A meta-analysis of amino acid δ\u3csup\u3e15\u3c/sup\u3eN trophic enrichment factors in fishes relative to nutritional and ecological drivers

The use of amino acid (AA) nitrogen stable isotopes (δ15N) from consumer tissues aims to provide precise estimates of trophic position (TP), but the drivers of AA isotope fractionation remain unclear. In particular, the main factors driving the variability in TEFAA among taxonomic groups and trophic levels remain largely unexplained, which challenges the application of universal values for TEFs. While the relationship between protein content and quality and TEFs has been examined, studies have yielded inconsistent results, and the role of protein and lipid nutritional requirements as well as feeding regime have not been considered. Likewise, drivers that influence physiological and nutritional processes have not been examined relative to TEFAA variation. We conducted a meta-analysis of controlled feeding experiments within a single group, teleosts fishes, to evaluate the relationship between five nutritional factors (protein and lipid content, protein and lipid content relative to nutritional requirements, and feeding regime) and three ecological drivers (diet type, life stage, and habitat type) on TEFAA. We considered a broad range of protein levels (8–71%) in diets and found no relationship between source TEFAAs and percent protein relative to nutritional requirements, whereas lipid content relative to nutrient requirements, feeding regime and habitat type partially explain the variability in TEFs of Lys, but not for Phe and Met TEFs. The variability for the latter was representative of robust source AAs. Among trophic AAs, Asp, Ile, Pro, and Leu TEFs were significantly higher in species from brackish than marine habitats possibly due to osmoregulation involvement. TEFGlu was sensitive to protein content and feeding regime within teleosts, but relatively constant when comparing TEFs among teleosts, non-teleosts, and all taxa. Our results indicate that TEFAA is less variable within a single taxon than among multiple taxa and that such variation is not negligible. Our results indicate that δ15NAA values could provide better TP estimates if using taxon-specific values, and highlights the need to explain the mechanisms of AA fractionation and quantify the variability in TEFs used during error propagation for TP estimates

The effect of an e-health intervention designed to reduce prolonged occupational sitting on mean arterial pressure

Objective: To evaluate the effect of a workplace health intervention designed to reduce prolonged occupational sitting on the mean arterial pressure (MAP) of desk-based employees. Methods: This randomized controlled trial involved an experimental group who received an e-health intervention and a control group who did not. The 13-week intervention passively prompted participants to stand and engage in short bouts of office-based physical activity by interrupting prolonged occupational sitting time periodically throughout the workday. Mean arterial pressure was measured at pretest and posttest. Results: Between pretest and posttest the experimental group significantly reduced their MAP, whereas MAP in the control group did not. Conclusions: A workplace e-health intervention designed to reduce prolonged occupational sitting was effective in decreasing MAP in desk-based employees

Synthetic oligosaccharides can replace animal-sourced low–molecular weight heparins

Full-sized and low–molecular weight heparins are widely used to treat a variety of clotting disorders. Although low–molecular weight heparins are safer and more convenient to use than full-size heparin, they are still animal-derived products that present a risk of contamination and supply chain interruptions and are limited with respect to standardization and reversibility of anticoagulation. A method developed by Xu et al . offers a potential alternative to animal-sourced heparins in the form of a chemical synthesis process that can be scaled up to produce heparin dodecasaccharides with reversible activity in adequate quantities for potential therapeutic use

Magnetism and superconductivity of uranium and intermetallic compounds

Heat capacity, resistivity, and phonon density of states have been measured on uranium and reported already. Many of the results are on single crystals of purity that has been unavailable before. Some intermetallic compounds have been measured that are in the class of so-called heavy-fermion materials. We present here the latest results along with a discussion of the occurrence of superconductivity or magnetism in these materials

Molecular Typing of Australian Scedosporium Isolates Showing Genetic Variability and Numerous S. aurantiacum

Molecular typing showed genetic diversity, dismissed 2 suspected outbreaks of scedosporiosis, and identified multiple strains of the newly described species S. aurantiacum

