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The Intestinal And Oral Microbiomes Are Robust Predictors Of Covid-19 Severity The Main Predictor Of Covid-19-Related Fatality [Preprint], Doyle V. Ward, Shakti Bhattarai, Mayra Rojas-Correa, Ayan Purkayastha, Devon Holler, Ming Da Qu, William G. Mitchell, Jason D. Yang, Samuel Fountain, Abigail Zeamer, Catherine Forconi, Gavin Fujimori, Boaz Odwar, Caitlin Cawley, Beth A. McCormick, Ann M. Moormann, Mireya Wessolossky, Vanni Bucci, Ana Maldonado-Contreras 2021 University of Massachusetts Medical School

The Intestinal And Oral Microbiomes Are Robust Predictors Of Covid-19 Severity The Main Predictor Of Covid-19-Related Fatality [Preprint], Doyle V. Ward, Shakti Bhattarai, Mayra Rojas-Correa, Ayan Purkayastha, Devon Holler, Ming Da Qu, William G. Mitchell, Jason D. Yang, Samuel Fountain, Abigail Zeamer, Catherine Forconi, Gavin Fujimori, Boaz Odwar, Caitlin Cawley, Beth A. Mccormick, Ann M. Moormann, Mireya Wessolossky, Vanni Bucci, Ana Maldonado-Contreras

University of Massachusetts Medical School Faculty Publications

The reason for the striking differences in clinical outcomes of SARS-CoV-2 infected patients is still poorly understood. While most recover, a subset of people become critically ill and succumb to the disease. Thus, identification of biomarkers that can predict the clinical outcomes of COVID-19 disease is key to help prioritize patients needing urgent treatment. Given that an unbalanced gut microbiome is a reflection of poor health, we aim to identify indicator species that could predict COVID-19 disease clinical outcomes. Here, for the first time and with the largest COVID-19 patient cohort reported for microbiome studies, we demonstrated that the intestinal ...


Quantifying The Regulatory Role Of Individual Transcription Factors In Escherichia Coli [Preprint], Sunil Guharajan, Shivani Chhabra, Vinuselvi Parisutham, Robert C. Brewster 2021 University of Massachusetts Medical School

Quantifying The Regulatory Role Of Individual Transcription Factors In Escherichia Coli [Preprint], Sunil Guharajan, Shivani Chhabra, Vinuselvi Parisutham, Robert C. Brewster

University of Massachusetts Medical School Faculty Publications

Transcription factors (TFs) modulate gene expression by binding to regulatory DNA sequences surrounding target genes. To isolate the fundamental regulatory interactions of E. coli TFs, we measure regulation of TFs acting on synthetic target genes that are designed to isolate the individual TF regulatory effect. This data is interpreted through a thermodynamic model that decouples the role of TF copy number and TF binding affinity from the interactions of the TF on RNA polymerase through two distinct mechanisms: (de)stabilization of the polymerase and (de)acceleration of transcription initiation. We find the contribution of each mechanism towards the observed regulation ...


Covid-19 Presenting With Spontaneous Pneumothorax, Intisar Ahmed, Hunaina Shahab, Muhammad Arslan Ahmed, Muhammad Sohaib 2021 Aga Khan University

Covid-19 Presenting With Spontaneous Pneumothorax, Intisar Ahmed, Hunaina Shahab, Muhammad Arslan Ahmed, Muhammad Sohaib

Section of Cardiology

The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease mainly affects respiratory system. Its common clinical findings include fever, cough and shortness of breath. Characteristic radiological features of the disease include peripherally distributed, bilateral ground-glass opacities, predominantly involving the lower lung zones. In this report, we present a case of COVID-19 disease presenting with spontaneous pneumothorax. A 26-year male patient was admitted to the Emergency Department with fever, dry cough, shortness of breath and right-sided chest pain. Radiographic imaging of the patient revealed pneumothorax on the right and peripherally distributed non-homogenous opacification ...


Evolution, Ecology, And Zoonotic Transmission Of Betacoronaviruses: A Review, Herbert F. Jelinek, Mira Mousa, Eman Alefishat, Wael Osman, Ian Spence, Dengpan Bu, Samuel F. Feng, Jason Byrd, Paola A. Magni, Shafi Sahibzada, Guan K. Tay, Habiba S. Alsafar 2021 Edith Cowan University

Evolution, Ecology, And Zoonotic Transmission Of Betacoronaviruses: A Review, Herbert F. Jelinek, Mira Mousa, Eman Alefishat, Wael Osman, Ian Spence, Dengpan Bu, Samuel F. Feng, Jason Byrd, Paola A. Magni, Shafi Sahibzada, Guan K. Tay, Habiba S. Alsafar

ECU Publications Post 2013

Coronavirus infections have been a part of the animal kingdom for millennia. The difference emerging in the twenty-first century is that a greater number of novel coronaviruses are being discovered primarily due to more advanced technology and that a greater number can be transmitted to humans, either directly or via an intermediate host. This has a range of effects from annual infections that are mild to full-blown pandemics. This review compares the zoonotic potential and relationship between MERS, SARS-CoV, and SARS-CoV-2. The role of bats as possible host species and possible intermediate hosts including pangolins, civets, mink, birds, and other ...


Covid-19: Race For Vaccine, L. Hayley Burgess, Jason J. Braithwaite, Emily Singleton, Aaron M. Young, Mandelin K. Cooper 2020 HCA Healthcare

Covid-19: Race For Vaccine, L. Hayley Burgess, Jason J. Braithwaite, Emily Singleton, Aaron M. Young, Mandelin K. Cooper

HCA Healthcare Journal of Medicine

The world is in the midst of a pandemic from COVID-19, a disease caused by the virus SARS-CoV-2. Despite broad mitigation efforts, new cases continue with 74 million cases and 1.6 million deaths worldwide. Regardless of previous research efforts, there is no commercially available vaccine for any coronavirus. Novel vaccine development has historically taken at least 10 years from discovery to availability with only a 6% market entry probability.

With the global impact, there is an urgency to expedite a vaccine to protect the population. The U.S. government launched Operation Warp Speed with the goal to produce and ...


Site Tolerance Of The Rada Intein, Chase Taul, Christopher Lennon Dr 2020 Murray State University

Site Tolerance Of The Rada Intein, Chase Taul, Christopher Lennon Dr

Honors College Theses

Inteins (intervening proteins) invade genes at the DNA level and splice out at the protein level. Once thought of as only a parasitic type of a mobile genetic element, recent work suggests a mutualistic relationship has formed in some cases within bacterial and archaeal hosts. After translation, a precursor protein is formed with the intein between two exteins. The intein is catalytic and can excise itself out through protein splicing. Intein insertion is biased towards the active site of the protein and is thought to cause inactivation of the host protein prior to splicing. Intein splicing is responsive to a ...


Eelgrass (Zostera Marina) Population Decline In Morro Bay, Ca: A Meta-Analysis Of Herbicide Application In San Luis Obispo County And Morro Bay Watershed, Tyler King Sinnott 2020 California Polytechnic State University, San Luis Obispo

Eelgrass (Zostera Marina) Population Decline In Morro Bay, Ca: A Meta-Analysis Of Herbicide Application In San Luis Obispo County And Morro Bay Watershed, Tyler King Sinnott

Master's Theses

The endemic eelgrass (Zostera marina) community of Morro Bay Estuary, located on the central coast of California, has experienced an estimated decline of 95% in occupied area (reduction of 344 acres to 20 acres) from 2008 to 2017 for reasons that are not yet definitively clear. One possible driver of degradation that has yet to be investigated is the role of herbicides from agricultural fields in the watershed that feeds into the estuary. Thus, the primary research goal of this project was to better understand temporal and spatial trends of herbicide use within the context of San Luis Obispo (SLO ...


Chytridiomycota In Tree Bark, Paige Strasko 2020 University of Maine - Main

Chytridiomycota In Tree Bark, Paige Strasko

Honors College

Chytridiomycota is a phylum of microscopic aquatic fungi that form motile spores that typically have a single posterior flagellum, thus they require water to disperse (James et al., 2000). Chytridiomycota, collectively called chytrids, have round shapes with structures called rhizoids that absorb nutrients and anchor them to their substrate (Mueller et al., 2004). Chytrids are typically found in aquatic environments and soils since zoospores require water to germinate (James et al., 2000), but they also have been found in a number of unexpected environments. Chytrids are difficult to find because they are microscopic and have time-sensitive life cycles (Mueller et ...


