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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, 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, 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 ...


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 ...


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 ...


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 Articles

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 ...


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 ...


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 Articles

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 Articles

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 ...


Characterization Of A Plasmid-Based Dna Vaccine For Simian Immunodeficiency Virus, Priya Sanipara 2020 University of Mississippi Main Campus

Characterization Of A Plasmid-Based Dna Vaccine For Simian Immunodeficiency Virus, Priya Sanipara

Honors Theses

Described as one of the world’s worst pandemics, HIV (Human Immunodeficiency Virus) infects millions of people each year and is the cause for AIDS (Acquired Immunodeficiency Syndrome). Despite the development of vaccines for numerous infectious diseases such as polio, small pox, and influenza, a vaccine for HIV remains elusive due to the virus’s high mutation rate and ability to evade the immune system. HIV causes depletion of CD4+ lymphocytes, resulting in a weakened immune system. However, the development of a plasmid-based DNA vaccine approach may help revolutionize vaccine development for HIV due to its ability to confer cellular ...


Discovery Of Distinct Mechanisms Underlying The Relationship Between Drug Taking And Predisposing Behaviors, Tyler A. Roy 2020 The Jackson Laboratory

Discovery Of Distinct Mechanisms Underlying The Relationship Between Drug Taking And Predisposing Behaviors, Tyler A. Roy

Electronic Theses and Dissertations

Drug addiction is a heritable disease characterized by compulsive drug use. The biological mechanisms driving addiction remain largely unknown.1 Previous studies show shared genetic mechanisms underlying addiction risk phenotypes such as anxiety, depression, and novelty/sensation seeking.2,3 Therefore, high-throughput behavioral screening of these traits in single gene knockout mice can allow for the rapid detection of addiction risk candidate genes and mechanisms. Many of these traits are represented in the Knock-Out Mouse Program (KOMP) phenotyping pipeline. Of the initial two hundred twenty-one strains screened in this program, we tested nineteen phenodeviant knock-out mouse strains with C57BL/6NJ ...


Linearized Siderophore Products Secreted Via Macab Efflux Pump Protect Salmonella Enterica Serovar Typhimurium From Oxidative Stress, L M. Bogomolnaya, Ronak Tilvawala, J. R. Elfenbein, J. D. Cirillo, H. L. Andrews-Polymenis 2020 Texas A&M University

Linearized Siderophore Products Secreted Via Macab Efflux Pump Protect Salmonella Enterica Serovar Typhimurium From Oxidative Stress, L M. Bogomolnaya, Ronak Tilvawala, J. R. Elfenbein, J. D. Cirillo, H. L. Andrews-Polymenis

Open Access Articles

Nontyphoidal salmonellae (NTS) are exposed to reactive oxygen species (ROS) during their residency in the gut. To survive oxidative stress encountered during infection, salmonellae employ several mechanisms. One of these mechanisms involves the multidrug efflux pump MacAB, although the natural substrate of this pump has not been identified. MacAB homologs in pseudomonads secrete products of nonribosomal peptide synthesis (NRPS). In Salmonella enterica serovar Typhimurium, the siderophore enterobactin is produced by NRPS in response to iron starvation and this molecule can be processed into salmochelin and several linear metabolites. We found that Salmonella mutants lacking the key NRPS enzyme EntF are ...


Life During A Pandemic, Srinivasan Ragothaman 2020 Srini.Ragothaman@usd.edu

Life During A Pandemic, Srinivasan Ragothaman

Creative Work

This is a short poem (6 stanzas) about the current pandemic and the trials and tribulations people are going through. This describes the heroic efforts by the doctors, nurses, and other frontline warriors in tackling the virus related illnesses and pays a rich tribute to all heroes from every walk of life who are in the front fighting this disease. It hopes for a plan, a vaccine, and a cure soon. This poem also describes the switchover to remote instruction at a reginal University, student and faculty adjustments to the pandemic and pokes gentle fun at the opportunity to watch ...


Smrt Sequencing Of Paramecium Bursaria Chlorella Virus-1 Reveals Diverse Methylation Stability In Adenines Targeted By Restriction Modification Systems, Samantha R. Coy, Eric R. Gann, Spiridon E. Papoulis, Michael E. Holder, Nadim J. Ajami, Joseph F. Petrosino, Erik R. Zinser, James L. Van Etten, Steven W. Wilhelm 2020 University of Tennessee, Knoxville & Rice University

Smrt Sequencing Of Paramecium Bursaria Chlorella Virus-1 Reveals Diverse Methylation Stability In Adenines Targeted By Restriction Modification Systems, Samantha R. Coy, Eric R. Gann, Spiridon E. Papoulis, Michael E. Holder, Nadim J. Ajami, Joseph F. Petrosino, Erik R. Zinser, James L. Van Etten, Steven W. Wilhelm

James Van Etten Publications

Chloroviruses (family Phycodnaviridae) infect eukaryotic, freshwater, unicellular green algae. A unique feature of these viruses is an abundance of DNA methyltransferases, with isolates dedicating up to 4.5% of their protein coding potential to these genes. This diversity highlights just one of the long-standing values of the chlorovirus model system; where group-wide epigenomic characterization might begin to elucidate the function(s) of DNA methylation in large dsDNA viruses. We characterized DNA modifications in the prototype chlorovirus, PBCV-1, using single-molecule real time (SMRT) sequencing (aka PacBio). Results were compared to total available sites predicted in silico based on DNA sequence alone ...


The Discovery Of Metarhizium Anisopliae (Metchnikoff) Sorokin Isolates From Arkansas And Their Pathogenicity To Amblyomma Americanum L., Austin Goldsmith 2020 University of Arkansas, Fayetteville

The Discovery Of Metarhizium Anisopliae (Metchnikoff) Sorokin Isolates From Arkansas And Their Pathogenicity To Amblyomma Americanum L., Austin Goldsmith

Theses and Dissertations

The lone star tick Amblyomma americanum L. is the most abundant tick in Arkansas and has been implicated as a vector of many important disease-causing pathogens. Many species of entomopathogenic fungi have been isolated from several species of ticks, with some of these fungi being utilized for tick biocontrol. However, few studies have assessed the pathogenicity of entomopathogenic fungi to A. americanum. The objectives of this study were to: isolate and identify native Arkansas isolates of entomopathogenic fungi from wild A. americanum ticks exposed to soil and to compare the pathogenicity of one isolate (Metarhizium anisopliae (Metchnikoff) Sorokin isolate Savoy ...


A Biogeographical Assessment Of Arctic Marine Fungi, Bentley E. Simpson 2020 University of Maine

A Biogeographical Assessment Of Arctic Marine Fungi, Bentley E. Simpson

Honors College

Marine fungi play a crucial role in recycling nutrients and channeling energy to higher trophic levels in the world oceans. Despite their critical role, their distributions and community composition, particularly in the Arctic, are largely unknown. This study reveals depth-related trends of abundance, diversity, and community composition of Arctic marine fungi through analysis of data obtained in the Tara Oceans expedition. With samples from surface (0-50 m), deep chlorophyll max (50-200 m), and mesopelagic (200-1000 m) depths, relative abundance, operational taxonomic unit (OTU) richness, and diversity were found to increase as a function of depth. Basidiomycota and Ascomycota were found ...


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