90 research outputs found
Staphylococcus aureus RNAIII Binds to Two Distant Regions of coa mRNA to Arrest Translation and Promote mRNA Degradation
Staphylococcus aureus RNAIII is the intracellular effector of the quorum sensing system that temporally controls a large number of virulence factors including exoproteins and cell-wall-associated proteins. Staphylocoagulase is one major virulence factor, which promotes clotting of human plasma. Like the major cell surface protein A, the expression of staphylocoagulase is strongly repressed by the quorum sensing system at the post-exponential growth phase. Here we used a combination of approaches in vivo and in vitro to analyze the mechanism used by RNAIII to regulate the expression of staphylocoagulase. Our data show that RNAIII represses the synthesis of the protein through a direct binding with the mRNA. Structure mapping shows that two distant regions of RNAIII interact with coa mRNA and that the mRNA harbors a conserved signature as found in other RNAIII-target mRNAs. The resulting complex is composed of an imperfect duplex masking the Shine-Dalgarno sequence of coa mRNA and of a loop-loop interaction occurring downstream in the coding region. The imperfect duplex is sufficient to prevent the formation of the ribosomal initiation complex and to repress the expression of a reporter gene in vivo. In addition, the double-strand-specific endoribonuclease III cleaves the two regions of the mRNA bound to RNAIII that may contribute to the degradation of the repressed mRNA. This study validates another direct target of RNAIII that plays a role in virulence. It also illustrates the diversity of RNAIII-mRNA topologies and how these multiple RNAIII-mRNA interactions would mediate virulence regulation
ĐĐŸŃĐ»ŃĐŽĐ¶Đ”ĐœĐœŃ ŃŃŃŃĐșŃŃŃĐž ĐżĐŸŃŃŃĐ”ĐœĐžŃ ĐČŃĐŽĐșŃĐžŃĐŸŃ ŃĐŸĐ·ŃĐŸĐ±ĐșĐŸŃ Đ·Đ”ĐŒĐ”Đ»Ń Đč ĐżĐŸŃŃĐș ŃĐ»ŃŃ ŃĐČ ĐČĐŽĐŸŃĐșĐŸĐœĐ°Đ»Đ”ĐœĐœŃ ŃĐ”ĐșŃĐ»ŃŃĐžĐČĐ°ŃŃŃ Đ·Đ°Đ»ĐžŃĐșĐŸĐČĐžŃ ĐČĐžŃĐŸĐ±ĐŸĐș ĐșĐ°Ń'ŃŃŃĐČ
ĐĄŃĐ°ŃŃŃ ĐżŃĐžŃĐČŃŃĐ”ĐœĐ° ĐŽĐŸŃĐ»ŃĐŽĐ¶Đ”ĐœĐœŃĐŒ ŃŃŃŃĐșŃŃŃĐž ĐżĐŸŃŃŃĐ”ĐœĐžŃ
Đ·Đ”ĐŒĐ”Đ»Ń, ĐœĐ° ĐŽŃĐ»ŃĐœĐșĐ°Ń
Đ· ĐČĐžĐŽĐŸĐ±ŃŃĐșŃ ĐșĐŸŃĐžŃĐœĐžŃ
ĐșĐŸĐżĐ°Đ»ĐžĐœ ĐČŃĐŽĐșŃĐžŃĐžĐŒ ŃĐżĐŸŃĐŸĐ±ĐŸĐŒ. ĐĐ°ĐČĐ”ĐŽĐ”ĐœĐŸ ĐżĐ»ĐŸŃŃ ĐżĐŸŃŃŃĐ”ĐœŃ Đ·Đ”ĐŒĐ”Đ»Ń ĐżŃĐž ŃĐŸĐ·ŃĐŸĐ±ŃŃ ĐŸŃĐœĐŸĐČĐœĐžŃ