Phantom Ocean, Real Impact: Natural Surf Sound Experiments Alter Foraging Activity And Habitat Use Across Taxa, Ryan N. Wardle 2020 California Polytechnic State University, San Luis Obispo

Phantom Ocean, Real Impact: Natural Surf Sound Experiments Alter Foraging Activity And Habitat Use Across Taxa, Ryan N. Wardle

Master's Theses

A growing body of research focuses on how background sounds shape and alter critical elements of animals’ lives, such as foraging behavior, habitat use, and ecological interactions (Bradbury & Vehrencamp, 2011; Barber et al., 2010; Kight & Swaddle, 2011; Shannon et al., 2016). Much of this research has centered on the effects of anthropogenic noise (Dominoni et al., 2020; Francis & Barber, 2013; Ortega, 2012; Swaddle et al., 2015), but recent studies have also revealed that natural sound sources can influence animal behavior (Davidson et al., 2017; Le et al., 2019). Natural sounds, such as crashing surf, can create conditions where signaling and listening are difficult, but how this ...


Host-Pathogen Genetic Interactions Underlie Tuberculosis Susceptibility In Genetically Diverse Mice [Preprint], Clare M. Smith, Richard E. Baker, Megan K. Proulx, Bibhuti B. Mishra, Jarukit E. Long, Michael C. Kiritsy, Michelle Bellerose, Andrew J. Olive, Kenan C. Murphy, Kadamba Papavinasasundaram, Frederick Boehm, Charlotte Reames, Christopher M. Sassetti 2020 University of Massachusetts Medical School

Host-Pathogen Genetic Interactions Underlie Tuberculosis Susceptibility In Genetically Diverse Mice [Preprint], Clare M. Smith, Richard E. Baker, Megan K. Proulx, Bibhuti B. Mishra, Jarukit E. Long, Michael C. Kiritsy, Michelle Bellerose, Andrew J. Olive, Kenan C. Murphy, Kadamba Papavinasasundaram, Frederick Boehm, Charlotte Reames, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen’s ability to adapt to the heterogeneous immune response of the host. Understanding this interplay has proven difficult, largely because experimentally tractable small animal models do not recapitulate the heterogenous disease observed in natural infections. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to associate bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and represent reproducible models of qualitatively distinct immune states. Global analysis of ...


Evolved Bacterial Resistance Against Fluoropyrimidines Can Lower Chemotherapy Impact In The Caenorhabditis Elegans Host, Brittany Rosener, Serkan Sayin, Peter O. Oluoch, Aurian Garcia-Gonzalez, Hirotada Mori, Albertha J. M. Walhout, Amir Mitchell 2020 University of Massachusetts Medical School

Evolved Bacterial Resistance Against Fluoropyrimidines Can Lower Chemotherapy Impact In The Caenorhabditis Elegans Host, Brittany Rosener, Serkan Sayin, Peter O. Oluoch, Aurian Garcia-Gonzalez, Hirotada Mori, Albertha J. M. Walhout, Amir Mitchell

Open Access Publications by UMMS Authors

Metabolism of host-targeted drugs by the microbiome can substantially impact host treatment success. However, since many host-targeted drugs inadvertently hamper microbiome growth, repeated drug administration can lead to microbiome evolutionary adaptation. We tested if evolved bacterial resistance against host-targeted drugs alters their drug metabolism and impacts host treatment success. We used a model system of Caenorhabditis elegans, its bacterial diet, and two fluoropyrimidine chemotherapies. Genetic screens revealed that most of loss-of-function resistance mutations in Escherichia coli also reduced drug toxicity in the host. We found that resistance rapidly emerged in E. coli under natural selection and converged to a handful ...


Bacteremia And Endocarditis, Steven C. Hatch 2020 University of Massachusetts Medical School

Bacteremia And Endocarditis, Steven C. Hatch

PEER Liberia Project

This presentation provides an overview of the pathogens that cause bacteremia and endocarditis. Manifestations, pathology and treatment are discussed. The goals of the presentation are: Consider major pathogens that cause bacteremia and endocarditis in both adults and children; Discuss pathogenesis; Review clinical manifestations; Discuss basic treatment strategies; and Highlight useful sources of information.


