Medicine and Health Sciences Commons^™

Handgrip Peak Force And Rate Of Force Development Measurements: Are They Reliable And Do They Correlate With Vertical Jump Power?, Pratibha S. Maurya, Kayla P. Sisneros, Evan Johnson, Ty B. Palmer

International Journal of Exercise Science: Conference Proceedings

Handgrip peak force and rate of force development (RFD) measurements have been shown to be effective parameters at characterizing the strength capacities of numerous muscle groups, including those of the lower extremities. However, the reliability of these measurements and their relationship with vertical jump (VJ) peak power remains uncertain. PURPOSE: The purpose of this study was to examine the reliability of handgrip peak force and RFD measurements. A secondary aim was to determine if these measurements are correlated with the peak power produced during a VJ test. METHODS: Twenty young, healthy women (age = 21 ± 3 years) …

Postprandial And Fasting Lipopolysaccharide Levels In Healthy Hispanic Residents Of Southeast Texas With Positive Family History Of Type 2 Diabetes, Amanda J. Wheeler, Yu Lun Tai, Smaran Marupudi, Ryan D. Russell

International Journal of Exercise Science: Conference Proceedings

PURPOSE: Healthy people with a family history (FH+) of type 2 diabetes (T2D) display impaired metabolic and microvascular function prior to glucose intolerance, and are at greater risk for developing T2D. While mechanisms to explain this disparity are lacking, it is possible that intestinal permeability plays a role, as it is also linked with insulin resistance, glucose intolerance, and chronic inflammation. Lipopolysaccharides (LPS) act as an outer membrane component of gram-negative bacteria in intestines and play a role in inflammation and chronic disease when in circulation, thus serving as a surrogate measure of intestinal permeability. However, the link between FH+ …

Morning Versus Afternoon Body Mass In Free-Living Or Controlled Euhydration, Madi M. Pomroy, Marcos Keefe, Nigel Jiwan, Jan-Joseph S. Rolloque, Casey Appell, Courteney L. Benjamin, Hui-Ying Luk, Yasuki Sekiguchi

International Journal of Exercise Science: Conference Proceedings

The standard protocol to assess hydration status is by measuring body mass in the early morning without controlling fluid intake. However, obtaining first-morning body mass is not necessarily feasible for many situations, for example, most physical activities take place in the afternoon. Thus, first-morning body mass might not be practical to assess hydration status. PURPOSE: To investigate first-morning body mass versus afternoon body mass in free- living and controlled euhydration. METHODS: 9 males (age: 21 ± 2; mass: 79.7 ± 17.8 kg) and 5 females (age: 22 ± 2; mass: 60.5 ± 13.6 kg) visited the laboratory in …

Effect Of Acute Exercise Mode On Test Anxiety: Aerobic Vs. Resistance, Natalie N. Trevino, Amber M. Shipherd, Christopher M. Hearon

International Journal of Exercise Science: Conference Proceedings

Test anxiety is a specific type of state anxiety when a person experiences perceived pressure to excel on a test. Test anxiety not only hinders test performance, but the person's long term psychophysiological health. Many students struggle with test anxiety, but females have a higher incidence of test anxiety than males. Bouts of aerobic exercise have been shown to decrease state anxiety, but no work has been done examining the effects of resistant training on state anxiety. PURPOSE: the purpose of this study was to compare the effects of acute aerobic and resistance exercise bouts on test anxiety among …

The Effects Of Acute Fasting On Anaerobic Performance In Naia Softball Players, Emily J. Sauers, Madison A. Garza, Jennifer M. Estrada

International Journal of Exercise Science: Conference Proceedings

Intermittent fasting has become a popular method for athletes to help manage body weight. Additionally, athletes with early morning athletic practice often omit breakfast and arrive in a fasted state. It is unclear how fasting impacts performance in softball players. PURPOSE: The purpose of this study was to evaluate anaerobic performance in NAIA Softball players following an overnight fast. METHODS: Eight NAIA female softball players participated in this randomized cross-over study. Athletes were on the active roster at Our Lady of the Lake University. Athletes were 20.7 ± 0.5 years old, 163.1 ± 2.1 cm tall, 151.5 ± 10.0 lb. …

