleptin Effectiveness And Safety Registry) is a post-authorization, voluntary registry that gathers long-term safety and effectiveness data on metreleptin. Here, we present the aims and evolution of MEASuRE.

METHODS: MEASuRE was established to collect data from patients receiving commercially supplied metreleptin in the United States (US) and European Union (EU). MEASuRE aims to determine the incidence and severity of …

Differential Response Of C9orf72 Transcripts Following Neuronal Depolarization, Layla T. Ghaffari, Davide Trotti, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

The (G4C2)n nucleotide repeat expansion (NRE) mutation in C9orf72 is the most common genetic cause of ALS and FTD. The biological functions of C9orf72 are becoming understood, but it is unclear if this gene is regulated in a neural-specific manner. Neuronal activity is a crucial modifier of biological processes in health and neurodegenerative disease contexts. Here, we show that prolonged membrane depolarization in healthy human iPSC-cortical neurons leads to a significant downregulation of a transcript variant 3 (V3) of C9orf72, with a concomitant increase in variant 2 (V2), which leads to total C9orf72 RNA transcript levels remaining unchanged. However, the …

Connecting Circuits With Networks In Addiction Neuroscience: A Salience Network Perspective, Adriana K Cushnie, Wei Tang, Sarah R Heilbronner

Faculty, Staff and Students Publications

Human neuroimaging has demonstrated the existence of large-scale functional networks in the cerebral cortex consisting of topographically distant brain regions with functionally correlated activity. The salience network (SN), which is involved in detecting salient stimuli and mediating inter-network communication, is a crucial functional network that is disrupted in addiction. Individuals with addiction display dysfunctional structural and functional connectivity of the SN. Furthermore, while there is a growing body of evidence regarding the SN, addiction, and the relationship between the two, there are still many unknowns, and there are fundamental limitations to human neuroimaging studies. At the same time, advances in …

Membrane Compression By Synaptic Vesicle Exocytosis Triggers Ultrafast Endocytosis, Tyler H Ogunmowo, Haoyuan Jing, Sumana Raychaudhuri, Grant F Kusick, Yuuta Imoto, Shuo Li, Kie Itoh, Ye Ma, Haani Jafri, Matthew B. Dalva, Edwin R Chapman, Taekjip Ha, Shigeki Watanabe, Jian Liu

Department of Neuroscience Faculty Papers

Compensatory endocytosis keeps the membrane surface area of secretory cells constant following exocytosis. At chemical synapses, clathrin-independent ultrafast endocytosis maintains such homeostasis. This endocytic pathway is temporally and spatially coupled to exocytosis; it initiates within 50 ms at the region immediately next to the active zone where vesicles fuse. However, the coupling mechanism is unknown. Here, we demonstrate that filamentous actin is organized as a ring, surrounding the active zone at mouse hippocampal synapses. Assuming the membrane area conservation is due to this actin ring, our theoretical model suggests that flattening of fused vesicles exerts lateral compression in the plasma …

An Opportunity To Increase Collaborative Science In Fetal, Infant, And Toddler Neuroimaging, Marta Korom, M Catalina Camacho, Aiden Ford, Hana Taha, Dustin Scheinost, Marisa Spann, Kelly A Vaughn

Faculty, Staff and Student Publications

The field of fetal, infant, and toddler (FIT) neuroimaging research—including magnetic resonance imaging (MRI), electroencephalography (EEG), magnetoencephalography, and functional near-infrared spectroscopy, among others—offers pioneering insights into early brain development and has grown in popularity over the past 2 decades. In broader neuroimaging research, multisite collaborative projects, data sharing, and open-source code have increasingly become the norm, fostering big data, consensus standards, and rapid knowledge transfer and development. Given the aforementioned benefits, along with recent initiatives from funding agencies to support multisite and multimodal FIT neuroimaging studies, the FIT field now has the opportunity to establish sustainable, collaborative, and open science …

Ragd Auto-Activating Mutations Impair Mit/Tfe Activity In Kidney Tubulopathy And Cardiomyopathy Syndrome, Irene Sambri, Marco Ferniani, Giulia Campostrini, Marialuisa Testa, Viviana Meraviglia, Mariana E G De Araujo, Ladislav Dokládal, Claudia Vilardo, Jlenia Monfregola, Nicolina Zampelli, Francesca Del Vecchio Blanco, Annalaura Torella, Carolina Ruosi, Simona Fecarotta, Giancarlo Parenti, Leopoldo Staiano, Milena Bellin, Lukas A Huber, Claudio De Virgilio, Francesco Trepiccione, Vincenzo Nigro, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Heterozygous mutations in the gene encoding RagD GTPase were shown to cause a novel autosomal dominant condition characterized by kidney tubulopathy and cardiomyopathy. We previously demonstrated that RagD, and its paralogue RagC, mediate a non-canonical mTORC1 signaling pathway that inhibits the activity of TFEB and TFE3, transcription factors of the MiT/TFE family and master regulators of lysosomal biogenesis and autophagy. Here we show that RagD mutations causing kidney tubulopathy and cardiomyopathy are "auto- activating", even in the absence of Folliculin, the GAP responsible for RagC/D activation, and cause constitutive phosphorylation of TFEB and TFE3 by mTORC1, without affecting the phosphorylation …