Cytomegalovirus-Specific T Cell Epitope Recognition In Congenital Cytomegalovirus Mother-Infant Pairs, Emma C. Materne, Daniele Lilleri, Francesca Garofoli, Giuseppina Lombardi, Milena Furione, Maurizio Zavattoni, Laura L. Gibson 2020 University of Massachusetts Medical School

Cytomegalovirus-Specific T Cell Epitope Recognition In Congenital Cytomegalovirus Mother-Infant Pairs, Emma C. Materne, Daniele Lilleri, Francesca Garofoli, Giuseppina Lombardi, Milena Furione, Maurizio Zavattoni, Laura L. Gibson

Open Access Publications by UMMS Authors

Background: Congenital cytomegalovirus (cCMV) infection is the most common infection acquired before birth and from which about 20% of infants develop permanent neurodevelopmental effects regardless of presence or absence of symptoms at birth. Viral escape from host immune control may be a mechanism of CMV transmission and infant disease severity. We sought to identify and compare CMV epitopes recognized by mother-infant pairs. We also hypothesized that if immune escape were occurring, then one pattern of longitudinal CD8 T cell responses restricted by shared HLA alleles would be maternal loss (by viral escape) and infant gain (by viral reversion to wildtype ...


Bifidobacterium Infantis Metabolizes 2'Fucosyllactose-Derived And Free Fucose Through A Common Catabolic Pathway Resulting In 1,2-Propanediol Secretion, Liv R. Dedon, Ezgi Ozcan, Asha Rani, David A. Sela 2020 University of Massachusetts Amherst

Bifidobacterium Infantis Metabolizes 2'Fucosyllactose-Derived And Free Fucose Through A Common Catabolic Pathway Resulting In 1,2-Propanediol Secretion, Liv R. Dedon, Ezgi Ozcan, Asha Rani, David A. Sela

Open Access Publications by UMMS Authors

Human milk oligosaccharides (HMOs) enrich beneficial bifidobacteria in the infant gut microbiome which produce molecules that impact development and physiology. 2'fucosyllactose (2'FL) is a highly abundant fucosylated HMO which is utilized by Bifidobacterium longum subsp. infantis, despite limited scientific understanding of the underlying mechanism. Moreover, there is not a current consensus on whether free fucose could be metabolized when not incorporated in a larger oligosaccharide structure. Based on metabolic and genomic analyses, we hypothesize that B. infantis catabolizes both free fucose and fucosyl oligosaccharide residues to produce 1,2-propanediol (1,2-PD). Accordingly, systems-level approaches including transcriptomics and proteomics ...


In Vitro And In Vivo Characterization Of A Recombinant Rhesus Cytomegalovirus Containing A Complete Genome, Husam Taher, Xiaofei E, Timothy F. Kowalik, Daniel Malouli 2020 Oregon Health and Science University

In Vitro And In Vivo Characterization Of A Recombinant Rhesus Cytomegalovirus Containing A Complete Genome, Husam Taher, Xiaofei E, Timothy F. Kowalik, Daniel Malouli

Open Access Publications by UMMS Authors

Cytomegaloviruses (CMVs) are highly adapted to their host species resulting in strict species specificity. Hence, in vivo examination of all aspects of CMV biology employs animal models using host-specific CMVs. Infection of rhesus macaques (RM) with rhesus CMV (RhCMV) has been established as a representative model for infection of humans with HCMV due to the close evolutionary relationships of both host and virus. However, the only available RhCMV clone that permits genetic modifications is based on the 68-1 strain which has been passaged in fibroblasts for decades resulting in multiple genomic changes due to tissue culture adaptations. As a result ...


A Microbiome Analysis Of The Relationship Among Crayfish Ectosymbionts And Their Environment, John Hoverson 2020 Liberty University

A Microbiome Analysis Of The Relationship Among Crayfish Ectosymbionts And Their Environment, John Hoverson

Senior Honors Theses

The purpose of this project was to determine if there are differences present between the α-diversities of the crayfish microbiome and its surrounding water and sediment. Furthermore, this project sought to discover if these differences hold when microbiomes are evaluated between crayfish of first and second stream orders. Finally, this project sought to determine if the presence of branchiobdellidan ectosymbionts on the crayfish caused further differences in the crayfish microbiome. While the hypothesized patterns between crayfish, ectosymbionts, and stream order were not found to exist, a significantly different microbiome was observed between water, sediment, and crayfish, and the α-diversity of ...


