Asymmetric Genome Organization in an RNA Virus Revealed via Graph-Theoretical Analysis of Tomographic Data

Cryo-electron microscopy permits 3-D structures of viral pathogens to be determined in remarkable detail. In particular, the protein containers encapsulating viral genomes have been determined to high resolution using symmetry averaging techniques that exploit the icosahedral architecture seen in many viruses. By contrast, structure determination of asymmetric components remains a challenge, and novel analysis methods are required to reveal such features and characterize their functional roles during infection. Motivated by the important, cooperative roles of viral genomes in the assembly of single-stranded RNA viruses, we have developed a new analysis method that reveals the asymmetric structural organization of viral genomes in proximity to the capsid in such viruses. The method uses geometric constraints on genome organization, formulated based on knowledge of icosahedrally-averaged reconstructions and the roles of the RNA-capsid protein contacts, to analyse cryo-electron tomographic data. We apply this method to the low-resolution tomographic data of a model virus and infer the unique asymmetric organization of its genome in contact with the protein shell of the capsid. This opens unprecedented opportunities to analyse viral genomes, revealing conserved structural features and mechanisms that can be targeted in antiviral drug desig

Moisture transport by Atlantic tropical cyclones onto the North American continent

Tropical Cyclones (TCs) are an important source of freshwater for the North American continent. Many studies have tried to estimate this contribution by identifying TC-induced precipitation events, but few have explicitly diagnosed the moisture fluxes across continental boundaries. We design a set of attribution schemes to isolate the column-integrated moisture fluxes that are directly associated with TCs and to quantify the flux onto the North American Continent due to TCs. Averaged over the 2004–2012 hurricane seasons and integrated over the western, southern and eastern coasts of North America, the seven schemes attribute 7 to 18 % (mean 14 %) of total net onshore flux to Atlantic TCs. A reduced contribution of 10 % (range 9 to 11 %) was found for the 1980–2003 period, though only two schemes could be applied to this earlier period. Over the whole 1980–2012 period, a further 8 % (range 6 to 9 % from two schemes) was attributed to East Pacific TCs, resulting in a total TC contribution of 19 % (range 17 to 22 %) to the ocean-to-land moisture transport onto the North American continent between May and November. Analysis of the attribution uncertainties suggests that incorporating details of individual TC size and shape adds limited value to a fixed radius approach and TC positional errors in the ERA-Interim reanalysis do not affect the results significantly, but biases in peak wind speeds and TC sizes may lead to underestimates of moisture transport. The interannual variability does not appear to be strongly related to the El Nino-Southern Oscillation phenomenon

Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk

Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. © 2008 Ding et al

The eMERGE Network: A consortium of biorepositories linked to electronic medical records data for conducting genomic studies

<p>Abstract</p> <p>Introduction</p> <p>The eMERGE (electronic MEdical Records and GEnomics) Network is an NHGRI-supported consortium of five institutions to explore the utility of DNA repositories coupled to Electronic Medical Record (EMR) systems for advancing discovery in genome science. eMERGE also includes a special emphasis on the ethical, legal and social issues related to these endeavors.</p> <p>Organization</p> <p>The five sites are supported by an Administrative Coordinating Center. Setting of network goals is initiated by working groups: (1) Genomics, (2) Informatics, and (3) Consent & Community Consultation, which also includes active participation by investigators outside the eMERGE funded sites, and (4) Return of Results Oversight Committee. The Steering Committee, comprised of site PIs and representatives and NHGRI staff, meet three times per year, once per year with the External Scientific Panel.</p> <p>Current progress</p> <p>The primary site-specific phenotypes for which samples have undergone genome-wide association study (GWAS) genotyping are cataract and HDL, dementia, electrocardiographic QRS duration, peripheral arterial disease, and type 2 diabetes. A GWAS is also being undertaken for resistant hypertension in ≈2,000 additional samples identified across the network sites, to be added to data available for samples already genotyped. Funded by ARRA supplements, secondary phenotypes have been added at all sites to leverage the genotyping data, and hypothyroidism is being analyzed as a cross-network phenotype. Results are being posted in dbGaP. Other key eMERGE activities include evaluation of the issues associated with cross-site deployment of common algorithms to identify cases and controls in EMRs, data privacy of genomic and clinically-derived data, developing approaches for large-scale meta-analysis of GWAS data across five sites, and a community consultation and consent initiative at each site.</p> <p>Future activities</p> <p>Plans are underway to expand the network in diversity of populations and incorporation of GWAS findings into clinical care.</p> <p>Summary</p> <p>By combining advanced clinical informatics, genome science, and community consultation, eMERGE represents a first step in the development of data-driven approaches to incorporate genomic information into routine healthcare delivery.</p

