Medical Microbiology Commons^™

P2y2 Purinergic Receptor Gene Deletion Protects Mice From Bacterial Endotoxin And Sepsis-Associated Liver Injury And Mortality, Athis R Arunachalam, Sanju S Samuel, Arunmani Mani, Janielle P Maynard, Kelsey M Stayer, Eric Dybbro, Subapradha Narayanan, Aalekhya Biswas, Saliha Pathan, Krishnakant Soni, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Moreshwar S Desai, Sundararajah Thevananther

Faculty, Staff and Students Publications

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications …

Targeted Inhibition Of Lncrna Malat1 Alters The Tumor Immune Microenvironment In Preclinical Syngeneic Mouse Models Of Triple-Negative Breast Cancer, Oluwatoyosi Adewunmi, Yichao Shen, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Long noncoding RNAs (lncRNA) play an important role in gene regulation in both normal tissues and cancer. Targeting lncRNAs is a promising therapeutic approach that has become feasible through the development of gapmer antisense oligonucleotides (ASO). Metastasis-associated lung adenocarcinoma transcript (Malat1) is an abundant lncRNA whose expression is upregulated in several cancers. Although Malat1 increases the migratory and invasive properties of tumor cells, its role in the tumor microenvironment (TME) is still not well defined. We explored the connection between Malat1 and the tumor immune microenvironment (TIME) using several immune-competent preclinical syngeneic Tp53-null triple-negative breast cancer (TNBC) mouse models that …

Pax3 Lineage-Specific Deletion Of Gpr161 Is Associated With Spinal Neural Tube And Craniofacial Malformations During Embryonic Development, Sung-Eun Kim, Pooja J Chothani, Rehana Shaik, Westley Pollard, Richard H Finnell

Faculty, Staff and Students Publications

Sonic hedgehog (Shh) signaling is the morphogen signaling that regulates embryonic craniofacial and neural tube development. G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling, and its inactivation in mice results in embryo lethality associated with craniofacial defects and neural tube defects. However, the structural defects of later embryonic stages and cell lineages underlying abnormalities have not been well characterized due to the limited lifespan of Gpr161 null mice. We found that embryos with Pax3 lineage-specific deletion of Gpr161 presented with tectal hypertrophy (anterior dorsal neuroepithelium), cranial vault and facial bone hypoplasia (cranial neural crest), vertebral abnormalities …

International Union Of Basic And Clinical Pharmacology Cxiii: Nuclear Receptor Superfamily-Update 2023, Thomas P Burris, Ian Mitchelle S De Vera, Isabelle Cote, Colin A Flaveny, Udayanga S Wanninayake, Arindam Chatterjee, John K Walker, Nickolas Steinauer, Jinsong Zhang, Laurel A Coons, Kenneth S Korach, Derek W Cain, Anthony N Hollenberg, Paul Webb, Douglas Forrest, Anton M Jetten, Dean P Edwards, Sandra L Grimm, Sean Hartig, Carol A Lange, Jennifer K Richer, Carol A Sartorius, Marc Tetel, Cyrielle Billon, Bahaa Elgendy, Lamees Hegazy, Kristine Griffett, Nahuel Peinetti, Kerry L Burnstein, Travis S Hughes, Sadichha Sitaula, Keitch R Stayrook, Alexander Culver, Meghan H Murray, Brian N Finck, John A Cidlowski

Faculty, Staff and Students Publications

The NR superfamily comprises 48 transcription factors in humans that control a plethora of gene network programs involved in a wide range of physiologic processes. This review will summarize and discuss recent progress in NR biology and drug development derived from integrating various approaches, including biophysical techniques, structural studies, and translational investigation. We also highlight how defective NR signaling results in various diseases and disorders and how NRs can be targeted for therapeutic intervention via modulation via binding to synthetic lipophilic ligands. Furthermore, we also review recent studies that improved our understanding of NR structure and signaling. SIGNIFICANCE STATEMENT: Nuclear …

Gastrointestinal Infections Modulate The Risk For Insulin Autoantibodies As The First-Appearing Autoantibody In The Teddy Study, Maria Lönnrot, Kristian F Lynch, Marian Rewers, Åke Lernmark, Kendra Vehik, Beena Akolkar, William Hagopian, Jeffrey Krischer, Rickhard A Mcindoe, Jorma Toppari, Anette-G Ziegler, Joseph F Petrosino, Richard Lloyd, Heikki Hyöty, Teddy Study Group

Faculty, Staff and Students Publications

OBJECTIVE: To investigate gastrointestinal infection episodes (GIEs) in relation to the appearance of islet autoantibodies in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort.