Sacral Stress Fracture — Wrestling, Billal Siddiq, Nikolaos Gravvanis, Charalampos Kyratzoglou, Brett Hayes, Andreas Stamatis

International Journal of Exercise Science: Conference Proceedings

CASE HISTORY: During preseason, a 35-year-old wrestler complained of pain in his lower back concurrently with a tingling sensation in the left thigh and buttocks. PHYSICAL EXAM: The wrestler was examined by a physical therapist (PT) and, while discussing prior medical history, the athlete mentioned a previous diagnosis of a mild herniated disk (Grade 1). Upon clinical examination, the athlete demonstrated a full range of motion with some discomfort in passive hip extension. The PT suggested rest and rehabilitation through electrical stimulation, alongside the strengthening of the lumbar spine and hip abductor muscles. Ten days later, the athlete …

Sublingual Caffeine Supplementation And Its Effects On Physical Performance Measures In Highly Fit United States Military Personnel, Reggie B. O'Hara

International Journal of Exercise Science: Conference Proceedings

Caffeine is a commonly used countermeasure to combat sleep deprivation and alleviate physiological and psychological performance degradations in highly trained military personnel operating in extreme environments for extending periods. Although the mechanisms of action of caffeine are well described in the literature, the ergogenic effects of caffeine are variable based on the individual’s nutritional status, sensitivity to caffeine, genetics, dose, timing, and overall physical condition. PURPOSE: To explore the effects of moderate doses of sublingual caffeine on physical performance measures and perceptions of fatigue in highly fit U.S. military personnel. METHODS: A convenience sample of eleven highly trained, …

Medical School Watercooler Newsletter - February 17, 2023, Lindsey Lyle

Watercooler Newsletter

This is the February 17, 2023 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents include:

• Inabnet to present Fazier / Leigh Memorial Lectures
• Faculty development to focus on conflict resolution
• Teaching kitchen provides hands-on culinary medicine experience for medical students
• Menger invited to present at international symposium
• Pierce presents talk on HPV, cervical cancer
• Solidarity Bingo winners announced for solidarity week
• Save the date: USA Neuroscience Symposium
• Distinguished Scientists seminar set for Feb. 16
• USA researchers uncover novel mechanism that supports survival of pancreatic cancel cells

2023-02-17 Michiganoverview_Covidbedppe, Michigan Department Of Health & Human Services

Michigan COVID-19 Hospital Data

Contains the tables Statewide Hospital Capacity Report for COVID-19, COVID-19 Metrics, Statewide Hospital Available PPE Tracking for COVID-19, as well as the tables PPE Days On Hand and Patient Census.

The Santa Clara, 2023-02-17, Santa Clara University

The Santa Clara

No abstract provided.

A Scoping Review Of Transgender Policies In The 15 Most Commonly Played Uk Professional Sports., Michael Mclarnon, Jane Thornton, Gail Knudson, Nigel Jones, Danny Glover, Andrew Murray, Michael Cummings, Neil Heron

Family Medicine Publications

INTRODUCTION: There has been much debate recently on the participation of transgender and gender-diverse (TGD) athletes in sport, particularly in relation to fairness, safety and inclusion. The 2021 IOC Framework on Fairness, Inclusion and Non-discrimination acknowledges the central role that eligibility criteria play in ensuring fairness, particularly in the female category, and states that athletes should not be excluded solely on the basis of their TGD identity.

AIMS: To identify policies that address TGD athlete participation in the 15 major United Kingdom (UK) sporting organisations and to summarise the evidence for each of these policies.

METHODS: A scoping review of …

Was Kaposi’S Sarcoma-Associated Herpesvirus Introduced Into China Via The Ancient Silk Road? An Evolutionary Perspective, Zhenqiu Liu, Qiwen Fang, Jialu Zuo, Veenu Minhas, Charles Wood, Na He, Tiejun Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) has become widely dispersed worldwide since it was first reported in 1994, but the seroprevalence of KSHV varies geographically. KSHV is relatively ubiquitous in Mediterranean areas and the Xinjiang Uygur Autonomous Region, China. The origin of KSHV has long been puzzling. In the present study, we collected and analysed 154 KSHV ORF-K1 sequences obtained from samples originating from Xinjiang, Italy, Greece, Iran and southern Siberia using Bayesian evolutionary analysis in BEAST to test the hypothesis that KSHV was introduced into Xinjiang via the ancient Silk Road. According to the phylogenetic analysis, 72 sequences were subtype A …

Transcatheter Aortic Valve Replacement-Associated Acute Kidney Injury: An Update, Frederick Berro Rivera, Abdullah Al-Abcha, Marie Francesca Mapua Ansay, John Vincent Usita Magalong, Vincent Anthony Songheng Tang, Hannah May Ona, Karissa Alyanna Miralles, Rausche Sausa, Rodie Abram Florendo Uy, Edgar V. Lerma, Fareed Moses S. Collado, Peter A. Mccullough, Annabelle Santos Volgman

Ateneo School of Medicine and Public Health Publications

Background

Transcatheter aortic valve replacement (TAVR) is a relatively novel minimally invasive procedure for the treatment of symptomatic patients with severe aortic stenosis. Although it has been proven effective in improving mortality and quality of life, TAVR is associated with serious complications, such as acute kidney injury (AKI).

Summary

TAVR-associated AKI is likely due to several factors such as sustained hypotension, transapical approach, volume of contrast use, and baseline low GFR. This narrative review aims to present an overview of the latest literature and evidence regarding the definition of TAVR-associated AKI, its risk factors, and its impact on morbidity and …

Conditioned Place Avoidance Is Associated With A Distinct Hippocampal Phenotype, Partly Preserved Pattern Separation, And Reduced Reactive Oxygen Species Production After Stress, D. Parker Kelley, Lucas Albrechet-Souza, Shealan Cruise, Rajani Maiya, Aspasia Destouni, Siva S.V.P. Sakamuri, Alexander Duplooy, Meghan Hibicke, Charles Nichols, Prasad V.G. Katakam, Nicholas W. Gilpin, Joseph Francis

School of Medicine Faculty Publications

Stress is associated with contextual memory deficits, which may mediate avoidance of trauma-associated contexts in posttraumatic stress disorder. These deficits may emerge from impaired pattern separation, the independent representation of similar experiences by the dentate gyrus-Cornu Ammonis 3 (DG-CA3) circuit of the dorsal hippocampus, which allows for appropriate behavioral responses to specific environmental stimuli. Neurogenesis in the DG is controlled by mitochondrial reactive oxygen species (ROS) production, and may contribute to pattern separation. In Experiment 1, we performed RNA sequencing of the dorsal hippocampus 16 days after stress in rats that either develop conditioned place avoidance to a predator urine-associated …

Antiangiogenic Drugs In Combination With Seaweed Fucoidan: A Mechanistic In Vitro And In Vivo Study Exploring The Vegf Receptor And Its Downstream Signaling Molecules In Hepatic Cancer, Maha R.A. Abdollah, Aya A. Ali, Hassnaa Hamed Elgohary, M. M. Elmazar

Pharmacy

Hepatocellular carcinoma (HCC) is one of the most common cancers reported worldwide with poor morbidity and high mortality rates. HCC is a very vascular solid tumour as angiogenesis is not only a key driver for tumour progression but also an exciting therapeutic target. Our research investigated the use of fucoidan, a sulfated polysaccharide readily abundant in edible seaweeds commonly consumed in Asian diet due to their extensive health benefits. Fucoidan was reported to possess a strong anti-cancer activity, but its anti-angiogenic potential is still to be fully unraveled. Our research investigated fucoidan in combination with sorafenib (an anti-VEGFR tyrosine kinase …

