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Gut Microbial Dysbiosis Differs In Two Distinct Cachectic Tumor-Bearing Models Consuming The Same Diet, Lauri O. Byerley, Brittany Lorenzen, Hsiao Man Chang, William G. Hartman, Michael J. Keenan, Ryan Page, Meng Luo, Scot E. Dowd, Christopher M. Taylor Apr 2024

Gut Microbial Dysbiosis Differs In Two Distinct Cachectic Tumor-Bearing Models Consuming The Same Diet, Lauri O. Byerley, Brittany Lorenzen, Hsiao Man Chang, William G. Hartman, Michael J. Keenan, Ryan Page, Meng Luo, Scot E. Dowd, Christopher M. Taylor

School of Medicine Faculty Publications

The impact of cancer cachexia on the colonic microbiota is poorly characterized. This study assessed the effect of two cachectic-producing tumor types on the gut microbiota to determine if a similar dysbiosis could be found. In addition, it was determined if a diet containing an immunonutrient-rich food (walnuts) known to promote the growth of probiotic bacteria in the colon could alter the dysbiosis and slow cachexia. Male Fisher 344 rats were randomly assigned to a semi-purified diet with or without walnuts. Then, within each diet group, rats were further assigned randomly to a treatment group: tumor-bearing ad libitum fed (TB), …


Genetic Ancestry And Radical Prostatectomy Findings In Hispanic/Latino Patients, Natalia L. Acosta-Vega, Rodolfo Varela, Jorge Andrés Mesa, Jone Garai, Alberto Gómez-Gutiérrez, Silvia J. Serrano-Gómez, Jovanny Zabaleta, María Carolina Sanabria-Salas, Alba L. Combita Apr 2024

Genetic Ancestry And Radical Prostatectomy Findings In Hispanic/Latino Patients, Natalia L. Acosta-Vega, Rodolfo Varela, Jorge Andrés Mesa, Jone Garai, Alberto Gómez-Gutiérrez, Silvia J. Serrano-Gómez, Jovanny Zabaleta, María Carolina Sanabria-Salas, Alba L. Combita

School of Medicine Faculty Publications

Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry …


Momkk1 And Moatg1 Dichotomously Regulating Autophagy And Pathogenicity Through Moatg9 Phosphorylation In Magnaporthe Oryzae, Yun Kong, Pusheng Guo, Jiayun Xu, Jiaxu Li, Miao Wu, Ziqi Zhang, Yifan Wang, Xinyu Liu, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang Mar 2024

Momkk1 And Moatg1 Dichotomously Regulating Autophagy And Pathogenicity Through Moatg9 Phosphorylation In Magnaporthe Oryzae, Yun Kong, Pusheng Guo, Jiayun Xu, Jiaxu Li, Miao Wu, Ziqi Zhang, Yifan Wang, Xinyu Liu, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

Autophagy is a central biodegradation pathway critical in eliminating intracellular cargo to maintain cellular homeostasis and improve stress resistance. At the same time, the key component of the mitogen-activated protein kinase cascade regulating cell wall integrity signaling MoMkk1 has an essential role in the autophagy of the rice blast fungus Magnaporthe oryzae. Still, the mechanism of how MoMkk1 regulates autophagy is unclear. Interestingly, we found that MoMkk1 regulates the autophagy protein MoAtg9 through phosphorylation. MoAtg9 is a transmembrane protein subjected to phosphorylation by autophagy-related protein kinase MoAtg1. Here, we provide evidence demonstrating that MoMkk1-dependent MoAtg9 phosphorylation is required for phospholipid …


Autophagy And Cell Wall Integrity Pathways Coordinately Regulate The Development And Pathogenicity Through Moatg4 Phosphorylation In Magnaporthe Oryzae, Pusheng Guo, Yurong Wang, Jiayun Xu, Zhixiang Yang, Ziqi Zhang, Jinyi Qian, Jiexiong Hu, Ziyi Yin, Leiyun Yang, Muxing Liu, Xinyu Liu, Gang Li, Haifeng Zhang, Ryan Rumsey, Ping Wang, Zhengguang Zhang Jan 2024

Autophagy And Cell Wall Integrity Pathways Coordinately Regulate The Development And Pathogenicity Through Moatg4 Phosphorylation In Magnaporthe Oryzae, Pusheng Guo, Yurong Wang, Jiayun Xu, Zhixiang Yang, Ziqi Zhang, Jinyi Qian, Jiexiong Hu, Ziyi Yin, Leiyun Yang, Muxing Liu, Xinyu Liu, Gang Li, Haifeng Zhang, Ryan Rumsey, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

Autophagy and Cell wall integrity (CWI) signaling are critical stress-responsive processes during fungal infection of host plants. In the rice blast fungus Magnaporthe oryzae, autophagy-related (ATG) proteins phosphorylate CWI kinases to regulate virulence; however, how autophagy interplays with CWI signaling to coordinate such regulation remains unknown. Here, we have identified the phosphorylation of ATG protein MoAtg4 as an important process in the coordination between autophagy and CWI in M. oryzae. The ATG kinase MoAtg1 phosphorylates MoAtg4 to inhibit the deconjugation and recycling of the key ATG protein MoAtg8. At the same time, MoMkk1, a core kinase of CWI, also phosphorylates …


Targeted Repression Of Topa By Crispri Reveals A Critical Function For Balanced Dna Topoisomerase I Activity In The Chlamydia Trachomatis Developmental Cycle, Li Shen, Leiqiong Gao, Abigail R. Swoboda, Scot P. Ouellette Jan 2024

Targeted Repression Of Topa By Crispri Reveals A Critical Function For Balanced Dna Topoisomerase I Activity In The Chlamydia Trachomatis Developmental Cycle, Li Shen, Leiqiong Gao, Abigail R. Swoboda, Scot P. Ouellette

School of Medicine Faculty Publications

Chlamydia trachomatis is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases contributes to controlling Chlamydia developmental processes. Utilizing catalytically inactivated Cas12 (dCas12)-based clustered regularly interspaced short palindromic repeats interference (CRISPRi) technology, we demonstrate targeted knockdown of chromosomal topA transcription in C. trachomatis without detected toxicity of dCas12. Repression of topA impaired the developmental cycle of C. trachomatis mostly through disruption of its differentiation from a replicative form …


Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding Jan 2024

Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding

School of Medicine Faculty Publications

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …


Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low Dec 2023

Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low

School of Medicine Faculty Publications

Introduction Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth. Methods and analysis This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and …


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 Oct 2023

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 …


Methionine Biosynthesis Enzyme Momet2 Is Required For Rice Blast Fungus Pathogenicity By Promoting Virulence Gene Expression Via Reducing 5mc Modification, Huimin Li, Pengcheng Mo, Jun Zhang, Zhuoer Xie, Xinyu Liu, Han Chen, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang Sep 2023

Methionine Biosynthesis Enzyme Momet2 Is Required For Rice Blast Fungus Pathogenicity By Promoting Virulence Gene Expression Via Reducing 5mc Modification, Huimin Li, Pengcheng Mo, Jun Zhang, Zhuoer Xie, Xinyu Liu, Han Chen, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

The emergence of fungicide resistance severely threatens crop production by limiting the availability and application of established fungicides. Therefore, it is urgent to identify new fungicidal targets for controlling plant diseases. Here, we characterized the function of a conserved homoserine O-acetyltransferase (HOA) from the rice blast fungus Magnaporthe oryzae that could serve as the candidate antifungal target. Deletion of the MoMET2 and MoCYS2 genes encoding HOAs perturbed the biosynthesis of methionine and S-adenyl methionine, a methyl group donor for epigenetic modifications, and severely attenuated the development and virulence of M. oryzae. The ΔMomet2 mutant is significantly increased in 5-methylcytosine (5mC) …


Relative And Quantitative Characterization Of The Bovine Bacterial Ocular Surface Microbiome In The Context Of Suspected Ocular Squamous Cell Carcinoma, Hannah B. Gafen, Chin-Chi Liu, Nikole E. Ineck, Clare M. Scully, Melanie A. Mironovich, Lauren Guarneri, Christopher M. Taylor, Meng Luo, Marina L. Leis, Erin M. Scott, Renee T. Carter, Andrew C. Lewin Jun 2023

Relative And Quantitative Characterization Of The Bovine Bacterial Ocular Surface Microbiome In The Context Of Suspected Ocular Squamous Cell Carcinoma, Hannah B. Gafen, Chin-Chi Liu, Nikole E. Ineck, Clare M. Scully, Melanie A. Mironovich, Lauren Guarneri, Christopher M. Taylor, Meng Luo, Marina L. Leis, Erin M. Scott, Renee T. Carter, Andrew C. Lewin

School of Medicine Faculty Publications

The ocular surface microbiome is altered in certain disease states. The aim of this study was to characterize the bovine bacterial ocular surface microbiome (BBOSM) in the context of ocular squamous cell carcinoma (OSCC). The conjunctiva of normal (n = 28) and OSCC (n = 10) eyes of cows aged 2 to 13 years from two farms in Louisiana and Wyoming were sampled using individual sterile swabs. DNA extraction followed by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and real-time polymerase chain reaction (RT-PCR) were performed to, respectively, assess the relative and absolute BBOSM. Discriminant analysis (DA) was performed using …


Biophysical Changes Of Leukocyte Activation (And Netosis) In The Cellular Host Response To Sepsis, Matt G. Sorrells, Yurim Seo, Melia Magnen, Bliss Broussard, Roya Sheybani, Ajay M. Shah, Hollis R. O’Neal, Henry T.K. Tse, Mark R. Looney, Dino Di Carlo Apr 2023

Biophysical Changes Of Leukocyte Activation (And Netosis) In The Cellular Host Response To Sepsis, Matt G. Sorrells, Yurim Seo, Melia Magnen, Bliss Broussard, Roya Sheybani, Ajay M. Shah, Hollis R. O’Neal, Henry T.K. Tse, Mark R. Looney, Dino Di Carlo

School of Medicine Faculty Publications

Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a …


Lkb1 Signaling And Patient Survival Outcomes In Hepatocellular Carcinoma, Khoa Nguyen, Katherine Hebert, Emily Mcconnell, Nicole Cullen, Thomas Cheng, Susanna Awoyode, Elizabeth Martin, Weina Chen, Tong Wu, Suresh K. Alahari, Reza Izadpanah, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow Apr 2023

Lkb1 Signaling And Patient Survival Outcomes In Hepatocellular Carcinoma, Khoa Nguyen, Katherine Hebert, Emily Mcconnell, Nicole Cullen, Thomas Cheng, Susanna Awoyode, Elizabeth Martin, Weina Chen, Tong Wu, Suresh K. Alahari, Reza Izadpanah, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow

School of Medicine Faculty Publications

The liver is a major organ that is involved in essential biological functions such as digestion, nutrient storage, and detoxification. Furthermore, it is one of the most metabolically active organs with active roles in regulating carbohydrate, protein, and lipid metabolism. Hepatocellular carcinoma is a cancer of the liver that is associated in settings of chronic inflammation such as viral hepatitis, repeated toxin exposure, and fatty liver disease. Furthermore, liver cancer is the most common cause of death associated with cirrhosis and is the 3rd leading cause of global cancer deaths. LKB1 signaling has been demonstrated to play a role in …


Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura Dec 2022

Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura

School of Medicine Faculty Publications

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was …


The Need For Sexual Health Clinics, Their Future Role, And Contribution To Public Health, Meena S. Ramchandani, Christopher Bourne, Lindley A. Barbee, Elske Hoornenborg, Preeti Pathela, Stephanie N. Taylor, Henry De Vries Aug 2022

The Need For Sexual Health Clinics, Their Future Role, And Contribution To Public Health, Meena S. Ramchandani, Christopher Bourne, Lindley A. Barbee, Elske Hoornenborg, Preeti Pathela, Stephanie N. Taylor, Henry De Vries

School of Medicine Faculty Publications

Specialised sexual health clinics (SHCs) play an important role in addressing the staggering rates of STIs seen in many high-income nations. Despite increasing healthcare coverage in the US and nationalised health care in some countries, there is a continued need for SHCs to meet the needs of patients and the community, especially for high-priority populations: those at high risk of STI acquisition and/or groups historically marginalised and underserved in the traditional healthcare system. We need to mobilise resources to support a stronger clinical infrastructure in specialised SHCs. This review describes the importance of SHCs, their future role, and some of …


Solid-State Nmr Analysis Of Unlabeled Fungal Cell Walls From Aspergillus And Candida Species, Liyanage D. Fernando, Malitha C. Dickwella Widanage, S. Chandra Shekar, Frederic Mentink-Vigier, Ping Wang, Sungsool Wi, Tuo Wang Jul 2022

Solid-State Nmr Analysis Of Unlabeled Fungal Cell Walls From Aspergillus And Candida Species, Liyanage D. Fernando, Malitha C. Dickwella Widanage, S. Chandra Shekar, Frederic Mentink-Vigier, Ping Wang, Sungsool Wi, Tuo Wang

School of Medicine Faculty Publications

Fungal infections cause high mortality in immunocompromised individuals, which has emerged as a significant threat to human health. The efforts devoted to the development of antifungal agents targeting the cell wall polysaccharides have been hindered by our incomplete picture of the assembly and remodeling of fungal cell walls. High-resolution solid-state nuclear magnetic resonance (ss NMR) studies have substantially revised our understanding of the polymorphic structure of polysaccharides and the nanoscale organization of cell walls in Aspergillus fumigatus and multiple other fungi. However, this approach requires 13C/15N-enrichment of the sample being studied, severely restricting its application. Here we employ the dynamic …


Editorial: Mucosal Vaccination: Strategies To Induce And Evaluate Mucosal Immunity, Pamela A. Kozlowski, Nicholas J. Mantis, Andreas Frey Apr 2022

Editorial: Mucosal Vaccination: Strategies To Induce And Evaluate Mucosal Immunity, Pamela A. Kozlowski, Nicholas J. Mantis, Andreas Frey

School of Medicine Faculty Publications

No abstract provided.


Resistant Starch Type 2 And Whole Grain Maize Flours Enrich Different Intestinal Bacteria And Metatranscriptomes, Zachary A. Bendiks, Justin Guice, Diana Coulon, Anne M. Raggio, Ryan C. Page, Diana G. Carvajal-Aldaz, Meng Luo, David A. Welsh, Brian D. Marx, Christopher M. Taylor, Claudia Husseneder, Michael J. Keenan, Maria L. Marco Feb 2022

Resistant Starch Type 2 And Whole Grain Maize Flours Enrich Different Intestinal Bacteria And Metatranscriptomes, Zachary A. Bendiks, Justin Guice, Diana Coulon, Anne M. Raggio, Ryan C. Page, Diana G. Carvajal-Aldaz, Meng Luo, David A. Welsh, Brian D. Marx, Christopher M. Taylor, Claudia Husseneder, Michael J. Keenan, Maria L. Marco

School of Medicine Faculty Publications

The intestinal microbiota of Sprague-Dawley (SD) rats were investigated following consumption of diets containing refined high-amylose cornstarch (RS), waxy whole-grain flour from maize (WG), or high-amylose whole-grain flour (WG + RS) together with moderate (MF, 30% of energy) or high (HF, 42% of energy) levels of fat. Compared with control (CON) diets, RS reduced bacterial alpha-diversity and enriched Bacteroidetes and WG increased Lactobacillus proportions by three-fold. WG + RS conferred a combined effect, but the changes were attenuated and greater inter-individual variation was observed. Proportions of fiber-degrading bacterial taxa were inversely correlated with cecal pH. Notably, there was little influence …


Trait Energy And Fatigue May Be Connected To Gut Bacteria Among Young Physically Active Adults: An Exploratory Study, Ali Boolani, Karyn M. Gallivan, Kristin S. Ondrak, Courtney J. Christopher, Hector F. Castro, Shawn R. Campagna, Christopher M. Taylor, Meng Luo, Scot E. Dowd, Matthew Lee Smith, Lauri O. Byerley Jan 2022

Trait Energy And Fatigue May Be Connected To Gut Bacteria Among Young Physically Active Adults: An Exploratory Study, Ali Boolani, Karyn M. Gallivan, Kristin S. Ondrak, Courtney J. Christopher, Hector F. Castro, Shawn R. Campagna, Christopher M. Taylor, Meng Luo, Scot E. Dowd, Matthew Lee Smith, Lauri O. Byerley

School of Medicine Faculty Publications

Recent scientific evidence suggests that traits energy and fatigue are two unique unipolar moods with distinct mental and physical components. This exploratory study investigated the correlation between mental energy (ME), mental fatigue (MF), physical energy (PE), physical fatigue (PF), and the gut microbiome. The four moods were assessed by survey, and the gut microbiome and metabolome were determined from 16 S rRNA analysis and untargeted metabolomics analysis, respectively. Twenty subjects who were 31 ± 5 y, physically active, and not obese (26.4 ± 4.4 kg/m2) participated. Bacteroidetes (45%), the most prominent phyla, was only negatively correlated with PF. The second …


Moerv29 Promotes Apoplastic Effector Secretion Contributing To Virulence Of The Rice Blast Fungus Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Danyu Shen, Han Chen, Haifeng Zhang, Ping Wang, Zhengguang Zhang Nov 2021

Moerv29 Promotes Apoplastic Effector Secretion Contributing To Virulence Of The Rice Blast Fungus Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Danyu Shen, Han Chen, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

