A Role for the Vacuolating Cytotoxin, VacA, in Colonization and Helicobacter pylori-Induced Metaplasia in the Stomach

Carriage of Helicobacter pylori strains producing more active (s1/i1) forms of VacA is strongly associated with gas-tric adenocarcinoma. To our knowledge, we are the first to determine effects of different polymorphic forms of VacA on inflammation and metaplasia in the mouse stomach. Bacteria producing the less active s2/i2 form of VacA colonized mice more efficiently than mutants null for VacA or producing more active forms of it, providing the first evidence of a positive role for the minimally active s2/i2 toxin. Strains producing more active toxin forms induced more severe and extensive metaplasia and in flammation in the mouse stomach than strains producing weakly active (s2/i2) toxin. We also examined the association in humans, controlling for cag PAI status. In human gastric biopsy specimens, the vacA i1 allele was strongly associated with precancerous intestinal metaplasia, with almost complete absence of intestinal metaplasia in subjects infected with i2-type strains, even in a vacA s1, cagA+ background

Variation resources at UC Santa Cruz

The variation resources within the University of California Santa Cruz Genome Browser include polymorphism data drawn from public collections and analyses of these data, along with their display in the context of other genomic annotations. Primary data from dbSNP is included for many organisms, with added information including genomic alleles and orthologous alleles for closely related organisms. Display filtering and coloring is available by variant type, functional class or other annotations. Annotation of potential errors is highlighted and a genomic alignment of the variant's flanking sequence is displayed. HapMap allele frequencies and linkage disequilibrium (LD) are available for each HapMap population, along with non-human primate alleles. The browsing and analysis tools, downloadable data files and links to documentation and other information can be found at

A comparison of single and intersectional social identities associated with discrimination and mental health service use: data from the 2014 Adult Psychiatric Morbidity Survey in England

Inequities in mental health service use (MHSU) and treatment are influenced by social stratification processes linked to socially contextualised interactions between individuals, organisations and institutions. These complex relations underpin observed inequities and their experience by people at the intersections of social statuses. Discrimination is one important mechanism influencing such differences. We compared inequities in MHSU/treatment through single and intersectional status analyses, accounting for need. We assessed whether past-year discrimination differentially influences MHSU/treatment across single and intersecting statuses. Data came from a population survey (collected 2014–2015) nationally representative of English households (N = 7546). We used a theory and datadriven approach (latent class analysis) which identified five intersectional groups in the population comprising common combinations of social statuses. Single status analyses identified characteristics associated with MHSU/treatment (being a sexual minority (adjusted odds ratio (AOR) 1.65 95% CI:1.09-2.50), female (AOR 1.71, 95% CI:1.45–2.02), economically inactive (AOR 2.02, 95% CI:1.05–3.90), in the most deprived quintile (AOR 1.33, 95% CI:1.02–1.74), and Black (AOR 0.36 95% CI:0.20–0.66)). Intersectional analyses detected patterns not apparent from single status analyses. Compared to the most privileged group (“White British, highly educated, employed, high social class”), “Retired WhiteBritish” had greater odds of MHSU/treatment (AOR 1.88, 95% CI:1.53-2.32) while “Employed migrants” had lower odds (AOR 0.39, 95% CI:0.27–0.55). Past-year discrimination was associated with certain disadvantaged social statuses and greater MHSU/treatment but—except for sexual minorities—adjusting for discrimination had little influence using either analytic approach. Observing patterns only by single social statuses masks potentially unanticipated and contextually varying inequities. The latent class approach offers policy-relevant insights into patterns and mechanisms of inequity but may mask other key intersectional patterns by statuses less common or under represented in surveys (e.g. UK-born ethnic minority groups). We propose multiple, context-relevant, theory-driven approaches to intersectional understanding of mental health inequalities