RESEARCH DESIGN AND METHODS: GIEs on risk of autoantibodies against either insulin (IAA) or GAD (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7,867 children. Stool virome was characterized in a nested case-control study.

RESULTS: GIE reports (odds ratio [OR] 2.17 [95% CI 1.39-3.39]) as well as Norwalk viruses found in stool (OR 5.69 [1.36-23.7]) at(OR 0.48 [0.35-0.68]). GIE reports at any other age were associated with an increase in …

Tumor-Resident Lactobacillus Iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring, Lauren E. Colbert, Molly B. El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J. Lynn, Timothy A. Harris, Jacob H. Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K. Bronk, Julie Sammouri, Ananta V. Yanamandra, Adilene V. Olvera, Lily G. Carlin, Travis Sims, Andrea Y. Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O. Abana, Hannah X. Li, Patricia J. Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M. Ramondetta, Andrew M. Futreal

School of Medicine Faculty Publications

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other …

The Effect Of Heat-Moisture Treatment Changed The Binding Of Starch, Protein And Lipid In Rice Flour To Affect Its Hierarchical Structure And Physicochemical Properties, Seung Hee Yoo, Mi Jin Jue, Yu-Hee Kim, Sooyoung Cho, Won-Joong Kim, Kye-Min Kim, Jong In Han, Heeseung Lee

Faculty, Staff and Student Publications

Dexmedetomidine prevents postoperative cognitive dysfunction by inhibiting high-mobility group box 1 (HMGB1), which acts as an inflammatory marker. This study investigated the HMGB1 levels and the cognitive function using a Mini-Cog© score in elderly patients undergoing orthopedic surgery with dexmedetomidine infusion. In total, 128 patients aged ≥ 65 years were analyzed. The patients received saline in the control group and dexmedetomidine in the dexmedetomidine group until the end of surgery. Blood sampling and the Mini-Cog© test were performed before the surgery and on postoperative days 1 and 3. The primary outcomes were the effect of dexmedetomidine on the HMGB1 levels …

A Retrospective, Observational Study Of 12 Cases Of Expanded-Access Customized Phage Therapy: Production, Characteristics, And Clinical Outcomes, Sabrina I Green, Justin R Clark, Haroldo H Santos, Kyle E Weesner, Keiko C Salazar, Saima Aslam, J William Campbell, Sarah B Doernberg, Emily Blodget, Michele I Morris, Gina A Suh, Karam Obeid, Fernanda P Silveira, Andrey A Filippov, Katrine L Whiteson, Barbara W Trautner, Austen L Terwilliger, Anthony Maresso

Faculty, Staff and Students Publications

BACKGROUND: Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections.

METHODS: We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration-approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related …

Rare Case Of Prosthetic Joint Infection Caused By Salmonella Enterica - A Case Report, Carlos Ramos, Shyama Appareddy, Peter J. Gonzalez

Research Colloquium

Introduction: Collectively, over 1 million total knee arthroplasties (TKA) and total hip arthroplasties (THA) are performed in the United States each year. In 2010 it was estimated that 1.58% of the United States general population has received a TKA. Prosthetic joint infections (PJI) are the most common indication for a TKA revision1 . In total, S. aureus is responsible for about 50% of all prosthetic joint infections, and about 15% are caused by gram negative pathogens2 .

