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Aims Treatment of patients with heart failure (HF) relies on measurement of LVEF. However, the extent to which EF is recorded varies markedly. We sought to characterize the patient group that is missing a measure of EF, and to explore the association between missing EF and outcome. Methods and results Individual data on 30 445 patients from 28 observational studies in the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) project were used to compare the prevalence of co-morbidities and outcome across three groups of HF patients: those with missing EF (HF-mEF), reduced EF (HF-REF), and preserved EF (HF-PEF). A total of 29% had HF-mEF, 52% HF-REF, and 19% HF-PEF. Compared with patients in whom EF was known, patients with HF-mEF were older, had a greater prevalence of COPD and previous stroke, and were smokers. Patients with HF-mEF were less likely to receive evidence-based treatment than those with HF-REF. Adjusted mortality in HF-mEF was similar to that in HF-REF and greater than that in HF-PEF at 3 years [HF-REF, hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.95–1.12); HF-PEF, HR 0.78, 95% CI 0.71–0.86]. Conclusion Missing EF is common. The short- and long-term outcome of patients with HF-mEF is poor and they exhibit different co-morbidity profiles and treatment patterns compared with patients with known EF. HF patients with missing EF represent a high risk group.

We hypothesize that phytoplankton have the sequential nutrient uptake strategy to maintain nutrient stoichiometry and high primary productivity in the water column. According to this hypothesis, phytoplankton take up the most limiting nutrient first until depletion, continue to draw down non-limiting nutrients and then take up the most limiting nutrient rapidly when it is available. These processes would result in the variation of ambient nutrient ratios in the water column around the Redfield ratio. We used high-resolution continuous vertical profiles of nutrients, nutrient ratios and on-board ship incubation experiments to test this hypothesis in the Strait of Georgia. At the surface in summer, ambient NO3− was depleted with excess PO43− and SiO4− remaining, and as a result, both N : P and N : Si ratios were low. The two ratios increased to about 10 : 1 and 0. 45 : 1, respectively, at 20 m. Time series of vertical profiles showed that the leftover PO43− continued to be removed, resulting in additional phosphorus storage by phytoplankton. The N : P ratios at the nutricline in vertical profiles responded differently to mixing events. Field incubation of seawater samples also demonstrated the sequential uptake of NO3− (the most limiting nutrient) and then PO43− and SiO4− (the non-limiting nutrients). This sequential uptake strategy allows phytoplankton to acquire additional cellular phosphorus and silicon when they are available and wait for nitrogen to become available through frequent mixing of NO3− (or pulsed regenerated NH4). Thus, phytoplankton are able to maintain high productivity and balance nutrient stoichiometry by taking advantage of vigorous mixing regimes with the capacity of the stoichiometric plasticity. To our knowledge, this is the first study to show the in situ dynamics of continuous vertical profiles of N : P and N : Si ratios, which can provide insight into the in situ dynamics of nutrient stoichiometry in the water column and the inference of the transient status of phytoplankton nutrient stoichiometry in the coastal ocean.

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. http://purl.org/eprint/status/PeerReviewed published version Article

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction. B.C.A.C. was funded through a European Community Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS); Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692); the National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), R01 grants (CA128978, CA176785, CA192393), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative); the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Breast Cancer Res. Foundation, and the Ovarian Cancer Research Fund. CIMBA genotyping was supported by National Institutes of Health grant (CA128978); the Department of Defence (W81XWH-10-1-0341); and the Breast Cancer Res. Foundation. CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. This study made use of data generated by the Wellcome Trust Case Control consortium. Functional studies were supported by the Florida Breast Cancer Foundation. A full description of funding and acknowledgments is provided in Supplementary Note 1.

Group A flavin-dependent monooxygenases catalyze the cleavage of the oxygen-oxygen bond of dioxygen, followed by the incorporation of one oxygen atom into the substrate molecule with the aid of NADPH and FAD. These flavoenzymes play an important role in many biological processes, and their most distinct structural feature is the choreographed motions of flavin, which typically adopts two distinct conformations (OUT and IN) to fulfill its function. Notably, these enzymes seem to have evolved a delicate control system to avoid the futile cycle of NADPH oxidation and FAD reduction in the absence of substrate, but the molecular basis of this system remains elusive. Using protein crystallography, size-exclusion chromatography coupled to multi-angle light scattering (SEC-MALS), and small-angle X-ray scattering (SEC-SAXS) and activity assay, we report here a structural and biochemical characterization of PieE, a member of the Group A flavin-dependent monooxygenases involved in the biosynthesis of the antibiotic piericidin A1. This analysis revealed that PieE forms a unique hexamer. Moreover, we found, to the best of our knowledge for the first time, that in addition to the classical OUT and IN conformations, FAD possesses a "sliding" conformation that exists in between the OUT and IN conformations. This observation sheds light on the underlying mechanism of how the signal of substrate binding is transmitted to the FAD-binding site to efficiently initiate NADPH binding and FAD reduction. Our findings bridge a gap currently missing in the orchestrated order of chemical events catalyzed by this important class of enzymes.

Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis. Communications Biology, 3 (1) ISSN:2399-3642

Abstract Economically important manganese deposits are hosted in the Middle Permian Maokou Formation of Zunyi, northern Guizhou, South China. During the Middle Permian, the intense rifting related to the initial stage of the Emeishan Large Igneous Province (ELIP) led to the development of carbonate platforms and inter-platform troughs. The manganese deposits occur in the transitional zone between carbonate platforms and troughs. Previous studies emphasized that the hydrothermal activities at the bottom of the trough basin controlled the formation of manganese deposits. In this study, new sedimentary, mineralogical, and stable isotope evidence are acquired from this manganese deposit, indicating that the microbially-mediated metallogenic mechanism also made an important contribution for the Middle Permian manganese deposition. The metallogenesis of this manganese deposit is highly like the combination of hydrothermal and microbial processes. Manganese ores in Zunyi are manganese carbonate, showing massive and clastic structures, no macroscopic nor microscopic lamination are found, samples are coarse-grained, diagenetically recrystallized with abundant mineralized microbial and microfossil biosignatures. FTIR, EPMA, and Raman analyses recognize micrometer-scale cyclic mineralogical assembly and help reconstruct the proposed new model of microbial manganese metallogenesis. Hydrothermal activity in the basin provided dissolved Mn 2+ ions into the anoxic basal watermass. In the syngenetic stage, microbial systems could be subdivided into three categories: (1) cyanobacterial system, (2) Mn-biomat system and (3) Fe-biomat system. Cyanobacterial activity led to the precipitation of calcite, and it could be partially affected by Mn-metasomatism and transformed to Mn-bearing calcite. Mn-oxidizing microbes led to the precipitation of manganese bio-oxide (δ-MnO2) near the redoxcline of the basin. Fe-biomat system was responsible for the precipitation of Fe-oxides (hematite) and Fe-hydroxides (ferrihydrite and lepidocrocite). After burial, manganese oxides reacted with the organic matter in the sediments through the microbially-mediated processes during the early diagenesis and the Mn-metasomatism of the cyanobacterial carbonate jointly contributed to formation of early diagenetic manganese carbonate ore. The redox fluctuations between oxic/suboxic and anoxic zones led to the re-oxidation process and resulted in cyclic marcasite. Anatase cycles observed in samples were interpreted as the diagenetic product of Fe-biomat system.

According to the core accretion theory, circumbinary embryos can form only beyond a critical semimajor axis (CSMA). However, due to the relatively high density of solid materials in the inner disk, significant amount of small planetesimals must exist in the inner zone when embryos were forming outside this CSMA. So embryos migration induced by the planetesimal swarm is possible after the gas disk depletion. Through numerical simulations, we found (i) the scattering-driven inward migration of embryos is robust, planets can form in the habitable zone if we adopt a mass distribution of MMSN-like disk; (ii) the total mass of the planetesimals in the inner region and continuous embryo-embryo scattering are two key factors that cause significant embryo migrations; (iii) the scattering-driven migration of embryos is a natural water-deliver mechanism. We propose that planet detections should focus on the close binary with its habitable zone near CSMA. Comment: Accepted for publication at ApJL

Abstract Tetracycline hydrochloride (TCH), as a typical antibiotic-pollutant, is desired to enhance its removal from public environment, due to its toxicity and persistence. Microbial electrochemical technology (MET) is a series complex microorganisms-driven processes with characteristics of simultaneous wastewater treatment and electricity generation. The study was presented to evaluate the TCH removal behavior and power generation performance through the co-metabolism under constant glucose with different TCH concentrations using MET. It was found that the TCH removal efficiency arrived at 40% during the first 6 h, when TCH concentrations ranged from 1 to 50 mg/L. It was interesting that TCH degradation rate increased to a maximum of 4.15 × 10−2 h−1 with its concentrations varying from 1 to 20 mg/L, however, the further increase to 50 mg/L in TCH concentration resulted in a reverse 66% reduction. In the meantime, the generated bioelectricity declared a similar fluctuation trend with a maximum power density of 600 mW/m2 under the condition of 20 mg/L TCH co-degradation with glucose. What's more, the TCH inhibition effect fitted well with Haldane's model, indicating that the microbial electrochemical system had a better potency toward TCH toxicity than that reported (EC50 = 2.2 mg/L). Thauera as mainly functional aromatics-degrading bacteria and Bdellovibrio against bacterial pathogens, only existed in the mixed cultures with TCH and glucose, indicating extremely remarkable changes in bacterial community with TCH addition. In summary, a new approach for the anaerobic biodegradation of TCH was explored through co-metabolism with glucose using MET. The results should be useful for antibiotics wastewater disposal of containing TCH.