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Post-Acute Sequelae Of Covid-19 (Pasc): Association With Inflammation And Autoimmunity, Raghava S. Ambadapoodi, Fnu Deepti, Javaria Anwer Mbbs, Rafael Fernandez-Botran Jul 2021

Post-Acute Sequelae Of Covid-19 (Pasc): Association With Inflammation And Autoimmunity, Raghava S. Ambadapoodi, Fnu Deepti, Javaria Anwer Mbbs, Rafael Fernandez-Botran

The University of Louisville Journal of Respiratory Infections

It has become increasingly evident that a high percentage of patients that recover from acute COVID-19 infection continue to suffer from a variety of persistent symptoms even months after viral clearance, the most common ones being fatigue, dyspnea, anosmia, dysgeusia, cognitive dysfunction, and psychological problems, including anxiety and depression. This syndrome, known as Post-acute sequelae of COVID-19 (PASC), can severely affect the life quality and represents an important health care concern. The exact causes for the symptoms observed in patients with PASC remain to be adequately characterized, but are likely to be associated with multiple factors, including residual disease and/or …


Chloride Sensing By Wnk1 Regulates Nlrp3 Inflammasome Activation And Pyroptosis., Lindsey Mayes-Hopfinger, Aura Enache, Jian Xie, Chou-Long Huang, Robert Köchl, Victor L.J. Tybulewicz, Teresa Fernandes-Alnemri, Emad S. Alnemri Jul 2021

Chloride Sensing By Wnk1 Regulates Nlrp3 Inflammasome Activation And Pyroptosis., Lindsey Mayes-Hopfinger, Aura Enache, Jian Xie, Chou-Long Huang, Robert Köchl, Victor L.J. Tybulewicz, Teresa Fernandes-Alnemri, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

The NLRP3 inflammasome mediates the production of proinflammatory cytokines and initiates inflammatory cell death. Although NLRP3 is essential for innate immunity, aberrant NLRP3 inflammasome activation contributes to a wide variety of inflammatory diseases. Understanding the pathways that control NLRP3 activation will help develop strategies to treat these diseases. Here we identify WNK1 as a negative regulator of the NLRP3 inflammasome. Macrophages deficient in WNK1 protein or kinase activity have increased NLRP3 activation and pyroptosis compared with control macrophages. Mice with conditional knockout of WNK1 in macrophages have increased IL-1β production in response to NLRP3 stimulation compared with control mice. Mechanistically, …


Dna Polymerase Θ: A Cancer Drug Target With Reverse Transcriptase Activity, Xiaojiang Chen, Richard T. Pomerantz Jul 2021

Dna Polymerase Θ: A Cancer Drug Target With Reverse Transcriptase Activity, Xiaojiang Chen, Richard T. Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

The emergence of precision medicine from the development of Poly (ADP‐ribose) polymerase (PARP) inhibitors that preferentially kill cells defective in homologous recombination has sparked wide interest in identifying and characterizing additional DNA repair enzymes that are synthetic lethal with HR factors. DNA polymerase theta (Polθ) is a validated anti‐cancer drug target that is synthetic lethal with HR factors and other DNA repair proteins and confers cellular resistance to various genotoxic cancer therapies. Since its initial characterization as a helicase‐polymerase fusion protein in 2003, many exciting and unexpected activities of Polθ in microhomology‐mediated end‐joining (MMEJ) and translesion synthesis (TLS) have been …


Bcr Affinity Influences T-B Interactions And B Cell Development In Secondary Lymphoid Organs, Alec J. Wishnie, Tzippora Chwat-Edelstein, Mary Attaway, Bao Q. Vuong Jul 2021

Bcr Affinity Influences T-B Interactions And B Cell Development In Secondary Lymphoid Organs, Alec J. Wishnie, Tzippora Chwat-Edelstein, Mary Attaway, Bao Q. Vuong

