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Genome-Wide Association Meta-Analysis Identifies Pleiotropic Risk Loci For Aerodigestive Squamous Cell Cancers, Corina Lesseur, Aida Ferreiro-Iglesias, James D. Mckay, Yohan Bossé, Mattias Johansson, Valerie Gaborieau, Maria Teresa Landi, David C. Christiani, Neil C. Caporaso, Stig E. Bojesen, Christopher I. Amos, Sanjay Shete, Geoffrey Liu, Gadi Rennert, Demetrius Albanes, Melinda C. Aldrich, Adonina Tardon, Chu Chen, Liloglou Triantafillos, John K. Field, Susanne Arnold Mar 2021

Genome-Wide Association Meta-Analysis Identifies Pleiotropic Risk Loci For Aerodigestive Squamous Cell Cancers, Corina Lesseur, Aida Ferreiro-Iglesias, James D. Mckay, Yohan Bossé, Mattias Johansson, Valerie Gaborieau, Maria Teresa Landi, David C. Christiani, Neil C. Caporaso, Stig E. Bojesen, Christopher I. Amos, Sanjay Shete, Geoffrey Liu, Gadi Rennert, Demetrius Albanes, Melinda C. Aldrich, Adonina Tardon, Chu Chen, Liloglou Triantafillos, John K. Field, Susanne Arnold

Markey Cancer Center Faculty Publications

Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta< 5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown …


The Evolutionary Conserved Swi/Snf Subunits Arid1a And Arid1b Are Key Modulators Of Pluripotency And Cell-Fate Determination, Luca Pagliaroli, Marco Trizzino Mar 2021

The Evolutionary Conserved Swi/Snf Subunits Arid1a And Arid1b Are Key Modulators Of Pluripotency And Cell-Fate Determination, Luca Pagliaroli, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Organismal development is a process that requires a fine-tuned control of cell fate and identity, through timely regulation of lineage-specific genes. These processes are mediated by the concerted action of transcription factors and protein complexes that orchestrate the interaction between cis-regulatory elements (enhancers, promoters) and RNA Polymerase II to elicit transcription. A proper understanding of these dynamics is essential to elucidate the mechanisms underlying developmental diseases. Many developmental disorders, such as Coffin-Siris Syndrome, characterized by growth impairment and intellectual disability are associated with mutations in subunits of the SWI/SNF chromatin remodeler complex, which is an essential regulator of transcription. ARID1B …


Historical Perspective Of The G Protein-Coupled Receptor Kinase Family., Jeffrey L Benovic Mar 2021

Historical Perspective Of The G Protein-Coupled Receptor Kinase Family., Jeffrey L Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

Agonist activation of G protein-coupled receptors promotes sequential interaction of the receptor with heterotrimeric G proteins, G protein-coupled receptor kinases (GRKs), and arrestins. GRKs play a central role in mediating the switch from G protein to arrestin interaction and thereby control processes such as receptor desensitization and trafficking and arrestin-mediated signaling. In this review, I provide a historical perspective on some of the early studies that identified the family of GRKs with a primary focus on the non-visual GRKs. These studies included identification, purification, and cloning of the β-adrenergic receptor kinase in the mid- to late-1980s and subsequent cloning and …


Presence Of Antibody-Dependent Cellular Cytotoxicity (Adcc) Against Sars-Cov-2 In Covid-19 Plasma, For Yue Tso, Salum J. Lidenge, Lisa K. Poppe, Phoebe B. Pena, Sara R. Privatt, Sydney J. Bennett, John R. Ngowi, Julius Mwaiselage, Michael Belshan, Jacob A. Siedlik, Morgan A. Raine, Juan B. Ochoa, Julia Garcia-Diaz, Bobby Nossaman, Lyndsey Buckner, W Mark Roberts, Matthew J. Dean, Augusto C. Ochoa, John T. West, Charles Wood Mar 2021

Presence Of Antibody-Dependent Cellular Cytotoxicity (Adcc) Against Sars-Cov-2 In Covid-19 Plasma, For Yue Tso, Salum J. Lidenge, Lisa K. Poppe, Phoebe B. Pena, Sara R. Privatt, Sydney J. Bennett, John R. Ngowi, Julius Mwaiselage, Michael Belshan, Jacob A. Siedlik, Morgan A. Raine, Juan B. Ochoa, Julia Garcia-Diaz, Bobby Nossaman, Lyndsey Buckner, W Mark Roberts, Matthew J. Dean, Augusto C. Ochoa, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here. Methods Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific …


Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Aortic Occlusion: A Case Report, Artem Minalyan, Franklin L. Thelmo, Vincent Chan, Stephanie Tzarnas, Faizan Ahmed Mar 2021

Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Aortic Occlusion: A Case Report, Artem Minalyan, Franklin L. Thelmo, Vincent Chan, Stephanie Tzarnas, Faizan Ahmed

Department of Medicine Faculty Papers

Background: Severe acute respiratory syndrome coronavirus 2 infection can lead to a constellation of viral and immune symptoms called coronavirus disease 2019. Emerging literature increasingly supports the premise that severe acute respiratory syndrome coronavirus 2 promotes a prothrombotic milieu. However, to date there have been no reports of acute aortic occlusion, itself a rare phenomenon. We report a case of fatal acute aortic occlusion in a patient with coronavirus disease 2019.

Case report: A 59-year-old Caucasian male with past medical history of peripheral vascular disease presented to the emergency department for evaluation of shortness of breath, fevers, and dry cough. …


Glucagon Blockade Restores Functional Β-Cell Mass In Type 1 Diabetic Mice And Enhances Function Of Human Islets, May-Yun Wang, E Danielle Dean, Ezekiel Quittner-Strom, Yi Zhu, Kamrul H Chowdhury, Zhuzhen Zhang, Shangang Zhao, Na Li, Reshing Ye, Young Lee, Yiyi Zhang, Shiuhwei Chen, Xinxin Yu, Derek C Leonard, Greg Poffenberger, Alison Von Deylen, S Kay Mccorkle, Amnon Schlegel, Kyle W Sloop, Alexander M Efanov, Ruth E Gimeno, Philipp E Scherer, Alvin C Powers, Roger H Unger, William L Holland Mar 2021

Glucagon Blockade Restores Functional Β-Cell Mass In Type 1 Diabetic Mice And Enhances Function Of Human Islets, May-Yun Wang, E Danielle Dean, Ezekiel Quittner-Strom, Yi Zhu, Kamrul H Chowdhury, Zhuzhen Zhang, Shangang Zhao, Na Li, Reshing Ye, Young Lee, Yiyi Zhang, Shiuhwei Chen, Xinxin Yu, Derek C Leonard, Greg Poffenberger, Alison Von Deylen, S Kay Mccorkle, Amnon Schlegel, Kyle W Sloop, Alexander M Efanov, Ruth E Gimeno, Philipp E Scherer, Alvin C Powers, Roger H Unger, William L Holland

Faculty, Staff and Students Publications

We evaluated the potential for a monoclonal antibody antagonist of the glucagon receptor (Ab-4) to maintain glucose homeostasis in type 1 diabetic rodents. We noted durable and sustained improvements in glycemia which persist long after treatment withdrawal. Ab-4 promoted β-cell survival and enhanced the recovery of insulin+ islet mass with concomitant increases in circulating insulin and C peptide. In PANIC-ATTAC mice, an inducible model of β-cell apoptosis which allows for robust assessment of β-cell regeneration following caspase-8–induced diabetes, Ab-4 drove a 6.7-fold increase in β-cell mass. Lineage tracing suggests that this restoration of functional insulin-producing cells was at least partially …


Discovery And Characterization Of Bromodomain 2-Specific Inhibitors Of Brdt, Zhifeng Yu, Angela F Ku, Justin L Anglin, Rajesh Sharma, Melek Nihan Ucisik, John C Faver, Feng Li, Pranavanand Nyshadham, Nicholas Simmons, Kiran L Sharma, Sureshbabu Nagarajan, Kevin Riehle, Gundeep Kaur, Banumathi Sankaran, Marta Storl-Desmond, Stephen S Palmer, Damian W Young, Choel Kim, Martin M Matzuk Mar 2021

Discovery And Characterization Of Bromodomain 2-Specific Inhibitors Of Brdt, Zhifeng Yu, Angela F Ku, Justin L Anglin, Rajesh Sharma, Melek Nihan Ucisik, John C Faver, Feng Li, Pranavanand Nyshadham, Nicholas Simmons, Kiran L Sharma, Sureshbabu Nagarajan, Kevin Riehle, Gundeep Kaur, Banumathi Sankaran, Marta Storl-Desmond, Stephen S Palmer, Damian W Young, Choel Kim, Martin M Matzuk

Faculty, Staff and Students Publications

Bromodomain testis (BRDT), a member of the bromodomain and extraterminal (BET) subfamily that includes the cancer targets BRD2, BRD3, and BRD4, is a validated contraceptive target. All BET subfamily members have two tandem bromodomains (BD1 and BD2). Knockout mice lacking BRDT-BD1 or both bromodomains are infertile. Treatment of mice with JQ1, a BET BD1/BD2 nonselective inhibitor with the highest affinity for BRD4, disrupts spermatogenesis and reduces sperm number and motility. To assess the contribution of each BRDT bromodomain, we screened our collection of DNA-encoded chemical libraries for BRDT-BD1 and BRDT-BD2 binders. High-enrichment hits were identified and resynthesized off-DNA and examined …


Prematurity Blunts The Insulin- And Amino Acid-Induced Stimulation Of Translation Initiation And Protein Synthesis In Skeletal Muscle Of Neonatal Pigs, Marko Rudar, Jane K Naberhuis, Agus Suryawan, Hanh V Nguyen, Barbara Stoll, Candace C Style, Mariatu A Verla, Oluyinka O Olutoye, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis Mar 2021

Prematurity Blunts The Insulin- And Amino Acid-Induced Stimulation Of Translation Initiation And Protein Synthesis In Skeletal Muscle Of Neonatal Pigs, Marko Rudar, Jane K Naberhuis, Agus Suryawan, Hanh V Nguyen, Barbara Stoll, Candace C Style, Mariatu A Verla, Oluyinka O Olutoye, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Children’s Nutrition Research Center Staff Publications

Extrauterine growth restriction in premature infants is largely attributed to reduced lean mass accretion and is associated with long-term morbidities. Previously, we demonstrated that prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in skeletal muscle of neonatal pigs. The objective of the current study was to determine whether the blunted feeding response is mediated by reduced responsiveness to insulin, amino acids, or both. Pigs delivered by cesarean section preterm (PT; 103 days,


Importance Of Pgc-1Α Gene Expression In Egyptian Hemodialysis Patients, Ashraf Donia, Azza A. I. Elmenyawi Mar 2021

Importance Of Pgc-1Α Gene Expression In Egyptian Hemodialysis Patients, Ashraf Donia, Azza A. I. Elmenyawi

Journal of Medicine in Scientific Research

Introduction The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is an upstream transcriptional regulator of mitochondrial biogenesis and function. Its function is immediate elimination of reactive oxygen species to get rid of their cellular destruction sequelae. Decreased PGC-1α count and less mitochondrial function take part in renal failure. COX6C gene encodes mitochondrial oxidative phosphorylation proteins. Reaction of excessive reactive oxygen species with linolenic acid results in malondialdehyde (MDA) as a breakdown product. It is an important marker for evaluating oxidative damage. Patients and methods A total of 58 hemodialysis (HD) patients in the National Institute of Urology and Nephrology and 20 …


Week Of March 1, 2021, New York Medical College Mar 2021

The Crosstalk Between Cardiomyocyte Calcium And Inflammasome Signaling Pathways In Atrial Fibrillation, Xiaolei Wang, Xiaohui Chen, Dobromir Dobrev, Na Li Mar 2021

The Crosstalk Between Cardiomyocyte Calcium And Inflammasome Signaling Pathways In Atrial Fibrillation, Xiaolei Wang, Xiaohui Chen, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

Atrial fibrillation (AF) is the most frequent arrhythmia in adults. The prevalence and incidence of AF is going to increase substantially over the next a few decades. Because AF increases the risk of stroke, heart failure, dementia, and others, it severely impacts the quality of life, morbidity and mortality. Although the pathogenesis of AF is multifaceted and complex, focal ectopic activity and reentry are considered as the fundamental proarrhythmic mechanisms underlying AF development. Over the past 2 decades, large amount of evidence points to the key role of intracellular Ca2+ dysregulation in both initiation and maintenance of AF. More recently, …


Deficiency Of Stat1 In Cd11c+ Cells Alters Adipose Tissue Inflammation And Improves Metabolic Dysfunctions In Mice Fed A High-Fat Diet, Antu Antony, Zeqin Lian, Xiaoyuan Dai Perrard, Jerry Perrard, Hua Liu, Aaron R Cox, Pradip Saha, Lothar Hennighausen, Sean M Hartig, Christie M Ballantyne, Huaizhu Wu Mar 2021

Deficiency Of Stat1 In Cd11c+ Cells Alters Adipose Tissue Inflammation And Improves Metabolic Dysfunctions In Mice Fed A High-Fat Diet, Antu Antony, Zeqin Lian, Xiaoyuan Dai Perrard, Jerry Perrard, Hua Liu, Aaron R Cox, Pradip Saha, Lothar Hennighausen, Sean M Hartig, Christie M Ballantyne, Huaizhu Wu

Faculty, Staff and Students Publications

CD11c+ macrophages/dendritic cells (MDCs) are increased and display the classically activated M1-like phenotype in obese adipose tissue (AT) and may contribute to AT inflammation and insulin resistance. Stat1 is a key transcription factor for MDC polarization into the M1-like phenotype. Here, we examined the role of Stat1 in obesity-induced AT MDC polarization and inflammation and insulin resistance using mice with specific knockout of Stat1 in MDCs (cKO). Stat1 was upregulated and phosphorylated, indicating activation, early and persistently in AT and AT MDCs of wild-type mice fed a high-fat diet (HFD). Compared with littermate controls, cKO mice fed an HFD (16 …


Is Covid-19-Induced Platelet Activation A Cause Of Concern For Patients With Cancer?, Lenard M Lichtenberger, K Vinod Vijayan Mar 2021

Is Covid-19-Induced Platelet Activation A Cause Of Concern For Patients With Cancer?, Lenard M Lichtenberger, K Vinod Vijayan

Faculty, Staff and Students Publications

Patients with cancer are more susceptible to be infected by SARS-CoV-2 and develop severe outcomes including ICU admittance, mechanical ventilator support, and a high rate of mortality. Like mid-to late-stage cancer, SARS-CoV-2 infection is associated with platelet hyperactivity, systemic inflammation, thrombotic complications, and coagulopathy. Platelets also promote cancer cell growth, survival in circulation, and angiogenesis at sites of metastases. In this article, we will discuss the potential for platelets in the development of systemic inflammation and thrombosis in SARS-CoV-2-infected patients with cancer, with the concern that the platelet-induced pathogenic events are likely magnified in cancer patients with COVID-19.


On The Application, Reporting, And Sharing Of In Silico Simulations For Genetic Studies, Kaleigh Riggs, Huann-Sheng Chen, Melissa Rotunno, Bing Li, Naoko I Simonds, Leah E Mechanic, Bo Peng Mar 2021

On The Application, Reporting, And Sharing Of In Silico Simulations For Genetic Studies, Kaleigh Riggs, Huann-Sheng Chen, Melissa Rotunno, Bing Li, Naoko I Simonds, Leah E Mechanic, Bo Peng

Faculty, Staff and Students Publications

In silico simulations play an indispensable role in the development and application of statistical models and methods for genetic studies. Simulation tools allow for the evaluation of methods and investigation of models in a controlled manner. With the growing popularity of evolutionary models and simulation-based statistical methods, genetic simulations have been applied to a wide variety of research disciplines such as population genetics, evolutionary genetics, genetic epidemiology, ecology, and conservation biology. In this review, we surveyed 1409 articles from five journals that publish on major application areas of genetic simulations. We identified 432 papers in which genetic simulations were used …


Pegylated Arginine Deiminase Depletes Plasma Arginine But Maintains Tissue Arginine Availability In Young Pigs, Mahmoud A Mohammad, Inka C Didelija, Barbara Stoll, Trung C Nguyen, Juan C Marini Mar 2021

Pegylated Arginine Deiminase Depletes Plasma Arginine But Maintains Tissue Arginine Availability In Young Pigs, Mahmoud A Mohammad, Inka C Didelija, Barbara Stoll, Trung C Nguyen, Juan C Marini

Faculty, Staff and Students Publications

Pegylated arginine deiminase (ADI-PEG20) results in the depletion of arginine with the production of isomolar amounts of citrulline. This citrulline has the potential to be utilized by the citrulline recycling pathway regenerating arginine and sustaining tissue arginine availability. The goal of this research was to test the hypothesis that ADI-PEG20 depletes circulating arginine in pigs but maintains tissue arginine concentration and function, and to characterize the kinetics of citrulline and arginine. Two multitracer approaches (bolus dose and primed-continuous infusion) were used to investigate the metabolism of arginine and citrulline in Control (


A Biallelic Pathogenic Variant In The Ogdh Gene Results In A Neurological Disorder With Features Of A Mitochondrial Disease, Zheng Yie Yap, Klaudia Strucinska, Satoshi Matsuzaki, Sukyeong Lee, Yue Si, Kenneth Humphries, Mark A Tarnopolsky, Wan Hee Yoon Mar 2021

A Biallelic Pathogenic Variant In The Ogdh Gene Results In A Neurological Disorder With Features Of A Mitochondrial Disease, Zheng Yie Yap, Klaudia Strucinska, Satoshi Matsuzaki, Sukyeong Lee, Yue Si, Kenneth Humphries, Mark A Tarnopolsky, Wan Hee Yoon

Faculty, Staff and Students Publications

2-Oxoglutarate dehydrogenase (OGDH) is a rate-limiting enzyme in the mitochondrial TCA cycle, encoded by the OGDH gene. α-Ketoglutarate dehydrogenase (OGDH) deficiency was previously reported in association with developmental delay, hypotonia, and movement disorders and metabolic decompensation, with no genetic data provided. Using whole exome sequencing, we identified two individuals carrying a homozygous missense variant c.959A>G (p.N320S) in the OGDH gene. These individuals presented with global developmental delay, elevated lactate, ataxia and seizure. Fibroblast analysis and modeling of the mutation in Drosophila were used to evaluate pathogenicity of the variant. Skin fibroblasts from subject # 2 showed a decrease in …


3d Printing Of Human Microbiome Constituents To Understand Spatial Relationships And Shape Parameters In Bacteriology, Jacques Izard, Teklu Kuru Gerbaba, Shara R. P. Yumul Mar 2021

3d Printing Of Human Microbiome Constituents To Understand Spatial Relationships And Shape Parameters In Bacteriology, Jacques Izard, Teklu Kuru Gerbaba, Shara R. P. Yumul

Department of Food Science and Technology: Faculty Publications

Effective laboratory and classroom demonstration of microbiome size and shape, diversity, and ecological relationships is hampered by a lack of high-resolution, easy-to-use, readily accessible physical or digital models for use in teaching. Three-dimensional (3D) representations are, overall, more effective in communicating visuospatial information, allowing for a better understanding of concepts not directly observable with the unaided eye. Published morphology descriptions and microscopy images were used as the basis for designing 3D digital models, scaled at 20,000×, using computer-aided design software (CAD) and generating printed models of bacteria on mass-market 3D printers. Sixteen models are presented, including rod-shaped, spiral, flask-like, vibroid, …


Development Of A Robust Methodology To Obtain And Assess Myogenic Precursor Cells For Their Use In Regenerative Therapies, Ricardo Lasa Mar 2021

Development Of A Robust Methodology To Obtain And Assess Myogenic Precursor Cells For Their Use In Regenerative Therapies, Ricardo Lasa

Master's Theses

Peripheral arterial occlusive disease (PAOD) is characterized by buildup of atherosclerotic plaque in peripheral arteries that leads to an occlusion that can interrupt the supply of blood to the peripheral tissue, causing downstream tissue ischemia/hypoxia. PAOD is estimated to affect over 200 million patients worldwide. Current surgical revascularization treatments can be effective in about half of the patient population, leading to a significant number of patients with no treatment options beyond pharmacological intervention and lifestyle modification. The decrease in blood flow downstream of the occlusion leads to increased blood pressure gradient in the microvasculature, specifically in vessels that connect arterial …


Hands-On Training About Overfitting, Janez Demšar, Blaž Zupan Mar 2021

Hands-On Training About Overfitting, Janez Demšar, Blaž Zupan

Faculty, Staff and Students Publications

Overfitting is one of the critical problems in developing models by machine learning. With machine learning becoming an essential technology in computational biology, we must include training about overfitting in all courses that introduce this technology to students and practitioners. We here propose a hands-on training for overfitting that is suitable for introductory level courses and can be carried out on its own or embedded within any data science course. We use workflow-based design of machine learning pipelines, experimentation-based teaching, and hands-on approach that focuses on concepts rather than underlying mathematics. We here detail the data analysis workflows we use …