Disseminated Juvenile Xanthogranuloma With A Novel Myh9-Flt3 Fusion Presenting As A Blueberry Muffin Rash In A Neonate., Emily E. Clark, Mollie Walton, Lionel M L Chow, J Todd Boyd, M David Yohannan, Shreyas Arya

Manuscripts, Articles, Book Chapters and Other Papers

Juvenile xanthogranuloma (JXG) is a benign proliferative histiocytic disorder of the dendritic cell phenotype. It mostly presents in the pediatric age group as a solitary skin lesion. We describe a rare case of an infant born with disseminated JXG who presented with a blueberry muffin rash at birth. A term infant was noted to have multiple petechiae, purple nodules, and macules (1 mm-2 cm in diameter) and hepatosplenomegaly, at the time of birth. Further investigations revealed thrombocytopenia and direct hyperbilirubinemia and a magnetic resonance imaging showed scattered tiny foci of restricted diffusion in multiple areas of the brain. Patient received …

Examination Of Geriatric Care Processes Implemented In Level 1 And Level 2 Geriatric Emergency Departments, Ilianna Santangelo, Surriya Ahmad, Shan Liu, Lauren Southerland, Christopher Carpenter, Ula Hwang, Adriane Lesser, Nicole Tidwell, Kevin Biese, Maura Kennedy

Journal of Geriatric Emergency Medicine

Background: Older adults constitute a large and growing proportion of the population and have unique care needs in the emergency department (ED) setting. The geriatric ED accreditation program aims to improve emergency care provided to older adults by standardizing care provided across accredited geriatric EDs (GED) and through implementation of geriatric-specific care processes.

Objective: The purpose of this study was to evaluate select care processes at accredited level 1 and level 2 GEDs.

Methods: This was a cross-sectional analysis of a cohort of level 1 and level 2 GEDs that received accreditation between May 7, 2018 and …

Adjuvant Chemotherapy Versus Adjuvant Concurrent Chemoradiotherapy After Radical Surgery For Early-Stage Cervical Cancer: A Randomized, Non-Inferiority, Multicenter Trial, Danhui Weng, Huihua Xiong, Changkun Zhu, Xiaoyun Wan, Yaxia Chen, Xinyu Wang, Youzhong Zhang, Jie Jiang, Xi Zhang, Qinglei Gao, Gang Chen, Hui Xing, Changyu Wang, Kezhen Li, Yaheng Chen, Yuyan Mao, Dongxiao Hu, Zimin Pan, Qingqin Chen, Baoxia Cui, Kun Song, Cunjian Yi, Guangcai Peng, Xiaobing Han, Ruifang An, Liangsheng Fan, Wei Wang, Tingchuan Xiong, Yile Chen, Zhenzi Tang, Lin Li, Xingsheng Yang, Xiaodong Cheng, Weiguo Lu, Hui Wang, Beihua Kong, Xing Xie, Ding Ma

Faculty, Staff and Student Publications

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant …

Cd5 Expression By Dendritic Cells Directs T Cell Immunity And Sustains Immunotherapy Responses, Mingyu He, Kate Roussak, Feiyang Ma, Nicholas Borcherding, Vince Garin, Mike White, Charles Schutt, Trine I Jensen, Yun Zhao, Courtney A Iberg, Kairav Shah, Himanshi Bhatia, Daniel Korenfeld, Sabrina Dinkel, Judah Gray, Alina Ulezko Antonova, Stephen Ferris, David Donermeyer, Cecilia Lindestam Arlehamn, Matthew M Gubin, Jingqin Luo, Laurent Gorvel, Matteo Pellegrini, Alessandro Sette, Thomas Tung, Rasmus Bak, Robert L Modlin, Ryan C Fields, Robert D Schreiber, Paul M Allen, Eynav Klechevsky

Faculty, Staff and Student Publications

The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c+CD5+ DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5+ DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T …

