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  1. Article ; Online: Meeting the Challenges of Chemical and Biological Weapons

    Brett Edwards / Tatyana Novossiolova / Michael Crowley / Simon Whitby / Malcolm Dando / Lijun Shang

    Frontiers in Political Science, Vol

    Strengthening the Chemical and Biological Disarmament and Non-proliferation Regimes

    2022  Volume 4

    Abstract: In this report, we identify some of the key technical and political challenges currently facing the broader Chemical and Biological Weapon (CBW) regime- with a particular emphasis on major forthcoming diplomatic meetings. Most significantly the Ninth ... ...

    Abstract In this report, we identify some of the key technical and political challenges currently facing the broader Chemical and Biological Weapon (CBW) regime- with a particular emphasis on major forthcoming diplomatic meetings. Most significantly the Ninth Review Conference of the Biological and Toxins Weapons Convention (1972) (BTWC) which will take place in 2022 and preparations for the Fifth Review Conference of the Chemical Weapons Convention (1993) (CWC), expected in 2023. This report is an output of an ongoing project, designed to stimulate thinking and discussion about these issues, within relevant stakeholder communities. The report provides an introduction to this issue area for the general reader before surveying key issues and developing a series of practical policy suggestions for further consideration.
    Keywords civil society ; chemical and biological disarmament ; non-proliferation regimes ; Chemical Weapons Convention ; Biological and Toxin Weapons Convention ; Political science ; J
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: An integrated analysis of the effects of maternal broccoli sprouts exposure on transcriptome and methylome in prevention of offspring mammary cancer

    Itika Arora / Manvi Sharma / Shizhao Li / Michael Crowley / David K. Crossman / Yuanyuan Li / Trygve O. Tollefsbol

    PLoS ONE, Vol 17, Iss

    2022  Volume 3

    Abstract: Broccoli sprouts (BSp), a cruciferous vegetable, has shown promising effects on prevention of many types of cancer including breast cancer (BC). BC has a developmental foundation, and maternal nutrition status may influence an offspring’s risk to BC ... ...

    Abstract Broccoli sprouts (BSp), a cruciferous vegetable, has shown promising effects on prevention of many types of cancer including breast cancer (BC). BC has a developmental foundation, and maternal nutrition status may influence an offspring’s risk to BC later in life. What is less understood, however, is the influence of maternal nutrition intervention on reversing epigenomic abnormalities that are essential in BC programming during early development. Our research focused on how maternal exposure to BSp diet prevents offspring BC and investigation of possible epigenetic mechanisms during these processes. Our results showed that maternal feeding of BSp can prevent mammary tumor development in the offspring of a transgenic mouse model. Through comprehensive integrated multi-omics studies on transcriptomic and methylomic analysis, we identified numerous target genes exhibiting significantly differential gene expression and DNA methylation patterns in the offspring mammary tumor. We discovered that maternal exposure to BSp diet can induce both gene and methylation changes in several key genes such as Avpr2, Cyp4a12b, Dpp6, Gria2, Pcdh9 and Tspan11 that are correlated with pivotal biological functions during carcinogenesis. In addition, we found an impact of maternal BSp treatment on DNA methyltransferase and histone deacetylases activity. Our study provides knowledgeable information regarding how maternal BSp diet influences key tumor-related gene expression and the epigenetic changes using a genome-wide perspective. Additionally, these findings provide mechanistic insights into the effectiveness of maternal BSp administration on the prevention of BC in the offspring later in life, which may lead to an early-life BC chemopreventive strategy that benefits the progenies’ long-term health.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: An integrated analysis of the effects of maternal broccoli sprouts exposure on transcriptome and methylome in prevention of offspring mammary cancer.

    Itika Arora / Manvi Sharma / Shizhao Li / Michael Crowley / David K Crossman / Yuanyuan Li / Trygve O Tollefsbol

    PLoS ONE, Vol 17, Iss 3, p e

    2022  Volume 0264858

    Abstract: Broccoli sprouts (BSp), a cruciferous vegetable, has shown promising effects on prevention of many types of cancer including breast cancer (BC). BC has a developmental foundation, and maternal nutrition status may influence an offspring's risk to BC ... ...