Objective: This is a case report which describes the presentation and clinical course of a 59-yearold female with Salmonella enterica septic arthritis of …

Functional Analysis Reveals Driver Cooperativity And Novel Mechanisms In Endometrial Carcinogenesis, Matthew Brown, Alicia Leon, Katarzyna Kedzierska, Charlotte Moore, Hayley L Belnoue-Davis, Susanne Flach, John P Lydon, Francesco J Demayo, Annabelle Lewis, Tjalling Bosse, Ian Tomlinson, David N Church

Faculty, Staff and Students Publications

High-risk endometrial cancer has poor prognosis and is increasing in incidence. However, understanding of the molecular mechanisms which drive this disease is limited. We used genetically engineered mouse models (GEMM) to determine the functional consequences of missense and loss of function mutations in Fbxw7, Pten and Tp53, which collectively occur in nearly 90% of high-risk endometrial cancers. We show that Trp53 deletion and missense mutation cause different phenotypes, with the latter a substantially stronger driver of endometrial carcinogenesis. We also show that Fbxw7 missense mutation does not cause endometrial neoplasia on its own, but potently accelerates carcinogenesis caused by Pten …

Dbapis: A Database Of Anti-Prokaryotic Immune System Genes, Yuchen Yan, Jinfang Zheng, Xinpeng Zhang, Yanbin Yin

Food for Health: Publications

Anti-prokary otic immune sy stem (APIS) proteins, typically encoded b y phages, prophages, and plasmids, inhibit prokaryotic immune systems (e.g. restriction modification, to xin-antito xin, CRISPR-Cas). A gro wing number of APIS genes ha v e been characterized and dispersed in the literature. Here w e de v eloped dbAPIS ( https:// bcb.unl.edu/ dbAPIS ), as the first literature curated data repository for experimentally verified APIS genes and their associated protein f amilies. T he k e y features of dbAPIS include: (i) e xperimentally v erified APIS genes with their protein sequences, functional annotation, PDB or AlphaFold predicted str …

Catheter-Associated Urinary Tract Infections: Patient Characteristics, Treatment, And Clinical Outcomes In One South Texas Acute Care Hospital, Kimberly A. Ambrosini, Jose Campo Maldonado

Research Colloquium

Background: Catheter-associated urinary tract infections (CA-UTIs) account for 40 percent of nosocomial infections worldwide. Their elimination is at the forefront of quality improvement in one South Texas acute care hospital.

Methods: Over a period of 6 months, five CA-UTIs occurred in one South Texas acute care hospital. These cases were identified via regular surveillance by Infection Prevention staff and the Laboratory Department of the hospital. This research reviews patient age, sex, length of stay, bacteria contracted, appropriate antibiotic use, patient characteristics, and overall outcomes.

Results: Between the months of July and December 2021, 5 CAUTIs were contracted. Patients ranged in …

Report Of The Assay Guidance Workshop On 3-Dimensional Tissue Models For Antiviral Drug Development, Robert Jordan, Stephanie L Ford-Scheimer, Rodolfo M Alarcon, Anthony Atala, Jeffrey T Borenstein, Kyle R Brimacombe, Sara Cherry, Hans Clevers, Mindy I Davis, Simon G P Funnell, Lee Gehrke, Linda G Griffith, Abigail C Grossman, Thomas Hartung, Donald E Ingber, Nicole C Kleinstreuer, Calvin J Kuo, Emily M Lee, Christine L Mummery, Thames E Pickett, Sasirekha Ramani, Edwin A Rosado-Olivieri, Evi B Struble, Zhengpeng Wan, Mark S Williams, Matthew D Hall, Marc Ferrer, Sarine Markossian

Faculty, Staff and Students Publications

The National Center for Advancing Translational Sciences (NCATS) Assay Guidance Manual (AGM) Workshop on 3D Tissue Models for Antiviral Drug Development, held virtually on 7-8 June 2022, provided comprehensive coverage of critical concepts intended to help scientists establish robust, reproducible, and scalable 3D tissue models to study viruses with pandemic potential. This workshop was organized by NCATS, the National Institute of Allergy and Infectious Diseases, and the Bill and Melinda Gates Foundation. During the workshop, scientific experts from academia, industry, and government provided an overview of 3D tissue models' utility and limitations, use of existing 3D tissue models for antiviral …

