Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.

Chromatin architecture has been implicated in cell type-specific gene regulatory programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries. The ability of HERV-H to create TAD boundaries depends on high transcription, as transcriptional repression of HERV-H elements prevents the formation of boundaries. This ability is not limited to hPSCs, as these actively transcribed HERV-H elements and their corresponding TAD boundaries also appear in pluripotent stem cells from other hominids but not in more distantly related species lacking HERV-H elements. Overall, our results provide direct evidence for retrotransposons in actively shaping cell type- and species-specific chromatin architecture

A school-based comprehensive lifestyle intervention among Chinese kids against Obesity (CLICK-Obesity) in Nanjing City, China: The baseline data

Background: urgent development of effective interventions to prevent rapidly rising childhood obesity in China is needed. Methods: Between May 2010 and December 2013, a cluster randomized controlled trial was conducted among 4 graders in eight urban primary schools randomly assigned to intervention or control groups in Nanjing, China. A multi-component intervention program was implemented within the treatment group, while students in the control group followed their usual health education curriculum without additional intervention. Results: At baseline, 638 and 544 students were enrolled in the intervention and control group, respectively. The prevalence of excess body weight was 26.8%, with 27.4% in the intervention group and 26.1% in the control group (p=0.61). The mean (SD) BMI and WC was 18.7 (3.0) and 63.0 (9.2) for participants in intervention schools, and 18.5 (2.9) and 63.6 (8.7) for students in control group, separately (p=0.24 and 0.41, respectively). Compared to those who were not aware of what lifestyle/behavior factors were unhealthy, students who were aware of the unhealthy lifestyle/ behavior factors consumed fewer fried snacks (0.46±0.76 serves/week vs 0.65±0.91 serves/week;

Community-acquired pneumonia in the United Kingdom:a call to action

Abstract Pneumococcal disease has a high burden in adults in the United Kingdom (UK); however, the total burden is underestimated, principally because most cases of community-acquired pneumonia (CAP) are non-invasive. Research into pneumonia receives poor funding relative to its disease burden (global mortality, disability-adjusted life years, and years lived with disability), ranking just 20 out of 25 for investment in infectious diseases in the UK. The current accuracy of data for establishing incidence rates is questionable, and it is a reflection of the paucity of research that much of the background information available derives from nearly 30 years ago. Given the relationship between CAP and mortality (pneumonia accounts for 29,000 deaths per annum in the UK, and 5–15% of patients hospitalised with CAP die within 30 days of admission), and the increasing threat of antimicrobial resistance associated with inappropriate antibiotic prescribing, such neglect of a highly prevalent problem is concerning. In this Call to Action, we explore the poorly understood burden of CAP in the UK, discuss the importance of an accurate diagnosis and appropriate treatment, and suggest how national collaboration could improve the management of an often life-threatening, yet potentially preventable disease

The polygenic nature of telomere length and the anti-ageing properties of lithium

Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10-5). Gene-enrichment analysis identified 13 genes associated with telomere length, with the most significant being the leucine rich repeat gene, LRRC34 (p = 3.69 × 10-18). In the context of lithium, we confirm that chronic use in a sample of 384 bipolar disorder patients is associated with longer telomeres (p = 0.03). As complementary evidence, we studied three orthologs of telomere length regulators in a Caenorhabditis elegans model of lithium-induced extended longevity and found all transcripts to be affected post-treatment (p  0.05). Consequently, this suggests that lithium may be catalysing the activity of endogenous mechanisms that promote telomere lengthening, whereby its efficacy eventually becomes limited by each individual's inherent telomere maintenance capabilities. Our work indicates a potential use of polygenic risk scoring for the prediction of adult telomere length and consequently lithium's anti-ageing efficacy

Factors Associated with Sleep Duration in Korean Adults: Results of a 2008 Community Health Survey in Gwangju Metropolitan City, Korea