Publications and Research

B cells produce high-affinity immunoglobulins (Igs), or antibodies, to eliminate foreign pathogens. Mature, naïve B cells expressing an antigen-specific cell surface Ig, or B cell receptor (BCR), are directed toward either an extrafollicular (EF) or germinal center (GC) response upon antigen binding. B cell interactions with CD4+ pre-T follicular helper (pre- Tfh) cells at the T-B border and effector Tfh cells in the B cell follicle and GC control B cell development in response to antigen. Here, we review recent studies demonstrating the role of B cell receptor (BCR) affinity in modulating T-B interactions and the subsequent differentiation of B …


Potential Benefits Of Bovine Colostrum In Pediatric Nutrition And Health, Per Torp Sangild, Caitlin Vonderohe, Valeria Melendez Hebib, Douglas G Burrin Jul 2021

Potential Benefits Of Bovine Colostrum In Pediatric Nutrition And Health, Per Torp Sangild, Caitlin Vonderohe, Valeria Melendez Hebib, Douglas G Burrin

Children’s Nutrition Research Center Staff Publications

Bovine colostrum (BC), the first milk produced from cows after parturition, is increasingly used as a nutritional supplement to promote gut function and health in other species, including humans. The high levels of whey and casein proteins, immunoglobulins (Igs), and other milk bioactives in BC are adapted to meet the needs of newborn calves. However, BC supplementation may improve health outcomes across other species, especially when immune and gut functions are immature in early life. We provide a review of BC composition and its effects in infants and children in health and selected diseases (diarrhea, infection, growth-failure, preterm birth, necrotizing …


Triple Negative Breast Cancer In An Appalachian Region: Exponential Tumor Grade Increase With Age Of Diagnosis, Gina Sizemore, Toni Marie Rudisill Jul 2021

Triple Negative Breast Cancer In An Appalachian Region: Exponential Tumor Grade Increase With Age Of Diagnosis, Gina Sizemore, Toni Marie Rudisill

Journal of Appalachian Health

Introduction: Triple negative breast cancer is an aggressive breast cancer with decreased five-year survival, increased risk for recurrence, and higher risk for metastases. Unlike other breast cancers, it has no targeted treatment and has heterogeneous genetics which make classification and treatment difficult.

Purpose: The purpose of our research was to compare triple negative breast cancer to non-triple negative breast cancer to identify key epidemiologic factors that might lead to improved basic science directives for biomarkers, treatments, and classification.

Methods: The state cancer registry was used to provide the first West Virginia state-wide population evaluation of triple negative breast cancer.

Results: …


Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino Jul 2021

Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino

Computational Medicine Center Faculty Papers

In animal germlines, PIWI proteins and the associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons. Here we report the extensive sequence and quantitative correlations between 2′,3′-cyclic phosphate-containing RNAs (cP-RNAs), identified using cP-RNA-seq, and piRNAs in the Bombyx germ cell line and mouse testes. The cP-RNAs containing 5′-phosphate (P-cP-RNAs) identified by P-cP-RNA-seq harbor highly consistent 5′-end positions as the piRNAs and are loaded onto PIWI protein, suggesting their direct utilization as piRNA precursors. We identified Bombyx RNase Kappa (BmRNase κ) as a mitochondria-associated endoribonuclease which produces cP-RNAs during piRNA biogenesis. BmRNase κ-depletion elevated transposon levels and disrupted a piRNA-mediated …


Characterization Of Hnrnpa1 Mutations Defines Diversity In Pathogenic Mechanisms And Clinical Presentation., Danique Beijer, Hong Joo Kim, Lin Guo, Kevin O'Donovan, Inès Mademan, Tine Deconinck, Kristof Van Schil, Charlotte M Fare, Lauren E Drake, Alice F Ford, Andrzej Kochański, Dagmara Kabzińska, Nicolas Dubuisson, Peter Van Den Bergh, Nicol C Voermans, Richard Jlf Lemmers, Silvère M Van Der Maarel, Devon Bonner, Jacinda B Sampson, Matthew T Wheeler, Anahit Mehrabyan, Steven Palmer, Peter De Jonghe, James Shorter, J Paul Taylor, Jonathan Baets Jul 2021

Characterization Of Hnrnpa1 Mutations Defines Diversity In Pathogenic Mechanisms And Clinical Presentation., Danique Beijer, Hong Joo Kim, Lin Guo, Kevin O'Donovan, Inès Mademan, Tine Deconinck, Kristof Van Schil, Charlotte M Fare, Lauren E Drake, Alice F Ford, Andrzej Kochański, Dagmara Kabzińska, Nicolas Dubuisson, Peter Van Den Bergh, Nicol C Voermans, Richard Jlf Lemmers, Silvère M Van Der Maarel, Devon Bonner, Jacinda B Sampson, Matthew T Wheeler, Anahit Mehrabyan, Steven Palmer, Peter De Jonghe, James Shorter, J Paul Taylor, Jonathan Baets

Department of Biochemistry and Molecular Biology Faculty Papers

Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP). hnRNPA1 is part of the group of RNA-binding proteins (RBPs) that assemble with RNA to form RNPs. hnRNPs are concentrated in the nucleus and function in pre-mRNA splicing, mRNA stability, and the regulation of transcription and translation. During stress, hnRNPs, mRNA, and other RBPs condense in the cytoplasm to form stress granules (SGs). SGs are implicated in the pathogenesis of (neuro-)degenerative diseases, including ALS and inclusion body myopathy (IBM). Mutations in RBPs that affect SG biology, including FUS, …


Structure And Function Of An Arabidopsis Thaliana Sulfate Transporter, Lie Wang, Kehan Chen, Ming Zhou Jul 2021

Structure And Function Of An Arabidopsis Thaliana Sulfate Transporter, Lie Wang, Kehan Chen, Ming Zhou

Faculty, Staff and Students Publications

Plant sulfate transporters (SULTR) mediate absorption and distribution of sulfate (SO42−) and are essential for plant growth; however, our understanding of their structures and functions remains inadequate. Here we present the structure of a SULTR from Arabidopsis thaliana, AtSULTR4;1, in complex with SO42− at an overall resolution of 2.8 Å. AtSULTR4;1 forms a homodimer and has a structural fold typical of the SLC26 family of anion transporters. The bound SO42− is coordinated by side-chain hydroxyls and backbone amides, and further stabilized electrostatically by the conserved Arg393 and two helix dipoles. Proton and SO42− are co-transported by AtSULTR4;1 and a …


Objective Physiological Measures Of Lingual And Jaw Function In Healthy Individuals And Individuals With Dysphagia Due To Neurodegenerative Diseases, Megan E. Cuellar, Elizabeth Oommen Jul 2021

Objective Physiological Measures Of Lingual And Jaw Function In Healthy Individuals And Individuals With Dysphagia Due To Neurodegenerative Diseases, Megan E. Cuellar, Elizabeth Oommen

Faculty Research, Scholarly, and Creative Activity

Swallowing is a neuromuscular process that involves a complex sequence of sensorimotor events, which are executed to efficiently and safely transport food and liquid from the mouth to the stomach. Safe oropharyngeal swallowing involves the activation, modulation, and coordination of oral, pharyngeal, laryngeal, and esophageal structures and musculature. Impaired or atypical patterns of swallowing are considered characteristic of a swallowing disorder, otherwise referred to as dysphagia, and affect the performance of all stages, i.e., oral preparatory, oral transit, pharyngeal, and esophageal. Lingual and jaw musculature play critical roles in mediating swallowing function, particularly during the oral preparatory and oral transit …


Week Of July 19, 2021, New York Medical College Jul 2021

Reducing Covid-19 Quarantine With Sars-Cov-2 Testing: A Simulation Study, Bo Peng, Wen Zhou, Rowland W Pettit, Patrick Yu, Peter G Matos, Alexander L Greninger, Julie Mccashin, Christopher I Amos Jul 2021

Reducing Covid-19 Quarantine With Sars-Cov-2 Testing: A Simulation Study, Bo Peng, Wen Zhou, Rowland W Pettit, Patrick Yu, Peter G Matos, Alexander L Greninger, Julie Mccashin, Christopher I Amos

Faculty, Staff and Students Publications

OBJECTIVE: To evaluate the effectiveness of SARS-CoV-2 testing on shortening the duration of quarantines for COVID-19 and to identify the most effective choices of testing schedules.

DESIGN: We performed extensive simulations to evaluate the performance of quarantine strategies when one or more SARS-CoV-2 tests were administered during the quarantine. Simulations were based on statistical models for the transmissibility and viral loads of SARS-CoV-2 infections and the sensitivities of available testing methods. Sensitivity analyses were performed to evaluate the impact of perturbations in model assumptions on the outcomes of optimal strategies.

RESULTS: We found that SARS-CoV-2 testing can effectively reduce the …


Cyclic Amp Is Dispensable For Allorecognition In Dictyostelium Cells Overexpressing Pka-C, Shigenori Hirose, Mariko Katoh-Kurasawa, Gad Shaulsky Jul 2021

Cyclic Amp Is Dispensable For Allorecognition In Dictyostelium Cells Overexpressing Pka-C, Shigenori Hirose, Mariko Katoh-Kurasawa, Gad Shaulsky

Faculty, Staff and Students Publications

Allorecognition and tissue formation are interconnected processes that require signaling between matching pairs of the polymorphic transmembrane proteins TgrB1 and TgrC1 in Dictyostelium. Extracellular and intracellular cAMP signaling are essential to many developmental processes. The three adenylate cyclase genes, acaA, acrA and acgA are required for aggregation, culmination and spore dormancy, respectively, and some of their functions can be suppressed by activation of the cAMP-dependent protein kinase PKA. Previous studies have suggested that cAMP signaling might be dispensable for allorecognition and tissue formation, while others have argued that it is essential throughout development. Here, we show that allorecognition and tissue …


The Development Of An Instrument To Measure Transdermal Hydrogen Sulfide As A Way To Evaluate Microvascular Health In Humans, Benjamin Thomas Matheson Jul 2021

The Development Of An Instrument To Measure Transdermal Hydrogen Sulfide As A Way To Evaluate Microvascular Health In Humans, Benjamin Thomas Matheson

Biomedical Engineering ETDs

Hydrogen sulfide (H2S) is a gasotransmitter critical in maintaining microcirculation homeostasis. Impaired microcirculation occurs in multiple disease states such as peripheral vascular disease, diabetes mellitus (DM), and hypertension. Early detection and identification of patients with DM who are at risk for heart attack, stroke and amputation due to microvascular disease is crucial. Human skin is an accessible vascular bed that provides an opportunity to non-invasively measure H2S, which could be used as a biomarker to evaluate microvascular health.

In this work, a novel H2S gas sensor, called the transdermal arterial gasotransmitter sensor (TAGSTM …


Later Sleep Timing Predicts Accelerated Summer Weight Gain Among Elementary School Children: A Prospective Observational Study, Jennette P Moreno, Javad Razjouyan, Houston Lester, Hafza Dadabhoy, Mona Amirmazaheri, Layton Reesor-Oyer, Teresia M O'Connor, Daphne C Hernandez, Bijan Najafi, Candice A Alfano, Stephanie J Crowley, Debbe Thompson, Tom Baranowski Jul 2021

Later Sleep Timing Predicts Accelerated Summer Weight Gain Among Elementary School Children: A Prospective Observational Study, Jennette P Moreno, Javad Razjouyan, Houston Lester, Hafza Dadabhoy, Mona Amirmazaheri, Layton Reesor-Oyer, Teresia M O'Connor, Daphne C Hernandez, Bijan Najafi, Candice A Alfano, Stephanie J Crowley, Debbe Thompson, Tom Baranowski

Children’s Nutrition Research Center Staff Publications

Objectives and background: Social demands of the school-year and summer environment may affect children's sleep patterns and circadian rhythms during these periods. The current study examined differences in children's sleep and circadian-related behaviors during the school-year and summer and explored the association between sleep and circadian parameters and change in body mass index (BMI) during these time periods.

