The interaction of human and Epstein–Barr virus miRNAs with Multiple Sclerosis risk loci

Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines of evidence suggest that Epstein–Barr virus (EBV) infection may contribute to the development of MS. Here, we aimed to identify the potential contribution of EBV-encoded and host cellular miRNAs to MS pathogenesis. We identified differentially expressed host miRNAs in EBV infected B cells (LCLs) and putative host/EBV miRNA interactions with MS risk loci. We estimated the genotype effect of MS risk loci on the identified putative miRNA:mRNA interactions in silico. We found that the protective allele of MS risk SNP rs4808760 reduces the expression of hsa-mir-3188-3p. In addition, our analysis suggests that hsa-let-7b-5p may interact with ZC3HAV1 differently in LCLs compared to B cells. In vitro assays indicated that the protective allele of MS risk SNP rs10271373 increases ZC3HAV1 expression in LCLs, but not in B cells. The higher expression for the protective allele in LCLs is consistent with increased IFN response via ZC3HAV1 and so decreased immune evasion by EBV. Taken together, this provides evidence that EBV infection dysregulates the B cell miRNA machinery, including MS risk miRNAs, which may contribute to MS pathogenesis via interaction with MS risk genes either directly or indirectly

Impact of recently upwelled water on productivity investigated using in situ and incubation-based methods in Monterey Bay

Author Posting. © American Geophysical Union, 2017. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 122 (2017): 1901–1926, doi:10.1002/2016JC012306.Photosynthetic conversion of inline image to organic carbon and the transport of this carbon from the surface to the deep ocean is an important regulator of atmospheric inline image. To understand the controls on carbon fluxes in a productive region impacted by upwelling, we measured biological productivity via multiple methods during a cruise in Monterey Bay, California. We quantified net community production and gross primary production from measurements of inline image/Ar and inline image triple isotopes ( inline image), respectively. We simultaneously conducted incubations measuring the uptake of 14C, inline image, and inline image, and nitrification, and deployed sediment traps. At the start of the cruise (Phase 1) the carbon cycle was at steady state and the estimated net community production was 35(10) and 35(8) mmol C m−2 d−1 from inline image/Ar and 15N incubations, respectively, a remarkably good agreement. During Phase 1, net primary production was 96(27) mmol C m−2 d−1 from C uptake, and gross primary production was 209(17) mmol C m−2 d−1 from inline image. Later in the cruise (Phase 2), recently upwelled water with higher nutrient concentrations entered the study area, causing 14C and inline image uptake to increase substantially. Continuous inline image/Ar measurements revealed submesoscale variability in water mass structure and likely productivity in Phase 2 that was not evident from the incubations. These data demonstrate that inline image/Ar and inline image incubation-based NCP estimates can give equivalent results in an N-limited, coastal system, when the nonsteady state inline image fluxes are negligible or can be quantified.Funding for this work was provided by NSF awards OCE-1060840 to R.H.R. Stanley, OCE-1129644 to D.P. Nicholson, OCE-1357042 to F.P. Chavez, NASA award NNX14AI06G to M.R. Fewings, the David and Lucile Packard Foundation through their generous annual donation to the Monterey Bay Aquarium Research Institute, an Ocean Ventures Fund award from the WHOI Academic Programs Office to CC Manning, and graduate scholarships from NSERC and CMOS to CC Manning.2017-09-1

PCIM:a project control and inhibiting‐factors management model

In construction projects, the aim of project control is to ensure projects finish on time, within budget, and achieve other project objectives. During the last few decades, numerous project control methods have been developed and adopted by project managers in practice. However, many existing methods focus on describing what the processes and tasks of project control are; not on how these tasks should be conducted. There is also a potential gap between principles that underly these methods and project control practice. As a result, time and cost overruns are still common in construction projects, partly attributable to deficiencies of existing project control methods and difficulties in implementing them. This paper describes a new project cost and time control model, the project control and inhibiting factors management (PCIM) model, developed through a study involving extensive interaction with construction practitioners in the UK, which better reflects the real needs of project managers. A set of good practice checklist is also developed to facilitate implementation of the model

Experiences of domestic violence prevention interventions and gender equality promotion work: a qualitative study of Nirdhar Groups in rural India [version 1; peer review: awaiting peer review]

Domestic violence and abuse (DVA) against women in India is a serious concern. To address this, community-based interventions to facilitate sustained change at local levels have been implemented in 37 villages by the Halo Medical Foundation (an NGO working in the Maharashtra state of India). This qualitative study of community led alliances (known as Nirdhar Groups) evaluates the experiences of these ‘community citizen groups’. Participants from 12 villages from the project area participated in qualitative focus group discussions. Nirdhar Groups used local interventions to address priorities such as safe and equal access to education and healthcare. They offered education to address financial oppression and used community pressure and ‘Responsible Couples’ as mechanisms for change, to instil ‘fairness, gender equality, kind and compassionate community values’ and a variety of techniques to reduce DVA. The drivers for change included role modelling, empowerment of women in communities and a focus on changing cultural practices for present and future generations. This paper reveals how local interventions empower communities to address gender disparities and DV

Design management: changing roles of the professions

This paper sets out to explore how recent changes in procurement in construction have affected the roles that professions play in the design process. It discusses how professions that traditionally took the role of design manager now find themselves participating within previously unforeseen contexts, working in multidisciplinary teams led by contractors and with changed responsibilities at the design stage. Supply chain members who were not previously involved during the early project phases are being engaged at the earliest phases of the project life cycle and even taking leadership roles while designers sometimes work as supply chain partners. A study of design in construction and other sectors shows that in dealing with design management issues it is critical to deepen appreciation for the unique characteristics of design and the design process. The paper argues that contractors and designers taking on design management roles in a dynamic industry seeking to explore best practice and innovative approaches to procurement and in the delivery of projects need to acquire new skills, management education and develop the necessary qualities

Stakeholder perceptions of the benefits and barriers of implementing environmental management systems in the Nigerian construction industry

© 2016 Vilnius Gediminas Technical University (VGTU) Press. This study investigates stakeholder opinions of the major benefits and barriers of Environmental Management Systems (EMS) to the Nigerian construction industry, and the perceived issues to EMS adoption among organisations in the industry. The study highlights the environment as an important stakeholder in the industry because it affects and is affected by construction activities on a regular basis. It identifies the importance of ISO 14001 in ensuring adequate consideration for the environment is maintained on construction projects. The research adopts a quantitative approach by analysing responses from an online survey among construction industry professionals in Nigeria. The questions on the survey were drawn from a similar study carried out in Asia and the results were analysed using the Weighted Average and Standard Deviation statistical approach. Results reveal that the major benefits of EMS to the Nigerian construction industry were improved efficiency in waste management and environmental protection, as well as an overall increase in employee motivation due to better opportunities for training and development. Lack of technological support in organisations and the high cost of implementing EMS were viewed as the major barriers towards its uptake in construction companies. The findings also indicate that a feasible EMS implementation strategy must not ignore the unique nature of the Nigerian construction industry, which comprises mostly small and medium enterprises. The study concludes by recommending the use of a waste management plan based on the Reuse-Reduce-Recycle-Recover model and an employee training plan to ensure continuous improvement in the organisation’s environmental management strategy

A framework to assist in the analysis of risks and rewards of adopting BIM for SMEs in the UK