Tbx5-Encoded T-Box Transcription Factor 5 Variant T223m Is Associated With Long Qt Syndrome And Pediatric Sudden Cardiac Death, Alexandra M Markunas, Perathu K R Manivannan, Jordan E Ezekian, Agnim Agarwal, William Eisner, Katherina Alsina, Hugh D Allen, Gregory A Wray, Jeffrey J Kim, Xander H T Wehrens, Andrew P Landstrom Mar 2021

Tbx5-Encoded T-Box Transcription Factor 5 Variant T223m Is Associated With Long Qt Syndrome And Pediatric Sudden Cardiac Death, Alexandra M Markunas, Perathu K R Manivannan, Jordan E Ezekian, Agnim Agarwal, William Eisner, Katherina Alsina, Hugh D Allen, Gregory A Wray, Jeffrey J Kim, Xander H T Wehrens, Andrew P Landstrom

Faculty, Staff and Students Publications

Long QT syndrome (LQTS) is a genetic disease resulting in a prolonged QT interval on a resting electrocardiogram, predisposing affected individuals to polymorphic ventricular tachycardia and sudden death. Although a number of genes have been implicated in this disease, nearly one in four individuals exhibiting the LQTS phenotype are genotype-negative. Whole-exome sequencing identified a missense T223M variant in TBX5 that cosegregates with prolonged QT interval in a family with otherwise genotype-negative LQTS and sudden death. The TBX5-T223M variant was absent among large ostensibly healthy populations (gnomAD) and predicted to be pathogenic by in silico modeling based on Panther, PolyPhen-2, Provean, …


Ceramide Synthase Tlcd3b Is A Novel Gene Associated With Human Recessive Retinal Dystrophy, Renae Elaine Bertrand, Jun Wang, Kaitlyn H Xiong, Chinthana Thangavel, Xinye Qian, Rola Ba-Abbad, Qingnan Liang, Renata T Simões, Shirley A M Sampaio, Keren J Carss, F Lucy Raymond, Anthony G Robson, Andrew R Webster, Gavin Arno, Fernanda Belga Ottoni Porto, Rui Chen Mar 2021

Ceramide Synthase Tlcd3b Is A Novel Gene Associated With Human Recessive Retinal Dystrophy, Renae Elaine Bertrand, Jun Wang, Kaitlyn H Xiong, Chinthana Thangavel, Xinye Qian, Rola Ba-Abbad, Qingnan Liang, Renata T Simões, Shirley A M Sampaio, Keren J Carss, F Lucy Raymond, Anthony G Robson, Andrew R Webster, Gavin Arno, Fernanda Belga Ottoni Porto, Rui Chen

Faculty, Staff and Students Publications

PURPOSE: Previous studies suggest that ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. However, no pathogenic variant in ceramide synthases has been identified in human patients and knockout of various ceramide synthases in mice has not led to photoreceptor degeneration.

METHODS: Exome sequencing was used to identify candidate disease genes in patients with vision loss as confirmed by standard evaluation methods, including electroretinography (ERG) and optical coherence tomography. The vision loss phenotype in mice was evaluated by ERG and histological analyses.

RESULTS: Here we have identified four patients with …


Inhibition Of Camkk2 Impairs Autophagy And Castration-Resistant Prostate Cancer Via Suppression Of Ampk-Ulk1 Signaling, Chenchu Lin, Alicia M Blessing, Thomas L Pulliam, Yan Shi, Sandi R Wilkenfeld, Jenny J Han, Mollianne M Murray, Alexander H Pham, Kevin Duong, Sonja N Brun, Reuben J Shaw, Michael M Ittmann, Daniel E Frigo Mar 2021

Inhibition Of Camkk2 Impairs Autophagy And Castration-Resistant Prostate Cancer Via Suppression Of Ampk-Ulk1 Signaling, Chenchu Lin, Alicia M Blessing, Thomas L Pulliam, Yan Shi, Sandi R Wilkenfeld, Jenny J Han, Mollianne M Murray, Alexander H Pham, Kevin Duong, Sonja N Brun, Reuben J Shaw, Michael M Ittmann, Daniel E Frigo