Methods: This was a prospective observational study with 119 children ages 5 to 8 years with three sequential BMI assessments: early school-year (fall), late school-year (spring), and beginning of the following school-year in Houston, Texas, USA. Sleep midpoint, sleep duration, variability of …


Elucidating The Structure And Functions Of Resolvin D6 Isomers On Nerve Regeneration With A Distinctive Trigeminal Transcriptome, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Robert Nshimiyimana, Nicos A. Petasis, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan Jul 2021

Elucidating The Structure And Functions Of Resolvin D6 Isomers On Nerve Regeneration With A Distinctive Trigeminal Transcriptome, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Robert Nshimiyimana, Nicos A. Petasis, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan

School of Medicine Faculty Publications

Innervation sustains cornea integrity. Pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) regenerated damaged nerves by stimulating the synthesis of a new stereoisomer of Resolvin D6 (RvD6si). Here, we resolved the structure of this lipid isolated from mouse tears after injured corneas were treated with PEDF + DHA. RvD6si synthesis was inhibited by fluvoxamine, a cytochrome P450 inhibitor, but not by 15- or 5-LOX inhibitors, suggesting that the 4- and 17-hydroxy of DHA have an RR- or SR-configuration. The two compounds were chemically synthesized. Using chiral phase HPLC, four peaks of RvD6si1-4 from tears were resolved. The RR-RvD6 standard eluted …


Myonuclear Transcriptional Dynamics In Response To Exercise Following Satellite Cell Depletion, Yuan Wen, Davis A. Englund, Bailey D. Peck, Kevin A. Murach, John J. Mccarthy, Charlotte A. Peterson Jul 2021

Myonuclear Transcriptional Dynamics In Response To Exercise Following Satellite Cell Depletion, Yuan Wen, Davis A. Englund, Bailey D. Peck, Kevin A. Murach, John J. Mccarthy, Charlotte A. Peterson

Physical Therapy Faculty Publications

Skeletal muscle is composed of post-mitotic myofibers that form a syncytium containing hundreds of myonuclei. Using a progressive exercise training model in the mouse and single nucleus RNA-sequencing (snRNA-seq) for high-resolution characterization of myonuclear transcription, we show myonuclear functional specialization in muscle. After 4 weeks of exercise training, snRNA-seq reveals that resident muscle stem cells, or satellite cells, are activated with acute exercise but demonstrate limited lineage progression while contributing to muscle adaptation. In the absence of satellite cells, a portion of nuclei demonstrates divergent transcriptional dynamics associated with mixed-fate identities compared with satellite cell replete muscles. These data provide …


Decoding Clinical Biomarker Space Of Covid-19: Exploring Matrix Factorization-Based Feature Selection Methods, Farshad Saberi-Movahed, Mahyar Mohammadifard, Adel Mehrpooya, Mohammad Rezaei-Ravari, Kamal Berahmand, Mehrdad Rostami, Saeed Karami, Mohammad Najafzadeh, Davood Hajinezhad, Mina Jamshidi, Farshid Abedi, Mahtab Mohammadifard, Elnaz Farbod, Farinaz Safavi, Mohammadreza Dorvash, Shahrzad Vahedi, Mahdi Eftekhari, Farid Saberi-Movahed, Iman Tavassoly Jul 2021