Glutamatergic Cerebellar Neurons Differentially Contribute To The Acquisition Of Motor And Social Behaviors, Meike E Van Der Heijden, Alejandro G Rey Hipolito, Linda H Kim, Dominic J Kizek, Ross M Perez, Tao Lin, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Insults to the developing cerebellum can cause motor, language, and social deficits. Here, we investigate whether developmental insults to different cerebellar neurons constrain the ability to acquire cerebellar-dependent behaviors. We perturb cerebellar cortical or nuclei neuron function by eliminating glutamatergic neurotransmission during development, and then we measure motor and social behaviors in early postnatal and adult mice. Altering cortical and nuclei neurons impacts postnatal motor control and social vocalizations. Normalizing neurotransmission in cortical neurons but not nuclei neurons restores social behaviors while the motor deficits remain impaired in adults. In contrast, manipulating only a subset of nuclei neurons leaves social …

Functional Variants Identify Sex-Specific Genes And Pathways In Alzheimer’S Disease, Thomas Bourquard, Kwanghyuk Lee, Ismael Al-Ramahi, Minh Pham, Dillon Shapiro, Yashwanth Lagisetty, Shirin Soleimani, Samantha Mota, Kevin Wilhelm, Maryam Samieinasab, Young Won Kim, Eunna Huh, Jennifer Asmussen, Panagiotis Katsonis, Juan Botas, Olivier Lichtarge

Faculty, Staff and Students Publications

The incidence of Alzheimer's Disease in females is almost double that of males. To search for sex-specific gene associations, we build a machine learning approach focused on functionally impactful coding variants. This method can detect differences between sequenced cases and controls in small cohorts. In the Alzheimer's Disease Sequencing Project with mixed sexes, this approach identified genes enriched for immune response pathways. After sex-separation, genes become specifically enriched for stress-response pathways in male and cell-cycle pathways in female. These genes improve disease risk prediction in silico and modulate Drosophila neurodegeneration in vivo. Thus, a general approach for machine learning on …

Efficient Cancer Modeling Through Crispr-Cas9/Hdr-Based Somatic Precision Gene Editing In Mice, Wen Bu, Chad J Creighton, Kelsey S Heavener, Carolina Gutierrez, Yongchao Dou, Amy T Ku, Yiqun Zhang, Weiyu Jiang, Jazmin Urrutia, Wen Jiang, Fei Yue, Luyu Jia, Ahmed Atef Ibrahim, Bing Zhang, Shixia Huang, Yi Li

Faculty, Staff and Student Publications

CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either

Investigating Physical Therapy Students’ Perceived Levels Of Self-Confidence To Apply Sensory Neuroscience Concepts, Jeanne Welch, Olawunmi Obisesan

Research Day

Purpose/Hypothesis: Guided by the theory of social constructivism, the purpose of this study was to investigate the overall impact of an experiential summative group assignment, The Great Toe Assignment (TGTA), on Doctor of Physical Therapy students’ perceptions of their level of self-confidence in applying sensory neuroscience concepts learned during an academic term. This study’s research questions were: What is the overall impact of an experiential summative group assignment on students’ perceptions of self-confidence in applying neuroscience concepts learned during an academic term? Are there any statistically significant differences in measurements of perceptions of students’ level of self-confidence measured at Week …

A Conditional Strategy For Cell-Type-Specific Labeling Of Endogenous Excitatory Synapses In Drosophila, Michael J. Parisi, Michael A. Aimino, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

Chemical neurotransmission occurs at specialized contacts where neurotransmitter release machinery apposes neurotransmitter receptors to underlie circuit function. A series of complex events underlies preand postsynaptic protein recruitment to neuronal connections. To better study synaptic development in individual neurons, we need cell-type-specific strategies to visualize endogenous synaptic proteins. Although presynaptic strategies exist, postsynaptic proteins remain less studied because of a paucity of cell-type-specific reagents. To study excitatory postsynapses with cell-type specificity, we engineered dlg1[4K], a conditionally labeled marker of Drosophila excitatory postsynaptic densities. With binary expression systems, dlg1[4K] labels central and peripheral postsynapses in larvae and adults. Using dlg1[4K], we find …

Sleep Problems In Old Age: Metabotropic Glutamate Receptor To The Rescue, Sho Inami, Dinis J.S. Afonso, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

No abstract provided.

Functional Neuronal Circuits Promote Disease Progression In Cancer, Anthony C Restaino, Austin Walz, Samuel J Vermeer, Jeffrey Barr, Attila Kovács, Robin R Fettig, Daniel W Vermeer, Hunter Reavis, Caitlin S Williamson, Christopher T Lucido, Tuany Eichwald, Dalia K Omran, Euihye Jung, Lauren E Schwartz, Maria Bell, Desirae M Muirhead, Jody E Hooper, William C Spanos, Ronny Drapkin, Sebastien Talbot, Paola D Vermeer

Faculty, Staff and Student Publications

The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the …