Medicine and Health Sciences Commons^™

Negligence In Biomedical Research: An Anti-Racist Approach For Substance Use Researchers, Jonathan Lehman, Danniella Balangoy, Angie P Mejia, Carlos Cardenas-Iniguez, Scott Marek, Anita C Randolph

2020-Current year OA Pubs

Racism is embedded in the fabric of society at structural, disciplinary, hegemonic, and interpersonal levels, working as a mechanism that drives health disparities. In particular, stigmatized views of substance use get entangled with racialization, serving as a tool to uphold oppressive systems. While national health institutions have made commitments to dismantle these systems in the United States, anti-racism has not been integrated into biomedical research practice. The ways in which substance use researchers use and interpret race data-without engaging in structural racism as a mechanism of health inequity-can only be described as inadequate. Drawing upon concepts from the Public Health …

Traversing The Bench To Bedside Journey For Inkt Cell Therapies, Julie O'Neal, Melissa Mavers, Reyka G Jayasinghe, John F Dipersio

2020-Current year OA Pubs

Invariant natural killer T (iNKT) cells are immune cells that harness properties of both the innate and adaptive immune system and exert multiple functions critical for the control of various diseases. Prevention of graft-versus-host disease (GVHD) by iNKT cells has been demonstrated in mouse models and in correlative human studies in which high iNKT cell content in the donor graft is associated with reduced GVHD in the setting of allogeneic hematopoietic stem cell transplants. This suggests that approaches to increase the number of iNKT cells in the setting of an allogeneic transplant may reduce GVHD. iNKT cells can also induce …

Microglycodb: A Database Of Microbial Glycans Using Semantic Web Technologies, Sunmyoung Lee, Louis-David Leclercq, Yann Guerardel, Christine M Szymanski, Thomas Hurtaux, Tamara L Doering, Takane Katayama, Kiyotaka Fujita, Kazuhiro Aoki, Kiyoko F Aoki-Kinoshita

2020-Current year OA Pubs

Glycoconjugates are present on microbial surfaces and play critical roles in modulating interactions with the environment and the host. Extensive research on microbial glycans, including elucidating the structural diversity of the glycan moieties of glycoconjugates and polysaccharides, has been carried out to investigate the function of glycans in modulating the interactions between the host and microbes, to explore their potential applications in the therapeutic targeting of pathogenic species, and in the use as probiotics in gut microbiomes. However, glycan-related information is dispersed across numerous databases and a vast amount of literature, which makes it laborious and time-consuming to identify and …

Systematic Computer-Aided Disulfide Design As A General Strategy To Stabilize Prefusion Class I Fusion Proteins, Karen J Gonzalez, Kevin C Yim, Jorge C G Blanco, Marina S Boukhvalova, Eva-Maria Strauch

2020-Current year OA Pubs

Numerous enveloped viruses, such as coronaviruses, influenza, and respiratory syncytial virus (RSV), utilize class I fusion proteins for cell entry. During this process, the proteins transition from a prefusion to a postfusion state, undergoing substantial and irreversible conformational changes. The prefusion conformation has repeatedly shown significant potential in vaccine development. However, the instability of this state poses challenges for its practical application in vaccines. While non-native disulfides have been effective in maintaining the prefusion structure, identifying stabilizing disulfide bonds remains an intricate task. Here, we present a general computational approach to systematically identify prefusion-stabilizing disulfides. Our method assesses the geometric …

Unmet Patient Needs In Monocarboxylate Transporter 8 (Mct8) Deficiency: A Review, Andrew J Bauer, Bethany Auble, Amy L Clark, Tina Y Hu, Amber Isaza, Kyle P Mcnerney, Daniel L Metzger, Lindsey Nicol, Samuel R Pierce, Richard Sidlow

2020-Current year OA Pubs

Monocarboxylate transporter 8 (MCT8) deficiency is a rare, X-linked disorder arising from mutations in the

Arterial Hypoperfusion As A Negative Predictive Marker For Primary Hepatic Malignancies Treated With Y-90 Glass Microsphere Transarterial Radioembolization, Bita Kalaghchi, Semra Ince, Justin Barnes, Kendall Kiser, Re-I Chin, Justin Mikell, Shahed Badiyan, Jose Garcia, Jacqueline Zoberi, Maria Bernadette Majella Doyle, Benjamin Tan, Seung Kim, Tyler Fraum, Hyun Kim

2020-Current year OA Pubs

BACKGROUND: Radioembolization with yttrium-90 (Y-90) is utilized to treat primary liver malignancies. The efficacy of this intra-arterial therapy in arterially hypoperfused tumors is not known.

METHODS: We reviewed data of patients with primary liver tumors treated with Y-90 prescription doses of at least 150 Gy. Baseline patient characteristics, treatment history, imaging-based tumor response assessments, and clinical outcome metrics were recorded. Tumors were classified as arterially hyperperfused versus hypoperfused on post-TARE Y-90 SPECT/CTs or pre-TARE hepatic perfusion SPECT/CTs. Perfusion status was correlated with tumor response assessments and clinical outcomes. Cox proportional hazards models were utilized to compare survival and progression-free survival. …

Isoflurane Conditioning Improves Functional Outcomes After Peripheral Nerve Injury In A Sciatic Cut Repair Murine Model, Yameng Xu, Ying Yan, Gregory J Zipfel, Matthew Macewan, Wilson Z Ray, Umeshkumar Athiraman

2020-Current year OA Pubs

INTRODUCTION: Anesthetic conditioning has been shown to provide neuroprotection in several neurological disorders. Whether anesthetic conditioning provides protection against peripheral nerve injuries remains unknown. The aim of our current study is to investigate the impact of isoflurane conditioning on the functional outcomes after peripheral nerve injury (PNI) in a rodent sciatic nerve injury model.

METHODS: Adult male Lewis rats underwent sciatic nerve cut and repair and exposed to none (Group 1, sham), single isoflurane exposure (Group 2), three-time isoflurane exposure (Group 3), and six-time isoflurane exposure (Group 4). Isoflurane conditioning was established by administration of 2% isoflurane for 1 hour, …

Overall And Non- Lung Cancer Incidence And Mortality In The National Lung Screening Trial: Opportunities For Multi-Cancer Early Detection, Alpa V. Patel, Ellen T. Chang, Allan Hackshaw, Sam M. Janes, Diana S.M. Buist, Earl Hubbell, Christina A. Clarke, Graham A. Colditz

2020-Current year OA Pubs

No abstract provided.

Neurocognitive Outcome In Children With Sickle Cell Disease After Myeloimmunoablative Conditioning And Haploidentical Hematopoietic Stem Cell Transplantation: A Non-Randomized Clinical Trial, Suzanne Braniecki, Shalini Shenoy, Robert C Mckinstry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Due to the risk of cerebral vascular injury, children and adolescents with high-risk sickle cell disease (SCD) experience neurocognitive decline over time. Haploidentical stem cell transplantation (HISCT) from human leukocyte antigen-matched sibling donors may slow or stop progression of neurocognitive changes.

OBJECTIVES: The study is to determine if HISCT can ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression, determine which specific areas of neurocognitive functioning are particularly vulnerable to SCD, and determine if there are age-related differences in neurocognitive functioning over time.

METHODS: We performed neurocognitive and neuroimaging in SCD recipients following HISCT. Children and adolescents with high-risk SCD …

Examining Heterogeneity In Dementia Using Data-Driven Unsupervised Clustering Of Cognitive Profiles, Sayantan Kumar, Inez Y. Oh, Suzanne E. Schindler, Nupur Ghoshal, Zachary Abrams, Philip R. O. Payne

2020-Current year OA Pubs

Dementia is characterized by a decline in memory and thinking that is significant enough to impair function in activities of daily living. Patients seen in dementia specialty clinics are highly heterogenous with a variety of different symptoms that progress at different rates. Recent research has focused on finding data-driven subtypes for revealing new insights into dementia's underlying heterogeneity, rather than assuming that the cohort is homogenous. However, current studies on dementia subtyping have the following limitations: (i) focusing on AD-related dementia only and not examining heterogeneity within dementia as a whole, (ii) using only cross-sectional baseline visit information for clustering …

Control Intervention Design For Preclinical And Clinical Trials: Consensus-Based Core Recommendations From The Third Stroke Recovery And Rehabilitation Roundtable, Kathryn S Hayward, Emily J Dalton, Jessica Barth, Marian Brady, Leora R Cherney, Leonid Churilov, Andrew N Clarkson, Jesse Dawson, Sean P Dukelow, Peter Feys, Maree Hackett, Steve R Zeiler, Catherine E Lang

2020-Current year OA Pubs

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was …

Examining Associations Between Genetic And Neural Risk For Externalizing Behaviors In Adolescence And Early Adulthood, Sarah J Brislin, Andrey P Anokhin, Et Al.

2020-Current year OA Pubs

BACKGROUND: Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers.

METHODS: Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA;

RESULTS: …

Cryptosporidium Infection Of Human Small Intestinal Epithelial Cells Induces Type Iii Interferon And Impairs Infectivity Of Rotavirus, Valentin Greigert, Iti Saraav, Juhee Son, Yinxing Zhu, Denise Dayao, Avan Antia, Saul Tzipori, William H Witola, Thaddeus S Stappenbeck, Siyuan Ding, L David Sibley

2020-Current year OA Pubs

Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen

The Type Ii Raf Inhibitor Tovorafenib In Relapsed/Refractory Pediatric Low-Grade Glioma: The Phase 2 Firefly-1 Trial, Lindsay B Kilburn, Mohamed S Abdelbaki, Et Al.

2020-Current year OA Pubs

BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system-penetrant, type II RAF inhibitor tovorafenib (420 mg m

Biology Of Childhood Hepatoblastoma And The Search For Novel Treatments, Marjut Pihlajoki, Katja Eloranta, Ruth Nousiainen, Ville Väyrynen, Tea Soini, Antti Kyrönlahti, Seppo Parkkila, Jukka Kanerva, David B. Wilson, Mikko P. Pakarinen, Markku Heikinheimo

2020-Current year OA Pubs

No abstract provided.

Bioactive Glycans In A Microbiome-Directed Food For Children With Malnutrition, Matthew C Hibberd, Daniel M Webber, Suzanne Henrissat, Robert Y Chen, Cyrus Zhou, Hannah M Lynn, Yi Wang, Hao-Wei Chang, Evan M Lee, Janaki Lelwala-Guruge, Ye Chen, Ishita Mostafa, Subhasish Das, Mustafa Mahfuz, Michael J Barratt, Tahmeed Ahmed, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition

Sirtuin3 Ensures The Metabolic Plasticity Of Neurotransmission During Glucose Deprivation, Anupama Tiwari, Arsalan Hashemiaghdam, Marissa A Laramie, Dario Maschi, Tristaan Haddad, Marion I Stunault, Carmen Bergom, Ali Javaheri, Vitaly Klyachko, Ghazaleh Ashrafi

2020-Current year OA Pubs

Neurotransmission is an energetically expensive process that underlies cognition. During intense electrical activity or dietary restrictions, the glucose level in the brain plummets, forcing neurons to utilize alternative fuels. However, the molecular mechanisms of neuronal metabolic plasticity remain poorly understood. Here, we demonstrate that glucose-deprived neurons activate the CREB and PGC1α transcriptional program, which induces expression of the mitochondrial deacetylase Sirtuin 3 (Sirt3) both in vitro and in vivo. We show that Sirt3 localizes to axonal mitochondria and stimulates mitochondrial oxidative capacity in hippocampal nerve terminals. Sirt3 plays an essential role in sustaining synaptic transmission in the absence of glucose …

Pectoral Muscle Removal In Mammogram Images: A Novel Approach For Improved Accuracy And Efficiency, Simin Chen, Debbie L Bennett, Graham A Colditz, Shu Jiang

2020-Current year OA Pubs

PURPOSE: Accurate pectoral muscle removal is critical in mammographic breast density estimation and many other computer-aided algorithms. We propose a novel approach to remove pectoral muscles form mediolateral oblique (MLO) view mammograms and compare accuracy and computational efficiency with existing method (Libra).

METHODS: A pectoral muscle identification pipeline was developed. The image is first binarized to enhance contrast and then the Canny algorithm was applied for edge detection. Robust interpolation is used to smooth out the pectoral muscle region. Accuracy and computational speed of pectoral muscle identification was assessed using 951 women (1,902 MLO mammograms) from the Joanne Knight Breast …

Perspectives From Public Health Practitioners And Advocates On Community Development For Active Living: What Are The Lasting Impacts?, Natalicio Serrano, Laurel Schmidt, Amy A Eyler, Ross C Brownson

2020-Current year OA Pubs

PURPOSE: Evidence suggests differential impacts of community development, including gentrification and displacement. Public health practitioners and advocates are key stakeholders involved in the community development process related to active living, yet little is known about their perceptions of its impacts. We explored the perspectives of relevant leaders of public health departments and key community and advocacy organizations on community development, gentrification, and displacement.

APPROACH: Purposive key informant interviews.

SETTING: CDC State Physical Activity and Nutrition (SPAN) funding recipients.

PARTICIPANTS: CDC SPAN recipient leadership (n = 10 of 16) and advocacy organizations they partnered with (n = 7 of 16).