Short (≤ 6 hr) and long (≥ 9 hr) sleep durations are both associated with risk factors for cardiovascular diseases and diabetes, depression, learning problems, accidents and excess mortality. However, little is known about factors associated with sleep duration in Korean adults. This study examined sleep patterns in Korean adults and identified factors associated with short and long sleep durations. This study analyzed cross-sectional data collected from 4,411 Korean adults aged 19 yr and older who participated in a community health survey conducted in Gwangju, Korea. Multinomial logistic regression analysis was used to identify associations between socio-demographic and health-related factors and short or long sleep durations. Of the population, 37.2% and 4.0% reported short and long sleep, respectively. Short sleep was associated with older age, lower levels of income, night or shift work, heavy smoking, and depression or anxiety; long sleep was associated with younger age, being divorced or widowed, heavy smoking, underweight, depression or anxiety, and poorer self-reported health. In conclusion, a relatively high prevalence of short sleep duration is identified in this population of Korean adults. Factors associated with short or long sleep may act as potential confounders of the relationship between sleep duration and health outcomes

Different atmospheric moisture divergence responses to extreme and moderate El Niños

On seasonal and inter-annual time scales, vertically integrated moisture divergence provides a useful measure of the tropical atmospheric hydrological cycle. It reflects the combined dynamical and thermodynamical effects, and is not subject to the limitations that afflict observations of evaporation minus precipitation. An empirical orthogonal function (EOF) analysis of the tropical Pacific moisture divergence fields calculated from the ERA-Interim reanalysis reveals the dominant effects of the El Niño-Southern Oscillation (ENSO) on inter-annual time scales. Two EOFs are necessary to capture the ENSO signature, and regression relationships between their Principal Components and indices of equatorial Pacific sea surface temperature (SST) demonstrate that the transition from strong La Niña through to extreme El Niño events is not a linear one. The largest deviation from linearity is for the strongest El Niños, and we interpret that this arises at least partly because the EOF analysis cannot easily separate different patterns of responses that are not orthogonal to each other. To overcome the orthogonality constraints, a self-organizing map (SOM) analysis of the same moisture divergence fields was performed. The SOM analysis captures the range of responses to ENSO, including the distinction between the moderate and strong El Niños identified by the EOF analysis. The work demonstrates the potential for the application of SOM to large scale climatic analysis, by virtue of its easier interpretation, relaxation of orthogonality constraints and its versatility for serving as an alternative classification method. Both the EOF and SOM analyses suggest a classification of “moderate” and “extreme” El Niños by their differences in the magnitudes of the hydrological cycle responses, spatial patterns and evolutionary paths. Classification from the moisture divergence point of view shows consistency with results based on other physical variables such as SST

Genetic Variation of Promoter Sequence Modulates XBP1 Expression and Genetic Risk for Vitiligo

Our previous genome-wide linkage analysis identified a susceptibility locus for generalized vitiligo on 22q12. To search for susceptibility genes within the locus, we investigated a biological candidate gene, X-box binding protein 1(XBP1). First, we sequenced all the exons, exon-intron boundaries as well as some 5′ and 3′ flanking sequences of XBP1 in 319 cases and 294 controls of Chinese Hans. Of the 8 common variants identified, the significant association was observed at rs2269577 (p_trend = 0.007, OR = 1.36, 95% CI = 1.09–1.71), a putative regulatory polymorphism within the promoter region of XBP1. We then sequenced the variant in an additional 365 cases and 404 controls and found supporting evidence for the association (p_trend = 0.008, OR = 1.31, 95% CI = 1.07–1.59). To further validate the association, we genotyped the variant in another independent sample of 1,402 cases and 1,288 controls, including 94 parent-child trios, and confirmed the association by both case-control analysis (p_trend = 0.003, OR = 1.18, 95% CI = 1.06–1.32) and the family-based transmission disequilibrium test (TDT, p = 0.005, OR = 1.93, 95% CI = 1.21–3.07). The analysis of the combined 2,086 cases and 1,986 controls provided highly significant evidence for the association (p_trend = 2.94×10−6, OR = 1.23, 95% CI = 1.13–1.35). Furthermore, we also found suggestive epistatic effect between rs2269577 and HLA-DRB1*07 allele on the development of vitiligo (p = 0.033). Our subsequent functional study showed that the risk-associated C allele of rs2269577 had a stronger promoter activity than the non-risk G allele, and there was an elevated expression of XBP1 in the lesional skins of patients carrying the risk-associated C allele. Therefore, our study has demonstrated that the transcriptional modulation of XBP1 expression by a germ-line regulatory polymorphism has an impact on the development of vitiligo

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO