Digital Commons Network^™

Foxo1 Is Present In Stomach Epithelium And Determines Gastric Cell Distribution, Wendy M Mckimpson, Taiyi Kuo, Takumi Kitamoto, Sei Higuchi, Jason C Mills, Rebecca A Haeusler, Domenico Accili

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.

METHODS: Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.

RESULTS: FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, …

Pathologic Inflammation In Malnutrition Is Driven By Proinflammatory Intestinal Microbiota, Large Intestine Barrier Dysfunction, And Translocation Of Bacterial Lipopolysaccharide, Grace T Patterson, Elvia Y Osorio, Alex Peniche, Sara M Dann, Erika Cordova, Geoffrey A Preidis, Ji Ho Suh, Ichiaki Ito, Omar A Saldarriaga, Michael Loeffelholz, Nadim J Ajami, Bruno L Travi, Peter C Melby

Faculty, Staff and Students Publications

Acute malnutrition, or wasting, is implicated in over half of all deaths in children under five and increases risk of infectious disease. Studies in humans and preclinical models have demonstrated that malnutrition is linked to an immature intestinal microbiota characterized by increased prevalence of Enterobacteriaceae. Observational studies in children with moderate acute malnutrition (MAM) have also observed heightened systemic inflammation and increased circulating bacterial lipopolysaccharides (LPS; endotoxin). However, the mechanisms that underpin the systemic inflammatory state and endotoxemia, and their pathophysiological consequences, remain uncertain. Understanding these pathophysiological mechanisms is necessary to design targeted treatments that will improve the unacceptable rate …

Hepatic Pparα Is Destabilized By Sirt1 Deacetylase In Undernourished Male Mice, Ji Ho Suh, Kang Ho Kim, Margaret E Conner, David D Moore, Geoffrey A Preidis

Faculty, Staff and Students Publications

The nutrient sensing nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) regulates the host response to short-term fasting by inducing hepatic transcriptional programming of ketogenesis, fatty acid oxidation and transport, and autophagy. This adaptation is ineffective in chronically undernourished individuals, among whom dyslipidemia and hepatic steatosis are common. We recently reported that hepatic PPARα protein is profoundly depleted in male mice undernourished by a low-protein, low-fat diet. Here, we identify PPARα as a deacetylation target of the NAD-dependent deacetylase sirtuin-1 (SIRT1) and link this to the decrease in PPARα protein levels in undernourished liver. Livers from undernourished male mice expressed high levels …

Clinical Outcome And Gut Development After Insulin-Like Growth Factor-1 Supplementation To Preterm Pigs, Kristine Holgersen, Martin Bo Rasmussen, Galen Carey, Douglas G Burrin, Thomas Thymann, Per Torp Sangild

Faculty, Staff and Students Publications

BACKGROUND: Elevation of circulating insulin-like growth factor-1 (IGF-1) within normal physiological levels may alleviate several morbidities in preterm infants but safety and efficacy remain unclear. We hypothesized that IGF-1 supplementation during the first 1-2 weeks after preterm birth improves clinical outcomes and gut development, using preterm pigs as a model for infants.

METHODS: Preterm pigs were given vehicle or recombinant human IGF-1/binding protein-3 (rhIGF-1, 2.25 mg/kg/d) by subcutaneous injections for 8 days (Experiment 1, n = 34), or by systemic infusion for 4 days (Experiment 2, n = 19), before collection of blood and organs for analyses.