Decoding Clinical Biomarker Space Of Covid-19: Exploring Matrix Factorization-Based Feature Selection Methods, Farshad Saberi-Movahed, Mahyar Mohammadifard, Adel Mehrpooya, Mohammad Rezaei-Ravari, Kamal Berahmand, Mehrdad Rostami, Saeed Karami, Mohammad Najafzadeh, Davood Hajinezhad, Mina Jamshidi, Farshid Abedi, Mahtab Mohammadifard, Elnaz Farbod, Farinaz Safavi, Mohammadreza Dorvash, Shahrzad Vahedi, Mahdi Eftekhari, Farid Saberi-Movahed, Iman Tavassoly

Publications and Research

One of the most critical challenges in managing complex diseases like COVID-19 is to establish an intelligent triage system that can optimize the clinical decision-making at the time of a global pandemic. The clinical presentation and patients’ characteristics are usually utilized to identify those patients who need more critical care. However, the clinical evidence shows an unmet need to determine more accurate and optimal clinical biomarkers to triage patients under a condition like the COVID-19 crisis. Here we have presented a machine learning approach to find a group of clinical indicators from the blood tests of a set of COVID-19 …


Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar Jul 2021

Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar

Journal of Wellness

The essential question of the relationship between consciousness and matter is ignored in medical school curricula, leading to a machine-like view of the human being that contributes to physician burnout and intellectual dissatisfaction. The evidence suggesting that the brain may not be the seat of consciousness is generally ignored to preserve the worldview of the primacy of matter. By investigating new frameworks detailing the nature of consciousness at different levels of hierarchy, we can bring intellectual rigor to a once opaque subject that supports a fundamental reality about our experience: We are human beings, not only human bodies.


Predicting Synchronized Gene Coexpression Patterns From Fibration Symmetries In Gene Regulatory Networks In Bacteria, Ian Leifer, Mishael Sánchez‑Pérez, Cecilia Ishida, Hernán A. Makse Jul 2021

Predicting Synchronized Gene Coexpression Patterns From Fibration Symmetries In Gene Regulatory Networks In Bacteria, Ian Leifer, Mishael Sánchez‑Pérez, Cecilia Ishida, Hernán A. Makse

Publications and Research

Background: Gene regulatory networks coordinate the expression of genes across physiological states and ensure a synchronized expression of genes in cellular subsystems, critical for the coherent functioning of cells. Here we address the question whether it is possible to predict gene synchronization from network structure alone. We have recently shown that synchronized gene expression can be predicted from symmetries in the gene regulatory networks described by the concept of symmetry fibrations. We showed that symmetry fibrations partition the genes into groups called fibers based on the symmetries of their ’input trees’, the set of paths in the network through which …


Platelet And Erythrocyte Extravasation Across Inflamed Corneal Venules Depend On Cd18, Neutrophils, And Mast Cell Degranulation, Angie De La Cruz, Aubrey Hargrave, Sri Magadi, Justin A Courson, Paul T Landry, Wanyu Zhang, Fong W Lam, Monica A Bray, C Wayne Smith, Alan R Burns, Rolando E Rumbaut Jul 2021

Platelet And Erythrocyte Extravasation Across Inflamed Corneal Venules Depend On Cd18, Neutrophils, And Mast Cell Degranulation, Angie De La Cruz, Aubrey Hargrave, Sri Magadi, Justin A Courson, Paul T Landry, Wanyu Zhang, Fong W Lam, Monica A Bray, C Wayne Smith, Alan R Burns, Rolando E Rumbaut

Faculty, Staff and Student Publications

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs …


Black And White Health Disparities: Racial Bias In American Healthcare, Yasmeen Almomani Jul 2021

Black And White Health Disparities: Racial Bias In American Healthcare, Yasmeen Almomani

Bridges: An Undergraduate Journal of Contemporary Connections

This paper explores the historical implications of race in American society that have led to implicit racism in the healthcare system. Racial bias in healthcare against Black people is a factor in the health disparities between Black and white people in America, such as the gap in life expectancy, infant death, and maternal mortality. Black people are more likely to report racial discrimination from healthcare providers, which is a reason for the decreased quality of care received. The past justifications of slavery, the Tuskegee syphilis study, and the medical experimentations on Black women are horrifying but were considered acceptable in …