A Pancreatic Player In Dementia: Pathological Role For Islet Amyloid Polypeptide Accumulation In The Brain, Angelina S Bortoletto, Ronald J Parchem

Faculty, Staff and Students Publications

Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia. While multiple factors contribute to this predisposition, one of these involves the increased secretion of amylin, or islet amyloid polypeptide, that accompanies the pathophysiology of type 2 diabetes mellitus. Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia, including Alzheimer’s disease and vascular dementia, but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear. In this review, we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage, ultimately leading to …

Human Intestinal Organoids As Models To Study Enteric Bacteria And Viruses, Grace Adeniyi-Ipadeola, Hephzibah Nwanosike, Sasirekha Ramani

Faculty, Staff and Students Publications

Laboratory studies of host-microbe interactions have historically been carried out using transformed cell lines and animal models. Although much has been learned from these models, recent advances in the development of multicellular, physiologically active, human intestinal organoid (HIO) cultures are allowing unprecedented discoveries of host-microbe interactions. Here, we review recent literature using HIOs as models to investigate the pathogenesis of clinically important enteric bacteria and viruses and study commensal intestinal microbes. We also discuss limitations of current HIO culture systems and how technical advances and innovative engineering approaches are providing new directions to improve the model. The studies discussed here …

Phenotype And Fate Of Liver-Resident Cd8 T Cells During Acute And Chronic Hepacivirus Infection, Piyush Dravid, Satyapramod Murthy, Zayed Attia, Cole Cassady, Rahul Chandra, Sheetal Trivedi, Ashish Vyas, John Gridley, Brantley Holland, Anuradha Kumari, Arash Grakoui, John M Cullen, Christopher M Walker, Himanshu Sharma, Amit Kapoor

Faculty, Staff and Student Publications

Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and chronic rodent HCV-like virus (RHV) infections in lab mice. Here, we developed MHC class I and class II tetramers to characterize the serial changes in RHV-specific CD8 and CD4 T cells during acute and chronic infection in C57BL/6J mice. RHV infection induced rapid expansion of T cells targeting viral structural and nonstructural proteins. After virus clearance, the virus-specific T cells transitioned from effectors to long-lived liver-resident memory T cells (TRM). The effector and …

Development Of A Xylose-Inducible Promoter And Riboswitch Combination System For Manipulating Gene Expression In Fusobacterium Nucleatum, Bibek G C, Peng Zhou, Arindam Naha, Jianhua Gu, Chenggang Wu

Faculty, Staff and Student Publications

Inducible gene expression systems are important for studying bacterial gene function, yet most exhibit leakage. In this study, we engineered a leakage-free hybrid system for precise gene expression controls in Fusobacterium nucleatum by integrating the xylose-inducible expression system with the theophylline-responsive riboswitch. This innovative method enables concurrent control of target gene expression at both transcription and translation initiation levels. Using luciferase and the indole-producing enzyme tryptophanase (TnaA) as reporters, we demonstrated that the hybrid system displays virtually no observable signal in the absence of inducers. We employed this system to express FtsX, a protein related to fusobacterial cytokinesis, in an …

Oral Dosages Of The Nsaid Aspirin Decreased The Growth Rate Of Species Found In The Human Gut Microbiome Including Akkermansia Muciniphila, Bacteroides Fragilis, Clostridium Sordellii, And Clostridium Difficile, Wyatt H. Greenbaum, Garrett J. Greenbaum, Anna Spiezio

PANDION: The Osprey Journal of Research and Ideas

Over past few decades, new insight has been revealed in the scientific community about the importance of the human gut microbiome relating to general health. It is known that imbalances in the species that reside in the human gut can cause organism-wide problems in humans. When prescribing or injecting oral medications, the thought of the downstream effects on the gut microbiome are not always considered. By exposing known healthy members of the gut; Akkermansia muciniphila, Bacteroides fragilis, Clostridium sordellii, and Clostridium difficile to the Aspirin, this study attempted to provide insight into the effects of the drug on bacterial growth. …