RESULTS: In both …

The Third International Hackathon For Applying Insights Into Large-Scale Genomic Composition To Use Cases In A Wide Range Of Organisms, Kimberly Walker, Divya Kalra, Rebecca Lowdon, Guangyi Chen, David Molik, Daniela C Soto, Fawaz Dabbaghie, Ahmad Al Khleifat, Medhat Mahmoud, Luis F Paulin, Muhammad Sohail Raza, Susanne P Pfeifer, Daniel Paiva Agustinho, Elbay Aliyev, Pavel Avdeyev, Enrico R Barrozo, Sairam Behera, Kimberley Billingsley, Li Chuin Chong, Deepak Choubey, Wouter De Coster, Yilei Fu, Alejandro R Gener, Timothy Hefferon, David Morgan Henke, Wolfram Höps, Anastasia Illarionova, Michael D Jochum, Maria Jose, Rupesh K Kesharwani, Sree Rohit Raj Kolora, Jędrzej Kubica, Priya Lakra, Damaris Lattimer, Chia-Sin Liew, Bai-Wei Lo, Chunhsuan Lo, Anneri Lötter, Sina Majidian, Suresh Kumar Mendem, Rajarshi Mondal, Hiroko Ohmiya, Nasrin Parvin, Carolina Peralta, Chi-Lam Poon, Ramanandan Prabhakaran, Marie Saitou, Aditi Sammi, Philippe Sanio, Nicolae Sapoval, Najeeb Syed, Todd Treangen, Gaojianyong Wang, Tiancheng Xu, Jianzhi Yang, Shangzhe Zhang, Weiyu Zhou, Fritz J Sedlazeck, Ben Busby

Faculty, Staff and Students Publications

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.

Adrenomedullin And Its Receptors Are Expressed In Mouse Pancreatic Β-Cells And Suppresses Insulin Synthesis And Secretion, Yuanlin Dong, Simone Hernandez Ruano, Akansha Mishra, Kathleen A Pennington, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, …

Selective Vulnerability Of The Intermediate Retinal Capillary Plexus Precedes Retinal Ganglion Cell Loss In Ocular Hypertension, Priyamvada M Pitale, Guofu Shen, Rohini R Sigireddi, Maria Polo-Prieto, Yong H Park, Solomon E Gibson, Peter D Westenskow, Roomasa Channa, Benjamin J Frankfort

Faculty, Staff and Students Publications

Introduction: Glaucoma, a disease of retinal ganglion cell (RGC) injury and potentially devastating vision loss, is associated with both ocular hypertension (OHT) and reduced ocular blood flow. However, the relationship between OHT and retinal capillary architecture is not well understood. In this project, we studied microvasculature damage in mice exposed to mild levels of induced OHT.

Methods: Mild OHT was induced with the microbead model for 2 weeks. At this time point, some retinas were immunostained with CD31 (endothelium), Collagen IV (basement membrane), and RBPMS (RGCs) for z-stack confocal microscopy. We processed these confocal images to distinguish the three retinal …

Problems In Csf And Ophthalmic Disease Research, Ryan Machiele, Benjamin Jay Frankfort, Hanspeter Esriel Killer, David Fleischman

Faculty, Staff and Students Publications

There has been significant interest and progress in the understanding of cerebrospinal fluid pressure and its relationship to glaucoma and other ophthalmic diseases. However, just as every physiologic fluid pressure fluctuates, cerebrospinal fluid pressure (CSFP) is similarly dynamic. Coupling this with the difficulty in measuring the pressure, there are many obstacles in furthering this field of study. This review highlights some of the difficulties in CSFP research, including fluid compartmentalization, estimation equations, and pressure fluctuation. Keeping these limitations in mind will hopefully improve the quality and context of this burgeoning field.

Systematic Profiling Of Dnmt3a Variants Reveals Protein Instability Mediated By The Dcaf8 E3 Ubiquitin Ligase Adaptor, Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell

Faculty, Staff and Students Publications

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and acute …

Selectively Targeting Disease-Restricted Secretogranin Iii To Alleviate Choroidal Neovascularization, Liyang Ji, Prabuddha Waduge, Lili Hao, Avinash Kaur, Wencui Wan, Yan Wu, Hong Tian, Jinsong Zhang, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Choroidal neovascularization (CNV), a leading cause of blindness in the elderly, is routinely treated with vascular endothelial growth factor (VEGF) inhibitors that have limited efficacy and potentially adverse side effects. An unmet clinical need is to develop novel therapies against other angiogenic factors for alternative or combination treatment to improve efficacy and safety. We recently described secretogranin III (Scg3) as a disease-selective angiogenic factor, causally linked to diabetic retinopathy and acting independently of the VEGF pathway. An important question is whether such a disease-selective Scg3 pathway contributes to other states of pathological angiogenesis beyond diabetic retinopathy. By applying a novel …

