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Articles 121 - 150 of 2008

Full-Text Articles in Medical Microbiology

A Stronger Impact On Career Development For Early- And Mid-Career Faculty, Daniel A Gorelick, Jason Gertz, Kaitlin J Basham, Lindsey S Treviño Oct 2024

A Stronger Impact On Career Development For Early- And Mid-Career Faculty, Daniel A Gorelick, Jason Gertz, Kaitlin J Basham, Lindsey S Treviño

Faculty, Staff and Students Publications

Nuclear receptors are important in normal physiology and disease. Physicians and scientists who study nuclear receptors organize and attend conferences and symposia devoted to foundational and translational nuclear receptor research, but the field lacks a platform for early-stage investigators and aspiring leaders. In 2019, Zeynep Madak-Erdogan, Rebecca Riggins, and Matthew Sikora founded Nuclear Receptor (NR) Interdisciplinary Meeting for Progress And Collaboration Together (IMPACT, https://nrimpact.com), a collaborative group designed for early- and mid-career faculty who study nuclear receptors in any context or organism [1]. NR IMPACT addresses challenges for early- and mid-career faculty. Here, we review the progress of NR IMPACT …


Periodontal Health In A Large Cohort Of Ugandans Living With Hiv: A Cross-Sectional Study, William Buwembo, Adriane Kamulegeya, Dunstan Kalanzi, Priscilla Naava Namuyonga, Proscovia Nakasujja, David P. Katete, F. Collins Semitala, Catherine Mwesigwa-Lutalo, Samuel Kalungi, Jennifer E. Cameron, Ian G. Munabi Oct 2024

Periodontal Health In A Large Cohort Of Ugandans Living With Hiv: A Cross-Sectional Study, William Buwembo, Adriane Kamulegeya, Dunstan Kalanzi, Priscilla Naava Namuyonga, Proscovia Nakasujja, David P. Katete, F. Collins Semitala, Catherine Mwesigwa-Lutalo, Samuel Kalungi, Jennifer E. Cameron, Ian G. Munabi

School of Medicine Faculty Publications

Background: The impact of periodontitis on large populations of people living with HIV (PLHIV) in resource-constrained settings remains largely un-investigated. This study aims to address this knowledge gap by providing a comprehensive description of the periodontal health status among a sizable cohort of Ugandans living with HIV. Methods: This was a cross-sectional study with 4,449 participants who were over 18-years old with data captured on their reported age, gender, tobacco use, length of time on HAART and alcohol use. Periodontal health was assessed using the WHO periodontal probe and the modified CPI data entry form. Descriptive statistics were reported using …


Construction And Characterization Of Dna Libraries From Cultured Phages And Environmental Viromes, Carmen Gu Liu, Brianna E Thompson, James D Chang, Lorna Min, Anthony W Maresso Oct 2024

Construction And Characterization Of Dna Libraries From Cultured Phages And Environmental Viromes, Carmen Gu Liu, Brianna E Thompson, James D Chang, Lorna Min, Anthony W Maresso

Faculty, Staff and Students Publications

Despite many efforts to understand and leverage the functional potential of environmental viromes, most bacteriophage genes are largely uncharacterized. To explore novel biology from uncultivated microbes like phages, metagenomics has emerged as a powerful tool to directly mine new genes without the need to culture the diverse microbiota and the viruses within. When a pure computational approach cannot infer gene function, it may be necessary to create a DNA library from environmental genomic DNA, followed by the screening of that library for a particular function. However, these screens are often initiated without a metagenomic analysis of the completed DNA library …


Penicillin Susceptibility Among Staphylococcus Aureus Skin And Soft Tissue Infections At A Children’S Hospital, J Chase Mcneil, Lauren M Sommer, Marritta Joseph, Kristina G Hulten, Sheldon L Kaplan Oct 2024

Penicillin Susceptibility Among Staphylococcus Aureus Skin And Soft Tissue Infections At A Children’S Hospital, J Chase Mcneil, Lauren M Sommer, Marritta Joseph, Kristina G Hulten, Sheldon L Kaplan

Faculty, Staff and Students Publications

Shortly after its introduction into clinical practice, Staphylococcus aureus isolates gained resistance to penicillin via the acquisition of β-lactamases. A number of centers have recently described an increase in the proportion of invasive methicillin-susceptible S. aureus (MSSA), which are also susceptible to penicillin (PSSA). Little data are available regarding the prevalence or impact of PSSA in skin and soft tissue infections (SSTI). Community-acquired MSSA SSTI isolates were obtained through a surveillance study at Texas Children’s Hospital from January 2017 to December 2021. A total of 200 random isolates underwent PCR for blaZ β-lactamase; blaZ-negative isolates then underwent penicillin susceptibility …


The Absence Of Cxcl10 Activity Does Not Affect The Capability Of Cd8+ T Cells To Migrate And Eliminate The Tissue Cysts Of Toxoplasma Gondii From The Brains Of Chronically Infected Mice, Rajesh Mani, Yasuhiro Suzuki Oct 2024

The Absence Of Cxcl10 Activity Does Not Affect The Capability Of Cd8+ T Cells To Migrate And Eliminate The Tissue Cysts Of Toxoplasma Gondii From The Brains Of Chronically Infected Mice, Rajesh Mani, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Toxoplasma gondii forms tissue cysts in neurons and astrocytes in the brain to establish chronic infection, and astrocytes express the CXCL10 chemokine in chronically infected mice. Since chemokines mediate the migration of T cells to attack their targets, and since CXCL10 plays key roles in T cell-mediated control of the proliferation of tachyzoites (the acute stage form) of T. gondii during the acute stage of infection, we examined whether CXCL10 is involved in recruiting anti-cyst CD8+ cytotoxic T cells to eliminate the cysts in their brains. We employed adoptive transfer of CD8+ immune T cells to infected, T cell-deficient SCID …


A Mouse Model For Conditional Expression Of Activated Β-Catenin In Epidermal Keratinocytes, Vineet K Maurya, Yan Ying, John P Lydon Oct 2024

A Mouse Model For Conditional Expression Of Activated Β-Catenin In Epidermal Keratinocytes, Vineet K Maurya, Yan Ying, John P Lydon

Faculty, Staff and Students Publications

We report the generation and characterization of the K5: CAT bigenic mouse in which the constitutively activated form of β-catenin (ΔN89 β-catenin) is conditionally expressed in cytokeratin-5 (K5) positive epidermal keratinocytes. Following short-term doxycycline intake during the telogen resting phase, the adult K5: CAT bigenic develops enlarged pilosebaceous units that expand deep into the dermis, an expansion usually observed during the anagen growth phase. Prolonged doxycycline treatment results in significant thickening and folding of the K5: CAT epidermis. During this persistent induction period, there is clear evidence of increased keratinocyte proliferation, particularly in the epidermal basal cell layer and the …


Behavioral Screening Reveals A Conserved Residue In Y-Box Rna-Binding Protein Required For Associative Learning And Memory In C Elegans, Ashley N Hayden, Katie L Brandel, Edward W Pietryk, Paul R Merlau, Priyadharshini Vijayakumar, Emily J Leptich, Elizabeth S Gaytan, Meredith I Williams, Connie W Ni, Hsiao-Tuan Chao, Jill A Rosenfeld, Rachel N Arey Oct 2024

Behavioral Screening Reveals A Conserved Residue In Y-Box Rna-Binding Protein Required For Associative Learning And Memory In C Elegans, Ashley N Hayden, Katie L Brandel, Edward W Pietryk, Paul R Merlau, Priyadharshini Vijayakumar, Emily J Leptich, Elizabeth S Gaytan, Meredith I Williams, Connie W Ni, Hsiao-Tuan Chao, Jill A Rosenfeld, Rachel N Arey

Faculty, Staff and Students Publications

RNA-binding proteins (RBPs) regulate translation and plasticity which are required for memory. RBP dysfunction has been linked to a range of neurological disorders where cognitive impairments are a key symptom. However, of the 2,000 RBPs in the human genome, many are uncharacterized with regards to neurological phenotypes. To address this, we used the model organism C. elegans to assess the role of 20 conserved RBPs in memory. We identified eight previously uncharacterized memory regulators, three of which are in the C. elegans Y-Box (CEY) RBP family. Of these, we determined that cey-1 is the closest ortholog to the mammalian Y-Box …


Mutant Npm1 Marginally Impacts Ribosome Footprint In Acute Myeloid Leukemia Cells, Lorenzo Brunetti, Giulia Pianigiani, Michael C Gundry, Margaret A Goodell, Brunangelo Falini Oct 2024

Mutant Npm1 Marginally Impacts Ribosome Footprint In Acute Myeloid Leukemia Cells, Lorenzo Brunetti, Giulia Pianigiani, Michael C Gundry, Margaret A Goodell, Brunangelo Falini

Faculty, Staff and Students Publications

BACKGROUND:NPM1‐mutated acute myeloid leukemia (AML) is the most frequent AML subtype. As wild‐type NPM1 is known to orchestrate ribosome biogenesis, it has been hypothesized that altered translation may contribute to leukemogenesis and leukemia maintenance in NPM1‐mutated AML. However, this hypothesis has never been investigated. We reasoned that if mutant NPM1 (NPM1c) directly impacts translation in leukemic cells, loss of NPM1c would result in acute changes in the ribosome footprint.

METHODS: Here, we performed ribosome footprint profiling (Ribo-seq) and bulk messenger RNA (mRNA) sequencing in two

RESULTS AND DISCUSSION: Incubation of degron cells with the small compound dTAG-13 …


Viability Discrimination Of Bacterial Microbiomes In Home Kitchen Dish Sponges Using Propidium Monoazide Treatment, Christina K Carstens, Joelle K Salazar, Shreela Sharma, Wenyaw Chan, Charles Darkoh Oct 2024

Viability Discrimination Of Bacterial Microbiomes In Home Kitchen Dish Sponges Using Propidium Monoazide Treatment, Christina K Carstens, Joelle K Salazar, Shreela Sharma, Wenyaw Chan, Charles Darkoh

Faculty, Staff and Student Publications

Dish sponges are known to support the proliferation of human bacterial pathogens, yet they are commonly used by consumers. Exposure to foodborne pathogens via sponge use may lead to illness, a serious concern among susceptible populations. The extent of exposure risks from sponge use has been limited by constraints associated with culture-independent or dependent methods for bacterial community characterization. Therefore, five used dish sponges were characterized to evaluate the presence of viable bacterial foodborne pathogens using the novel application of propidium monoazide (PMA) treatment and targeted 16S rRNA gene amplicon sequencing. Select pathogen viability was confirmed using targeted selective enrichment. …


Phenotypic Diversity Of Type Iii Secretion System Activity In Enteropathogenic Escherichia Coli Clinical Isolates, Carmen A Contreras, Tracy H Hazen, Carmen Guadarrama, Ramón Cervantes-Rivera, Theresa J Ochoa, Pablo Vinuesa, David A Rasko, Jose L Puente Oct 2024

Phenotypic Diversity Of Type Iii Secretion System Activity In Enteropathogenic Escherichia Coli Clinical Isolates, Carmen A Contreras, Tracy H Hazen, Carmen Guadarrama, Ramón Cervantes-Rivera, Theresa J Ochoa, Pablo Vinuesa, David A Rasko, Jose L Puente

Faculty, Staff and Student Publications

Introduction. Enteropathogenic Escherichia coli (EPEC) strains pose a significant threat as a leading cause of severe childhood diarrhoea in developing nations. EPEC pathogenicity relies on the type III secretion system (T3SS) encoded by the locus of enterocyte effacement (LEE), facilitating the secretion and translocation of bacterial effector proteins.

Gap Statement. While the regulatory roles of PerC (plasmid-encoded regulator) and GrlA (global regulator of LEE-activator) in ler expression and LEE gene activation are well-documented in the EPEC prototype strain E2348/69, understanding the variability in LEE gene expression control mechanisms among clinical EPEC isolates remains an area requiring further investigation.

Aim. This …


High Fat, High Sucrose Diet Promotes Increased Expression Of Ace2 Receptor In The Siv-Infected Host: Implications For Sars-Cov-2 Infection, Elizabeth C. Delery, Danielle E. Levitt, Angela M. Amedee, Patricia E. Molina, Liz Simon Sep 2024

High Fat, High Sucrose Diet Promotes Increased Expression Of Ace2 Receptor In The Siv-Infected Host: Implications For Sars-Cov-2 Infection, Elizabeth C. Delery, Danielle E. Levitt, Angela M. Amedee, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Introduction: People with pre-existing conditions, including metabolic comorbidities, are at greater risk for complications of SARS-CoV-2 infection and expression of machinery required for viral entry into host cells may be a contributing factor. This study tested the hypothesis that high fat, high sucrose diet (HFSD) and alcohol use increase expression of angiotensin converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2) in tissues isolated from simian immunodeficiency virus (SIV) infected macaques, the most clinically relevant model for the study of HIV. Methods: Biospecimens obtained from a longitudinal study of SIV-infected, antiretroviral therapy (ART)-treated female rhesus macaques (Macaca mulatta) …


Creb-Binding Protein/P300 Bromodomain Inhibition Reduces Neutrophil Accumulation And Activates Antitumor Immunity In Triple-Negative Breast Cancer, Xueying Yuan, Xiaoxin Hao, Hilda L Chan, Na Zhao, Diego A Pedroza, Fengshuo Liu, Kang Le, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Michael J Soth, Philip Jones, Xiang Hf Zhang, Jeffrey M Rosen Sep 2024

Creb-Binding Protein/P300 Bromodomain Inhibition Reduces Neutrophil Accumulation And Activates Antitumor Immunity In Triple-Negative Breast Cancer, Xueying Yuan, Xiaoxin Hao, Hilda L Chan, Na Zhao, Diego A Pedroza, Fengshuo Liu, Kang Le, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Michael J Soth, Philip Jones, Xiang Hf Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB-binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing …


Houston, We Have A Problem: Diagnostic Difficulties In The Aids Patient With Tuberculosis Infection, Hector D. Preciado, Maria E. Torres, Muhammad A. Siddiqui, Liza Salloum, Lee Gelpi, Jose E. Campo Maldonado Sep 2024

Houston, We Have A Problem: Diagnostic Difficulties In The Aids Patient With Tuberculosis Infection, Hector D. Preciado, Maria E. Torres, Muhammad A. Siddiqui, Liza Salloum, Lee Gelpi, Jose E. Campo Maldonado

Research Colloquium

Background: Tuberculosis (TB) is the leading cause of infectious death worldwide with 1.5 million deaths annually and nearly 1/4th of the world’s population (1.7 billion) infected with latent tuberculosis infection (LTBI) in 2014. Its diagnosis conventionally relies on tuberculin skin testing (TST), and Interferon-Gamma Release Assay (IGRA) which relies on the production of Interferon Gamma (IFN-y) in response to Mycobacterium tuberculosis (MTB) specific antigens. IGRA is a useful tool for detecting latent TB disease, and can be used as an adjunct for the diagnosis of active TB cases. Increases in IFN-y levels might support the diagnosis of a new TB …


Fcrider: A Recombinant Fc Nanoparticle With Endogenous Adjuvant Activities For Hybrid Immunization, Changchuin Mao, Karen Eberle, Xiaojie Chen, Yiming Zhou, Jun Li, Hong Xin, Wenda Gao Sep 2024

Fcrider: A Recombinant Fc Nanoparticle With Endogenous Adjuvant Activities For Hybrid Immunization, Changchuin Mao, Karen Eberle, Xiaojie Chen, Yiming Zhou, Jun Li, Hong Xin, Wenda Gao

School of Graduate Studies Faculty Publications

Active immunization (vaccination) induces long-lasting immunity with memory, which takes weeks to months to develop. Passive immunization (transfer of neutralizing antibodies) provides immediate protection, yet with high cost and effects being comparatively short-lived. No currently approved adjuvants are compatible with formulations to combine active and passive immunizations, not to mention their huge disparities in administration routes and dosage. To solve this, we engineered the Fc fragment of human IgG1 into a hexamer nanoparticle and expressed its afucosylated form in Fut8−/− CHO cells, naming it “FcRider.” FcRider is highly soluble with long-term stability, easily produced at high levels equivalent to those …


Targeting Nuclear Receptor Coactivator Src-1 Prevents Colorectal Cancer Immune Escape By Reducing Transcription And Protein Stability Of Pd-L1, Yilin Hong, Qiang Chen, Zinan Wang, Yong Zhang, Bei Li, Hanshi Guo, Chuanzhong Huang, Xu Kong, Pingli Mo, Nengming Xiao, Jianming Xu, Yunbin Ye, Chundong Yu Sep 2024

Targeting Nuclear Receptor Coactivator Src-1 Prevents Colorectal Cancer Immune Escape By Reducing Transcription And Protein Stability Of Pd-L1, Yilin Hong, Qiang Chen, Zinan Wang, Yong Zhang, Bei Li, Hanshi Guo, Chuanzhong Huang, Xu Kong, Pingli Mo, Nengming Xiao, Jianming Xu, Yunbin Ye, Chundong Yu

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC-1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC-1 is positively correlated with PD-L1 in human CRC specimens. SRC-1 deficiency significantly inhibits PD-L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8


Characterization Of High-Risk-Other Human Papillomavirus Genotypes In Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, And Cervical Cancer, Caitlin E. Witt, Elizabeth F. Sutton, Ashley M. Stansbury, Ashley N. Winters, Luke C. Konur, Meng Luo, Jennifer E. Cameron, Beverly Ogden Sep 2024

Characterization Of High-Risk-Other Human Papillomavirus Genotypes In Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, And Cervical Cancer, Caitlin E. Witt, Elizabeth F. Sutton, Ashley M. Stansbury, Ashley N. Winters, Luke C. Konur, Meng Luo, Jennifer E. Cameron, Beverly Ogden

School of Medicine Faculty Publications

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for …


Natural Killer Cell Effector Function Is Critical For Host Defense Against Alcohol-Associated Bacterial Pneumonia, Daniel Villageliu, Kelly C. Cunningham, Deandra R. Smith, Daren L. Knoell, Mason Mandolfo, Todd A. Wyatt, Derrick R. Samuelson Aug 2024

Natural Killer Cell Effector Function Is Critical For Host Defense Against Alcohol-Associated Bacterial Pneumonia, Daniel Villageliu, Kelly C. Cunningham, Deandra R. Smith, Daren L. Knoell, Mason Mandolfo, Todd A. Wyatt, Derrick R. Samuelson

Food for Health: Publications

Alcohol use is an independent risk factor for the development of bacterial pneumonia due, in part, to impaired mucus-facilitated clearance, macrophage phagocytosis, and recruitment of neutrophils. Alcohol consumption is also known to reduce peripheral natural killer (NK) cell numbers and compromise NK cell cytolytic activity, especially NK cells with a mature phenotype. However, the role of innate lymphocytes, such as NK cells during host defense against alcohol-associated bacterial pneumonia is essentially unknown. We have previously shown that indole supplementation mitigates increases in pulmonary bacterial burden and improves pulmonary NK cell recruitment in alcohol-fed mice, which were dependent on aryl hydrocarbon …


The Experience Of Homelessness And Its Effects On Gut Eubiosis, Kamerin Villagomez Aug 2024

The Experience Of Homelessness And Its Effects On Gut Eubiosis, Kamerin Villagomez

University Honors Theses

Microorganisms which populate the human gastrointestinal tract (GIT) have a profound effect on overall human health. The relationship between host health and eubiosis, or balance, of the GIT microbiome is symbiotic and can have reciprocal relationships with quality of sleep, quality of diet, stress and mental health, and the experience of pain. These specific aspects of health are unique in populations experiencing homelessness due to the multi-dimensional and complex nature of their lived experience. Very few studies explore populations experiencing homelessness, with even fewer investigating the intersection between this population and the human GIT microbiome. It is important to do …


Development Of A Novel Amplifiable System To Quantify Hydrogen Peroxide In Living Cells, Lingfei Wang, Hanfeng Lin, Bin Yang, Xiqian Jiang, Jianwei Chen, Sandipan Roy Chowdhury, Ninghui Cheng, Paul A Nakata, David M Lonard, Meng C Wang, Jin Wang Aug 2024

Development Of A Novel Amplifiable System To Quantify Hydrogen Peroxide In Living Cells, Lingfei Wang, Hanfeng Lin, Bin Yang, Xiqian Jiang, Jianwei Chen, Sandipan Roy Chowdhury, Ninghui Cheng, Paul A Nakata, David M Lonard, Meng C Wang, Jin Wang

Faculty, Staff and Students Publications

Although many redox signaling molecules are present at low concentrations, typically ranging from micromolar to sub-micromolar levels, they often play essential roles in a wide range of biological pathways and disease mechanisms. However, accurately measuring low abundant analytes has been a significant challenge due to the lack of sensitivity and quantitative capability of existing measurement methods. In this study, we introduced a novel chemically induced amplifiable system for quantifying low-abundance redox signaling molecules in living cells. We utilized H2O2 as a proof-of-concept analyte and developed a probe that quantifies cellular peroxide levels by combining the NanoBiT system with androgen receptor …


Persistence Of Daptomycin-Resistant And Vancomycin-Resistant Enterococci In Hospitalized Patients With Underlying Malignancies: A 7-Year Follow-Up Study, Lynn El Haddad, Georgios Angelidakis, Yuting Zhai, Layale Yaghi, Cesar A Arias, Samuel A Shelburne, Kwangcheol Casey Jeong, Roy F Chemaly Aug 2024

Persistence Of Daptomycin-Resistant And Vancomycin-Resistant Enterococci In Hospitalized Patients With Underlying Malignancies: A 7-Year Follow-Up Study, Lynn El Haddad, Georgios Angelidakis, Yuting Zhai, Layale Yaghi, Cesar A Arias, Samuel A Shelburne, Kwangcheol Casey Jeong, Roy F Chemaly

Faculty, Staff and Student Publications

Vancomycin-resistant enterococci (VRE) commonly colonize the gut of individuals with hematologic malignancies or undergoing hematopoietic cell transplant (HCT) and may cause bacteremia. In 2012, we identified VRE isolates from patients and patients' rooms and showed transmission networks of highly genetically related daptomycin-resistant (DR)-VRE strains. This is a follow-up study performing whole-genome sequencing (WGS) and phylogenetic analyses on 82 clinical VRE strains isolated from stools and blood cultures of patients with leukemia and HCT between 2015 and 2019. Here, we observed transmission of highly genetically related strains between rooms on the same or on different floors, including a DR-VRE strain identified …


Identification And Characterization Of A Skin Microbiome On Caenorhabditis Elegans Suggests Environmental Microbes Confer Cuticle Protection, Nadia B Haghani, Robert H Lampe, Buck S Samuel, Sreekanth H Chalasani, Molly A Matty Aug 2024

Identification And Characterization Of A Skin Microbiome On Caenorhabditis Elegans Suggests Environmental Microbes Confer Cuticle Protection, Nadia B Haghani, Robert H Lampe, Buck S Samuel, Sreekanth H Chalasani, Molly A Matty

Faculty, Staff and Students Publications

In the wild, C. elegans are emersed in environments teeming with a veritable menagerie of microorganisms. The C. elegans cuticular surface serves as a barrier and first point of contact with their microbial environments. In this study, we identify microbes from C. elegans natural habitats that associate with its cuticle, constituting a simple “skin microbiome.” We rear our animals on a modified CeMbio, mCeMbio, a consortium of ecologically relevant microbes. We first combine standard microbiological methods with an adapted micro skin-swabbing tool to describe the skin-resident bacteria on the C. elegans surface. Furthermore, we conduct 16S rRNA gene sequencing studies …


Women In Stem Becoming Independent: Our Shared Motivation And Enthusiasm Are Our Driving Force, Liudmila Andreeva, Lidia Bosurgi, Shu Zhen Chong, Coco Chu, Yejing Ge, Esther Hoste, Kellie A Jurado, Jette Lengefeld, Archita Mishra, Stefanie Wculek, Arabella Young Aug 2024

Women In Stem Becoming Independent: Our Shared Motivation And Enthusiasm Are Our Driving Force, Liudmila Andreeva, Lidia Bosurgi, Shu Zhen Chong, Coco Chu, Yejing Ge, Esther Hoste, Kellie A Jurado, Jette Lengefeld, Archita Mishra, Stefanie Wculek, Arabella Young

Faculty, Staff and Student Publications

This year at JEM, we are highlighting women in science by sharing their stories and amplifying their voices. In this Viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher.