Both Size and GC-Content of Minimal Introns Are Selected in Human Populations

Background: We previously have studied the insertion and deletion polymorphism by sequencing no more than one hundred introns in a mixed human population and found that the minimal introns tended to maintain length at an optimal size. Here we analyzed re-sequenced 179 individual genomes (from African, European, and Asian populations) from the data released by the 1000 Genome Project to study the size dynamics of minimal introns. Principal Findings: We not only confirmed that minimal introns in human populations are selected but also found two major effects in minimal intron evolution: (i) Size-effect: minimal introns longer than an optimal size (87 nt) tend to have a higher ratio of deletion to insertion than those that are shorter than the optimal size; (ii) GC-effect: minimal introns with lower GC content tend to be more frequently deleted than those with higher GC content. The GC-effect results in a higher GC content in minimal introns than their flanking exons as opposed to larger introns ($125 nt) that always have a lower GC content than that of their flanking exons. We also observed that the two effects are distinguishable but not completely separable within and between populations. Conclusions: We validated the unique mutation dynamics of minimal introns in keeping their near-optimal size and GC content, and our observations suggest potentially important functions of human minimal introns in transcript processin

Two new ArrayTrack libraries for personalized biomedical research

<p>Abstract</p> <p>Background</p> <p>Recent advances in high-throughput genotyping technology are paving the way for research in personalized medicine and nutrition. However, most of the genetic markers identified from association studies account for a small contribution to the total risk/benefit of the studied phenotypic trait. Testing whether the candidate genes identified by association studies are causal is critically important to the development of personalized medicine and nutrition. An efficient data mining strategy and a set of sophisticated tools are necessary to help better understand and utilize the findings from genetic association studies. </p> <p>Description</p> <p>SNP (single nucleotide polymorphism) and QTL (quantitative trait locus) libraries were constructed and incorporated into ArrayTrack, with user-friendly interfaces and powerful search features. Data from several public repositories were collected in the SNP and QTL libraries and connected to other domain libraries (genes, proteins, metabolites, and pathways) in ArrayTrack. Linking the data sets within ArrayTrack allows searching of SNP and QTL data as well as their relationships to other biological molecules. The SNP library includes approximately 15 million human SNPs and their annotations, while the QTL library contains publically available QTLs identified in mouse, rat, and human. The QTL library was developed for finding the overlap between the map position of a candidate or metabolic gene and QTLs from these species. Two use cases were included to demonstrate the utility of these tools. The SNP and QTL libraries are freely available to the public through ArrayTrack at <url>http://www.fda.gov/ArrayTrack</url>. </p> <p>Conclusions</p> <p>These libraries developed in ArrayTrack contain comprehensive information on SNPs and QTLs and are further cross-linked to other libraries. Connecting domain specific knowledge is a cornerstone of systems biology strategies and allows for a better understanding of the genetic and biological context of the findings from genetic association studies. </p

The ENCODE Project at UC Santa Cruz

The goal of the Encyclopedia Of DNA Elements (ENCODE) Project is to identify all functional elements in the human genome. The pilot phase is for comparison of existing methods and for the development of new methods to rigorously analyze a defined 1% of the human genome sequence. Experimental datasets are focused on the origin of replication, DNase I hypersensitivity, chromatin immunoprecipitation, promoter function, gene structure, pseudogenes, non-protein-coding RNAs, transcribed RNAs, multiple sequence alignment and evolutionarily constrained elements. The ENCODE project at UCSC website () is the primary portal for the sequence-based data produced as part of the ENCODE project. In the pilot phase of the project, over 30 labs provided experimental results for a total of 56 browser tracks supported by 385 database tables. The site provides researchers with a number of tools that allow them to visualize and analyze the data as well as download data for local analyses. This paper describes the portal to the data, highlights the data that has been made available, and presents the tools that have been developed within the ENCODE project. Access to the data and types of interactive analysis that are possible are illustrated through supplemental examples

ENCODE whole-genome data in the UCSC Genome Browser

The Encyclopedia of DNA Elements (ENCODE) project is an international consortium of investigators funded to analyze the human genome with the goal of producing a comprehensive catalog of functional elements. The ENCODE Data Coordination Center at The University of California, Santa Cruz (UCSC) is the primary repository for experimental results generated by ENCODE investigators. These results are captured in the UCSC Genome Bioinformatics database and download server for visualization and data mining via the UCSC Genome Browser and companion tools (Rhead et al. The UCSC Genome Browser Database: update 2010, in this issue). The ENCODE web portal at UCSC (http://encodeproject.org or http://genome.ucsc.edu/ENCODE) provides information about the ENCODE data and convenient links for access

Ethnic inequalities among NHS staff in England: workplace experiences during the COVID-19 pandemic