Gut Microbiota From Sjögren Syndrome Patients Causes Decreased T Regulatory Cells In The Lymphoid Organs And Desiccation-Induced Corneal Barrier Disruption In Mice, Laura Schaefer, Claudia M Trujillo-Vargas, Firas S Midani, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Sjögren syndrome (SS) is an autoimmune inflammatory disorder characterized by secretory dysfunction in the eye and mouth; in the eye, this results in tear film instability, reduced tear production, and corneal barrier disruption. A growing number of studies show that homeostasis of the ocular surface is impacted by the intestinal microbiome, and several 16S sequencing studies have demonstrated dysbiosis of the intestinal microbiota in SS patients. In this study, we utilized metagenomic sequencing to perform a deeper analysis of the intestinal microbiome using stools collected from sex- and age-matched healthy (n = 20), dry eye (n = 4) …

Interleukin-1Β Secretion Induced By Mucosa-Associated Gut Commensal Bacteria Promotes Intestinal Barrier Repair, Wan-Jung H Wu, Myunghoo Kim, Lin-Chun Chang, Adrien Assie, Fatima B Saldana-Morales, Daniel F Zegarra-Ruiz, Kendra Norwood, Buck S Samuel, Gretchen E Diehl

Faculty, Staff and Students Publications

The gut microbiota is essential for maintenance and repair of the intestinal epithelial barrier. As shifts in both intestinal epithelial barrier function and microbiota composition are found in inflammatory bowel disease patients, it is critical to understand the role of distinct bacteria in regulating barrier repair. We identified a mouse commensal E. coli isolate, GDAR2-2, that protects mice from Citrobacter rodentium infection and dextran sulfate sodium-induced colitis. Colonization with GDAR2-2 in mice resulted in expansion of CX3CR1+ mononuclear phagocytes, including CX3CR1+ macrophages/dendritic cells and monocytes, along with IL-22-secreting type 3 innate lymphoid cells and improved epithelial barrier function. In vitro …

Clonal Hematopoiesis Analyses In Clinical, Epidemiologic, And Genetic Aging Studies To Unravel Underlying Mechanisms Of Age-Related Dysfunction In Humans, Kenneth Walsh, Nalini Raghavachari, Candace Kerr, Alexander G Bick, Steven R Cummings, Todd Druley, Cynthia E Dunbar, Giulio Genovese, Margaret A Goodell, Siddhartha Jaiswal, Jaroslaw Maciejewski, Pradeep Natarajan, Anastasia V Shindyapina, Alan R Shuldiner, Erik B Van Den Akker, Jan Vijg

Faculty, Staff and Students Publications

Aging is characterized by increased mortality, functional decline, and exponential increases in the incidence of diseases such as cancer, stroke, cardiovascular disease, neurological disease, respiratory disease, etc. Though the role of aging in these diseases is widely accepted and considered to be a common denominator, the underlying mechanisms are largely unknown. A significant age-related feature observed in many population cohorts is somatic mosaicism, the detectable accumulation of somatic mutations in multiple cell types and tissues, particularly those with high rates of cell turnover (e.g., skin, liver, and hematopoietic cells). Somatic mosaicism can lead to the development of cellular clones that …

Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li

Faculty, Staff and Students Publications

Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone …

Nuclear Progesterone Receptor Expressed By The Cortical Thymic Epithelial Cells Dictates Thymus Involution In Murine Pregnancy, Soo Hyun Ahn, Sean L Nguyen, Tae Hoon Kim, Jae-Wook Jeong, Ripla Arora, John P Lydon, Margaret G Petroff

Faculty, Staff and Students Publications

Progesterone is a gonadal pro-gestational hormone that is absolutely necessary for the success of pregnancy. Most notable actions of progesterone are observed in the female reproductive organs, the uterus and the ovary. Acting through the nuclear progesterone receptor (PGR), progesterone prepares the endometrium for implantation of the embryo. Interestingly, the maternal thymus also is a known expressor of Pgr; its absence is associated with murine pregnancy complications. However, the localization of its expression and its functional importance were not known. Here, we used a transgenic dual fluorescent reporter mouse model and genetic deletion of Pgr in Foxn1+ thymic epithelial …