Genomic analysis of oceanic cyanobacterial myoviruses compared with T4-like myoviruses from diverse hosts and environments

T4-like myoviruses are ubiquitous, and their genes are among the most abundant documented in ocean systems. Here we compare 26 T4-like genomes, including 10 from non-cyanobacterial myoviruses, and 16 from marine cyanobacterial myoviruses (cyanophages) isolated on diverse Prochlorococcus or Synechococcus hosts. A core genome of 38 virion construction and DNA replication genes was observed in all 26 genomes, with 32 and 25 additional genes shared among the non-cyanophage and cyanophage subsets, respectively. These hierarchical cores are highly syntenic across the genomes, and sampled to saturation. The 25 cyanophage core genes include six previously described genes with putative functions (psbA,mazG, phoH, hsp20, hli03, cobS), a hypothetical protein with a potential phytanoyl-CoA dioxygenase domain, two virion structural genes, and 16 hypothetical genes. Beyond previously described cyanophageencoded photosynthesis and phosphate stress genes, we observed core genes that may play a role in nitrogen metabolism during infection through modulation of 2-oxoglutarate. Patterns among non-core genes that may drive niche diversification revealed that phosphorus-related gene content reflects source waters rather than host strain used for isolation, and that carbon metabolism genes appear associated with putative mobile elements. As well, phages isolated on Synechococcus had higher genome-wide %G+C and often contained different gene subsets (e.g. petE, zwf, gnd, prnA, cpeT) than those isolated on Prochlorococcus. However, no clear diagnostic genes emerged to distinguish these phage groups, suggesting blurred boundaries possibly due to cross-infection. Finally, genome-wide comparisons of both diverse and closely related, co-isolated genomes provide a locus-to-locus variability metric that will prove valuable forinterpreting metagenomic data sets.Gordon and Betty Moore FoundationNational Science Foundation (U.S.)Massachusetts Institute of Technology. Undergraduate Research Opportunities ProgramUnited States. Dept. of Energy. Genomics:GTLNational Science Foundation (U.S.) (DBI-0850105)University of Arizona (Fulbright Scholarship)University of Arizona (BIO5 and Biosphere 2 funds)National Institute of Environmental Health Sciences (1-P50-ES012742)National Science Foundation (U.S.) (OCE-0430724

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

A comprehensive analysis of common genetic variation around six candidate loci for intrahepatic cholestasis of pregnancy.

OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) has a complex etiology with a significant genetic component. Heterozygous mutations of canalicular transporters occur in a subset of ICP cases and a population susceptibility allele (p.444A) has been identified in ABCB11. We sought to expand our knowledge of the detailed genetic contribution to ICP by investigation of common variation around candidate loci with biological plausibility for a role in ICP (ABCB4, ABCB11, ABCC2, ATP8B1, NR1H4, and FGF19). METHODS: ICP patients (n=563) of white western European origin and controls (n=642) were analyzed in a case-control design. Single-nucleotide polymorphism (SNP) markers (n=83) were selected from the HapMap data set (Tagger, Haploview 4.1 (build 22)). Genotyping was performed by allelic discrimination assay on a robotic platform. Following quality control, SNP data were analyzed by Armitage's trend test. RESULTS: Cochran-Armitage trend testing identified six SNPs in ABCB11 together with six SNPs in ABCB4 that showed significant evidence of association. The minimum Bonferroni corrected P value for trend testing ABCB11 was 5.81×10(-4) (rs3815676) and for ABCB4 it was 4.6×10(-7)(rs2109505). Conditional analysis of the two clusters of association signals suggested a single signal in ABCB4 but evidence for two independent signals in ABCB11. To confirm these findings, a second study was performed in a further 227 cases, which confirmed and strengthened the original findings. CONCLUSIONS: Our analysis of a large cohort of ICP cases has identified a key role for common variation around the ABCB4 and ABCB11 loci, identified the core associations, and expanded our knowledge of ICP susceptibility

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension