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Molecular Mechanisms Lead To Sex-Specific Covid-19 Prognosis And Targeted Therapies, Thushara Galbadage, Brent M. Peterson, Jeffrey S. Wang, Avishka Jayasekara, Danny A. Ramirez, Joseph Awada, John P. Walsh, Richard S. Gunasekera 2020 Biola University

Molecular Mechanisms Lead To Sex-Specific Covid-19 Prognosis And Targeted Therapies, Thushara Galbadage, Brent M. Peterson, Jeffrey S. Wang, Avishka Jayasekara, Danny A. Ramirez, Joseph Awada, John P. Walsh, Richard S. Gunasekera

Faculty Articles & Research

Clinical and epidemiological studies have identified male sex as an important risk factor for COVID-19 clinical outcomes and mortality. This raises the question as to how this risk factor can be addressed in the prognosis, clinical management, and the treatment of patients with Coronavirus disease 2019 (COVID-19). Currently, there are no guidelines or protocols to help alter the course of sex-specific COVID-19 prognosis, especially in severe disease presentations. This is partly due to the lack of research studies characterizing the differences in male vs. female host response to the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection and a lack of ...


Delayed Interventions, Low Compliance, And Health Disparities Amplified The Early Spread Of Covid-19, Aliea M. Jalali, Sumaia G. Khoury, JongWon See, Alexis M. Gulsvig, Brent M. Peterson, Richard S. Gunasekera, Gentian Buzi, Jason Wilson, Thushara Galbadage 2020 Biola University

Delayed Interventions, Low Compliance, And Health Disparities Amplified The Early Spread Of Covid-19, Aliea M. Jalali, Sumaia G. Khoury, Jongwon See, Alexis M. Gulsvig, Brent M. Peterson, Richard S. Gunasekera, Gentian Buzi, Jason Wilson, Thushara Galbadage

Faculty Articles & Research

The United States (US) public health interventions were rigorous and rapid, yet failed to arrest the spread of the Coronavirus Disease 2019 (COVID-19) pandemic as infections spread throughout the US. Many factors have contributed to the spread of COVID-19, and the success of public health interventions depends on the level of community adherence to preventative measures. Public health professionals must also understand regional demographic variation in health disparities and determinants to target interventions more effectively. In this study, a systematic evaluation of three significant interventions employed in the US, and their effectiveness in slowing the early spread of COVID-19 was ...


Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System [Preprint], Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti 2020 Michigan State University

Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System [Preprint], Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer of cell-autonomous immunity is the lymphocyte-derived cytokine IFNγ. While the production of IFNγ by T cells is essential to protect against Mtb, it is not capable of fully eradicating Mtb infection. This suggests that Mtb evades a subset of IFNγ-mediated antimicrobial responses, yet what mechanisms Mtb resists remains unclear. The IFNγ-inducible Guanylate binding proteins (GBPs) are key host defense proteins able to control infections with intracellular pathogens. GBPs were previously shown ...


Invasive Pulmonary Infection By Syncephalastrum Species: Two Case Reports And Review Of Literature, Memoona Irshad, Nosheen Nasir, Urooj Haider Hashmi, Joveria Farooqi, Syed Faisal Mahmood 2020 Aga Khan University

Invasive Pulmonary Infection By Syncephalastrum Species: Two Case Reports And Review Of Literature, Memoona Irshad, Nosheen Nasir, Urooj Haider Hashmi, Joveria Farooqi, Syed Faisal Mahmood

Section of Internal Medicine

Background: Syncephalastrum species belong to the class Zygomycetes and order Mucorale. These are found in the environment and tropical soil, usually presenting as colonizers and rarely cause human infection. Syncephalastrum racemosum is a species of the genus Syncephalastrum and is the most commonly identified pathogen. Most cases are reported in immunocompromised individuals, such as patients on long term steroids, poorly controlled diabetes, or patients with malignancy.
Case presentation: We are describing two cases of rare fungal infection by Syncephalastrum species causing invasive pulmonary manifestation. Both patients had compromised immune status and presented with worsening dyspnea to the emergency room. Both ...


A Race Against Time: Reduced Azithromycin Susceptibility In Salmonella Enterica Serovar Typhi In Pakistan, Junaid Iqbal, Irum Fatima Dehraj, Megan E. Carey, Zoe A. Dyson, Denise Garrett, Jessica C. Seidman, Furqan Kabir, Senjuti Saha, Stephen Baker, Farah Naz Qamar 2020 Aga Khan University

A Race Against Time: Reduced Azithromycin Susceptibility In Salmonella Enterica Serovar Typhi In Pakistan, Junaid Iqbal, Irum Fatima Dehraj, Megan E. Carey, Zoe A. Dyson, Denise Garrett, Jessica C. Seidman, Furqan Kabir, Senjuti Saha, Stephen Baker, Farah Naz Qamar

Department of Paediatrics and Child Health

Antimicrobial resistance is an ongoing issue in the treatment of typhoid fever. Resistance to first-line antimicrobials and extensively drug resistant (XDR) Salmonella Typhi isolates in Pakistan have left azithromycin as the only remaining effective oral treatment. Here, we report the emergence of organisms with a single point mutation in acrB gene, implicated in azithromycin resistance, in a S. Typhi isolate from Pakistan. The isolation of this organism is worrisome and highlights the significance of the introduction of typhoid conjugate vaccine in South Asia.
Importance: The emergence of XDR Salmonella Typhi in Pakistan has left azithromycin as the only viable oral ...


Wild Mice With Different Social Network Sizes Vary In Brain Gene Expression, Patricia C. Lopes, Barbara König 2020 Chapman University

Wild Mice With Different Social Network Sizes Vary In Brain Gene Expression, Patricia C. Lopes, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background

Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution ...


Do Plant Secondary Metabolite‐Containing Forages Influence Soil Processes In Pasture Systems?, Andrea K. Clemensen, Juan J. Villalba, George E. Rottinghaus, Stephen T. Lee, Frederick D. Provenza, Jennifer R. Reeve 2020 Utah State University

Do Plant Secondary Metabolite‐Containing Forages Influence Soil Processes In Pasture Systems?, Andrea K. Clemensen, Juan J. Villalba, George E. Rottinghaus, Stephen T. Lee, Frederick D. Provenza, Jennifer R. Reeve

Wildland Resources Faculty Publications

Grazed pastures are susceptible to N loss from urine/manure additions, which increases eutrophication, affecting the global N cycle. Plant secondary metabolites (PSM), such as condensed tannins (CT) and terpenes, influence silviculture soil dynamics by generally decreasing N mineralization. We investigated whether cattle‐grazed pastures of non‐traditional grass and legume forage monoculture strips including CT‐containing sainfoin (Onobrychis viciifolia Scop.) and tall fescue (TF) [Schedonorus arundinaceus (Schreb.) Dumort.] influenced soil dynamics compared with traditional grass and legume forage monoculture strips of alfalfa (Medicago sativa L.), without tannins, and TF. Throughout the study, CT in sainfoin averaged 58.9 g ...


Structural Analysis Of Potent Hybrid Hiv-1 Protease Inhibitors Containing Bis-Tetrahydrofuran In A Pseudo-Symmetric Dipeptide Isostere, Linah Rusere, Gordon J. Lockbaum, Mina Henes, Sook-Kyung Lee, Ean Spielvogel, Desaboini Nageswara Rao, Klajdi Kosovrasti, Ellen A. Nalivaika, Ronald Swanstrom, Nese Kurt Yilmaz, Celia A. Schiffer, Akbar Ali 2020 University of Massachusetts Medical School

Structural Analysis Of Potent Hybrid Hiv-1 Protease Inhibitors Containing Bis-Tetrahydrofuran In A Pseudo-Symmetric Dipeptide Isostere, Linah Rusere, Gordon J. Lockbaum, Mina Henes, Sook-Kyung Lee, Ean Spielvogel, Desaboini Nageswara Rao, Klajdi Kosovrasti, Ellen A. Nalivaika, Ronald Swanstrom, Nese Kurt Yilmaz, Celia A. Schiffer, Akbar Ali

University of Massachusetts Medical School Faculty Publications

The design, synthesis, and X-ray structural analysis of hybrid HIV-1 protease inhibitors (PIs) containing bis-tetrahydrofuran (bis-THF) in a pseudo-C2-symmetric dipeptide isostere are described. A series of PIs were synthesized by incorporating bis-THF of darunavir on either side of the Phe-Phe isostere of lopinavir in combination with hydrophobic amino acids on the opposite P2/P2' position. Structure-activity relationship studies indicated that the bis-THF moiety can be attached at either the P2 or P2' position without significantly affecting potency. However, the group on the opposite P2/P2' position had a dramatic effect on potency depending on the size and shape of the ...


Acidic Ph Triggers Lipid Mixing Mediated By Lassa Virus Gp, Uriel Bulow, Ramesh Govindan, James B. Munro 2020 Tufts University

Acidic Ph Triggers Lipid Mixing Mediated By Lassa Virus Gp, Uriel Bulow, Ramesh Govindan, James B. Munro

Open Access Publications by UMMS Authors

Lassa virus (LASV) is the causative agent of Lassa hemorrhagic fever, a lethal disease endemic to Western Africa. LASV entry is mediated by the viral envelope glycoprotein (GP), a class I membrane fusogen and the sole viral surface antigen. Previous studies have identified components of the LASV entry pathway, including several cellular receptors and the requirement of endosomal acidification for infection. Here, we first demonstrate that incubation at a physiological temperature and pH consistent with the late endosome is sufficient to render pseudovirions, bearing LASV GP, non-infectious. Antibody binding indicates that this loss of infectivity is due to a conformational ...


Trichosporon Species And Fusarium Species As A Cause Of Empyema Thoracis In A Diabetic Patient, Nousheen Iqbal, Muhammad Ammar, Muhammad Irfan, Kauser Jabeen 2020 Aga Khan University

Trichosporon Species And Fusarium Species As A Cause Of Empyema Thoracis In A Diabetic Patient, Nousheen Iqbal, Muhammad Ammar, Muhammad Irfan, Kauser Jabeen

Section of Pulmonary & Critical Care

Of late, fungal infections are increasingly being recognized in diabetic patients. Here we present a case of polymicrobial fungal empyema due to Trichosporon species and Fusarium species developed after community-acquired pneumonia in a diabetic patient. Trichosporon species are basidiomycetous yeast and Fusarium species are soil saprophytes with a worldwide distribution. Fungal empyema cases are rare and are mostly caused by Aspergillus and Candida species. Polymicrobial fungal empyema with Trichosporon species and Fusarium species has not been reported previously. Our patient was successfully treated with antifungal therapy. This case highlights that fungal empyema should be considered in diabetic patients especially if ...


Biofilm Structure Promotes Coexistence Of Phage-Resistant And Phage-Susceptible Bacteria, Emilia L. Simmons, Matthew C. Bond, Britt Koskella, Knut Drescher, Vanni Bucci, Carey D. Nadell 2020 Dartmouth College

Biofilm Structure Promotes Coexistence Of Phage-Resistant And Phage-Susceptible Bacteria, Emilia L. Simmons, Matthew C. Bond, Britt Koskella, Knut Drescher, Vanni Bucci, Carey D. Nadell

Open Access Publications by UMMS Authors

Encounters among bacteria and their viral predators (bacteriophages) are among the most common ecological interactions on Earth. These encounters are likely to occur with regularity inside surface-bound communities that microbes most often occupy in natural environments. Such communities, termed biofilms, are spatially constrained: interactions become limited to near neighbors, diffusion of solutes and particulates can be reduced, and there is pronounced heterogeneity in nutrient access and physiological state. It is appreciated from prior theoretical work that phage-bacteria interactions are fundamentally different in spatially structured contexts, as opposed to well-mixed liquid culture. Spatially structured communities are predicted to promote the protection ...


Synergistic Effects Of Non Contact Induction Heating & Antibiotics On Staphylococcus Aureus Biofilm, Rajeshwar Singh Sidhu 2020 The University of Western Ontario

Synergistic Effects Of Non Contact Induction Heating & Antibiotics On Staphylococcus Aureus Biofilm, Rajeshwar Singh Sidhu

Electronic Thesis and Dissertation Repository

Staphylococcus aureus is a major cause of prosthetic joint infection (PJI) in which it forms adherent biofilms, thick aggregates of extracellular polymeric substances (EPS) produced by the bacteria. Biofilm associated infections are difficult to treat as they have increased resistance to various antimicrobial agents, which means infected implants often require multiple procedures and prolonged antibiotic therapy. However, a new and emerging method of treatment of PJI is non-contact induction heating (NCIH) of metal implants. We sought to investigate the feasibility and effectiveness of NCIH along with synergistic effects of antibiotics (Vancomycin) in reducing bacterial load within surface associated biofilms in ...


Fecal Microbiota Transplantation And Gut Microbiome Effects On Psychiatric Illnesses, Mona Seresht 2020 Dominican University of California

Fecal Microbiota Transplantation And Gut Microbiome Effects On Psychiatric Illnesses, Mona Seresht

Physician Assistant Studies | Student Articles

Despite the medical advances that have been made in regards to mental health, psychiatric medications, and alternative therapies, many patients continue to suffer day in and day out, unable to live the type of life they desire. Many times, the medication route includes many episodes of trial and error, side effects, and no significant improvement in actual symptoms. Therapy, although effective, typically necessitates a supplemental medication for the best results. Fecal microbiota transplantation (FMT) is a method where feces from a healthy donor is transferred to an affected patient, typically via colonoscopy. Theoretically, this alters the gut microbiome in a ...


Multicenter Clinical Evaluation Of The Revogene Strep A Molecular Assay For Detection Of Streptococcus Pyogenes From Throat Swab Specimens, Dithi Banerjee, Jeff Michael, B. Schmitt, H. Salimnia, N. Mhaissen, D. M. Goldfarb, P. Lachance, M. L. Faron, T. Aufderheide, N. Ledeboer, A. Weissfeld, Rangaraj Selvarangan 2020 Children's Mercy Hospital

Multicenter Clinical Evaluation Of The Revogene Strep A Molecular Assay For Detection Of Streptococcus Pyogenes From Throat Swab Specimens, Dithi Banerjee, Jeff Michael, B. Schmitt, H. Salimnia, N. Mhaissen, D. M. Goldfarb, P. Lachance, M. L. Faron, T. Aufderheide, N. Ledeboer, A. Weissfeld, Rangaraj Selvarangan

Manuscripts, Articles, Book Chapters and Other Papers

Copyright © 2020 Banerjee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license Group A streptococcus (GAS) species cause bacterial pharyngitis in both adults and children. Early and accurate diagnosis of GAS is important for appropriate antibiotic therapy to prevent GAS sequalae. The Revogene Strep A molecular assay (Meridian Bioscience Canada Inc, Quebec City, QC, Canada) is an automated real-time PCR assay for GAS detection from throat swab specimens within approximately 70 min. This multicenter prospective study evaluated the performance of the Revogene Strep A molecular assay compared to that ...


Understanding Human Astrovirus From Pathogenesis To Treatment, Virginia Hargest 2020 University of Tennessee Health Science Center

Understanding Human Astrovirus From Pathogenesis To Treatment, Virginia Hargest

Theses and Dissertations (ETD)

While human astroviruses (HAstV) were discovered nearly 45 years ago, these small positive-sense RNA viruses remain critically understudied. These studies provide fundamental new research on astrovirus pathogenesis and disruption of the gut epithelium by induction of epithelial-mesenchymal transition (EMT) following astrovirus infection. Here we characterize HAstV-induced EMT as an upregulation of SNAI1 and VIM with a down regulation of CDH1 and OCLN, loss of cell-cell junctions most notably at 18 hours post-infection (hpi), and loss of cellular polarity by 24 hpi. While active transforming growth factor- (TGF-) increases during HAstV infection, inhibition of TGF- signaling does not hinder EMT induction ...


Screening For Iron-Deficiency Anemia In The Pediatric Population (Ages 1-17) In Gonaïves, Haiti, Cara Rose Fratianni 2020 University of San Diego

Screening For Iron-Deficiency Anemia In The Pediatric Population (Ages 1-17) In Gonaïves, Haiti, Cara Rose Fratianni

Doctor of Nursing Practice Final Manuscripts

Abstract

Purpose: The purpose of this pilot project is to screen for iron-deficiency anemia in pediatric patients (ages 1-17) in a primary school in Gonaïves, Haiti. Patients with anemia will be treated with oral supplemental iron for a period of four weeks according to WHO guidelines (WHO, 2011). All students will be treated empirically for helminths per WHO guidelines, unless treated elsewhere in the last six months (WHO, 2017). Nutritional status will also be assessed using MUAC according to WHO guidelines (2017).

Background Summary: Malnutrition contributes significantly to the problem of iron-deficiency anemia, with one in four children exhibiting stunting ...


Mrna Stem-Loops Can Pause The Ribosome By Hindering A-Site Trna Binding, Chen Bao, Sarah Loerch, Clarence Ling, Andrei A. Korostelev, Nikolaus Grigorieff, Dmitri N. Ermolenko 2020 University of Rochester

Mrna Stem-Loops Can Pause The Ribosome By Hindering A-Site Trna Binding, Chen Bao, Sarah Loerch, Clarence Ling, Andrei A. Korostelev, Nikolaus Grigorieff, Dmitri N. Ermolenko

Open Access Publications by UMMS Authors

Although the elongating ribosome is an efficient helicase, certain mRNA stem-loop structures are known to impede ribosome movement along mRNA and stimulate programmed ribosome frameshifting via mechanisms that are not well understood. Using biochemical and single-molecule Forster resonance energy transfer (smFRET) experiments, we studied how frameshift-inducing stem-loops from E. coli dnaX mRNA and the gag-pol transcript of Human Immunodeficiency Virus (HIV) perturb translation elongation. We find that upon encountering the ribosome, the stem-loops strongly inhibit A-site tRNA binding and ribosome intersubunit rotation that accompanies translation elongation. Electron cryo-microscopy (cryo-EM) reveals that the HIV stem-loop docks into the A site of ...


Tim, A Targeted Insertional Mutagenesis Method Utilizing Crispr/Cas9 In Chlamydomonas Reinhardtii, Tyler Picariello, Yuqing Hou, Tomohiro Kubo, Nathan A. McNeill, Haru-Aki Yanagisawa, Toshiyuki Oda, George B. Witman 2020 University of Massachusetts Medical School

Tim, A Targeted Insertional Mutagenesis Method Utilizing Crispr/Cas9 In Chlamydomonas Reinhardtii, Tyler Picariello, Yuqing Hou, Tomohiro Kubo, Nathan A. Mcneill, Haru-Aki Yanagisawa, Toshiyuki Oda, George B. Witman

Radiology Publications

Generation and subsequent analysis of mutants is critical to understanding the functions of genes and proteins. Here we describe TIM, an efficient, cost-effective, CRISPR-based targeted insertional mutagenesis method for the model organism Chlamydomonas reinhardtii. TIM utilizes delivery into the cell of a Cas9-guide RNA (gRNA) ribonucleoprotein (RNP) together with exogenous double-stranded (donor) DNA. The donor DNA contains gene-specific homology arms and an integral antibiotic-resistance gene that inserts at the double-stranded break generated by Cas9. After optimizing multiple parameters of this method, we were able to generate mutants for six out of six different genes in two different cell-walled strains with ...


Gp41-Targeted Antibodies Restore Infectivity Of A Fusion-Deficient Hiv-1 Envelope Glycoprotein, Vinita R. Joshi, Ruchi M. Newman, Melissa L. Pack, Karen A. Power, James B. Munro, Ken Okawa, Navid Madani, Joseph G. Sodroski, Aaron G. Schmidt, Todd M. Allen 2020 Harvard Medical School

Gp41-Targeted Antibodies Restore Infectivity Of A Fusion-Deficient Hiv-1 Envelope Glycoprotein, Vinita R. Joshi, Ruchi M. Newman, Melissa L. Pack, Karen A. Power, James B. Munro, Ken Okawa, Navid Madani, Joseph G. Sodroski, Aaron G. Schmidt, Todd M. Allen

Open Access Publications by UMMS Authors

The HIV-1 envelope glycoprotein (Env) mediates viral entry via conformational changes associated with binding the cell surface receptor (CD4) and coreceptor (CCR5/CXCR4), resulting in subsequent fusion of the viral and cellular membranes. While the gp120 Env surface subunit has been extensively studied for its role in viral entry and evasion of the host immune response, the gp41 transmembrane glycoprotein and its role in natural infection are less well characterized. Here, we identified a primary HIV-1 Env variant that consistently supports >300% increased viral infectivity in the presence of autologous or heterologous HIV-positive plasma. However, in the absence of HIV-positive ...


Identifying Determinants Of Target Specificity In Two Related Bacterial Peptide Toxins, Andrew D. Holmes 2020 University of South Dakota

Identifying Determinants Of Target Specificity In Two Related Bacterial Peptide Toxins, Andrew D. Holmes

Honors Thesis

Toxin-antitoxin (TA) systems were originally identified as two-component systems ensuring the stable inheritance of plasmids in bacterial populations. Recently, they have been identified on bacterial chromosomes where their functions remain mostly undefined. The par locus of E. faecalis plasmid pAD1 (parpAD1) was the first TA system defined in a Gram-positive bacterium and a homolog encoded on the E. faecalis chromosome (parEF0409) was later described. Related loci numbering in the hundreds have been identified throughout Gram-positive bacteria based on homology to the toxin of the system, Fst, and similarities in genetic organization and regulation. Despite their similar sequences, over-expression ...


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