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Using Empirical And Theoretical Approaches To Control Outbreaks Of An Emerging Disease (Swimmer’S Itch) In The Midwest Of The U.S.A., Gregory J. Sandland, James Peirce 2019 University of Wisconsin - La Crosse

Using Empirical And Theoretical Approaches To Control Outbreaks Of An Emerging Disease (Swimmer’S Itch) In The Midwest Of The U.S.A., Gregory J. Sandland, James Peirce

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Report Of A Meeting On Contemporary Topics In Zebrafish Husbandry And Care, Nikki Osborne, Gregory Paull, Adam Grierson, Karen Dunford, Elisabeth M. Busch-Nentwich, Lynne U. Sneddon, Natalie Wren, Joe Higgins, Penny Hawkins 2019 Royal Society for the Prevention of Cruelty to Animals

Report Of A Meeting On Contemporary Topics In Zebrafish Husbandry And Care, Nikki Osborne, Gregory Paull, Adam Grierson, Karen Dunford, Elisabeth M. Busch-Nentwich, Lynne U. Sneddon, Natalie Wren, Joe Higgins, Penny Hawkins

Lynne Sneddon, PhD

A meeting on Contemporary Topics in Zebrafish Husbandry and Care was held in the United Kingdom in 2014, with the aim of providing a discussion forum for researchers, animal technologists, and veterinarians from academia and industry to share good practice and exchange ideas. Presentation topics included protocols for optimal larval rearing, implementing the 3Rs (replacement, reduction, and refinement) in large-scale colony management, and environmental enrichment. The audience also participated in a survey of current practice relating to practical husbandry, cryopreservation, and the provision of enrichment.


Coccidioidomycosis: Medical And Spatio-Temporal Perspectives, Nikias Sarafoglou, Rafael Laniado-Laborin, Menas Kafatos 2019 George Mason University

Coccidioidomycosis: Medical And Spatio-Temporal Perspectives, Nikias Sarafoglou, Rafael Laniado-Laborin, Menas Kafatos

Mathematics, Physics, and Computer Science Faculty Articles and Research

Coccidioidomycosis (CM) is a disease of major public health importance due to the challenges in its diagnosis and treatment. To understand CM requires the attributes of a multidisciplinary network analysis to appreciate the complexity of the medical, the environmental and the social issues involved: public health, public policy, geology, atmospheric science, agronomy, social sciences and finally humanities, all which provide insight into this population transformation.

In section 1 of this paper, we describe the CM-epidemiology, the clinical features, the diagnosis and finally the treatment.

In section 2, we highlight the most important contributions and controversies in the history of the ...


Extensive Ribosome And Rf2 Rearrangements During Translation Termination, Egor Svidritskiy, Gabriel Demo, Anna B. Loveland, Chen Xu, Andrei A. Korostelev 2019 University of Massachusetts Medical School

Extensive Ribosome And Rf2 Rearrangements During Translation Termination, Egor Svidritskiy, Gabriel Demo, Anna B. Loveland, Chen Xu, Andrei A. Korostelev

Open Access Articles

Protein synthesis ends when a ribosome reaches an mRNA stop codon. Release factors (RFs) decode the stop codon, hydrolyze peptidyl-tRNA to release the nascent protein, and then dissociate to allow ribosome recycling. To visualize termination by RF2, we resolved a cryo-EM ensemble of E. coli 70S*RF2 structures at up to 3.3 A in a single sample. Five structures suggest a highly dynamic termination pathway. Upon peptidyl-tRNA hydrolysis, the CCA end of deacyl-tRNA departs from the peptidyl transferase center. The catalytic GGQ loop of RF2 is rearranged into a long beta-hairpin that plugs the peptide tunnel, biasing a nascent ...


Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge 2019 Washington University in St. Louis

Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge

University of Massachusetts Medical School Faculty Publications

Cryptococcus gattii R265 is a hyper-virulent fungal strain responsible for the major outbreak of cryptococcosis in Vancouver Island of British Columbia in 1999. It differs significantly from C. neoformans in its natural environment, its preferred site in the mammalian host, and in the nature and mode of pathogenesis. Our previous studies in C. neoformans have shown that the presence of chitosan, the deacetylated form of chitin, in the cell wall attenuates inflammatory responses in the host, while its absence induces robust immune responses, which in turn facilitate clearance of the fungus and induces a protective response. The results of the ...


The Aminoalkylindole, Bml-190, Negatively Regulates Chitosan Synthesis Via The Camp/Pka1 Pathway In Cryptococcus Neoformans, Brian T. Maybruck, Woei C. Lam, Charles A. Specht, Ma Xenia G. Ilagan, Maureen J. Donlin, Jennifer K. Lodge 2019 Washington University in St. Louis

The Aminoalkylindole, Bml-190, Negatively Regulates Chitosan Synthesis Via The Camp/Pka1 Pathway In Cryptococcus Neoformans, Brian T. Maybruck, Woei C. Lam, Charles A. Specht, Ma Xenia G. Ilagan, Maureen J. Donlin, Jennifer K. Lodge

University of Massachusetts Medical School Faculty Publications

Cryptococcus neoformans can cause fatal meningoencephalitis in patients with AIDS or other immune-compromising conditions. Current antifungals are suboptimal to treat this disease, therefore, novel targets and new therapies are needed. Previously, we have shown that chitosan is a critical component of the cryptococcal cell wall, is required for survival in the mammalian host, and that chitosan deficiency results in rapid clearance from the mammalian host. We had also identified several specific proteins that were required for chitosan biosynthesis, and we hypothesize that screening for compounds that inhibit chitosan biosynthesis would identify additional genes/proteins that influence chitosan biosynthesis.


Oral Administration Of An Anti-Cfae Secretory Iga Antibody Protects Against Enterotoxigenic Escherichia Coli Diarrheal Disease In A Non-Human Primate Model, Matteo Stoppato, Carlos Gaspar, James Regeimbal, Gladys Nunez, Serena Giuntini, Melissa A. Gawron, Jessica R. Pondish, Joseph C. Martin III, Matthew Schneider, Zachary A. Schiller, Mark S. Klempner, Lisa A. Cavacini, Yang Wang 2019 University of Massachusetts Medical School

Oral Administration Of An Anti-Cfae Secretory Iga Antibody Protects Against Enterotoxigenic Escherichia Coli Diarrheal Disease In A Non-Human Primate Model, Matteo Stoppato, Carlos Gaspar, James Regeimbal, Gladys Nunez, Serena Giuntini, Melissa A. Gawron, Jessica R. Pondish, Joseph C. Martin Iii, Matthew Schneider, Zachary A. Schiller, Mark S. Klempner, Lisa A. Cavacini, Yang Wang

University of Massachusetts Medical School Faculty Publications

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea-associated illness in developing countries. There is currently no vaccine licensed to prevent ETEC and the development of an efficacious prophylaxis would provide an intervention with significant impact. Recent studies suggested that effective protection could be achieved by inducing immunity to block colonization of ETEC. Here, we evaluated the efficacy of secretory (s) IgA2 and dimeric (d) IgA2 of an anti-colonization factor antigen antibody, 68-61, in the Aotus nancymaae non-human primate (NHP) ETEC challenge model via oral and parental delivery. Thirty-nine animals were distributed across 3 groups of 13, and challenged ...


Malanda Gold: The Tale Of A Unique Rainbowfish From The Atherton Table-Lands, Now On The Verge Of Extinction., Peter J. Unmack, Keith Martin, Michael P. Hammer, Brendan Ebner, Karl Moy, Culum Brown 2019 University of Canberra

Malanda Gold: The Tale Of A Unique Rainbowfish From The Atherton Table-Lands, Now On The Verge Of Extinction., Peter J. Unmack, Keith Martin, Michael P. Hammer, Brendan Ebner, Karl Moy, Culum Brown

Culum Brown, PhD

No abstract provided.


The Effect Of Prescribed Burning On Wood-Decay Fungi In The Forests Of Northwest Arkansas, Nawaf Ibrahim Alshammari 2019 University of Arkansas, Fayetteville

The Effect Of Prescribed Burning On Wood-Decay Fungi In The Forests Of Northwest Arkansas, Nawaf Ibrahim Alshammari

Theses and Dissertations

Prescribed burning is defined as the process of the planned application of fire to a predetermined area under specific environmental conditions in order to achieve a desired outcome such as land management. This project used both morphological and molecular methods to identify and characterize the wood-decay fungi associated with the forests of northwest Arkansas—Pea Ridge National Military Park, Devil’s Den State Park, and the Buffalo National River—through frequent visits made between February 2018 and February 2019. In addition, in order to assess the effects of prescribed burning, incubation chambers were used to compare the growth of fungi ...


Selectivity Of Infrared Heat Treatment On Inactivation Of Mycotoxigenic Fungi On Stored Grain, Shantae A. Wilson 2019 University of Arkansas, Fayetteville

Selectivity Of Infrared Heat Treatment On Inactivation Of Mycotoxigenic Fungi On Stored Grain, Shantae A. Wilson

Theses and Dissertations

Selective Infrared (IR) heating holds great potential to decontaminate spores of unsafe fungi in corn. The objectives for this study were to investigate the impact of exposing corn to infrared energy at selected peak wavelengths (λ), infrared intensities and treatment durations, followed by tempering for further inactivation of microbes on the grain and explore a method for decontaminating Aspergillus flavus (A. flavus) spores on corn. Freshly harvested corn with initial moisture contents (IMCs) of 16%, 20%, and 24% wet basis (w.b.) were used. The corn samples were treated at different infrared wavelengths (3.2, 4.5, and 5.8 ...


Plasticity In The Human Gut Microbiome Defies Evolutionary Constraints, Andres Gomez, Ashok Kumar Sharma, Elizabeth K. Mallott, Klara J. Petrzelkova, Carolyn A. Jost Robinson, Carl J. Yeoman, Franck Carbonero, Barbora Pafco, Jessica M. Rothman, Alexander Ulanov, Klara Vickova, Katherine R. Amato, Stephanie L. Schnorr, Nathaniel J. Dominy, David Modry, Angelique Todd, Manolito Torralba, Karen E. Nelson, Michael B. Burns, Ran Blekhman, Melissa Remis, Rebecca M. Stumpf, Brenda A. Wilson, H. Rex Gaskins, Paul A. Garber, Bryan A. White, Steven R. Leigh 2019 University of Minnesota

Plasticity In The Human Gut Microbiome Defies Evolutionary Constraints, Andres Gomez, Ashok Kumar Sharma, Elizabeth K. Mallott, Klara J. Petrzelkova, Carolyn A. Jost Robinson, Carl J. Yeoman, Franck Carbonero, Barbora Pafco, Jessica M. Rothman, Alexander Ulanov, Klara Vickova, Katherine R. Amato, Stephanie L. Schnorr, Nathaniel J. Dominy, David Modry, Angelique Todd, Manolito Torralba, Karen E. Nelson, Michael B. Burns, Ran Blekhman, Melissa Remis, Rebecca M. Stumpf, Brenda A. Wilson, H. Rex Gaskins, Paul A. Garber, Bryan A. White, Steven R. Leigh

Anthropology Faculty Publications

The gut microbiome of primates, including humans, is reported to closely follow host evolutionary history, with gut microbiome composition being specific to the genetic background of its primate host. However, the comparative models used to date have mainly included a limited set of closely related primates. To further understand the forces that shape the primate gut microbiome, with reference to human populations, we expanded the comparative analysis of variation among gut microbiome compositions and their primate hosts, including 9 different primate species and 4 human groups characterized by a diverse set of subsistence patterns (n = 448 samples). The results show ...