© 2017 The Author(s) Published by VGTU Press and Informa UK Limited, [trading as Taylor & Francis Group]. Building information modelling (BIM) adoption amongst larger construction firms and innovators seems to be on the increase. However, there is evidence to suggest that small and medium sized enterprises (SMEs) are currently lagging behind and are losing out in winning publicly funded projects. Guidance and frameworks to assist SMEs to make an informed decision about BIM adoption are currently lacking. There has been no systematic effort to date to bring together the results of research in SMEs’ BIM adoption. Consequently, this paper seeks to bridge this gap and provide a conceptual framework to give a theoretical foundation to the study of brokering risks and rewards in the adoption of BIM for project delivery. This framework is comprehensive and includes trading off risks and rewards associated with several criteria, such as stage of involvement, project value, funding, and the procurement route chosen. The approach has been validated by a representative sample of BIM users and the findings of the validation are also presented. The findings of the framework validation reveal that early design stage, project size between £5 m and £50 m, private funding, and integrated project delivery procurement are the best opportunities that enable SMEs to maximise the benefits and minimise the risks, when adopting BIM

A functionally impaired missense variant identified in French Canadian families implicates FANCI as a candidate ovarian cancer-predisposing gene.

BACKGROUND: Familial ovarian cancer (OC) cases not harbouring pathogenic variants in either of the BRCA1 and BRCA2 OC-predisposing genes, which function in homologous recombination (HR) of DNA, could involve pathogenic variants in other DNA repair pathway genes. METHODS: Whole exome sequencing was used to identify rare variants in HR genes in a BRCA1 and BRCA2 pathogenic variant negative OC family of French Canadian (FC) ancestry, a population exhibiting genetic drift. OC cases and cancer-free individuals from FC and non-FC populations were investigated for carrier frequency of FANCI c.1813C>T; p.L605F, the top-ranking candidate. Gene and protein expression were investigated in cancer cell lines and tissue microarrays, respectively. RESULTS: In FC subjects, c.1813C>T was more common in familial (7.1%, 3/42) than sporadic (1.6%, 7/439) OC cases (P = 0.048). Carriers were detected in 2.5% (74/2950) of cancer-free females though female/male carriers were more likely to have a first-degree relative with OC (121/5249, 2.3%; Spearman correlation = 0.037; P = 0.011), suggesting a role in risk. Many of the cancer-free females had host factors known to reduce risk to OC which could influence cancer risk in this population. There was an increased carrier frequency of FANCI c.1813C>T in BRCA1 and BRCA2 pathogenic variant negative OC families, when including the discovery family, compared to cancer-free females (3/23, 13%; OR = 5.8; 95%CI = 1.7-19; P = 0.005). In non-FC subjects, 10 candidate FANCI variants were identified in 4.1% (21/516) of Australian OC cases negative for pathogenic variants in BRCA1 and BRCA2, including 10 carriers of FANCI c.1813C>T. Candidate variants were significantly more common in familial OC than in sporadic OC (P = 0.04). Localization of FANCD2, part of the FANCI-FANCD2 (ID2) binding complex in the Fanconi anaemia (FA) pathway, to sites of induced DNA damage was severely impeded in cells expressing the p.L605F isoform. This isoform was expressed at a reduced level, destabilized by DNA damaging agent treatment in both HeLa and OC cell lines, and exhibited sensitivity to cisplatin but not to a poly (ADP-ribose) polymerase inhibitor. By tissue microarray analyses, FANCI protein was consistently expressed in fallopian tube epithelial cells and only expressed at low-to-moderate levels in 88% (83/94) of OC samples. CONCLUSIONS: This is the first study to describe candidate OC variants in FANCI, a member of the ID2 complex of the FA DNA repair pathway. Our data suggest that pathogenic FANCI variants may modify OC risk in cancer families

Characterization of the macrophage transcriptome in glomerulonephritis-susceptible and -resistant rat strains

Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. WKY rats show marked susceptibility to CRGN, while Lewis rats are resistant. Glomerular injury and crescent formation are macrophage-dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterised Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% False Discovery Rate) for basal and LPS-stimulated macrophages. Moreover, we identified 8 genes with differentially expressed alternatively spliced isoforms, by using an in depth analysis at probe-level that allowed us to discard false positives due to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7, and define groups of genes that play a significant role in differential regulation of macrophage activity