Objectives This study aims to determine how workplace experiences of National Health Service (NHS) staff varied by ethnicity during the COVID-19 pandemic and how these experiences are associated with mental and physical health at the time of the study. Methods An online Inequalities Survey was conducted by the Tackling Inequalities and Discrimination Experiences in Health Services study in collaboration with NHS CHECK. This Inequalities Survey collected measures relating to workplace experiences (such as personal protective equipment (PPE), risk assessments, redeployments and discrimination) as well as mental health (Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder 7 (GAD-7)), and physical health (PHQ-15) from NHS staff working in the 18 trusts participating with the NHS CHECK study between February and October 2021 (N=4622). Results Regression analysis of this cross-sectional data revealed that staff from black and mixed/other ethnic groups had greater odds of experiencing workplace harassment (adjusted OR (AOR) 2.43 (95% CI 1.56 to 3.78) and 2.38 (95% CI 1.12 to 5.07), respectively) and discrimination (AOR 4.36 (95% CI 2.73 to 6.96) and 3.94 (95% CI 1.67 to 9.33), respectively) compared with white British staff. Staff from black ethnic groups also had greater odds than white British staff of reporting PPE unavailability (AOR 2.16 (95% CI 1.16 to 4.00)). Such workplace experiences were associated with negative physical and mental health outcomes, though this association varied by ethnicity. Conversely, understanding employment rights around redeployment, being informed about and having the ability to inform redeployment decisions were associated with lower odds of poor physical and mental health. Conclusions Structural changes to the way staff from ethnically minoritised groups are supported, and how their complaints are addressed by leaders within the NHS are urgently required

MicroRNA profiling of rhesus macaque embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) play important roles in embryonic stem cell (ESC) self-renewal and pluripotency. Numerous studies have revealed human and mouse ESC miRNA profiles. As a model for human-related study, the rhesus macaque is ideal for delineating the regulatory mechanisms of miRNAs in ESCs. However, studies on rhesus macaque (r)ESCs are lacking due to limited rESC availability and a need for systematic analyses of fundamental rESC characteristics.</p> <p>Results</p> <p>We established three rESC lines and profiled microRNA using Solexa sequencing resulting in 304 known and 66 novel miRNAs. MiRNA profiles were highly conserved between rESC lines and predicted target genes were significantly enriched in differentiation pathways. Further analysis of the miRNA-target network indicated that gene expression regulated by miRNAs was negatively correlated to their evolutionary rate in rESCs. Moreover, a cross-species comparison revealed an overall conservation of miRNA expression patterns between human, mouse and rhesus macaque ESCs. However, we identified three miRNA clusters (miR-467, the miRNA cluster in the imprinted Dlk1-Dio3 region and C19MC) that showed clear interspecies differences.</p> <p>Conclusions</p> <p>rESCs share a unique miRNA set that may play critical roles in self-renewal and pluripotency. MiRNA expression patterns are generally conserved between species. However, species and/or lineage specific miRNA regulation changed during evolution.</p

Race, ethnicity and COVID-19 vaccination: a qualitative study of UK healthcare staff

Objective: COVID-19-related inequities experienced by racial and ethnic minority groups including healthcare professionals mirror wider health inequities, which risk being perpetuated by lower uptake of vaccination. We aim to better understand lower uptake among racial and ethnic minority staff groups to inform initiatives to enhance uptake. Design: Twenty-five semi-structured interviews were conducted (October 2020–January 2021) with UK-based healthcare staff. Data were inductively and thematically analysed. Results: Vaccine decision-making processes were underpinned by an overarching theme, ‘weighing up risks of harm against potential benefits to self and others’. Sub-themes included ‘fear of harm’, ‘moral/ethical objections’, ‘potential benefits to self and others’, ‘information and misinformation’, and ‘institutional or workplace pressure’. We identified ways in which these were weighted more heavily towards vaccine hesitancy for racial and ethnic minority staff groups influenced by perceptions about institutional and structural discrimination. This included suspicions and fear around institutional pressure to be vaccinated, racial injustices in vaccine development and testing, religious or ethical concerns, and legitimacy and accessibility of vaccine messaging and communication. Conclusions: Drawing on a critical race perspective, we conclude that acknowledging historical and contemporary abuses of power is essential to avoid perpetuating and aggravating mistrust by de-contextualising hesitancy from the social processes affecting hesitancy, undermining efforts to increase vaccine uptake