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https://www.readbyqxmd.com/read/28830075/streptococcal-heme-binding-protein-shp-promotes-virulence-and-contributes-to-the-pathogenesis-of-group-a-streptococcus-infection
#1
Xiaolan Zhang, Chunmei Lu, Fengmin Zhang, Yingli Song, Minghui Cai, Hui Zhu
Streptococcal heme binding protein (Shp) is involved in the process of heme acquisition in group A Streptococcus (GAS). However, no research thus far has examined the contribution of Shp to the virulence of GAS. To this end, we generated an isogenic strain lacking the shp gene (Δshp) and its complemented strain (Δshp-c) using the parent strain MGAS5005 (WT). Deletion of shp increased survival rates and neutrophil recruitment and reduced skin lesion sizes and GAS loads in the blood and the liver, lung, kidney and spleen in subcutaneous infections of mice...
September 29, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28830073/platelet-activating-factor-increases-reactive-oxygen-species-mediated-microbicidal-activity-of-human-macrophages-infected-with-leishmania-viannia-braziliensis
#2
Arissa Felipe Borges, Camila Imai Morato, Rodrigo Saar Gomes, Miriam Leandro Dorta, Milton Adriano Pelli de Oliveira, Fátima Ribeiro-Dias
Platelet-activating factor (PAF) is produced by macrophages during inflammation and infections. We evaluated whether PAF is able to modulate the infection of human macrophages by Leishmania braziliensis, the main Leishmania sp. in Brazil. Monocyte-derived macrophages were incubated with promastigote forms in absence or presence of exogenous PAF. We observed that the treatment of macrophages with low concentrations of PAF prior to infection increased the phagocytosis of L. braziliensis. More importantly, exogenous PAF reduced the parasitism when it was added before, during or after infection...
September 29, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28829997/msx2-is-required-for-vascular-smooth-muscle-cells-osteoblastic-differentiation-but-not-calcification-in-insulin-resistant-ob-ob-mice
#3
Maria Claudina Andrade, Luciana S Carmo, Elisangela Farias-Silva, Marcel Liberman
BACKGROUND AND AIMS: Obesity and diabetes potentiate vascular calcification by increasing vascular smooth muscle cells osteoblastic differentiation mediated by the transcription factor Msx2 and bone morphogenetic protein-2 signaling. However, Bmp-2/Msx2 crosstalk to induce VSMC osteogenic phenotype transition and calcification is poorly understood in diabetes. We aimed to investigate mechanisms underlying Bmp-2-driven VSMC osteogenic differentiation and calcification in leptin-deficient ob/ob mice...
July 29, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28829969/cell-polarity-spot-on-cdc42-polarization-achieved-on-demand
#4
Andrew B Goryachev, Marcin Leda
A new study deploys optogenetics to induce the yeast bud on demand, at a site determined by a laser spot. The authors definitively prove that the initiation of cell polarization is driven by the Bem1-mediated positive feedback loop and reveal novel features of its regulation by the cell cycle.
August 21, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28829947/a-single-cell-biochemistry-approach-reveals-par-complex-dynamics-during-cell-polarization
#5
Daniel J Dickinson, Francoise Schwager, Lionel Pintard, Monica Gotta, Bob Goldstein
Regulated protein-protein interactions are critical for cell signaling, differentiation, and development. For the study of dynamic regulation of protein interactions in vivo, there is a need for techniques that can yield time-resolved information and probe multiple protein binding partners simultaneously, using small amounts of starting material. Here we describe a single-cell protein interaction assay. Single-cell lysates are generated at defined time points and analyzed using single-molecule pull-down, yielding information about dynamic protein complex regulation in vivo...
