Genome-Wide Transcriptional Profiling Reveals MicroRNA-Correlated Genes and Biological Processes in Human Lymphoblastoid Cell Lines

Expression level of many genes shows abundant natural variation in human populations. The variations in gene expression are believed to contribute to phenotypic differences. Emerging evidence has shown that microRNAs (miRNAs) are one of the key regulators of gene expression. However, past studies have focused on the miRNA target genes and used loss- or gain-of-function approach that may not reflect natural association between miRNA and mRNAs.To examine miRNA regulatory effect on global gene expression under endogenous condition, we performed pair-wise correlation coefficient analysis on expression levels of 366 miRNAs and 14,174 messenger RNAs (mRNAs) in 90 immortalized lymphoblastoid cell lines, and observed significant correlations between the two species of RNA transcripts. We identified a total of 7,207 significantly correlated miRNA-mRNA pairs (false discovery rate q<0.01). Of those, 4,085 pairs showed positive correlations while 3,122 pairs showed negative correlations. Gene ontology analyses on the miRNA-correlated genes revealed significant enrichments in several biological processes related to cell cycle, cell communication and signal transduction. Individually, each of three miRNAs (miR-331, -98 and -33b) demonstrated significant correlation with the genes in cell cycle-related biological processes, which is consistent with important role of miRNAs in cell cycle regulation.This study demonstrates feasibility of using naturally expressed transcript profiles to identify endogenous correlation between miRNA and miRNA. By applying this genome-wide approach, we have identified thousands of miRNA-correlated genes and revealed potential role of miRNAs in several important cellular functions. The study results along with accompanying data sets will provide a wealth of high-throughput data to further evaluate the miRNA-regulated genes and eventually in phenotypic variations of human populations

Milestones in the Observations of Cosmic Magnetic Fields

Magnetic fields are observed everywhere in the universe. In this review, we concentrate on the observational aspects of the magnetic fields of Galactic and extragalactic objects. Readers can follow the milestones in the observations of cosmic magnetic fields obtained from the most important tracers of magnetic fields, namely, the star-light polarization, the Zeeman effect, the rotation measures (RMs, hereafter) of extragalactic radio sources, the pulsar RMs, radio polarization observations, as well as the newly implemented sub-mm and mm polarization capabilities. (Another long paragraph is omitted due to the limited space here)Comment: Invited Review (ChJA&A); 32 pages. Sorry if your significant contributions in this area were not mentioned. Published pdf & ps files (with high quality figures) now availble at http://www.chjaa.org/2002_2_4.ht

The implementation evaluation of primary care groups of practice: a focus on organizational identity

<p>Abstract</p> <p>Background</p> <p>Since 2002 the Health Ministry of Québec (Canada) has been implementing a primary care organizational innovation called 'family medicine groups'. This is occurring in a political context in which the reorganization of primary care is considered necessary to improve health care system performance. More specifically, the purpose of this reform has been to overcome systemic deficiencies in terms of accessibility and continuity of care. This paper examines the first years of implementation of the family medicine group program, with a focus on the emergence of the organizational identity of one of the pilot groups located in the urban area of Montreal.</p> <p>Methods</p> <p>An in-depth longitudinal case study was conducted over two and a half years. Face to face individual interviews with key informants from the family medicine group under study were conducted over the research period considered. Data was gathered throuhg observations and documentary analysis. The data was analyzed using temporal bracketing and Fairclough's three-dimensional critical discourse analytical techniques.</p> <p>Results</p> <p>Three different phases were identified over the period under study. During the first phase, which corresponded to the official start-up of the family medicine group program, new resources and staff were only available at the end of the period, and no changes occurred in medical practices. Power struggles between physicians and nurses characterized the second phase, resulting in a very difficult integration of advanced nurse practitioners into the group. Indeed, the last phase was portrayed by initial collaborative practices associated with a sensegiving process prompted by a new family medicine group director.</p> <p>Conclusions</p> <p>The creation of a primary care team is a very challenging process that goes beyond the normative policy definitions of who is on the team or what the team has to do. To fulfil expectations of quality improvement through team-based care, health care professionals who are required to work together need shared time/space contexts to communicate; to overcome interprofessional and interpersonal conflicts; and to make sense of and define who they collectively are and what they do as a clinical team.</p

Inherited variants in regulatory T cell genes and outcome of ovarian cancer.

Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence of inherited prognostic factors. However, the role of inherited variants in genes encoding Treg-related immune molecules has not been fully explored. We analyzed expression quantitative trait loci (eQTL) and sequence-based tagging single nucleotide polymorphisms (tagSNPs) for 54 genes associated with Tregs in 3,662 invasive ovarian cancer cases. With adjustment for known prognostic factors, suggestive results were observed among rarer histological subtypes; poorer survival was associated with minor alleles at SNPs in RGS1 (clear cell, rs10921202, p = 2.7×10(-5)), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5×10(-4), and rs3753348, p = 9.0×10(-4), respectively), and CD80 (endometrioid, rs13071247, p = 8.0×10(-4)). Fo0r the latter, correlative data support a CD80 rs13071247 genotype association with CD80 tumor RNA expression (p = 0.006). An additional eQTL SNP in CD80 was associated with shorter survival (rs7804190, p = 8.1×10(-4)) among all cases combined. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of Tregs, these results suggest the need for follow-up phenotypic studies

Integration of a nationally procured electronic health record system into user work practices

BACKGROUND: Evidence suggests that many small- and medium-scale Electronic Health Record (EHR) implementations encounter problems, these often stemming from users' difficulties in accommodating the new technology into their work practices. There is the possibility that these challenges may be exacerbated in the context of the larger-scale, more standardised, implementation strategies now being pursued as part of major national modernisation initiatives. We sought to understand how England's centrally procured and delivered EHR software was integrated within the work practices of users in selected secondary and specialist care settings. METHODS: We conducted a qualitative longitudinal case study-based investigation drawing on sociotechnical theory in three purposefully selected sites implementing early functionality of a nationally procured EHR system. The complete dataset comprised semi-structured interview data from a total of 66 different participants, 38.5 hours of non-participant observation of use of the software in context, accompanying researcher field notes, and hospital documents (including project initiation and lessons learnt reports). Transcribed data were analysed thematically using a combination of deductive and inductive approaches, and drawing on NVivo8 software to facilitate coding. RESULTS: The nationally led "top-down" implementation and the associated focus on interoperability limited the opportunity to customise software to local needs. Lack of system usability led users to employ a range of workarounds unanticipated by management to compensate for the perceived shortcomings of the system. These had a number of knock-on effects relating to the nature of collaborative work, patterns of communication, the timeliness and availability of records (including paper) and the ability for hospital management to monitor organisational performance. CONCLUSIONS: This work has highlighted the importance of addressing potentially adverse unintended consequences of workarounds associated with the introduction of EHRs. This can be achieved with customisation, which is inevitably somewhat restricted in the context of attempts to implement national solutions. The tensions and potential trade-offs between achieving large-scale interoperability and local requirements is likely to be the subject of continuous debate in England and beyond with no easy answers in sight

Enumeration of Functional T-Cell Subsets by Fluorescence-Immunospot Defines Signatures of Pathogen Burden in Tuberculosis

IFN-γ and IL-2 cytokine-profiles define three functional T-cell subsets which may correlate with pathogen load in chronic intracellular infections. We therefore investigated the feasibility of the immunospot platform to rapidly enumerate T-cell subsets by single-cell IFN-γ/IL-2 cytokine-profiling and establish whether immunospot-based T-cell signatures distinguish different clinical stages of human tuberculosis infection.We used fluorophore-labelled anti-IFN-γ and anti-IL-2 antibodies with digital overlay of spatially-mapped colour-filtered images to enumerate dual and single cytokine-secreting M. tuberculosis antigen-specific T-cells in tuberculosis patients and in latent tuberculosis infection (LTBI). We validated results against established measures of cytokine-secreting T-cells.Fluorescence-immunospot correlated closely with single-cytokine enzyme-linked-immunospot for IFN-γ-secreting T-cells and IL-2-secreting T-cells and flow-cytometry-based detection of dual IFN-γ/IL-2-secreting T-cells. The untreated tuberculosis signature was dominated by IFN-γ-only-secreting T-cells which shifted consistently in longitudinally-followed patients during treatment to a signature dominated by dual IFN-γ/IL-2-secreting T-cells in treated patients. The LTBI signature differed from active tuberculosis, with higher proportions of IL-2-only and IFN-γ/IL-2-secreting T-cells and lower proportions of IFN-γ-only-secreting T-cells.Fluorescence-immunospot is a quantitative, accurate measure of functional T-cell subsets; identification of cytokine-signatures of pathogen burden, distinct clinical stages of M. tuberculosis infection and long-term immune containment suggests application for treatment monitoring and vaccine evaluation