Sakurabonsai: Protocol Design Of A Novel, Prospective Study To Explore Clinical, Imaging, And Biomarker Outcomes In Patients With Aqp4-Igg-Seropositive Neuromyelitis Optica Spectrum Disorder Receiving Open-Label Satralizumab, Jeffrey L Bennett, Kazuo Fujihara, Ho Jin Kim, Romain Marignier, Kevin C O'Connor, Robert C Sergott, Anthony Traboulsee, Heinz Wiendl, Jens Wuerfel, Scott S Zamvil, Veronica G Anania, Regine Buffels, Thomas Künzel, Annemarie N Lekkerkerker, Siân Lennon-Chrimes, Sean J Pittock

Wills Eye Hospital Papers

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that produces acute, unpredictable relapses causing cumulative neurological disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced NMOSD relapse risk vs. placebo in two Phase 3 trials: SAkuraSky (satralizumab ± immunosuppressive therapy; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279). Satralizumab is approved to treat aquaporin-4 IgG-seropositive (AQP4-IgG+) NMOSD. SAkuraBONSAI (NCT05269667) will explore fluid and imaging biomarkers to better understand the mechanism of action of satralizumab and the neuronal and immunological changes following treatment in AQP4-IgG+ NMOSD.

Objectives: …

Tracking The Evolution Of Esophageal Squamous Cell Carcinoma Under Dynamic Immune Selection By Multi-Omics Sequencing, Sijia Cui, Nicholas Mcgranahan, Jing Gao, Peng Chen, Wei Jiang, Lingrong Yang, Li Ma, Junfang Liao, Tian Xie, Congying Xie, Tariq Enver, Shixiu Wu

Children’s Nutrition Research Center Staff Publications

Intratumoral heterogeneity (ITH) has been linked to decreased efficacy of clinical treatments. However, although genomic ITH has been characterized in genetic, transcriptomic and epigenetic alterations are hallmarks of esophageal squamous cell carcinoma (ESCC), the extent to which these are heterogeneous in ESCC has not been explored in a unified framework. Further, the extent to which tumor-infiltrated T lymphocytes are directed against cancer cells, but how the immune infiltration acts as a selective force to shape the clonal evolution of ESCC is unclear. In this study, we perform multi-omic sequencing on 186 samples from 36 primary ESCC patients. Through multi-omics analyses, …

Exploiting Prmt5 As A Target For Combination Therapy In Mantle Cell Lymphoma Characterized By Frequent Atm And Tp53 Mutations, Yuxuan Che, Yang Liu, Yixin Yao, Holly A Hill, Yijing Li, Qingsong Cai, Fangfang Yan, Preetesh Jain, Wei Wang, Lixin Rui, Michael Wang

Faculty, Staff and Student Publications

Constant challenges for the treatment of mantle cell lymphoma (MCL) remain to be recurrent relapses and therapy resistance, especially in patients harboring somatic mutations in the tumor suppressors ATM and TP53, which are accumulated as therapy resistance emerges and the disease progresses, consistent with our OncoPrint results that ATM and TP53 alterations were most frequent in relapsed/refractory (R/R) MCL. We demonstrated that protein arginine methyltransferase-5 (PRMT5) was upregulated in R/R MCL, which predicted a poor prognosis. PRMT5 inhibitors displayed profound antitumor effects in the mouse models of MCL with mutated ATM and/or TP53, or refractory to CD19-targeted CAR T-cell therapy. …

Drug-Like Small Molecules That Inhibit Expression Of The Oncogenic Microrna-21, Matthew D Shortridge, Bhawna Chaubey, Huanyu J Zhang, Thomas Pavelitz, Venkata Vidadala, Changyan Tang, Gregory L Olsen, George A Calin, Gabriele Varani

Faculty, Staff and Student Publications

We report the discovery of drug-like small molecules that bind specifically to the precursor of the oncogenic and pro-inflammatory microRNA-21 with mid-nanomolar affinity. The small molecules target a local structure at the Dicer cleavage site and induce distinctive structural changes in the RNA, which correlate with specific inhibition of miRNA processing. Structurally conservative single nucleotide substitutions eliminate the conformational change induced by the small molecules, which is also not observed in other miRNA precursors. The most potent of these compounds reduces cellular proliferation and miR-21 levels in cancer cell lines without inhibiting kinases or classical receptors, while closely related compounds …

The Gut Microbiota Of People With Asthma Influences Lung Inflammation In Gnotobiotic Mice, Naomi G Wilson, Ariel Hernandez-Leyva, Anne L Rosen, Natalia Jaeger, Ryan T Mcdonough, Jesus Santiago-Borges, Michael A Lint, Thomas R Rosen, Christopher P Tomera, Leonard B Bacharier, S Joshua Swamidass, Andrew L Kau

2020-Current year OA Pubs

The gut microbiota in early childhood is linked to asthma risk, but may continue to affect older patients with asthma. Here, we profile the gut microbiota of 38 children (19 asthma, median age 8) and 57 adults (17 asthma, median age 28) by 16S rRNA sequencing and find individuals with asthma harbored compositional differences from healthy controls in both adults and children. We develop a model to aid the design of mechanistic experiments in gnotobiotic mice and show enterotoxigenic

Alternative Polyadenylation Alters Protein Dosage By Switching Between Intronic And 3’Utr Sites, Nicola De Prisco, Caitlin Ford, Nathan D Elrod, Winston Lee, Lauren C Tang, Kai-Lieh Huang, Ai Lin, Ping Ji, Venkata S Jonnakuti, Lia Boyle, Maximilian Cabaj, Salvatore Botta, Katrin Õunap, Karit Reinson, Monica H Wojcik, Jill A Rosenfeld, Weimin Bi, Kristian Tveten, Trine Prescott, Thorsten Gerstner, Audrey Schroeder, Chin-To Fong, Jaya K George-Abraham, Catherine A Buchanan, Andrea Hanson-Khan, Jonathan A Bernstein, Aikaterini A Nella, Wendy K Chung, Vicky Brandt, Marko Jovanovic, Kimara L Targoff, Hari Krishna Yalamanchili, Eric J Wagner, Vincenzo A Gennarino

Faculty, Staff and Students Publications

Alternative polyadenylation (APA) creates distinct transcripts from the same gene by cleaving the pre-mRNA at poly(A) sites that can lie within the 3' untranslated region (3'UTR), introns, or exons. Most studies focus on APA within the 3'UTR; however, here, we show that CPSF6 insufficiency alters protein levels and causes a developmental syndrome by deregulating APA throughout the transcript. In neonatal humans and zebrafish larvae, CPSF6 insufficiency shifts poly(A) site usage between the 3'UTR and internal sites in a pathway-specific manner. Genes associated with neuronal function undergo mostly intronic APA, reducing their expression, while genes associated with heart and skeletal function …

Batf2 Promotes Hsc Myeloid Differentiation By Amplifying Ifn Response Mediators During Chronic Infection, Duy T Le, Marcus A Florez, Pawel Kus, Brandon T Tran, Bailee Kain, Yingmin Zhu, Kurt Christensen, Antrix Jain, Anna Malovannaya, Katherine Y King

Faculty, Staff and Students Publications

Basic leucine zipper ATF-like transcription factor 2 (BATF2), an interferon-activated immune response regulator, is a key factor responsible for myeloid differentiation and depletion of HSC during chronic infection. To delineate the mechanism of BATF2 function in HSCs, we assessed Batf2 KO mice during chronic infection and found that they produced less pro-inflammatory cytokines, less immune cell recruitment to the spleen, and impaired myeloid differentiation with better preservation of HSC capacity compared to WT. Co-IP analysis revealed that BATF2 forms a complex with JUN to amplify pro-inflammatory signaling pathways including CCL5 during infection. Blockade of CCL5 receptors phenocopied Batf2 KO differentiation …

Transcriptome, Proteome, And Protein Synthesis Within The Intracellular Cytomatrix, Tattym E Shaiken, Sandra L Grimm, Mohamad Siam, Amanda Williams, Abdol-Hossein Rezaeian, Daniel Kraushaar, Emily Ricco, Matthew J Robertson, Cristian Coarfa, Antrix Jain, Anna Malovannaya, Fabio Stossi, Antone R Opekun, Alyssa P Price, Julien Dubrulle