Increasing Antibiotic Resistance In Shigella Bacteria In The United States, William J. Pharr 2020 Georgia College and State University

Increasing Antibiotic Resistance In Shigella Bacteria In The United States, William J. Pharr

The Corinthian

Shigella bacteria cause half a million infections, 6,000 hospitalizations, and 70 deaths annually in the United States. These bacteria are of particular concern due to their high survivability, low infectious dose, and high adaptability. Cases of shigellosis from Shigella sonnei are becoming a more prevalent issue in the U.S. as the bacteria continues to develop higher resistance to today’s strongest antibiotics. Much of this resistance is connected to the exchange of genes between strains of Shigella due to insertion sequences (IS), intercontinental travel, and men who have sex with men (MSM). As a result of increased resistance ...


Dormancy-To-Death Transition In Yeast Spores Occurs Due To Gradual Loss Of Gene-Expressing Ability, Theo Maire, Tim Allertz, Max A. Betjes, Hyun Youk 2020 Delft University of Technology

Dormancy-To-Death Transition In Yeast Spores Occurs Due To Gradual Loss Of Gene-Expressing Ability, Theo Maire, Tim Allertz, Max A. Betjes, Hyun Youk

Open Access Publications by UMMS Authors

Dormancy is colloquially considered as extending lifespan by being still. Starved yeasts form dormant spores that wake-up (germinate) when nutrients reappear but cannot germinate (die) after some time. What sets their lifespans and how they age are open questions because what processes occur-and by how much-within each dormant spore remains unclear. With single-cell-level measurements, we discovered how dormant yeast spores age and die: spores have a quantifiable gene-expressing ability during dormancy that decreases over days to months until it vanishes, causing death. Specifically, each spore has a different probability of germinating that decreases because its ability to-without nutrients-express genes decreases ...


Deep Gene Sequence Cluster Analyses Of Multi-Virus Infected Mucosal Tissue Reveal Enhanced Transmission Of Acute Hiv-1, Katja Klein, Nicholas J. Hathaway, Eric J. Arts 2020 University of Western Ontario

Deep Gene Sequence Cluster Analyses Of Multi-Virus Infected Mucosal Tissue Reveal Enhanced Transmission Of Acute Hiv-1, Katja Klein, Nicholas J. Hathaway, Eric J. Arts

Open Access Publications by UMMS Authors

Exposure of the genital mucosa to a genetically diverse viral swarm from the donor HIV-1 can result in breakthrough and systemic infection by a single transmitted/founder (TF) virus in the recipient. The highly diverse HIV-1 envelope (Env) in this inoculating viral swarm may have critical role in transmission and subsequent immune response. Thus, chronic (Envchronic) and acute (Envacute) Env chimeric HIV-1 were tested using multi-virus competition assays in human mucosal penile and cervical tissues. Viral competition analysis revealed that Envchronic viruses resided and replicated mainly in the tissue while Envacute viruses penetrated the human tissue and established infection of ...


Investigating Microbial And Host Factors That Modulate Severity Of Clostridioides Difficile Associated Disease, Armando Lerma 2020 University of Nebraska-Lincoln

Investigating Microbial And Host Factors That Modulate Severity Of Clostridioides Difficile Associated Disease, Armando Lerma

Dissertations, Theses, & Student Research in Food Science and Technology

Clostridioides difficile is recognized as one of the most important pathogens in hospital and community healthcare settings. The clinical outcome of infection of toxigenic C. difficile infection (CDI) ranges from asymptomatic colonization to fulminant pseudomembranous colitis and death. In recent studies, it has been suggested that a high proportion of nosocomial CDI cases are transmitted from asymptomatic carriers which might be acting as infection reservoirs. Understanding what causes the different responses to infection could lead to the development of novel prevention and treatment strategies. Although several explanations have been proposed to explain variations in susceptibility, understanding of the exact mechanisms ...


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