August 21, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28829913/virtual-screening-of-acyclovir-derivatives-as-potential-antiviral-agents-design-synthesis-and-biological-evaluation-of-new-acyclic-nucleoside-protides
#6
Marco Derudas, Christophe Vanpouille, Davide Carta, Sonia Zicari, Graciela Andrei, Robert Snoeck, Andrea Brancale, Leonid Margolis, Jan Balzarini, Christopher McGuigan
Following our findings on the anti-human immunodeficiency virus (HIV) activity of acyclovir (ACV) phosphate prodrugs, we herein report the ProTide approach applied to a series of acyclic nucleosides aimed at the identification of novel and selective antiviral, in particular anti-HIV agents. Acyclic nucleoside analogues used in this study were identified through a virtual screening using HIV-reverse transcriptase (RT), adenylate/guanylate kinase, and human DNA polymerase. A total of thirty-nine new phosphate prodrugs were synthesised and evaluated against HIV-1 (in in vitro and in ex-vivo human tonsillar tissue system) and human herpes viruses...
August 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28829890/mir-367-promotes-uveal-melanoma-cell-proliferation-and-migration-by-regulating-pten
#7
J W Ling, P R Lu, Y B Zhang, S Jiang, Z C Zhang
We aimed to investigate the biological role of miR-367 in uveal melanoma cell growth and migration, and the underlying mechanism responsible. Quantitative real-time polymerase chain reaction was performed to evaluate miR-367 expression in uveal melanoma tissue samples and cell lines. A miR-367 mimic, miR-367 inhibitor, and negative control oligonucleotide were transfected into these cells to investigate the function of this microRNA. In addition, the role of PTEN in miR-367-mediated uveal melanoma cell growth and migration was evaluated...
August 17, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28829877/effect-of-ganciclovir-on-il-6-levels-among-cytomegalovirus-seropositive-adults-with-critical-illness-a-randomized-clinical-trial
#8
Ajit P Limaye, Renee D Stapleton, Lili Peng, Scott R Gunn, Louise E Kimball, Robert Hyzy, Matthew C Exline, D Clark Files, Peter E Morris, Stephen K Frankel, Mark E Mikkelsen, Duncan Hite, Kyle B Enfield, Jay Steingrub, James O'Brien, Polly E Parsons, Joseph Cuschieri, Richard G Wunderink, David L Hotchkin, Ying Q Chen, Gordon D Rubenfeld, Michael Boeckh
Importance: The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown. Objective: To determine whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized clinical trial (conducted March 10, 2011-April 29, 2016) with a follow-up of 180 days (November 10, 2016) that included 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure at 14 university intensive care units (ICUs) across the United States...
August 22, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28829844/conditional-genetically-encoded-small-molecule-regulated-inhibition-of-nf%C3%AE%C2%BAb-signaling-in-rpe-cells
#9
Khiem T Vu, Fang Zhang, John D Hulleman
Purpose: Nuclear factor κB (NFκB) is a ubiquitously expressed, proinflammatory transcription factor that controls the expression of genes involved in cell survival, angiogenesis, complement activation, and inflammation. Studies have implicated NFκB-dependent cytokines or complement-related factors as being detrimentally involved in retinal diseases, thus making inhibition of NFκB signaling a potential therapeutic target. We sought to develop a conditional and reversible method that could regulate pathogenic NFκB signaling by the addition of a small molecule...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28829832/allergen-homologs-in-the-euroglyphus-maynei-draft-genome
#10
S Dean Rider, Marjorie S Morgan, Larry G Arlian
Euroglyphus maynei is a house dust mite commonly found in homes worldwide and is the source of allergens that sensitize and induce allergic reactions in humans. It is the source of species-specific allergens as well as allergens that are cross-reactive with the allergens from house dust mites Dermatophagoides farinae and D. pteronyssinus, and the ectoparasitic scabies mite Sarcoptes scabiei. The genomics, proteomics and molecular biology of E. maynei and its allergens have not been as extensively investigated as those of D...
2017: PloS One
https://www.readbyqxmd.com/read/28829817/genomic-correlates-of-glatiramer-acetate-adverse-cardiovascular-effects-lead-to-a-novel-locus-mediating-coronary-risk
#11
Ingrid Brænne, Lingyao Zeng, Christina Willenborg, Vinicius Tragante, Thorsten Kessler, Cristen J Willer, Markku Laakso, Lars Wallentin, Paul W Franks, Veikko Salomaa, Abbas Dehghan, Thomas Meitinger, Nilesh J Samani, Folkert W Asselbergs, Jeanette Erdmann, Heribert Schunkert
Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes...