Common Variants In The Glycerol Kinase Gene Reduce Tuberculosis Drug Efficacy, Michelle M. Bellerose, Seung-Hun Baek, Chuan-Chin Huang, Caitlin E. Moss, Eun-Ik Koh, Megan K. Proulx, Clare M. Smith, Richard E. Baker, Jong Seok Lee, Seokyong Eum, Sung Jae Shin, Sang-Nae Cho, Megan Murray, Christopher M. Sassetti 2019 University of Massachusetts Medical School

Common Variants In The Glycerol Kinase Gene Reduce Tuberculosis Drug Efficacy, Michelle M. Bellerose, Seung-Hun Baek, Chuan-Chin Huang, Caitlin E. Moss, Eun-Ik Koh, Megan K. Proulx, Clare M. Smith, Richard E. Baker, Jong Seok Lee, Seokyong Eum, Sung Jae Shin, Sang-Nae Cho, Megan Murray, Christopher M. Sassetti

Open Access Articles

Despite the administration of multiple drugs that are highly effective in vitro, tuberculosis (TB) treatment requires prolonged drug administration and is confounded by the emergence of drug-resistant strains. To understand the mechanisms that limit antibiotic efficacy, we performed a comprehensive genetic study to identify Mycobacterium tuberculosis genes that alter the rate of bacterial clearance in drug-treated mice. Several functionally distinct bacterial genes were found to alter bacterial clearance, and prominent among these was the glpK gene that encodes the glycerol-3-kinase enzyme that is necessary for glycerol catabolism. Growth on glycerol generally increased the sensitivity of M. tuberculosis to antibiotics in ...


Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas 2019 University of Alberta

Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common ...


Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman 2019 University of Massachusetts Medical School

Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman

Neal Silverman

The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-kappaB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur ...


Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang 2019 Duke University

Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang

Katherine A. Fitzgerald

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates ...


Molecular And Structural Mechanism Of Pan-Genotypic Hcv Ns3/4a Protease Inhibition By Glecaprevir, Jennifer Timm, Klajdi Kosovrasti, Mina Henes, Florian Leidner, Shurong Hou, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer 2019 University of Massachusetts Medical School

Molecular And Structural Mechanism Of Pan-Genotypic Hcv Ns3/4a Protease Inhibition By Glecaprevir, Jennifer Timm, Klajdi Kosovrasti, Mina Henes, Florian Leidner, Shurong Hou, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

Hepatitis C virus (HCV), causative agent of chronic viral hepatitis, infects 71 million people worldwide and is divided into seven genotypes and multiple subtypes with sequence identities between 68 to 82%. While older generation direct-acting antivirals (DAAs) had varying effectiveness against different genotypes, the newest NS3/4A protease inhibitors including glecaprevir (GLE) have pan-genotypic activity. The structural basis for pan-genotypic inhibition and effects of polymorphisms on inhibitor potency were not well known due to lack of crystal structures of GLE-bound NS3/4A or genotypes other than 1. In this study, we determined the crystal structures of NS3/4A from genotypes ...


Complex History Of Codiversification And Host Switching Of A Newfound Soricid-Borne Orthohantavirus In North America, Schuyler W. Liphardt, Hae Ji Kang, Laurie J. Dizney, Luis A. Ruedas, Joseph A. Cook, Richard Yanagihara 2019 University of New Mexico

Complex History Of Codiversification And Host Switching Of A Newfound Soricid-Borne Orthohantavirus In North America, Schuyler W. Liphardt, Hae Ji Kang, Laurie J. Dizney, Luis A. Ruedas, Joseph A. Cook, Richard Yanagihara

Biology Faculty Publications and Presentations

Orthohantaviruses are tightly linked to the ecology and evolutionary history of their mammalian hosts. We hypothesized that in regions with dramatic climate shifts throughout the Quaternary, orthohantavirus diversity and evolution are shaped by dynamic host responses to environmental change through processes such as host isolation, host switching, and reassortment. Jemez Springs virus (JMSV), an orthohantavirus harbored by the dusky shrew (Sorex monticola) and five close relatives distributed widely in western North America, was used to test this hypothesis. Total RNAs, extracted from liver or lung tissue from 164 shrews collected from western North America during 1983–2007, were analyzed for ...