    Abstract Broccoli sprouts (BSp), a cruciferous vegetable, has shown promising effects on prevention of many types of cancer including breast cancer (BC). BC has a developmental foundation, and maternal nutrition status may influence an offspring's risk to BC later in life. What is less understood, however, is the influence of maternal nutrition intervention on reversing epigenomic abnormalities that are essential in BC programming during early development. Our research focused on how maternal exposure to BSp diet prevents offspring BC and investigation of possible epigenetic mechanisms during these processes. Our results showed that maternal feeding of BSp can prevent mammary tumor development in the offspring of a transgenic mouse model. Through comprehensive integrated multi-omics studies on transcriptomic and methylomic analysis, we identified numerous target genes exhibiting significantly differential gene expression and DNA methylation patterns in the offspring mammary tumor. We discovered that maternal exposure to BSp diet can induce both gene and methylation changes in several key genes such as Avpr2, Cyp4a12b, Dpp6, Gria2, Pcdh9 and Tspan11 that are correlated with pivotal biological functions during carcinogenesis. In addition, we found an impact of maternal BSp treatment on DNA methyltransferase and histone deacetylases activity. Our study provides knowledgeable information regarding how maternal BSp diet influences key tumor-related gene expression and the epigenetic changes using a genome-wide perspective. Additionally, these findings provide mechanistic insights into the effectiveness of maternal BSp administration on the prevention of BC in the offspring later in life, which may lead to an early-life BC chemopreventive strategy that benefits the progenies' long-term health.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: 52350 PKM2 mediates anti-tumor immunity and T cell dysfunction

    Geoffrey Markowitz / Yi Ban / Michael Crowley / Diamile Tavarez / Stephen T.C. Wong / Kenneth Chang / Andrea Schietinger / Nasser Altorki / Vivek Mittal

    Journal of Clinical and Translational Science, Vol 5, Pp 89-

    2021  Volume 89

    Abstract: ABSTRACT IMPACT: T cell dysfunction is a dominant suppressor of anti-tumor immunity, reducing immunotherapeutic efficacy and benefit to patients; our work will identify novel mediators of this process for both therapeutic potential and underlying ... ...

    Abstract ABSTRACT IMPACT: T cell dysfunction is a dominant suppressor of anti-tumor immunity, reducing immunotherapeutic efficacy and benefit to patients; our work will identify novel mediators of this process for both therapeutic potential and underlying mechanism, allowing for both potential immediate clinical utility and identification of future targets based on new mechanistic insights. OBJECTIVES/GOALS: T cell dysfunction is a dominant suppressor of anti-tumor immunity, reducing immunotherapeutic efficacy and clinical benefit to the majority of patients. We aim to interrogate a novel mediator of dysfunction identified from transcriptome analyses, pyruvate kinase muscle isozyme isoform 2 (PKM2), for therapeutic utility and underlying mechanism. METHODS/STUDY POPULATION: Transcriptome analyses of CD8+ lymphocytes from tumor-bearing lungs from both murine KrasG12D p53-/- and human non-small cell lung cancer (NSCLC) patients were performed, and differentially expressed genes identified. Flow cytometric analyses for PKM isoform expression and effects of target knockdown on accumulation of dysfunctional characteristics, including checkpoint and transcription factor expression, proliferation, and cytokine production, were performed using an in vitro co-culture of murine antigen-specific T (OT-I) cells and antigen-expressing NSCLC (HKP1-ova) cells. In vivo examination of the same was performed using adoptive transfer of OT-I cells into immunocompetent recipient mice with engraftment of HKP1-ova cells, and subsequent evaluation of mouse survival and T cell phenotypes. RESULTS/ANTICIPATED RESULTS: Transcriptome analyses demonstrated that PKM expression was upregulated in dysfunctional T cells from both murine and human samples. This was confirmed both in vitro with co-culture and in vivo with adoptive transfer approaches, with both activated and dysfunctional OT-I cells expressing higher levels of isoform 2 of PKM than naive OT-I cells. Expression of PKM2 mimicked the kinetics of the transcription factor Tox, a known driver ...
    Keywords Medicine ; R
    Subject code 570 ; 610
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Cambridge University Press
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Cytokine storm–based mechanisms for extrapulmonary manifestations of SARS-CoV-2 infection

    Maria Del Nogal Avila / Ranjan Das / Joubert Kharlyngdoh / Eduardo Molina-Jijon / Hector Donoro Blazquez / Stéphanie Gambut / Michael Crowley / David K. Crossman / Rasheed A. Gbadegesin / Sunveer S. Chugh / Sunjeet S. Chugh / Carmen Avila-Casado / Camille Macé / Lionel C. Clement / Sumant S. Chugh

    JCI Insight, Vol 8, Iss

    2023  Volume 10

    Abstract: Viral illnesses like SARS-CoV-2 have pathologic effects on nonrespiratory organs in the absence of direct viral infection. We injected mice with cocktails of rodent equivalents of human cytokine storms resulting from SARS-CoV-2/COVID-19 or rhinovirus ... ...