ĐČОЎŃĐČ ĐșĐŸŃĐžŃĐœĐžŃ
ĐșĐŸĐżĐ°Đ»ĐžĐœ. ĐŃĐŸĐ°ĐœĐ°Đ»ŃĐ·ĐŸĐČĐ°ĐœĐŸ ŃОзОĐșĐž, ŃĐŸ ĐČĐžĐœĐžĐșĐ°ŃŃŃ ŃĐ· ĐœĐ”ŃĐČĐŸŃŃĐ°ŃĐœĐŸŃ ŃĐ”ĐșŃĐ»ŃŃĐžĐČĐ°ŃŃŃŃ Đ·Đ”ĐŒĐ”Đ»Ń ĐłŃŃĐœĐžŃĐŸĐłĐŸ ĐČŃĐŽĐČĐŸĐŽŃ, Đ° ŃĐ°ĐșĐŸĐ¶ ĐČŃĐŽ ĐżĐŸĐșĐžĐœŃŃĐžŃ
ĐłŃŃĐœĐžŃĐžŃ
ĐČĐžŃĐŸĐ±ĐŸĐș ŃŃĐ°ŃĐžŃ
ĐșĐ°Ń'ŃŃŃĐČ. ĐĐ°ŃалДлŃĐœĐŸ ŃĐŸĐ·ĐłĐ»ŃĐœŃŃŃ ĐŸĐ±ŃŃгО ĐČŃĐŽŃ
ĐŸĐŽŃĐČ ĐłŃŃĐœĐžŃĐŸĐłĐŸ ĐČĐžŃĐŸĐ±ĐœĐžŃŃĐČĐ° ŃĐ° ŃŃ
ĐżĐŸĐČŃĐŸŃĐœĐ” ĐČĐžĐșĐŸŃĐžŃŃĐ°ĐœĐœŃ ĐČ ŃĐșĐŸŃŃŃ Đ·Đ°ĐżĐŸĐČĐœŃĐČĐ°ŃĐ° ĐŽĐ»Ń Đ·Đ°Đ»ĐžŃĐșĐŸĐČĐžŃ
ĐČĐžŃĐŸĐ±Đ»Đ”ĐœĐžŃ
ĐżŃĐŸŃŃĐŸŃŃĐČ ĐșĐ°Ń'ŃŃŃĐČ.The article is devoted to the research of land violation indicators at the extraction of minerals by surface mining method. Data gives about the land violations area at the mining key minerals. Ana-lyzed the risks from the not-on-time reclamation of the mining clam and abandoned excavations of the old quarries. In parallel considered the volumes of mining wastes and their reuse as aggregate for filling residual spaces of surface mines.ĐĄŃĐ°ŃŃŃ ĐżĐŸŃĐČŃŃĐ”ĐœĐ° ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃĐŒ ĐżĐ»ĐŸŃĐ°ĐŽĐ”Đč ĐœĐ°ŃŃŃĐ”ĐœĐžŃ Đ·Đ”ĐŒĐ”Đ»Ń, ŃĐČŃĐ·Đ°ĐœĐœŃŃ
Ń ĐŽĐŸĐ±ŃŃĐ”Đč ĐżĐŸĐ»Đ”Đ·ĐœŃŃ
ĐžŃĐșĐŸĐżĐ°Đ”ĐŒŃŃ
ĐŸŃĐșŃŃŃŃĐŒ ŃĐżĐŸŃĐŸĐ±ĐŸĐŒ. ĐŃĐžĐČĐ”ĐŽĐ”ĐœŃ ĐżĐ»ĐŸŃĐ°ĐŽĐž ĐœĐ°ŃŃŃĐ”ĐœĐžĐč Đ·Đ”ĐŒĐ”Đ»Ń ĐżŃĐž ŃĐ°Đ·ŃĐ°Đ±ĐŸŃĐșĐ” ĐŸŃĐœĐŸĐČĐœŃŃ
ĐČĐžĐŽĐŸĐČ ĐżĐŸĐ»Đ”Đ·ĐœŃŃ
ĐžŃĐșĐŸĐżĐ°Đ”ĐŒŃŃ
. ĐŃĐŸĐ°ĐœĐ°Đ»ĐžĐ·ĐžŃĐŸĐČĐ°ĐœŃ ŃĐžŃĐșĐž, ĐżŃДЎŃŃĐ°ĐČĐ»ŃĐ”ĐŒŃĐ” ĐœĐ”ŃĐČĐŸĐ”ĐČŃĐ”ĐŒĐ”ĐœĐœĐŸĐč ŃĐ”ĐșŃĐ»ŃŃĐžĐČĐ°ŃОДĐč Đ·Đ”ĐŒĐ”Đ»Ń ĐłĐŸŃĐœĐŸĐłĐŸ ĐŸŃĐČĐŸĐŽĐ°, Đ° ŃĐ°ĐșжД забŃĐŸŃĐ”ĐœĐœŃĐŒĐž ĐłĐŸŃĐœŃĐŒĐž ĐČŃŃĐ°Đ±ĐŸŃĐșĐ°ĐŒĐž ŃŃĐ°ŃŃŃ
ĐșĐ°ŃŃĐ”ŃĐŸĐČ. ĐĐ°ŃаллДлŃĐœĐŸ ŃĐ°ŃŃĐŒĐŸŃŃĐ”ĐœŃ ĐŸĐ±ŃĐ”ĐŒŃ ĐŸŃŃ
ĐŸĐŽĐŸĐČ ĐłĐŸŃĐœĐŸĐłĐŸ ĐżŃĐŸĐžĐ·ĐČĐŸĐŽŃŃĐČĐ° Đž ĐžŃ
ĐżĐŸĐČŃĐŸŃĐœĐŸĐ” ĐžŃĐżĐŸĐ»ŃĐ·ĐŸĐČĐ°ĐœĐžĐ” ĐČ ĐșĐ°ŃĐ”ŃŃĐČĐ” Đ·Đ°ĐżĐŸĐ»ĐœĐžŃĐ”Đ»Ń ĐŽĐ»Ń ĐŸŃŃĐ°ŃĐŸŃĐœŃŃ
ĐČŃŃĐ°Đ±ĐŸŃĐ°ĐœĐœŃŃ
ĐżŃĐŸŃŃŃĐ°ĐœŃŃĐČ ĐșĐ°ŃŃĐ”ŃĐŸĐČ
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification
Search for dark matter produced in association with bottom or top quarks in âs = 13 TeV pp collisions with the ATLAS detector
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fbâ1 of protonâproton collision data recorded by the ATLAS experiment at âs = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe
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