Phylogenetic Estimates Of Hiv-1 Gp120 Indel Rates Across The Group M Subtypes, John Palmer, Art Poon 2019 Western University

Phylogenetic Estimates Of Hiv-1 Gp120 Indel Rates Across The Group M Subtypes, John Palmer, Art Poon

Western Research Forum

Insertions and deletions (indels) in the HIV-1 envelope glycoprotein gp120 play a significant role in the evolution of HIV pathogenesis and transmission fitness. While substitution rates in HIV-1 are well characterized by phylogenetic models, there is a lack of quantitative measures of indel rates in HIV-1. Here we use a dated-tip phylogenetic analysis of gp120 sequences to estimate indel rates for 7 subtypes and CRFs of HIV-1 group M.

We obtained and processed 26,359 HIV-1 gp120 sequences from the Los Alamos National Laboratory HIV Sequence database. After filtering these sequences, we extracted the conserved and variable regions from the ...


High-Resolution Cryo-Em Structures Of Outbreak Strain Human Norovirus Shells Reveal Size Variations, James Jung, Timothy Grant, Dennis R. Thomas, Chris W. Diehnelt, Nikolaus Grigorieff, Leemor Joshua-Tor 2019 Cold Spring Harbor Laboratory

High-Resolution Cryo-Em Structures Of Outbreak Strain Human Norovirus Shells Reveal Size Variations, James Jung, Timothy Grant, Dennis R. Thomas, Chris W. Diehnelt, Nikolaus Grigorieff, Leemor Joshua-Tor

Open Access Articles

Noroviruses are a leading cause of foodborne illnesses worldwide. Although GII.4 strains have been responsible for most norovirus outbreaks, the assembled virus shell structures have been available in detail for only a single strain (GI.1). We present high-resolution (2.6- to 4.1-A) cryoelectron microscopy (cryo-EM) structures of GII.4, GII.2, GI.7, and GI.1 human norovirus outbreak strain virus-like particles (VLPs). Although norovirus VLPs have been thought to exist in a single-sized assembly, our structures reveal polymorphism between and within genogroups, with small, medium, and large particle sizes observed. Using asymmetric reconstruction, we were able ...


In Situ Structure Of Rotavirus Vp1 Rna-Dependent Rna Polymerase, Simon Jenni, Eric N. Salgado, Tobias Herrmann, Zongli Li, Timothy Grant, Nikolaus Grigorieff, Stefano Trapani, Leandro F. Estrozi, Stephen C. Harrison 2019 Harvard Medical School

In Situ Structure Of Rotavirus Vp1 Rna-Dependent Rna Polymerase, Simon Jenni, Eric N. Salgado, Tobias Herrmann, Zongli Li, Timothy Grant, Nikolaus Grigorieff, Stefano Trapani, Leandro F. Estrozi, Stephen C. Harrison

Open Access Articles

Rotaviruses, like other non-enveloped, double-strand RNA viruses, package an RNA-dependent RNA polymerase (RdRp) with each duplex of their segmented genomes. Rotavirus cell entry results in loss of an outer protein layer and delivery into the cytosol of an intact, inner capsid particle (the "double-layer particle," or DLP). The RdRp, designated VP1, is active inside the DLP; each VP1 achieves many rounds of mRNA transcription from its associated genome segment. Previous work has shown that one VP1 molecule lies close to each 5-fold axis of the icosahedrally symmetric DLP, just beneath the inner surface of its protein shell, embedded in tightly ...


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