Transcriptomic Analysis Of Stem Cells From Chorionic Villi Uncovers The Impact Of Chromosomes 2, 6 And 22 In The Clinical Manifestations Of Down Syndrome, Salvatore Vaiasicca, Gianmarco Melone, David W James, Marcos Quintela, Alessandra Preziuso, Richard H Finnell, Robert Steven Conlan, Lewis W Francis, Bruna Corradetti

Faculty, Staff and Students Publications

BACKGROUND: Down syndrome (DS) clinical multisystem condition is generally considered the result of a genetic imbalance generated by the extra copy of chromosome 21. Recent discoveries, however, demonstrate that the molecular mechanisms activated in DS compared to euploid individuals are more complex than previously thought. Here, we utilize mesenchymal stem cells from chorionic villi (CV) to uncover the role of comprehensive functional genomics-based understanding of DS complexity.

METHODS: Next-generation sequencing coupled with bioinformatic analysis was performed on CV obtained from women carrying fetuses with DS (DS-CV) to reveal specific genome-wide transcriptional changes compared to their euploid counterparts. Functional assays were …

Applications Of Degradable Hydrogels In Novel Approaches To Disease Treatment And New Modes Of Drug Delivery, Bo Hu, Jinyuan Gao, Yu Lu, Yuji Wang

Faculty, Staff and Student Publications

Hydrogels are particularly suitable materials for loading drug delivery agents; their high water content provides a biocompatible environment for most biomolecules, and their cross-linked nature protects the loaded agents from damage. During delivery, the delivered substance usually needs to be released gradually over time, which can be achieved by degradable cross-linked chains. In recent years, biodegradable hydrogels have become a promising technology in new methods of disease treatment and drug delivery methods due to their many advantageous properties. This review briefly discusses the degradation mechanisms of different types of biodegradable hydrogel systems and introduces the specific applications of degradable hydrogels …

Global Proteomic Identifies Multiple Cancer-Related Signaling Pathways Altered By A Gut Pathobiont Associated With Colorectal Cancer, Ewa Pasquereau-Kotula, Giulia Nigro, Florent Dingli, Damarys Loew, Patrick Poullet, Yi Xu, Scott Kopetz, Jennifer Davis, Lucie Peduto, Catherine Robbe-Masselot, Philippe Sansonetti, Patrick Trieu-Cuot, Shaynoor Dramsi

Faculty, Staff and Student Publications

In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of …

Proteogenomic Insights Suggest Druggable Pathways In Endometrial Carcinoma, Yongchao Dou, Lizabeth Katsnelson, Marina A Gritsenko, Yingwei Hu, Boris Reva, Runyu Hong, Yi-Ting Wang, Iga Kolodziejczak, Rita Jui-Hsien Lu, Chia-Feng Tsai, Wen Bu, Wenke Liu, Xiaofang Guo, Eunkyung An, Rebecca C Arend, Jasmin Bavarva, Lijun Chen, Rosalie K Chu, Andrzej Czekański, Teresa Davoli, Elizabeth G Demicco, Deborah Delair, Kelly Devereaux, Saravana M Dhanasekaran, Peter Dottino, Bailee Dover, Thomas L Fillmore, Mckenzie Foxall, Catherine E Hermann, Tara Hiltke, Galen Hostetter, Marcin Jędryka, Scott D Jewell, Isabelle Johnson, Andrea G Kahn, Amy T Ku, Chandan Kumar-Sinha, Paweł Kurzawa, Alexander J Lazar, Rossana Lazcano, Jonathan T Lei, Yi Li, Yuxing Liao, Tung-Shing M Lih, Tai-Tu Lin, John A Martignetti, Ramya P Masand, Rafał Matkowski, Wilson Mckerrow, Mehdi Mesri, Matthew E Monroe, Jamie Moon, Ronald J Moore, Michael D Nestor, Chelsea Newton, Tatiana Omelchenko, Gilbert S Omenn, Samuel H Payne, Vladislav A Petyuk, Ana I Robles, Henry Rodriguez, Kelly V Ruggles, Dmitry Rykunov, Sara R Savage, Athena A Schepmoes, Tujin Shi, Zhiao Shi, Jimin Tan, Mason Taylor, Mathangi Thiagarajan, Joshua M Wang, Karl K Weitz, Bo Wen, C M Williams, Yige Wu, Matthew A Wyczalkowski, Xinpei Yi, Xu Zhang, Rui Zhao, David Mutch, Arul M Chinnaiyan, Richard D Smith, Alexey I Nesvizhskii, Pei Wang, Maciej Wiznerowicz, Li Ding, D R Mani, Hui Zhang, Matthew L Anderson, Karin D Rodland, Bing Zhang, Tao Liu, David Fenyö