    Abstract Viral illnesses like SARS-CoV-2 have pathologic effects on nonrespiratory organs in the absence of direct viral infection. We injected mice with cocktails of rodent equivalents of human cytokine storms resulting from SARS-CoV-2/COVID-19 or rhinovirus common cold infection. At low doses, COVID-19 cocktails induced glomerular injury and albuminuria in zinc fingers and homeoboxes 2 (Zhx2) hypomorph and Zhx2+/+ mice to mimic COVID-19–related proteinuria. Common Cold cocktail induced albuminuria selectively in Zhx2 hypomorph mice to model relapse of minimal change disease, which improved after depletion of TNF-α, soluble IL-4Rα, or IL-6. The Zhx2 hypomorph state increased cell membrane to nuclear migration of podocyte ZHX proteins in vivo (both cocktails) and lowered phosphorylated STAT6 activation (COVID-19 cocktail) in vitro. At higher doses, COVID-19 cocktails induced acute heart injury, myocarditis, pericarditis, acute liver injury, acute kidney injury, and high mortality in Zhx2+/+ mice, whereas Zhx2 hypomorph mice were relatively protected, due in part to early, asynchronous activation of STAT5 and STAT6 pathways in these organs. Dual depletion of cytokine combinations of TNF-α with IL-2, IL-13, or IL-4 in Zhx2+/+ mice reduced multiorgan injury and eliminated mortality. Using genome sequencing and CRISPR/Cas9, an insertion upstream of ZHX2 was identified as a cause of the human ZHX2 hypomorph state.
    Keywords Nephrology ; Medicine ; R
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: New microbe genomic variants in patients fecal community following surgical disruption of the upper human gastrointestinal tract

    Ranjit Kumar / Jayleen Grams / Daniel I. Chu / David K. Crossman / Richard Stahl / Peter Eipers / Kelly Goldsmith / Michael Crowley / Elliot J. Lefkowitz / Casey D. Morrow

    Human Microbiome Journal, Vol 10, Iss , Pp 37-

    2018  Volume 42

    Abstract: Recent studies have shown that microbe strains in normal individuals fecal microbe community are relatively stable over time. Given the role the gut microbe community plays in human health, it is important to understand if disruption of the ... ...

    Abstract Recent studies have shown that microbe strains in normal individuals fecal microbe community are relatively stable over time. Given the role the gut microbe community plays in human health, it is important to understand if disruption of the gastrointestinal tract environment results in emergence of new genomic variants. To address this, we have used a new technique called Window-based single nucleotide similarity (WSS) to analyze the impact of several surgical procedures of the human gastrointestinal tract on the stability of the fecal microbes. Previously, we established a WSS boundary score cutoff to determine if microbe genomic variants were similar. Based on analysis of normal individuals from the Human Microbiome Project, 93% of microbes in paired fecal samples up to 1 year apart were above the cutoff, indicating similar (stable) microbes. For the current study, we analyzed fecal samples from 18 patients undergoing Roux-en-Y gastric bypass (RYGB) or 6 patients undergoing gastric sleeve for extreme obesity. From comparison of the pre-RYGB versus 1–2 year post RYGB samples from the same patients, 65% of the WSS were above the boundary cutoff, while for pre versus 1–2 year samples post surgery for patients undergoing sleeve gastrectomy, 75% of the WSS were above the cutoff. In contrast, analysis of fecal samples from 5 patients pre and post removal of segments of the sigmoid colon revealed that 97% of WSS scores were above the cutoff. Our study establishes emergence of new microbe genomic variants in the fecal community following alteration of the upper gastrointestinal environment. Keywords: Roux-en-Y gastric bypass, Sleeve gastrectomy, Single nucleotide variants, Window-based SNV Similarity, Microbe strains
    Keywords Medicine (General) ; R5-920 ; Microbiology ; QR1-502
    Subject code 610
    Language English
    Publishing date 2018-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Metagenomics approach to the study of the gut microbiome structure and function in zebrafish Danio rerio fed with gluten formulated diet

    Koo, Hyunmin / Asim K. Bej / Casey D. Morrow / Elliot J. Lefkowitz / Joseph A. Hakim / Michael Crowley / Mickie L. Powell / Peter G. Eipers / Ranjit Kumar / Stephen A. Watts

    Journal of microbiological methods. 2017 Apr., v. 135

    2017  

    Abstract: In this study, we report the gut microbial composition and predictive functional profiles of zebrafish, Danio rerio, fed with a control formulated diet (CFD), and a gluten formulated diet (GFD) using a metagenomics approach and bioinformatics tools. The ... ...

    Abstract In this study, we report the gut microbial composition and predictive functional profiles of zebrafish, Danio rerio, fed with a control formulated diet (CFD), and a gluten formulated diet (GFD) using a metagenomics approach and bioinformatics tools. The microbial communities of the GFD-fed D. rerio displayed heightened abundances of Legionellales, Rhizobiaceae, and Rhodobacter, as compared to the CFD-fed counterparts. Predicted metagenomics of microbial communities (PICRUSt) in GFD-fed D. rerio showed KEGG functional categories corresponding to bile secretion, secondary bile acid biosynthesis, and the metabolism of glycine, serine, and threonine. The CFD-fed D. rerio exhibited KEGG functional categories of bacteria-mediated cobalamin biosynthesis, which was supported by the presence of cobalamin synthesizers such as Bacteroides and Lactobacillus. Though these bacteria were absent in GFD-fed D. rerio, a comparable level of the cobalamin biosynthesis KEGG functional category was observed, which could be contributed by the compensatory enrichment of Cetobacterium. Based on these results, we conclude D. rerio to be a suitable alternative animal model for the use of a targeted metagenomics approach along with bioinformatics tools to further investigate the relationship between the gluten diet and microbiome profile in the gut ecosystem leading to gastrointestinal diseases and other undesired adverse health effects.
    Keywords adverse effects ; animal models ; bacteria ; Bacteroides ; bile acids ; bile secretion ; bioinformatics ; biosynthesis ; Danio rerio ; diet ; digestive system ; digestive system diseases ; ecosystems ; gluten ; intestinal microorganisms ; Lactobacillus ; Legionellales ; metagenomics ; microbial communities ; microbiome ; Rhizobiaceae ; Rhodobacter ; serine ; threonine ; vitamin B12
    Language English
    Dates of publication 2017-04
    Size p. 69-76.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 604916-3
    ISSN 1872-8359 ; 0167-7012
    ISSN (online) 1872-8359
    ISSN 0167-7012
    DOI 10.1016/j.mimet.2017.01.016
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

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  8. Article: The Structure of the Catalytic Domain of a Plant Cellulose Synthase and Its Assembly into Dimers

    Olek, Anna T / Catherine Rayon / Daisuke Kihara / Hyung Rae Kim / Jeffrey T. Bolin / John Badger / Lake N. Paul / Lee Makowski / Michael Crowley / Michael E. Himmel / Nicholas C. Carpita / Peter Ciesielski / Subhangi Ghosh

    plant cell. 2014 July, v. 26, no. 7

    2014  

    Abstract: Small-angle x-ray scattering gives a glimpse at the solution structure of the catalytic domains of plant cellulose synthase and their dimerization. Dimerization through the plant-specific sequences of the catalytic domain provides important clues for how ...

    Abstract Small-angle x-ray scattering gives a glimpse at the solution structure of the catalytic domains of plant cellulose synthase and their dimerization. Dimerization through the plant-specific sequences of the catalytic domain provides important clues for how Zn-finger domains couple these fundamental scaffold units into large, multimeric synthase complexes.
    Keywords active sites ; cellulose synthase ; dimerization ; X-radiation
    Language English
    Dates of publication 2014-07
    Size p. 2996-3009.
    Publishing place American Society of Plant Biologists
    Document type Article
    ZDB-ID 623171-8
    ISSN 1532-298X ; 1040-4651
    ISSN (online) 1532-298X
    ISSN 1040-4651
    DOI 10.1105/tpc.114.126862
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 4952: Show issues

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