Characterization Of Turbo, A Tlr Ligand-Based Adjuvant For Glycoconjugate Vaccines, Kishore R. Alugupalli Aug 2024

Characterization Of Turbo, A Tlr Ligand-Based Adjuvant For Glycoconjugate Vaccines, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

Many bacterial polysaccharide vaccines, including the typhoid Vi polysaccharide (ViPS) and tetravalent meningococcal polysaccharide conjugate (MCV4) vaccines, do not incorporate adjuvants and are not highly immunogenic, particularly in infants. I found that endotoxin, a TLR4 ligand in ViPS, contributes to the immunogenicity of typhoid vaccines. Because endotoxin is pyrogenic, and its levels are highly variable in vaccines, I developed monophosphoryl lipid A, a nontoxic TLR4 ligand-based adjuvant named Turbo. Admixing Turbo with ViPS and MCV4 vaccines improved their immunogenicity across all ages and eliminated booster requirement. To understand the characteristics of this adjuvanticity, I compared Turbo with alum. Unlike alum, …


Fine-Tuning Ampk In Physiology And Disease Using Point-Mutant Mouse Models, Naghmana Ashraf, Jeanine L Van Nostrand Aug 2024

Fine-Tuning Ampk In Physiology And Disease Using Point-Mutant Mouse Models, Naghmana Ashraf, Jeanine L Van Nostrand

Faculty, Staff and Students Publications

AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that monitors the cellular energy status to adapt it to the fluctuating nutritional and environmental conditions in an organism. AMPK plays an integral part in a wide array of physiological processes, such as cell growth, autophagy and mitochondrial function, and is implicated in diverse diseases, including cancer, metabolic disorders, cardiovascular diseases and neurodegenerative diseases. AMPK orchestrates many different physiological outcomes by phosphorylating a broad range of downstream substrates. However, the importance of AMPK-mediated regulation of these substrates in vivo remains an ongoing area of investigation to better understand its precise …


Addendum: A Small Molecule Produced By Lactobacillus Species Blocks Candida Albicans Filamentation By Inhibiting A Dyrk1-Family Kinase, Jessie Macalpine, Martin Daniel-Ivad, Zhongle Liu, Junko Yano, Nicole M. Revie, Robert T. Todd, Peter J. Stogios, Hiram Sanchez, Teresa R. O'Meara, Thomas A. Tompkins, Alexei Savchenko, Anna Selmecki, Amanda O. Veri, David R. Andes, Paul L. Fidel, Nicole Robbins, Justin Nodwell, Luke Whitesell, Leah E. Cowen Aug 2024

Addendum: A Small Molecule Produced By Lactobacillus Species Blocks Candida Albicans Filamentation By Inhibiting A Dyrk1-Family Kinase, Jessie Macalpine, Martin Daniel-Ivad, Zhongle Liu, Junko Yano, Nicole M. Revie, Robert T. Todd, Peter J. Stogios, Hiram Sanchez, Teresa R. O'Meara, Thomas A. Tompkins, Alexei Savchenko, Anna Selmecki, Amanda O. Veri, David R. Andes, Paul L. Fidel, Nicole Robbins, Justin Nodwell, Luke Whitesell, Leah E. Cowen

School of Dentistry Faculty Publications

No abstract provided.


Vertebrate And Invertebrate Animal Infection Models Of Candida Auris Pathogenicity, Melissa Martinez, Danielle A Garsin, Michael C Lorenz Aug 2024

Vertebrate And Invertebrate Animal Infection Models Of Candida Auris Pathogenicity, Melissa Martinez, Danielle A Garsin, Michael C Lorenz

Faculty, Staff and Student Publications

Candida auris is an emerging fungal pathogen with several concerning qualities. First recognized in 2009, it has arisen in multiple geographically distinct genomic clades nearly simultaneously. C. auris strains are typically multidrug resistant and colonize the skin much better than most other pathogenic fungi; it also persists on abiotic surfaces, enabling outbreaks due to transmission in health care facilities. All these suggest a biology substantially different from the 'model' fungal pathogen, Candida albicans and support intensive investigation of C. auris biology directly. To uncover novel virulence mechanisms in this species requires the development of appropriate animal infection models. Various studies …


Adaptative Survival Of Aspergillus Fumigatus To Echinocandins Arises From Cell Wall Remodeling Beyond Β−1,3-Glucan Synthesis Inhibition, Malitha C. Dickwella Widanage, Isha Gautam, Daipayan Sarkar, Frederic Mentink-Vigier, Josh V. Vermaas, Shi You Ding, Andrew S. Lipton, Thierry Fontaine, Jean Paul Latgé, Ping Wang, Tuo Wang Jul 2024

Adaptative Survival Of Aspergillus Fumigatus To Echinocandins Arises From Cell Wall Remodeling Beyond Β−1,3-Glucan Synthesis Inhibition, Malitha C. Dickwella Widanage, Isha Gautam, Daipayan Sarkar, Frederic Mentink-Vigier, Josh V. Vermaas, Shi You Ding, Andrew S. Lipton, Thierry Fontaine, Jean Paul Latgé, Ping Wang, Tuo Wang

School of Graduate Studies Faculty Publications

Antifungal echinocandins inhibit the biosynthesis of β−1,3-glucan, a major and essential polysaccharide component of the fungal cell wall. However, the efficacy of echinocandins against the pathogen Aspergillus fumigatus is limited. Here, we use solid-state nuclear magnetic resonance (ssNMR) and other techniques to show that echinocandins induce dynamic changes in the assembly of mobile and rigid polymers within the A. fumigatus cell wall. The reduction of β−1,3-glucan induced by echinocandins is accompanied by a concurrent increase in levels of chitin, chitosan, and highly polymorphic α−1,3-glucans, whose physical association with chitin maintains cell wall integrity and modulates water permeability. The rearrangement of …


Interpreting Ppv And Npv Of Diagnostic Tests With Uncertain Prevalence, Yakov Ben-Haim, Clifford C Dacso Jul 2024

Interpreting Ppv And Npv Of Diagnostic Tests With Uncertain Prevalence, Yakov Ben-Haim, Clifford C Dacso

Faculty, Staff and Students Publications

OBJECTIVE: Medical decision-making is often uncertain. The positive predictive value (PPV) and negative predictive value (NPV) are conditional probabilities characterizing diagnostic tests and assessing diagnostic interventions in clinical medicine and epidemiology. The PPV is the probability that a patient has a specified disease, given a positive test result for that disease. The NPV is the probability that a patient does not have the disease, given a negative test result for that disease. Both values depend on disease incidence or prevalence, which may be highly uncertain for unfamiliar diseases, epidemics, etc. Probability distributions for this uncertainty are usually unavailable. We develop …


The Significant Role Of Amino Acid Metabolic Reprogramming In Cancer, Xiaohong Liu, Bo Ren, Jie Ren, Minzhi Gu, Lei You, Yupei Zhao Jul 2024

The Significant Role Of Amino Acid Metabolic Reprogramming In Cancer, Xiaohong Liu, Bo Ren, Jie Ren, Minzhi Gu, Lei You, Yupei Zhao

Faculty, Staff and Student Publications

Amino acid metabolism plays a pivotal role in tumor microenvironment, influencing various aspects of cancer progression. The metabolic reprogramming of amino acids in tumor cells is intricately linked to protein synthesis, nucleotide synthesis, modulation of signaling pathways, regulation of tumor cell metabolism, maintenance of oxidative stress homeostasis, and epigenetic modifications. Furthermore, the dysregulation of amino acid metabolism also impacts tumor microenvironment and tumor immunity. Amino acids can act as signaling molecules that modulate immune cell function and immune tolerance within the tumor microenvironment, reshaping the anti-tumor immune response and promoting immune evasion by cancer cells. Moreover, amino acid metabolism can …


N-Myc And Stat Interactor Is An Endometriosis Suppressor, Yuri Park, Xiaoming Guan, Sang Jun Han Jul 2024

N-Myc And Stat Interactor Is An Endometriosis Suppressor, Yuri Park, Xiaoming Guan, Sang Jun Han

Faculty, Staff and Students Publications

In patients with endometriosis, refluxed endometrial fragments evade host immunosurveillance, developing into endometriotic lesions. However, the mechanisms underlying this evasion have not been fully elucidated. N-Myc and STAT Interactor (NMI) have been identified as key players in host immunosurveillance, including interferon (IFN)-induced cell death signaling pathways. NMI levels are markedly reduced in the stromal cells of human endometriotic lesions due to modulation by the Estrogen Receptor beta/Histone Deacetylase 8 axis. Knocking down NMI in immortalized human endometrial stromal cells (IHESCs) led to elevated RNA levels of genes involved in cell-to-cell adhesion and extracellular matrix signaling following IFNA treatment. Furthermore, NMI …