Faculty, Staff and Students Publications

Despite the knowledge that protein translation and various metabolic reactions that create and sustain cellular life occur in the cytoplasm, the structural organization within the cytoplasm remains unclear. Recent models indicate that cytoplasm contains viscous fluid and elastic solid phases. We separated these viscous fluid and solid elastic compartments, which we call the cytosol and cytomatrix, respectively. The distinctive composition of the cytomatrix included structural proteins, ribosomes, and metabolome enzymes. High-throughput analysis revealed unique biosynthetic pathways within the cytomatrix. Enrichment of biosynthetic pathways in the cytomatrix indicated the presence of immobilized biocatalysis. Enzymatic immobilization and segregation can surmount spatial impediments, …

Deepbend: An Interpretable Model Of Dna Bendability, Samin Rahman Khan, Sadman Sakib, M Sohel Rahman, Md Abul Hassan Samee

Faculty, Staff and Students Publications

The bendability of genomic DNA impacts chromatin packaging and protein-DNA binding. However, we do not have a comprehensive understanding of the motifs influencing DNA bendability. Recent high-throughput technologies such as Loop-Seq offer an opportunity to address this gap but the lack of accurate and interpretable machine learning models still remains. Here we introduce DeepBend, a convolutional neural network model with convolutions designed to directly capture the motifs underlying DNA bendability and their periodic occurrences or relative arrangements that modulate bendability. DeepBend consistently performs on par with alternative models while giving an extra edge through mechanistic interpretations. Besides confirming the known …

Exploiting Metabolic Vulnerabilities After Anti-Vegf Antibody Therapy In Ovarian Cancer, Deanna Glassman, Mark S Kim, Meredith Spradlin, Sunil Badal, Mana Taki, Pratip Bhattacharya, Prasanta Dutta, Charles V Kingsley, Katherine I Foster, Olamide Animasahun, Jin Heon Jeon, Abhinav Achreja, Anusha Jayaraman, Praveen Kumar, Minal Nenwani, Fulei Wuchu, Emine Bayraktar, Yutuan Wu, Elaine Stur, Lingegowda Mangala, Sanghoon Lee, Timothy A Yap, Shannon N Westin, Livia S Eberlin, Deepak Nagrath, Anil K Sood

Faculty, Staff and Student Publications

Despite modest clinical improvement with anti-vascular endothelial growth factor antibody (AVA) therapy in ovarian cancer, adaptive resistance is ubiquitous and additional options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance and we aimed to investigate the utility of a GLS inhibitor (GLSi). Our in vitro findings demonstrated increased glutamine abundance and a significant cytotoxic effect in AVA-resistant tumors when GLSi was administered in combination with bevacizumab. In vivo, GLSi led to a reduction in tumor growth as monotherapy and when combined with AVA. Furthermore, GLSi initiated after the emergence …

Endothelial-To-Osteoblast Transition In Normal Mouse Bone Development, Song-Chang Lin, Guoyu Yu, Yu-Chen Lee, Jian H Song, Xingzhi Song, Jianhua Zhang, Theocharis Panaretakis, Christopher J Logothetis, Yoshihiro Komatsu, Li-Yuan Yu-Lee, Guocan Wang, Sue-Hwa Lin

Faculty, Staff and Student Publications

Metastatic prostate cancer (PCa) in bone induces bone-forming lesions. We have previously shown that PCa-induced bone originates from endothelial cells (ECs) that have undergone EC-to-osteoblast (OSB) transition. Here, we investigated whether EC-to-OSB transition also occurs during normal bone formation. We developed an EC and OSB dual-color reporter mouse (DRM) model that marks EC-OSB hybrid cells with red and green fluorescent proteins. We observed EC-to-OSB transition (RFP and GFP co-expression) in both endochondral and intramembranous bone formation during embryonic development and in adults. Co-expression was confirmed in cells isolated from DRM. Bone marrow– and lung-derived ECs underwent transition to OSBs and …