Faculty, Staff and Students Publications

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render …

The Classification Of Obesity Based On Metabolic Status Redefines The Readmission Of Non-Hodgkin’S Lymphoma—An Observational Study, Eunju Kim, Kazuaki Mawatari, Seung-Hee Yoo, Zheng Chen

Faculty, Staff and Student Publications

Obesity is a known risk factor for metabolic diseases and is often associated with chronic inflammation in adipose tissue. We previously identified the polyethoxylated flavonoid Nobiletin (NOB) as a circadian clock modulator that directly binds to and activates the ROR receptors in the core oscillator, markedly improving metabolic fitness in obese mice. Here, we show that NOB enhanced the oscillation of core clock genes in differentiated 3T3-L1 adipocytes, including ROR target genes such as Bmal1, Cry1, Dec1, and Dec2. NOB inhibited lipid accumulation in 3T3-L1 and SVF cells, concomitant with the dysregulated circadian expression of adipogenic …

Antibiotic-Induced Gut Dysbiosis And Cognitive, Emotional, And Behavioral Changes In Rodents: A Systematic Review And Meta-Analysis, Shivdeep S. Hayer, Soonjo Hwang, Jonathan B. Clayton

Food for Health: Publications

There are previous epidemiological studies reporting associations between antibiotic use and psychiatric symptoms. Antibiotic-induced gut dysbiosis and alteration of microbiota-gut-brain axis communication has been proposed to play a role in this association. In this systematic review and meta-analysis, we reviewed published articles that have presented results on changes in cognition, emotion, and behavior in rodents (rats and mice) after antibiotic-induced gut dysbiosis. We searched three databases—PubMed, Web of Science, and SCOPUS to identify such articles using dedicated search strings and extracted data from 48 articles. Increase in anxiety and depression-like behavior was reported in 32.7 and 40.7 percent of the …

Antibiotic-Induced Gut Dysbiosis And Cognitive, Emotional, And Behavioral Changes In Rodents: A Systematic Review And Meta-Analysis, Shivdeep S. Hayer, Soonjo Hwang, Jonathan B. Clayton

Food for Health: Publications

There are previous epidemiological studies reporting associations between antibiotic use and psychiatric symptoms. Antibiotic-induced gut dysbiosis and alteration of microbiota-gut-brain axis communication has been proposed to play a role in this association. In this systematic review and meta-analysis, we reviewed published articles that have presented results on changes in cognition, emotion, and behavior in rodents (rats and mice) after antibiotic-induced gut dysbiosis. We searched three databases—PubMed, Web of Science, and SCOPUS to identify such articles using dedicated search strings and extracted data from 48 articles. Increase in anxiety and depression-like behavior was reported in 32.7 and 40.7 percent of the …

Myths And Methodologies: Cardiopulmonary Exercise Testing For Surgical Risk Stratification In Patients With An Abdominal Aortic Aneurysm; Balancing Risk Over Benefit, Damian M Bailey, Richard G Davies, George A Rose, Michael H Lewis, Ahmed Abd Aldayem, Chistopher P Twine, Wael Awad, Matti Jubouri, Idhrees Mohammed, Carlos A Mestres, Edward P Chen, Joseph S Coselli, Ian M Williams, Mohamad Bashir, International Academic Surgical Consortium (Thalamus)