Rotavirus-Induced Lipid Droplet Biogenesis Is Critical For Virus Replication, Jeanette M Criglar, Mary K Estes, Sue E Crawford

Faculty, Staff and Students Publications

A variety of pathogens, including viruses, bacteria and parasites, target cellular lipid droplets for their replication. Rotaviruses (RVs) infect the villous epithelium of the small intestine and are a major cause of acute gastroenteritis in infants and young children worldwide. RVs induce and require lipid droplets for the formation of viroplasms, sites of virus genome replication, and nascent particle assembly. Here we review the role of lipid droplets in RV replication. Inhibitors of fatty acid synthesis or chemicals that interfere with lipid droplet homeostasis decrease the number and size of viroplasms and the yield of infectious virus. We used a …

Development Of Phage Cocktails To Treate Coli Catheter-Associated Urinary Tract Infection And Associated Biofilms, Belkys C Sanchez, Emmaline R Heckmann, Sabrina I Green, Justin R Clark, Heidi B Kaplan, Robert F Ramig, Casey Hines-Munson, Felicia Skelton, Barbara W Trautner, Anthony W Maresso

Faculty, Staff and Students Publications

High rates of antimicrobial resistance and formation of biofilms makes treatment of Escherichia coli catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particularly as an etiology for sepsis. Phage have been proposed as a potential therapeutic option. Here, we report the development of phage cocktails that lyse contemporary E. coli strains isolated from the urine of patients with spinal cord injury (SCI) and display strong biofilm-forming properties. We characterized E. coli phage against biofilms in two in vitro CAUTI models. Biofilm viability was …

Modified Vaccinia Ankara Expressing Eehv1a Glycoprotein B Elicits Humoral And Cell-Mediated Immune Responses In Mice, Taylor Pursell, Jennifer L Spencer Clinton, Jie Tan, Rongsheng Peng, Paul D Ling

Faculty, Staff and Students Publications

Elephant endotheliotropic herpesvirus (EEHV) can cause lethal hemorrhagic disease (EEHV-HD) in Asian elephants and is the largest cause of death in captive juvenile Asian elephants in North America and Europe. EEHV-HD also has been documented in captive and wild elephants in their natural range countries. A safe and effective vaccine to prevent lethal EEHV infection would significantly improve conservation efforts for this endangered species. Recent studies from our laboratory suggest that EEHV morbidity and mortality are often associated with primary infection. Therefore, we aim to generate a vaccine, particularly for EEHV1 naïve animals, with the goal of preventing lethal EEHV-HD. …

Threat Imminence Reveals Links Among Unfolding Of Anticipatory Physiological Response, Cortical-Subcortical Intrinsic Functional Connectivity, And Anxiety, Rany Abend, Sonia G. Ruiz, Mira A. Bajaj, Anita Harrewijn, Julia O. Linke, Lauren Y. Atlas, Anderson M. Winkler, Daniel S. Pine

School of Medicine Publications

Excessive expression of fear responses in anticipation of threat occurs in anxiety, but understanding of underlying pathophysiological mechanisms is limited. Animal research indicates that threat-anticipatory defensive responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from basic neuroscience research in animals on threat imminence could guide mechanistic research in humans mapping abnormal function in this circuitry to aberrant defensive responses in pathological anxiety.

50 pediatric anxiety patients and healthy-comparisons (33 females) completed an instructed threat-anticipation task whereby cues signaled delivery of painful (threat) or non-painful (safety) thermal stimulation. Temporal changes in skin-conductance indexed anxiety effects on …

Sex-Dependent Shared And Nonshared Genetic Architecture Across Mood And Psychotic Disorders, Gabriëlla A. M. Blokland, Jakob Grove, Chia Yen Chen, Chris Cotsapas, Ney Alliey Rodriguez

School of Medicine Publications

Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10^{−8 …}

Epidemiology And Characteristics Of Chronic Pancreatitis—Do The East And West Meet?, Nikita Desai, Tarun Kaura, Maharaj Singh, Field F. Willingham, Surinder Rana, Saurabh Chawla

College of Nursing Faculty Research and Publications

Background and Aims

Previous large studies on the epidemiology and clinical profile of chronic pancreatitis have suggested significant differences in presentation and management in the eastern and western hemispheres. The aim of this systematic review was to compare large multicenter studies across different geographic regions of the world to detect meaningful differences in the presentation and management of this poorly understood disease.