Impacts of 4D BIM on Construction Project Performance

A significant proportion of construction projects are failing to achieve their deadline finish dates. This advocate for solutions that could address the root causes of time impacting risks, leading to the use of 4D BIM for project planning. This study investigates the impacts of 4D BIM on construction projects. An exploratory sequential mixed method research was conducted to initially explore the topic via interviews and literature review, and, subsequently, the themes derived were put into questionnaires to elicit expert knowledge on a wider industry scale. The data were analysed using thematic analysis, reliability analysis, Kruskal-Wallis test and factor analysis. Across the objectives around the impacts of 4D BIM on project reliability, monitoring and diagnosis, the findings presented eight key ways the 4D BIM support project performance. Examples of component factors that were raised was planning efficiency to enhance planner output, assessment and directive with a better comparison of planned and actual progress, and thorough/comprehensive risk reflection to cover wide ranges of issues. Upon further reflection, the finding highlighted the issues of the lack of shared responsibility outside of the planner and BIM coordinator, severe lack of understanding and training regarding 4D BIM and complexity of carrying out the process effectively

Mechanical and Assembly Units of Viral Capsids Identified via Quasi-Rigid Domain Decomposition

Key steps in a viral life-cycle, such as self-assembly of a protective protein container or in some cases also subsequent maturation events, are governed by the interplay of physico-chemical mechanisms involving various spatial and temporal scales. These salient aspects of a viral life cycle are hence well described and rationalised from a mesoscopic perspective. Accordingly, various experimental and computational efforts have been directed towards identifying the fundamental building blocks that are instrumental for the mechanical response, or constitute the assembly units, of a few specific viral shells. Motivated by these earlier studies we introduce and apply a general and efficient computational scheme for identifying the stable domains of a given viral capsid. The method is based on elastic network models and quasi-rigid domain decomposition. It is first applied to a heterogeneous set of well-characterized viruses (CCMV, MS2, STNV, STMV) for which the known mechanical or assembly domains are correctly identified. The validated method is next applied to other viral particles such as L-A, Pariacoto and polyoma viruses, whose fundamental functional domains are still unknown or debated and for which we formulate verifiable predictions. The numerical code implementing the domain decomposition strategy is made freely available

Associations Between Neighborhood-Level Factors Related to a Healthful Lifestyle and Dietary Intake, Physical Activity, and Support for Obesity Prevention Polices Among Rural Adults

PURPOSE: To examine cross-sectional associations among neighborhood- and individual-level factors related to a healthful lifestyle and dietary intake, physical activity (PA), and support for obesity prevention polices in rural eastern North Carolina adults. METHODS: We examined perceived neighborhood barriers to a healthful lifestyle, and associations between neighborhood barriers to healthy eating and PA, participants’ support for seven obesity prevention policies, and dependent variables of self-reported dietary and PA behaviors, and measured body mass index (BMI) (n = 366 study participants). We then used participants’ residential addresses and Geographic Information Systems (GIS) software to assess neighborhood-level factors related to access to healthy food and PA opportunities. Correlational analyses and adjusted linear regression models were used to examine associations between neighborhood-level factors related to a healthful lifestyle and dietary and PA behaviors, BMI, and obesity prevention policy support. RESULTS: The most commonly reported neighborhood barriers (from a list of 18 potential barriers) perceived by participants included: not enough bicycle lanes and sidewalks, not enough affordable exercise places, too much crime, and no place to buy a quick, healthy meal to go. Higher diet quality was inversely related to perceived and GIS-assessed neighborhood nutrition barriers. There were no significant associations between neighborhood barriers and PA. More perceived neighborhood barriers were positively associated with BMI. Support for obesity prevention policy change was positively associated with perceptions of more neighborhood barriers. CONCLUSIONS: Neighborhood factors that promote a healthful lifestyle were associated with higher diet quality and lower BMI. Individuals who perceived more neighborhood-level barriers to healthy eating and PA usually supported policies to address those barriers. Future studies should examine mechanisms to garner such support for health-promoting neighborhood changes