2017: PloS One
https://www.readbyqxmd.com/read/28829816/matriptase-shedding-is-closely-coupled-with-matriptase-zymogen-activation-and-requires-de-novo-proteolytic-cleavage-likely-involving-its-own-activity
#12
Chun-Che Tseng, Bailing Jia, Robert Barndt, Yayun Gu, Chien-Yu Chen, I-Chu Tseng, Sheng-Fang Su, Jehng-Kang Wang, Michael D Johnson, Chen-Yong Lin
The type 2 transmembrane serine protease matriptase is involved in many pathophysiological processes probably via its enzymatic activity, which depends on the dynamic relationship between zymogen activation and protease inhibition. Matriptase shedding can prolong the life of enzymatically active matriptase and increase accessibility to substrates. We show here that matriptase shedding occurs via a de novo proteolytic cleavage at sites located between the SEA domain and the CUB domain. Point or combined mutations at the four positively charged amino acid residues in the region following the SEA domain allowed Arg-186 to be identified as the primary cleavage site responsible for matriptase shedding...
2017: PloS One
https://www.readbyqxmd.com/read/28829804/classes-1-and-2-integrons-in-faecal-escherichia-coli-strains-isolated-from-mother-child-pairs-in-nigeria
#13
Babatunde W Odetoyin, Amy S Labar, Adebayo Lamikanra, Aaron O Aboderin, Iruka N Okeke
BACKGROUND: Antimicrobial resistance among enteric bacteria in Africa is increasingly mediated by integrons on horizontally acquired genetic elements. There have been recent reports of such elements in invasive pathogens across Africa, but very little is known about the faecal reservoir of integron-borne genes. METHODS AND FINDINGS: We screened 1098 faecal Escherichia coli isolates from 134 mother-child pairs for integron cassettes by PCR using primers that anneal to the 5' and 3' conserved ends of the cassette regions and for plasmid replicons...
2017: PloS One
https://www.readbyqxmd.com/read/28829795/identification-of-factors-involved-in-dimorphism-and-pathogenicity-of-zymoseptoria-tritici
#14
Alexander Yemelin, Annamaria Brauchler, Stefan Jacob, Julian Laufer, Larissa Heck, Andrew J Foster, Luis Antelo, Karsten Andresen, Eckhard Thines
A forward genetics approach was applied in order to investigate the molecular basis of morphological transition in the wheat pathogenic fungus Zymoseptoria tritici. Z. tritici is a dimorphic plant pathogen displaying environmentally regulated morphogenetic transition between yeast-like and hyphal growth. Considering the infection mode of Z. tritici, the switching to hyphal growth is essential for pathogenicity allowing the fungus the host invasion through natural openings like stomata. We exploited a previously developed Agrobacterium tumefaciens-mediated transformation (ATMT) to generate a mutant library by insertional mutagenesis including more than 10,000 random mutants...
2017: PloS One
https://www.readbyqxmd.com/read/28829777/the-activation-of-oseil1-on-yuc8m-transcription-and-auxin-biosynthesis-is-required-for-ethylene-inhibited-root-elongation-in-rice-early-seedling-development
#15
Hua Qin, Zhijin Zhang, Juan Wang, Xinbing Chen, Pengcheng Wei, Rongfeng Huang
Rice is an important monocotyledonous crop worldwide; it differs from the dicotyledonous plant Arabidopsis in many aspects. In Arabidopsis, ethylene and auxin act synergistically to regulate root growth and development. However, their interaction in rice is still unclear. Here, we report that the transcriptional activation of OsEIL1 on the expression of YUC8/REIN7 and indole-3-pyruvic acid (IPA)-dependent auxin biosynthesis is required for ethylene-inhibited root elongation. Using an inhibitor of YUC activity, which regulates auxin biosynthesis via the conversion of IPA to indole-3-acetic acid (IAA), we showed that ethylene-inhibited primary root elongation is dependent on YUC-based auxin biosynthesis...