Methods

We identified 237 manuscripts through a comprehensive literature review aiming to identify multicenter studies enrolling more than 200 patients to limit reporting biases. After rigorous screening, 12 studies were included for the final analysis. The Asian studies …

Research Symposium 2022: International Conference On Health Disparities: Treatment And Recovery From Opioid And Alcohol Use Disorders And Related Comorbidities (Ichd-Recover), The University Of Texas Rio Grande Valley. School Of Medicine

School of Medicine Publications

No abstract provided.

Meta-Analysis Comparing Outcomes Of High-Power Short-Duration And Low-Power Long-Duration Radiofrequency Ablation For Atrial Fibrillation, Dibbendhu Khanra, Abdul Hamid, Saurabh Deshpande, Anindya Mukherjee, Sanjiv Petkar, Mohammad Saeed, Indranill Basu-Ray

Faculty, Staff and Students Publications

OBJECTIVE: High power short duration (HPSD) ablation strategy is proposed to be more effective than low power long duration (LPLD) for radiofrequency ablation of atrial fibrillation. Although small trials abound, data from a large cohort are lacking. This meta-analysis compares all the existing studies comparing these two approaches to evaluate perceived advantages of one over the other.

METHODS: A systematic search of PubMed, EMBASE, and Cochrane databases identified studies comparing HPSD to LPLD ablation. All the analyses used the random-effects model.

RESULTS: Ablation settings varied widely across 20 studies comprising 2,136 patients who underwent HPSD and 1,753 patients who underwent …

Exercise-Induced Myokines Downregulates The Ace2 Level In Bronchial Epithelial Cells: Implications For Sars-Cov-2 Prevention, Vaishali Bhardwaj, Mart Dela Cruz, Deepika Subramanyam, Rohit Kumar, Sandeep Markan, Beth Parker, Hemant K Roy

Faculty, Staff and Students Publications

BACKGROUND: The Covid-19 pandemic has emerged as the leading public health challenge of our time (20th century). While vaccinations have finally blunted the death rate, concern has remained about more virulent forms highlighting the need for alternative approaches. Epidemiological studies indicate that physical activity has been shown to decrease the risk of infection of some respiratory viruses. Part of the salutary effects of exercise is believed to be through the elaboration of cytokines by contracting skeletal muscles (termed myokines). The objective of this study was to investigate whether exercise-induced myokines would mitigate the SARS-CoV-2 infectivity of the bronchial epithelium through …

Native And Non-Native Plant Species Differentially Affect Arthropod Community Dynamics With Consequences For Crop Production In Lower Rio Grande Valley, Kaitlynn Lavallee, Pushpa G. Soti, Alexis Racelis, Rupesh R. Kariyat

School of Earth, Environmental, & Marine Sciences Faculty Publications

In agricultural ecosystems, arthropods play critical roles- including biocontrol, pollination services, and as herbivores. While herbivory negatively affects crop production, the recent decline in beneficial insect numbers have created a global concern, and consequently have led into multiple lines of conservation strategies. Agroecological practices that can provide sustenance, nesting, and refuge for beneficial organisms are considered as some of them, except we lack a better understanding of how seasonal and crop specific variation can affect their community dynamics. In this study, we examined this by investigating how native and non-native plants, when incorporated into a vegetable agroecosystem in Lower Rio …

Pcsk9 Inhibitors In The Management Of Cardiovascular Risk: A Practical Guidance, Xiaoming Jia, Mahmoud Al Rifai, Anum Saeed, Christie M Ballantyne, Salim S Virani