Clinical characteristics and role of early cardiac magnetic resonance imaging in patients with suspected ST-elevation myocardial infarction and normal coronary arteries

A variety of conditions other than acute myocardial infarction may cause ST-elevation. Our objective was to evaluate the impact of cardiac magnetic resonance (CMR) on differential diagnosis from a prospective series of patients with suspected ST-elevation myocardial infarction (STEMI) and completely normal coronary arteries. Among 1,145 patients with suspected STEMI, 49 patients had completely normal coronary arteries and entered a prospective registry. CMR was done within 24 h, if possible, and included function analyses, T2-weighted imaging (T2 ratio), T1-weighted imaging before and after gadolineum administration (global relative enhancement; gRE), and late gadolineum enhancement (LGE). All patients were asked for a follow-up CMR after approximately 3 months. The incidence of patients with suspected STEMI and normal coronary arteries was 4.3% and mean age was 45 ± 14 years (STEMI group 64 ± 13 years; P < 0.001). 55% had a recent history of infection. Cardiac biomarkers showed a moderate elevation on admission. There was a significant change from baseline to follow-up for LV end-diastolic volumes (EDV) (P < 0.001), LV mass (P < 0.05), mean T2 ratio (P < 0.05), and LGE volume (P < 0.05). Major diagnostic groups were myocarditis (29%), pericarditis (27%), and takotsubo cardiomyopathy (10%). 18% were regarded as non-diagnostic. The study showed an incidence of 4.3% of patients with suspected STEMI and completely normal coronary arteries. Early CMR was valuable in the evaluation of the differential diagnoses and to exclude myocardial abnormalities in patients with uncertain aetiology. Further studies are needed for the assessment of long-term outcome

Developing an agenda for research about policies to improve access to healthy foods in rural communities: a concept mapping study

Background Policies that improve access to healthy, affordable foods may improve population health and reduce health disparities. In the United States most food access policy research focuses on urban communities even though residents of rural communities face disproportionately higher risk for nutrition-related chronic diseases compared to residents of urban communities. The purpose of this study was to (1) identify the factors associated with access to healthy, affordable food in rural communities in the United States; and (2) prioritize a meaningful and feasible rural food policy research agenda. Methods This study was conducted by the Rural Food Access Workgroup (RFAWG), a workgroup facilitated by the Nutrition and Obesity Policy Research and Evaluation Network. A national sample of academic and non-academic researchers, public health and cooperative extension practitioners, and other experts who focus on rural food access and economic development was invited to complete a concept mapping process that included brainstorming the factors that are associated with rural food access, sorting and organizing the factors into similar domains, and rating the importance of policies and research to address these factors. As a last step, RFAWG members convened to interpret the data and establish research recommendations. Results Seventy-five participants in the brainstorming exercise represented the following sectors: non-extension research (n = 27), non-extension program administration (n = 18), “other� (n = 14), policy advocacy (n = 10), and cooperative extension service (n = 6). The brainstorming exercise generated 90 distinct statements about factors associated with rural food access in the United States; these were sorted into 5 clusters. Go Zones were established for the factors that were rated highly as both a priority policy target and a priority for research. The highest ranked policy and research priorities include strategies designed to build economic viability in rural communities, improve access to federal food and nutrition assistance programs, improve food retail systems, and increase the personal food production capacity of rural residents. Respondents also prioritized the development of valid and reliable research methodologies to measure variables associated with rural food access. Conclusions This collaborative, trans-disciplinary, participatory process, created a map to guide and prioritize research about polices to improve healthy, affordable food access in rural communities