Week Of July 6, 2021, New York Medical College Jul 2021

Therapeutic Efficacy Of A Potent Anti-Venezuelan Equine Encephalitis Virus Antibody Is Contingent On Fc Effector Function, Vanja Krneta-Stankic, Mark E Corkins, Adriana Paulucci-Holthauzen, Malgorzata Kloc, Andrew B Gladden, Rachel K Miller Jul 2021

Therapeutic Efficacy Of A Potent Anti-Venezuelan Equine Encephalitis Virus Antibody Is Contingent On Fc Effector Function, Vanja Krneta-Stankic, Mark E Corkins, Adriana Paulucci-Holthauzen, Malgorzata Kloc, Andrew B Gladden, Rachel K Miller

Faculty, Staff and Student Publications

E-cadherin junctions facilitate assembly and disassembly of cell contacts that drive development and homeostasis of epithelial tissues. In this study, using Xenopus embryonic kidney and Madin-Darby canine kidney (MDCK) cells, we investigate the role of the Wnt/planar cell polarity (PCP) formin Daam1 (Dishevelled-associated activator of morphogenesis 1) in regulating E-cadherin-based intercellular adhesion. Using live imaging, we show that Daam1 localizes to newly formed cell contacts in the developing nephron. Furthermore, analyses of junctional filamentous actin (F-actin) upon Daam1 depletion indicate decreased microfilament localization and slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional …


Novel Scalable And Simplified System To Generate Microglia-Containing Cerebral Organoids From Human Induced Pluripotent Stem Cells, Brittany Bodnar, Yongang Zhang, Jinbiao Liu, Yuan Lin, Peng Wang, Zhengyu Wei, Sami Saribas, Yuanjun Zhu, Fang Li, Xu Wang, Wenli Yang, Qingsheng Li, Wen-Zhe Ho, Wenhui Hu Jul 2021

Novel Scalable And Simplified System To Generate Microglia-Containing Cerebral Organoids From Human Induced Pluripotent Stem Cells, Brittany Bodnar, Yongang Zhang, Jinbiao Liu, Yuan Lin, Peng Wang, Zhengyu Wei, Sami Saribas, Yuanjun Zhu, Fang Li, Xu Wang, Wenli Yang, Qingsheng Li, Wen-Zhe Ho, Wenhui Hu

Nebraska Center for Virology: Faculty Publications

Human cerebral organoid (CO) is a three-dimensional (3D) cell culture system that recapitulates the developing human brain. While CO has proved an invaluable tool for studying neurological disorders in a more clinically relevant matter, there have still been several shortcomings including CO variability and reproducibility as well as lack of or underrepresentation of certain cell types typically found in the brain. As the technology to generate COs has continued to improve, more efficient and streamlined protocols have addressed some of these issues. Here we present a novel scalable and simplified system to generate microglia-containing CO (MCO). We characterize the cell …


A Synthetic Circuit For Buffering Gene Dosage Variation Between Individual Mammalian Cell, Jin Yang, Jihwan Lee, Michelle A Land, Shujuan Lai, Oleg A Igoshin, François St-Pierre Jul 2021

A Synthetic Circuit For Buffering Gene Dosage Variation Between Individual Mammalian Cell, Jin Yang, Jihwan Lee, Michelle A Land, Shujuan Lai, Oleg A Igoshin, François St-Pierre

Faculty, Staff and Students Publications

Precise control of gene expression is critical for biological research and biotechnology. However, transient plasmid transfections in mammalian cells produce a wide distribution of copy numbers per cell, and consequently, high expression heterogeneity. Here, we report plasmid-based synthetic circuits - Equalizers - that buffer copy-number variation at the single-cell level. Equalizers couple a transcriptional negative feedback loop with post-transcriptional incoherent feedforward control. Computational modeling suggests that the combination of these two topologies enables Equalizers to operate over a wide range of plasmid copy numbers. We demonstrate experimentally that Equalizers outperform other gene dosage compensation topologies and produce as low cell-to-cell …


Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown Jul 2021

Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Preeclampsia (PE) is a multisystemic, pregnancy-specific disorder and a leading cause of maternal and fetal death. PE is also associated with an increased risk for chronic morbidities later in life for mother and offspring. Abnormal placentation or placental function has been well-established as central to the genesis of PE; yet much remains to be determined about the factors involved in the development of this condition. Despite decades of investigation and many clinical trials, the only definitive treatment is parturition. To better understand the condition and identify potential targets preclinically, many approaches to simulate PE in mice have been developed and …


Association Of Nonacute Opioid Use And Cardiovascular Diseases: A Scoping Review Of The Literature, Jade H. Singleton, Erin L. Abner, Peter D. Akpunonu, Anna M. Kucharska-Newton Jul 2021

Association Of Nonacute Opioid Use And Cardiovascular Diseases: A Scoping Review Of The Literature, Jade H. Singleton, Erin L. Abner, Peter D. Akpunonu, Anna M. Kucharska-Newton

Epidemiology and Environmental Health Faculty Publications

BACKGROUND

In this scoping review, we identified and reviewed 23 original articles from the PubMed database that investigated the relationship between nonacute opioid use (NOU) and cardiovascular outcomes.

METHODS AND RESULTS

We defined NOU to include both long-term opioid therapy and opioid use disorder. We summarized the association between NOU and 5 classes of cardiovascular disease, including infective endocarditis, coronary heart disease (including myocardial infarction), congestive heart failure, cardiac arrythmia (including cardiac arrest), and stroke. The most commonly studied outcomes were coronary heart disease and infective endocarditis. There was generally consistent evidence of a positive association between community prevalence of …


The Intersection Of Hiv, Covid-19 And Systemic Racism, Gary F. Spinner Jul 2021

The Intersection Of Hiv, Covid-19 And Systemic Racism, Gary F. Spinner

Journal of Health Disparities Research and Practice

ABSTRACT

The Human Immunodeficiency Virus (HIV) pandemic has taken the greatest toll on racial and ethnic minorities in the United States. Blacks and Latinxs suffer greater disease incidence, prevalence, morbidity and mortality from HIV as compared with Whites. Similarly, the Covid-19 pandemic caused by SARS-CoV-2 has disproportionately affected Blacks, Latinxs, and Native Americans causing higher rates of infection, more severe disease, and higher rates of mortality as compared with Whites. The pandemic of racism is as ubiquitous as the pandemics of HIV and Covid-19. Its sustaining forces drive wealth inequality, poverty, racially segregated and overcrowded housing, unequal employment opportunities, unequal …


Image Segmentation For Neuroscience: Lymphatics, Nazia Tabassum, Jie Wang, Michael Ferguson, Jasmin Herz, Michael Dong, Antoine Louveau, Jonathan Kipnis, Scott Thomas Acton Jul 2021

Image Segmentation For Neuroscience: Lymphatics, Nazia Tabassum, Jie Wang, Michael Ferguson, Jasmin Herz, Michael Dong, Antoine Louveau, Jonathan Kipnis, Scott Thomas Acton

Division of Internal Medicine Faculty Papers & Presentations

A recent discovery in neuroscience prompts the need for innovation in image analysis. Neuroscientists have discovered the existence of meningeal lymphatic vessels in the brain and have shown their importance in preventing cognitive decline in mouse models of Alzheimer s disease. With age, lymphatic vessels narrow and poorly drain cerebrospinal fluid, leading to plaque accumulation, a marker for Alzheimer s disease. The detection of vessel boundaries and width are performed by hand in current practice and thereby suffer from high error rates and potential observer bias. The existing vessel segmentation methods are dependent on user-defined initialization, which is time-consuming and …