August 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28829772/correction-ovate-family-protein-8-positively-mediates-brassinosteroid-signaling-through-interacting-with-the-gsk3-like-kinase-in-rice
#16
Chao Yang, Wenjin Shen, Yong He, Zhihong Tian, Jianxiong Li
[This corrects the article DOI: 10.1371/journal.pgen.1006118.].
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28829765/rnai-screen-reveals-synthetic-lethality-between-cyclin-g-associated-kinase-and-fbxw7-by-inducing-aberrant-mitoses
#17
Saoirse O Dolly, Mark D Gurden, Konstantinos Drosopoulos, Paul Clarke, Johann de Bono, Stan Kaye, Paul Workman, Spiros Linardopoulos
BACKGROUND: F-box and WD40 repeat domain-containing 7 (FBXW7) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of multiple oncogenic substrates. The tumour suppressor function is frequently lost in multiple cancers through genetic deletion and mutations in a broad range of tumours. Loss of FBXW7 functionality results in the stabilisation of multiple major oncoproteins, culminating in increased cellular proliferation and pro-survival pathways, cell cycle deregulation, chromosomal instability and altered metabolism...
August 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28829764/rna-helicase-dhx15-acts-as-a-tumour-suppressor-in-glioma
#18
Shingo Ito, Hideto Koso, Kazuhiro Sakamoto, Sumiko Watanabe
BACKGROUND: Glioblastoma is the most common form of malignant brain cancer and has a poor prognosis in adults. We identified Dhx15 as a candidate tumour suppressor gene in glioma by transposon-based mutagenesis. Dhx15 is an adenosine triphosphate (ATP)-dependent RNA helicase belonging to the DEAH-box (DHX) helicase family, but its role in cancer remains elusive. METHODS: DHX15 expression levels were examined in glioma cell lines. DHX15 functions were examined by gain- and loss-of-function analyses...
August 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28829739/allosteric-control-of-an-asymmetric-transduction-in-a-g-protein-coupled-receptor-heterodimer
#19
Junke Liu, Zongyong Zhang, David Moreno-Delgado, James Ar Dalton, Xavier Rovira, Ana Trapero, Cyril Goudet, Amadeu Llebaria, Jesús Giraldo, Qilin Yuan, Philippe Rondard, Siluo Huang, Jianfeng Liu, Jean-Philippe Pin
GPCRs play critical roles in cell communication. Although GPCRs can form heteromers, their role in signaling remains elusive. Here we used rat metabotropic glutamate (mGlu) receptors as prototypical dimers to study the functional interaction between each subunit. mGluRs can form both constitutive homo- and heterodimers. Whereas both mGlu2 and mGlu4 couple to G proteins, G protein activation is mediated by mGlu4 heptahelical domain (HD) exclusively in mGlu2-4 heterodimers. Such asymmetric transduction results from the action of both the dimeric extracellular domain, and an allosteric activation by the partially-activated non-functional mGlu2 HD...
August 10, 2017: ELife
https://www.readbyqxmd.com/read/28829698/the-pro-%C3%AE-1-v-collagen-gene-col5a1-is-coordinately-regulated-by-mir-29b-with-core-promoter-in-cultured-cells
#20
Juan Juan Zhang, Hiroyuki Yano, Takako Sasaki, Noritaka Matsuo, Hidekatsu Yoshioka
AIMS: Col5a1 encodes the α1 chain of type V collagen, a quantitatively minor fibrillar collagen that is critical for the formation and function of the organs in the body. MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate biological functions by binding to the 3'- untranslated region (3'UTR) of specific target mRNA. In this study, we investigated the post-transcriptional regulation of miRNAs on the Col5a1 gene expression. MATERIALS AND METHODS: We cultured osteoblasts and fibroblasts of cell lines...
August 22, 2017: Connective Tissue Research
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