During plant-pathogenic fungi and host plants interactions, numerous pathogen-derived proteins are secreted resulting in the activation of the unfolded protein response (UPR) pathway. For efficient trafficking of secretory proteins, including those important in disease progression, the cytoplasmic coat protein complex II (COPII) exhibits a multifunctional role whose elucidation remains limited. Here, we discovered that the COPII cargo receptor MoErv29 functions as a target of MoHac1, a previously identified transcription factor of the UPR pathway. In Magnaporthe oryzae, deletion of MoERV29 severely affected the vegetative growth, conidiation and biotrophic invasion of the fungus in susceptible rice hosts. We demonstrated that MoErv29 …


Dysregulation Of Il-17/Il-22 Effector Functions In Blood And Gut Mucosal Gamma Delta T Cells Correlates With Increase In Circulating Leaky Gut And Inflammatory Markers During Cart-Treated Chronic Siv Infection In Macaques, Edith M. Walker, Nadia Slisarenko, Giovanni L. Gerrets, Brooke F. Grasperge, Julie A. Mattison, Patricia J. Kissinger, David A. Welsh, Ronald S. Veazey, S. Michal Jazwinski, Namita Rout Feb 2021

Dysregulation Of Il-17/Il-22 Effector Functions In Blood And Gut Mucosal Gamma Delta T Cells Correlates With Increase In Circulating Leaky Gut And Inflammatory Markers During Cart-Treated Chronic Siv Infection In Macaques, Edith M. Walker, Nadia Slisarenko, Giovanni L. Gerrets, Brooke F. Grasperge, Julie A. Mattison, Patricia J. Kissinger, David A. Welsh, Ronald S. Veazey, S. Michal Jazwinski, Namita Rout

School of Medicine Faculty Publications

HIV-associated inflammation has been implicated in the premature aging and increased risk of age-associated comorbidities in cART-treated individuals. However, the immune mechanisms underlying the chronic inflammatory state of cART-suppressed HIV infection remain unclear. Here, we investigated the role of γδT cells, a group of innate IL-17 producing T lymphocytes, in the development of systemic inflammation and leaky gut phenotype during cART-suppressed SIV infection of macaques. Plasma levels of inflammatory mediators, intestinal epithelial barrier disruption (IEBD) and microbial translocation (MT) biomarkers, and Th1/Th17-type cytokine functions were longitudinally assessed in blood and gut mucosa of SIV-infected, cART-suppressed macaques. Among the various gut …


Genetic Transformation In Cryptococcus Species, Ping Wang Jan 2021

Genetic Transformation In Cryptococcus Species, Ping Wang

School of Medicine Faculty Publications

Genetic transformation plays an imperative role in our understanding of the biology in unicellular yeasts and filamentous fungi, such as Saccharomyces cerevisiae, Aspergillus nidulans, Cryphonectria parasitica, and Magnaporthe oryzae. It also helps to understand the virulence and drug resistance mechanisms of the pathogenic fungus Cryptococcus that causes cryptococcosis in health and immunocompromised individuals. Since the first attempt at DNA transformation in this fungus by Edman in 1992, various methods and techniques have been developed to introduce DNA into this organism and improve the efficiency of homology-mediated gene disruption. There have been many excellent summaries or reviews covering the subject. Here …


Balancing Of The Mitotic Exit Network And Cell Wall Integrity Signaling Governs The Development And Pathogenicity In Magnaporthe Oryzae, Wanzhen Feng, Ziyi Yin, Haowen Wu, Peng Liu, Xinyu Liu, Muxing Liu, Rui Yu, Chuyun Gao, Haifeng Zhang, Xiaobo Zheng, Ping Wang, Zhengguang Zhang Jan 2021

Balancing Of The Mitotic Exit Network And Cell Wall Integrity Signaling Governs The Development And Pathogenicity In Magnaporthe Oryzae, Wanzhen Feng, Ziyi Yin, Haowen Wu, Peng Liu, Xinyu Liu, Muxing Liu, Rui Yu, Chuyun Gao, Haifeng Zhang, Xiaobo Zheng, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

The fungal cell wall plays an essential role in maintaining cell morphology, transmitting external signals, controlling cell growth, and even virulence. Relaxation and irreversible stretching of the cell wall are the prerequisites of cell division and development, but they also inevitably cause cell wall stress. Both Mitotic Exit Network (MEN) and Cell Wall Integrity (CWI) are signaling pathways that govern cell division and cell stress response, respectively, how these pathways cross talk to govern and coordinate cellular growth, development, and pathogenicity remains not fully understood. We have identified MoSep1, MoDbf2, and MoMob1 as the conserved components of MEN from the …


Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan Oct 2020

Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan

School of Medicine Faculty Publications

Scc4 is an unusual bi-functional protein from Chlamydia trachomatis (CT) that functions as a type III secretion system (T3SS) chaperone and an RNA polymerase (RNAP)-binding protein. Both functions require interactions with protein partners during specific stages of the CT developmental cycle. As a T3SS chaperone, Scc4 binds Scc1 during the late stage of development to form a heterodimer complex, which chaperones the essential virulence effector, CopN. During the early-middle stage of development, Scc4 regulates T3SS gene expression by binding the σ66-containing RNAP holoenzyme. In order to study the structure and association mechanism of the Scc4:Scc1 T3SS chaperone complex using nuclear …


Cd147 And Downstream Adamtss Promote The Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus Infected Endothelial Cells, Lu Dai, Jimena Trillo-Tinoco, Yihan Chen, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Augusto C. Ochoa, Jovanny Zabaleta, Bryan P. Toole, Zhiqiang Qin Jan 2016

Cd147 And Downstream Adamtss Promote The Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus Infected Endothelial Cells, Lu Dai, Jimena Trillo-Tinoco, Yihan Chen, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Augusto C. Ochoa, Jovanny Zabaleta, Bryan P. Toole, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi's sarcoma (KS), which preferentially arise in immunocompromised patients and lack effective therapeutic options. We have previously shown that KSHV or viral protein LANA up-regulates the glycoprotein CD147, thereby inducing primary endothelial cell invasiveness. In the current study, we identify the global network controlled by CD147 in KSHV-infected endothelial cells using Illumina microarray analysis. Among downstream genes, two specific metalloproteases, ADAMTS1 and 9, are strongly expressed in AIDS-KS tissues and contribute to KSHV-infected endothelial cell invasiveness through up-regulation of IL-6 and VEGF. By using a KS-like nude …


Ceramides Promote Apoptosis For Virus-Infected Lymphoma Cells Through Induction Of Ceramide Synthases And Viral Lytic Gene Expression, Lu Dai, Jimena Trillo-Tinoco, Aiping Bai, Yihan Chen, Jacek Bielawski, Luis Del Valle, Charles D. Smith, Augusto C. Ochoa, Zhiqiang Qin, Chris Parsons Jul 2015

Ceramides Promote Apoptosis For Virus-Infected Lymphoma Cells Through Induction Of Ceramide Synthases And Viral Lytic Gene Expression, Lu Dai, Jimena Trillo-Tinoco, Aiping Bai, Yihan Chen, Jacek Bielawski, Luis Del Valle, Charles D. Smith, Augusto C. Ochoa, Zhiqiang Qin, Chris Parsons

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for several human cancers including primary effusion lymphoma (PEL), a rapidly progressive malignancy arising preferentially in immunocompromised patients. With conventional chemotherapy, PEL continues to portend high mortality, dictating the development of novel therapeutic strategies. Sphingosine kinase 2 (SphK2) represents a key gatekeeper for sphingolipid metabolism, responsible for conversion of ceramides to sphingosine-1-phosphate (S1P). We have previously demonstrated that targeting SphK2 using a novel selective inhibitor, ABC294640, leads to intracellular accumulation of ceramides and induces apoptosis for KSHV-infected PEL cells, while suppressing tumor progression in vivo. In the current study, we sought to …


Role Of Host Micrornas In Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis, Zhiqiang Qin, Francesca Peruzzi, Krzysztof Reiss, Lu Dai Nov 2014

Role Of Host Micrornas In Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis, Zhiqiang Qin, Francesca Peruzzi, Krzysztof Reiss, Lu Dai

School of Medicine Faculty Publications

MicroRNAs (miRNAs) are small non-coding RNA species that can bind to both untranslated and coding regions of target mRNAs, causing their degradation or post-transcriptional modification. Currently, over 2500 miRNAs have been identified in the human genome. Burgeoning evidence suggests that dysregulation of human miRNAs can play a role in the pathogenesis of a variety of diseases, including cancer. In contrast, only a small subset of human miRNAs has been functionally validated in the pathogenesis of oncogenic viruses, in particular, Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is the etiologic agent of several human cancers, such as primary effusion lymphoma (PEL) and Kaposi's …


Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin Feb 2014

Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells …


Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya Nov 2011

Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya

School of Medicine Faculty Publications

Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release …