Faculty, Staff and Students Publications

The extent to which patients with an abdominal aortic aneurysm (AAA) should exercise remains unclear, given theoretical concerns over the perceived risk of blood pressure-induced rupture, which is often catastrophic. This is especially pertinent during cardiopulmonary exercise testing, when patients are required to perform incremental exercise to symptom-limited exhaustion for the determination of cardiorespiratory fitness. This multimodal metric is being used increasingly as a complementary diagnostic tool to inform risk stratification and subsequent management of patients undergoing AAA surgery. In this review, we bring together a multidisciplinary group of physiologists, exercise scientists, anaesthetists, radiologists and surgeons to challenge the enduring …

Maternal Metabolism Influences Neural Tube Closure, Rachel A Keuls, Richard H Finnell, Ronald J Parchem

Faculty, Staff and Students Publications

Changes in maternal nutrient availability due to diet or disease significantly increase the risk of neural tube defects (NTDs). Because the incidence of metabolic disease continues to rise, it is urgent that we better understand how altered maternal nutrient levels can influence embryonic neural tube development. Furthermore, primary neurulation occurs before placental function during a period of histiotrophic nutrient exchange. In this review we detail how maternal metabolites are transported by the yolk sac to the developing embryo. We discuss recent advances in understanding how altered maternal levels of essential nutrients disrupt development of the neuroepithelium, and identify points of …

Cell Entry And Release Of Quasi-Enveloped Human Hepatitis Viruses, Anshuman Das, Efraín E Rivera-Serrano, Xin Yin, Christopher M Walker, Zongdi Feng, Stanley M Lemon

Faculty, Staff and Student Publications

Infectious hepatitis type A and type E are caused by phylogenetically distinct single-stranded, positive-sense RNA viruses that were once considered to be non-enveloped. However, studies show that both are released nonlytically from hepatocytes as 'quasi-enveloped' virions cloaked in host membranes. These virion types predominate in the blood of infected individuals and mediate virus spread within the liver. They lack virally encoded proteins on their surface and are resistant to neutralizing anti-capsid antibodies induced by infection, yet they efficiently enter cells and initiate new rounds of virus replication. In this Review, we discuss the mechanisms by which specific peptide sequences in …

Bame Directly Interacts With Bama And Bamd Coordinating Their Functions, Santosh Kumar, Anna Konovalova

Faculty, Staff and Student Publications

The β-barrel assembly machinery (Bam) complex facilitates the assembly of outer membrane proteins (OMPs) in gram-negative bacteria. The Bam complex is conserved and essential for bacterial viability and consists of five subunits, BamA-E. BamA is the transmembrane component, and its β-barrel domain opens laterally to allow folding and insertion of incoming OMPs. The remaining components are regulatory, among which only BamD is essential. Previous studies suggested that BamB regulates BamA directly, while BamE and BamC serve as BamD regulators. However, specific molecular details of their functions remain unknown. Our previous research demonstrated that BamE plays a specialized role in assembling …

A Non-Coding Insertional Mutation Of Grhl2 Causes Gene Over-Expression And Multiple Structural Anomalies Including Cleft Palate, Spina Bifida And Encephalocele, Zoe Crane-Smith, Sandra C P De Castro, Evanthia Nikolopoulou, Paul Wolujewicz, Damian Smedley, Yunping Lei, Emma Mather, Chloe Santos, Mark Hopkinson, Andrew A Pitsillides, Richard H Finnell, M Elisabeth Ross, Andrew J Copp, Nicholas D E Greene

Faculty, Staff and Students Publications

Orofacial clefts, including cleft lip and palate (CL/P) and neural tube defects (NTDs) are among the most common congenital anomalies, but knowledge of the genetic basis of these conditions remains incomplete. The extent to which genetic risk factors are shared between CL/P, NTDs and related anomalies is also unclear. While identification of causative genes has largely focused on coding and loss of function mutations, it is hypothesized that regulatory mutations account for a portion of the unidentified heritability. We found that excess expression of Grainyhead-like 2 (Grhl2) causes not only spinal NTDs in Axial defects (Axd) mice but also multiple …