Faculty, Staff and Students Publications

Previous work has suggested androgen receptor (AR) signaling mediates prostate cancer progression in part through the modulation of autophagy. However, clinical trials testing autophagy inhibition using chloroquine derivatives in men with castration-resistant prostate cancer (CRPC) have yet to yield promising results, potentially due to the side effects of this class of compounds. We hypothesized that identification of the upstream activators of autophagy in prostate cancer could highlight alternative, context-dependent targets for blocking this important cellular process during disease progression. Here, we used molecular, genetic and pharmacological approaches to elucidate an AR-mediated autophagy cascade involving Ca2+/calmodulin-dependent protein kinase kinase 2 (CAMKK2; …


In Vivo Transplantation Of Human Intestinal Organoids Enhances Select Tight Junction Gene Expression, Mariaelena A Boyle, David J Sequeira, Eoin P Mcneill, Zachary K Criss, Noah F Shroyer, Allison L Speer Mar 2021

In Vivo Transplantation Of Human Intestinal Organoids Enhances Select Tight Junction Gene Expression, Mariaelena A Boyle, David J Sequeira, Eoin P Mcneill, Zachary K Criss, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

BACKGROUND: Short bowel syndrome is a potentially fatal condition with inadequate management options. Tissue-engineered small intestine (TESI) is a promising solution, but confirmation of TESI function will be crucial before human application. We sought to define intestinal epithelial barrier function in human intestinal organoid (HIO)-derived TESI.

MATERIALS AND METHODS: HIOs were generated in vitro from human embryonic stem cells. After 1 mo, HIOs were collected for analysis or transplanted into the kidney capsule of immunocompromised mice. Transplanted HIOs (tHIOs) were harvested for analysis at 4 or 8 wk. Reverse transcription quantitative polymerase chain reaction and immunofluorescent staining were performed for …


Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Indian Institute Of Technology Indore, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak Mar 2021

Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Indian Institute Of Technology Indore, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted Flavivirus, emerged in the last decade causing serious diseases and affecting human health globally. Currently, no licensed vaccines or antivirals are available to combat ZIKV, although several vaccine candidates are in the pipeline. In recent years, the presence of non-canonical G-quadruplex (GQ) secondary structures in viral genomes has ignited significant attention as potential targets for antiviral strategy. In this study, we identified several novel conserved potential GQ structures by analyzing published ZIKV genome sequences using an in-house algorithm. Biophysical and biochemical analysis of the RNA sequences containing these potential GQ sequences suggested the existence of …


Tools For Visualizing And Analyzing Fourier Space Sampling In Cryo-Em, Philip R Baldwin, Dmitry Lyumkis Mar 2021

Tools For Visualizing And Analyzing Fourier Space Sampling In Cryo-Em, Philip R Baldwin, Dmitry Lyumkis

Faculty, Staff and Students Publications

A complete understanding of how an orientation distribution contributes to a cryo-EM reconstruction remains lacking. It is necessary to begin critically assessing the set of views to gain an understanding of its effect on experimental reconstructions. Toward that end, we recently suggested that the type of orientation distribution may alter resolution measures in a systematic manner. We introduced the sampling compensation factor (SCF), which incorporates how the collection geometry might change the spectral signal-to-noise ratio (SSNR), irrespective of the other experimental aspects. We show here that knowledge of the sampling restricted to spherical surfaces of sufficiently large radii in Fourier …


Redo-Mitral Valve Replacement And Predictors Of Operative Mortality: A Single-Institute Experience, Ahmed M. E. Abdelgawad, Ahmed Abdelaziz Mar 2021

Redo-Mitral Valve Replacement And Predictors Of Operative Mortality: A Single-Institute Experience, Ahmed M. E. Abdelgawad, Ahmed Abdelaziz

Journal of Medicine in Scientific Research

Background In spite of improved survival of first-time mitral valve replacement (MVR), operative mortality associated with redo-mitral valve surgery is still higher than that of the primary operation. Consequently, more patients require redo-MVR, and studies investigating the operative outcome with current techniques and prostheses are thus needed. Patients and methods This is a nonrandomized prospective study that included 83 patients who underwent redo-MVR with either bioprosthetic or mechanical valves between March 2014 and December 2017 at National Heart Institute. Recorded data were analyzed using the statistical package for social sciences, version 23.0 (IBM SPSS). All preoperative and operative data were …