Faculty, Staff and Students Publications

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent medications in the toolkit for treatment of atherosclerotic cardiovascular disease. These agents have been well studied in clinical trials supporting their efficacy in dramatically reducing low-density lipoprotein cholesterol (LDL-C) and impact on cardiovascular outcomes. Since the approval of commercial use for PCSK9 inhibitors in 2015, we have also gained significant experience in the use of these therapeutics in the real-world setting. In this article, we review current guideline recommendations, clinical trial evidence on efficacy and safety as well as data on cost-effectiveness, prescription and adherence. We focus primarily on the monoclonal …

In Silico Integrative Analysis Of Multi-Omics Reveals Regulatory Layers For Diurnal Gene Expression In Mouse Liver, Chunjie Jiang, Panpan Liu, Cam Mong La, Dongyin Guan

Faculty, Staff and Students Publications

Diurnal oscillation persists throughout the body and plays an essential role in maintaining physiological homeostasis. Disruption of diurnal rhythm contributes to many diseases including type 2 diabetes. The regulatory mechanism of the transcription-translation feedback loop (TTFL) of core clock genes is well-established, while a systematic study across all regulatory layers of gene expression, including gene transcription, RNA translation, and DNA binding protein (DBP) activities, is still lacking. We comprehensively bioinformatics analyzed the rhythmicity of gene transcription, mature RNA abundance, protein abundance and DBP activity using publicly available omic-datasets from mouse livers. We found that the core clock genes,

Genetic And Genomic Architecture In Eight Strains Of The Laboratory Opossum Monodelphis Domestica, Xiao Xiong, Paul B. Samollow, Wenqi Cao, Richard Metz, Chao Zhang, Ana C. Leandro, John L. Vandeberg, Xu Wang

School of Medicine Publications

The gray short-tailed opossum (Monodelphis domestica) is an established laboratory-bred marsupial model for biomedical research. It is a critical species for comparative genomics research, providing the pivotal phylogenetic outgroup for studies of derived vs ancestral states of genomic/epigenomic characteristics for eutherian mammal lineages. To characterize the current genetic profile of this laboratory marsupial, we examined 79 individuals from eight established laboratory strains. Double digest restriction site-associated DNA sequencing and whole-genome resequencing experiments were performed to investigate the genetic architecture in these strains. A total of 66,640 highquality single nucleotide polymorphisms (SNPs) were identified. We analyzed SNP density, average heterozygosity, nucleotide …

Reciprocal Regulation Of Mitofusin 2-Mediated Mitophagy And Mitochondrial Fusion By Different Pink1 Phosphorylation Events, Jiajia Li, Xiawei Dang, Antonietta Franco, Gerald W Dorn

2020-Current year OA Pubs

Mitochondrial repair is essential to metabolic homeostasis. Outer mitochondrial membrane mitofusin (MFN) proteins orchestrate mitochondrial fusion that opposes mitochondrial degeneration caused by senescence. Depending upon physiological context, MFN2 can either mediate mitochondrial fusion or recruit cytosolic Parkin to initiate mitophagic elimination. Because it is not clear how these events are counter-regulated we engineered and expressed MFN2 mutants that mimic phosphorylated or non-phosphorylatable MFN2 at its PINK1 phosphorylation sites: T111, S378, and S442. By interrogating mitochondrial fusion, polarization status, and Parkin binding/mitophagy as a function of inferred MFN2 phosphorylation, we discovered that individual MFN2 phosphorylation events act as a biological "bar-code", …

Channa Reddy In Telangana Statehood Movement: Initiation, Intervention And Contribution, Jakkula Koteswar Rao, Ram Shepherd Bheenaveni

School of Social Work Faculty Publications

The present paper tries to explore some of the repeated accusations and half-truths against the Telangana leader – Dr. Marri Channa Reddy, who led the movement in 1969. It is believed that the leaders started the Telangana Statehood movement as a problem-solving movement against subregionalism. Dr. Reddy was a staunch opponent of Andhra’s internal colonization. This is not only absurd but also a parody of the truth. This is mainly due to the lack of original documents in an organized campaign for the separate state of Telangana. The print and electronic media reports speak of alarming national integration at the …