Nervous System Commons^™

The Atr-Chek1 Pathway Inhibits Axon Regeneration In Response To Piezo-Dependent Mechanosensation, Feng Li, Tsz Y. Lo, Leann Miles, Qin Wang, Harun N. Noristani, Dan Li, Jingwen Niu, Shannon Trombley, Jessica I. Goldshteyn, Chuxi Wang, Shuchao Wang, Jingyun Qiu, Katarzyna Pogoda, Kalpana Mandal, Megan Brewster, Panteleimon Rompolas, Ye He, Pau A. Janmey, Gareth M. Thomas, Shuxin Li, Yuanquan Song

Advanced Science Research Center

Atr is a serine/threonine kinase, known to sense single-stranded DNA breaks and activate the DNA damage checkpoint by phosphorylating Chek1, which inhibits Cdc25, causing cell cycle arrest. This pathway has not been implicated in neuroregeneration. We show that in Drosophila sensory neurons removing Atr or Chek1, or overexpressing Cdc25 promotes regeneration, whereas Atr or Chek1 overexpression, or Cdc25 knockdown impedes regeneration. Inhibiting the Atr-associated checkpoint complex in neurons promotes regeneration and improves synapse/behavioral recovery after CNS injury. Independent of DNA damage, Atr responds to the mechanical stimulus elicited during regeneration, via the mechanosensitive ion channel Piezo and its downstream NO …

Tick Extracellular Vesicles Enable Arthropod Feeding And Promote Distinct Outcomes Of Bacterial Infection, Adela S. Oliva Chávez, Xiaowei Wang, Liron Marnin, Nathan K. Archer, Holly L. Hammond, Erin E. Mcclure Carroll, Dana K. Shaw, Brenden G. Tully, Amanda D. Buskirk, Shelby L. Ford, L. Rainer Butler, Preeti Shahi, Kateryna Morozova, Cristina C. Clement, Lauren Lawres, Anya J. O'Neal, Choukri Ben Mamoun, Kathleen L. Mason, Brandi E. Hobbs, Glen A. Scoles, Eileen M. Barry, Daniel E. Sonenshine, Utpal Pal, Jesus G. Valenzuela, Marcelo B. Sztein, Marcela F. Pasetti, Michael L. Levin, Michail Kotsyfakis, Steven M. Jay, Jason F. Huntley, Lloyd S. Miller, Laura Santambrogio, Joao H.F. Pedra

Biological Sciences Faculty Publications

Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting …

Cardiac Arrest And Global Ischemia Reperfusion Injury: Role Of Mitochondria And Cannabinoid Receptor 2 Signaling., Jennifer L. Bradley

Theses and Dissertations

We explored the effects of cardiac arrest on mitochondria populations and heart whole tissue lysate proteomics utilizing the Weil Institute’s in vivo rat model of cardiac arrest and cardiopulmonary resuscitation. We have discovered that brain mitochondria are more sensitive to global ischemia compared to heart mitochondria. Additionally, complex I is the most sensitive electron transport chain complex to ischemic injury and is a major control point of the rate of oxidative phosphorylation following cardiac arrest and cardiopulmonary resuscitation. Preservation of brain mitochondrial activity and function during cardiac arrest may enhance outcomes and recovery.

A recent article focusing on acute myocardial …

Conformational Modulation Of Α-Helical N-Acetylated Α-Synuclein, Ricardo Fernandez

Theses and Dissertations

Human N-acetylated α-synuclein (^NAcαSyn) has long been accepted as an intrinsically disordered protein (IDP) predominantly found in terminal nerve regions in healthy subjects. ^NAcαSyn structural fluidity enables the formation of transient or dynamic assemblies. Some of these assemblies may serve functional, yet undefined purposes. ^NAcαSyn is highly susceptible to the surrounding environment, leading to misfolding under high cytosolic oxidative stress conditions, which in turn assemble in the form of toxic oligomers or amyloid fibrils. These ^NAcαSyn inclusions along with their accretion and migration within neurons, are pathological hallmarks of Parkinson’s disease (PD), dementia, and multiple …

Effects Of Buprenorphine Treatment On Myelin Following Traumatic Brain Injury In A Rat Model, Jane Ryu

Theses and Dissertations

Traumatic brain injury (TBI) is a common phenomenon, accounting for significant cost and adverse health effects. While there is information about focal pathologies following TBI, knowledge of more diffuse processes is lacking, particularly regarding how analgesics affect this pathology. As Buprenorphine (Bup) is the most commonly used analgesic in experimental TBI models, the current study investigated the effects of the opioid analgesic Buprenorphine-sustained release-Lab (Bup-SR-Lab) on physiology and myelin alterations at 1d and 4w following central fluid percussion injury (cFPI) in adult male rats. Microscopic assessments were performed at 1 day and 4w post-injury. Myelin pathology was assessed by evaluating …

Extracellular Vesicles Released By Human Retinal Pigment Epithelium Mediate Increased Polarised Secretion Of Drusen Proteins In Response To Amd Stressors, Miguel Flores-Bellver, Jason Mighty, Silvia Aparicio-Domingo, Kang V. Li, Cui Shi, Jing Zhou, Hannah Cobb, Patrick Mcgrath, German Michelis, Patricia Lenhart, Ganna Bilousova, Søren Heissel, Michael J. Rudy, Christina Coughlan, Andrew E. Goodspeed, S. Patricia Becerra, Stephen Redenti, M. Valeria Canto-Soler

Publications and Research

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Drusen are key contributors to the etiology of AMD and the ability to modulate drusen biogenesis could lead to therapeutic strategies to slow or halt AMD progression. The mechanisms underlying drusen biogenesis, however, remain mostly unknown. Here we demonstrate that under homeostatic conditions extracellular vesicles (EVs) secreted by retinal pigment epithelium (RPE) cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology, including oxidative stress, immune response, inflammation, complement system and drusen composition. Furthermore, we provide first evidence that drusen-associated proteins are released as cargo of extracellular …

Short-Term Fasting And Autonomic Control, Joshua Gonzalez

Dissertations, Master's Theses and Master's Reports

Obesity is a chronic metabolic disorder associated with increased risk of cardiovascular disease. Evidence suggests that chronic intermittent fasting improves cardiometabolic health and reduces arterial blood pressure. However, the mechanisms underlying the reductions in blood pressure and improved cardiovascular health observed from chronic fasting studies remain unclear. The autonomic nervous system has a central role in the regulation of blood pressure and is essential for cardiovascular homeostasis. We conducted a study to investigate how acute fasting influences autonomic control of blood pressure at rest and during stress. Twenty-five young, healthy, normal weight, normotensive participants were tested twice, once in the …

Deep Neural Network Analysis Of Pathology Images With Integrated Molecular Data For Enhanced Glioma Classification And Grading, Linmin Pei, Karra A. Jones, Zeina A. Shboul, James Y. Chen, Khan M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Gliomas are primary brain tumors that originate from glial cells. Classification and grading of these tumors is critical to prognosis and treatment planning. The current criteria for glioma classification in central nervous system (CNS) was introduced by World Health Organization (WHO) in 2016. This criteria for glioma classification requires the integration of histology with genomics. In 2017, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) was established to provide up-to-date recommendations for CNS tumor classification, which in turn the WHO is expected to adopt in its upcoming edition. In this work, we propose a novel …