METHOD: …

Sc2menetdrug: A Computational Tool To Uncover Inter-Cell Signaling Targets And Identify Relevant Drugs Based On Single Cell Rna-Seq Data, Jiarui Feng, S. Peter Goedegebuure, Amanda Zeng, Ye Bi, Ting Wang, Philip Payne, Li Ding, David Denardo, William Hawkins, Ryan C. Fields, Fuhai Li

2020-Current year OA Pubs

Single-cell RNA sequencing (scRNA-seq) is a powerful technology to investigate the transcriptional programs in stromal, immune, and disease cells, like tumor cells or neurons within the Alzheimer's Disease (AD) brain or tumor microenvironment (ME) or niche. Cell-cell communications within ME play important roles in disease progression and immunotherapy response and are novel and critical therapeutic targets. Though many tools of scRNA-seq analysis have been developed to investigate the heterogeneity and sub-populations of cells, few were designed for uncovering cell-cell communications of ME and predicting the potentially effective drugs to inhibit the communications. Moreover, the data analysis processes of discovering signaling …

Efficacy And Health-Related Quality Of Life Impact Of Fecal Microbiota, Live-Jslm: A Post Hoc Analysis Of Punch Cd3 Patients At First Recurrence Of Clostridioides Difficile Infection, Paul Feuerstadt, Jessica R Allegretti, Erik R Dubberke, Amy Guo, Adam Harvey, Min Yang, Viviana Garcia-Horton, Mirko Fillbrunn, Glenn Tillotson, Lindy L Bancke, Kerry Laplante, Kevin W Garey, Sahil Khanna

2020-Current year OA Pubs

INTRODUCTION: Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase 3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3.

METHODS: This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea …

Cep120 Is Essential For Kidney Stromal Progenitor Cell Growth And Differentiation, Ewa Langner, Tao Cheng, Eirini Kefaloyianni, Charles Gluck, Baolin Wang, Moe R Mahjoub

2020-Current year OA Pubs

Mutations in genes that disrupt centrosome structure or function can cause congenital kidney developmental defects and lead to fibrocystic pathologies. Yet, it is unclear how defective centrosome biogenesis impacts renal progenitor cell physiology. Here, we examined the consequences of impaired centrosome duplication on kidney stromal progenitor cell growth, differentiation, and fate. Conditional deletion of the ciliopathy gene Cep120, which is essential for centrosome duplication, in the stromal mesenchyme resulted in reduced abundance of interstitial lineages including pericytes, fibroblasts and mesangial cells. These phenotypes were caused by a combination of delayed mitosis, activation of the mitotic surveillance pathway leading to apoptosis, …

Non-Invasive Auricular Vagus Nerve Stimulation For Subarachnoid Hemorrhage (Navsah): Protocol For A Prospective, Triple-Blinded, Randomized Controlled Trial, Anna Huguenard, Gansheng Tan, Gabrielle Johnson, Markus Adamek, Andrew Coxon, Terrance Kummer, Joshua Osbun, Ananth Vellimana, David Limbrick, Gregory Zipfel, Peter Brunner, Eric Leuthardt

2020-Current year OA Pubs

BACKGROUND: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive …

Characterization And Individual-Level Prediction Of Cognitive State In The First Year After 'Mild' Stroke, Juan Pablo Saa, Tamara Tse, Gerald Choon-Huat Koh, Philip Yap, Carolyn M. Baum, David E. Uribe-Rivera, Saras M. Windecker, Henry Ma, Stephen M. Davis, Geoffrey A. Donnan, Leeanne M. Carey

2020-Current year OA Pubs

BACKGROUND: Mild stroke affects more than half the stroke population, yet there is limited evidence characterizing cognition over time in this population, especially with predictive approaches applicable at the individual-level. We aimed to identify patterns of recovery and the best combination of demographic, clinical, and lifestyle factors predicting individual-level cognitive state at 3- and 12-months after mild stroke.

METHODS: In this prospective cohort study, the Montreal Cognitive Assessment (MoCA) was administered at 3-7 days, 3- and 12-months post-stroke. Raw changes in MoCA and impairment rates (defined as MoCA<24 points) were compared between assessment time-points. Trajectory clusters were identified using variations of ≥1 point in MoCA scores. To further compare clusters, additional assessments administered at 3- and 12-months were included. Gamma and Quantile mixed-effects regression were used to predict individual MoCA scores over time, using baseline clinical and demographic variables. Model predictions were fitted for each stroke survivor and evaluated using model cross-validation to identify the overall best predictors of cognitive recovery.

RESULTS: Participants' (n = 119) MoCA scores improved from baseline to 3-months …

A Novel Crispr/Cas9-Mediated Mouse Model Of Colon Carcinogenesis, Hajime Kashima, Anthony Fischer, Daniel A Veronese-Paniagua, Vered A Gazit, Changqing Ma, Yan Yan, Marc S Levin, Blair B Madison, Deborah C Rubin

2020-Current year OA Pubs

BACKGROUND & AIMS: Human sporadic colorectal cancer (CRC) results from a multistep pathway with sequential acquisition of specific genetic mutations in the colorectal epithelium. Modeling CRC in vivo is critical for understanding the tumor microenvironment. To accurately recapitulate human CRC pathogenesis, mouse models must include these multi-step genetic abnormalities. The aim of this study was to generate a sporadic CRC model that more closely mimics this multi-step process and to use this model to study the role of a novel Let7 target PLAGL2 in CRC pathogenesis.

METHODS: We generated a CRISPR/Cas9 somatic mutagenesis mouse model that is inducible and multiplexed …

Evolution Of Proton Radiation Therapy Brainstem Constraints On The Pediatric Proton/Photon Consortium Registry, Dora Correia, Stephanie M Perkins, Et Al.

2020-Current year OA Pubs

PURPOSE: Increasing concern that brainstem toxicity incidence after proton radiation therapy might be higher than with photons led to a 2014 University of Florida (UF) landmark paper identifying its risk factors and proposing more conservative dose constraints. We evaluated how practice patterns changed among the Pediatric Proton/Photon Consortium Registry (PPCR).

MATERIAL AND METHODS: This prospective multicenter cohort study gathered data from patients under the age of 22 years enrolled on the PPCR, treated between 2002 and 2019 for primary posterior fossa brain tumors. After standardizing brainstem contours, we garnered dosimetry data and correlated those meeting the 2014 proton-specific brainstem constraint …

The Forkhead Transcription Factor Foxj1 Controls Vertebrate Olfactory Cilia Biogenesis And Sensory Neuron Differentiation, Dheeraj Rayamajhi, Steven L. Brody, Et Al.

2020-Current year OA Pubs

In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause anosmia, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a forkhead domain-containing transcription factor traditionally linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium (OE) formation. In keeping with the immotile nature of olfactory cilia, we observed that ciliary motility genes are repressed in zebrafish, mouse, and human OSNs. Strikingly, we also found that besides ciliogenesis, Foxj1 controls the …

Transcription Factor Interactions Explain The Context-Dependent Activity Of Crx Binding Sites, Kaiser J. Loell, Ryan Z. Friedman, Connie A. Myers, Joseph C. Corbo, Barak A. Cohen, Michael A. White

2020-Current year OA Pubs

The effects of transcription factor binding sites (TFBSs) on the activity of a cis-regulatory element (CRE) depend on the local sequence context. In rod photoreceptors, binding sites for the transcription factor (TF) Cone-rod homeobox (CRX) occur in both enhancers and silencers, but the sequence context that determines whether CRX binding sites contribute to activation or repression of transcription is not understood. To investigate the context-dependent activity of CRX sites, we fit neural network-based models to the activities of synthetic CREs composed of photoreceptor TFBSs. The models revealed that CRX binding sites consistently make positive, independent contributions to CRE activity, while …

Is Multidimensional Poverty Associated To Dementia Risk? The Case Of Older Adults In Pakistan, Jean-François Trani, Yiqi Zhu, Soobin Park, Ganesh M Babulal

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Multidimensional poverty is associated with dementia. We aimed at establishing this association in Pakistan.

RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted in Punjab and Sindh, Pakistan, between March 30, 2002, and August 22, 2022, among adults aged 50 and older. Multidimensional poverty measures were composed of 6 dimensions and 15 indicators. Poverty was compared between adults with and without dementia using the Rowland Universal Dementia Assessment Scale, adjusting for sex, age, marital status, and household size. Associations between dementia and poverty were investigated using a multivariate logistic regression model.

RESULTS: We found that 594 (72.7%), …

The Response Of Dual-Leucine Zipper Kinase (Dlk) To Nocodazole: Evidence For A Homeostatic Cytoskeletal Repair Mechanism, Laura Devault, Chase Mateusiak, John Palucki, Michael Brent, Jeffrey Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

Genetic and pharmacological perturbation of the cytoskeleton enhances the regenerative potential of neurons. This response requires Dual-leucine Zipper Kinase (DLK), a neuronal stress sensor that is a central regulator of axon regeneration and degeneration. The damage and repair aspects of this response are reminiscent of other cellular homeostatic systems, suggesting that a cytoskeletal homeostatic response exists. In this study, we propose a framework for understanding DLK mediated neuronal cytoskeletal homeostasis. We demonstrate that low dose nocodazole treatment activates DLK signaling. Activation of DLK signaling results in a DLK-dependent transcriptional signature, which we identify through RNA-seq. This signature includes genes likely …