Pirnas As Modulators Of Disease Pathogenesis, Kayla J. Rayford, Ayorinde Cooley, Jelonia T. Rumph, Ashutosh Arun, Girish Rachakonda, Fernando Villalta, Maria F. Lima, Siddharth Pratap, Smita Misra, Pius N. Nde Feb 2021

Pirnas As Modulators Of Disease Pathogenesis, Kayla J. Rayford, Ayorinde Cooley, Jelonia T. Rumph, Ashutosh Arun, Girish Rachakonda, Fernando Villalta, Maria F. Lima, Siddharth Pratap, Smita Misra, Pius N. Nde

Publications and Research

Advances in understanding disease pathogenesis correlates to modifications in gene expression within different tissues and organ systems. In depth knowledge about the dysregulation of gene expression profiles is fundamental to fully uncover mechanisms in disease development and changes in host homeostasis. The body of knowledge surrounding mammalian regulatory elements, specifically regulators of chromatin structure, transcriptional and translational activation, has considerably surged within the past decade. A set of key regulators whose function still needs to be fully elucidated are small non-coding RNAs (sncRNAs). Due to their broad range of unfolding functions in the regulation of gene expression during transcription and …


Mast Cell Involvement In Fibrosis In Chronic Graft-Versus-Host Disease, Ethan Strattan, Gerhard Carl Hildebrandt Feb 2021

Mast Cell Involvement In Fibrosis In Chronic Graft-Versus-Host Disease, Ethan Strattan, Gerhard Carl Hildebrandt

Markey Cancer Center Faculty Publications

Allogeneic hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host disease (GVHD), classified as either acute or chronic GVHD. While the pathology of acute GVHD is better understood, factors driving GVHD at the cellular and molecular level are less clear. Mast cells are an arm of the immune system that are known for atopic disease. However, studies have demonstrated that they can play important roles in tissue homeostasis and wound healing, and mast cell dysregulation can lead …


Immunological And Anti-Oxidant Profiles Of Malarial Children In Abuja, Nigeria, Idris Nasir Abdullahi, Sanusi Musa, Anthony Uchenna Emeribe, Musa Muhammed, Jelili Olaide Mustapha, Halima Ali Shuwa, Shamsuddeen Haruna, Sharafudeen Dahiru Abubakar, Olusoji Matthew Billyrose, Mustapha Bakare Feb 2021

Immunological And Anti-Oxidant Profiles Of Malarial Children In Abuja, Nigeria, Idris Nasir Abdullahi, Sanusi Musa, Anthony Uchenna Emeribe, Musa Muhammed, Jelili Olaide Mustapha, Halima Ali Shuwa, Shamsuddeen Haruna, Sharafudeen Dahiru Abubakar, Olusoji Matthew Billyrose, Mustapha Bakare

BioMedicine

Background:

The clinical symptoms, cellular immune response, and serum cytokine homeostasis during falciparum malaria among children living in endemic regions depend on the parasite densities. This study aims to evaluate the CD4+ and CD8+ T cells, leucocytes subpopulations, IL-6, IL-10 and biomarkers of oxidative stress among children infected with varying grades of malaria attending the University of Abuja Teaching Hospital and National Hospital, Abuja, Nigeria.

Materials and Methods:

This case-control study involved blood samples collected from 165 children (between 5 -12 years). This comprised 45 children with mild malaria, 40 each with moderate, severe malaria and apparently healthy …


Predicting Mental Health Of Prisoners By Artificial Neural Network, Elahe Allahyari, Mozhgan Moshtagh Feb 2021

Predicting Mental Health Of Prisoners By Artificial Neural Network, Elahe Allahyari, Mozhgan Moshtagh

BioMedicine

Introduction: Maintaining and improving prisoners’ health and their rehabilitation can be effective steps towards eliminating health inequalities and approaching the UN’s Sustainable Development Goals. Accordingly, identifying protective factors and health barriers of this vulnerable group and changing the prison into an environment that can deliver health interventions tailored to the needs of inmates can provide the basis for attaining justice in health.

Purpose: This study builds on an artificial neural network model to determine the effect of demographic, psychological, criminological, and physical activity factors on prisoners’ general health.

Methods: The study detected the patterns between variables using a neural network …