Epistasis not needed to explain low dN/dS

An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a phenomenon known as epistasis. In a recent letter to Nature, Breen et al. (2012) argued that epistasis must be "pervasive throughout protein evolution" because the observed ratio between the per-site rates of non-synonymous and synonymous substitutions (dN/dS) is much lower than would be expected in the absence of epistasis. However, when calculating the expected dN/dS ratio in the absence of epistasis, Breen et al. assumed that all amino acids observed in a protein alignment at any particular position have equal fitness. Here, we relax this unrealistic assumption and show that any dN/dS value can in principle be achieved at a site, without epistasis. Furthermore, for all nuclear and chloroplast genes in the Breen et al. dataset, we show that the observed dN/dS values and the observed patterns of amino acid diversity at each site are jointly consistent with a non-epistatic model of protein evolution.Comment: This manuscript is in response to "Epistasis as the primary factor in molecular evolution" by Breen et al. Nature 490, 535-538 (2012

The 6-GHz multibeam maser survey III: comparison between the MMB and HOPS

We have compared the occurrence of 6.7-GHz and 12.2-GHz methanol masers with 22-GHz water masers and 6035-MHz excited-state OH masers in the 100 square degree region of the southern Galactic plane common to the Methanol Multibeam (MMB) and H2O southern Galactic Plane surveys (HOPS). We find the most populous star formation species to be 6.7-GHz methanol, followed by water, then 12.2-GHz and, finally, excited-state OH masers. We present association statistics, flux density (and luminosity where appropriate) and velocity range distributions across the largest, fully surveyed portion of the Galactic plane for four of the most common types of masers found in the vicinity of star formation regions. Comparison of the occurrence of the four maser types with far-infrared dust temperatures shows that sources exhibiting excited-state OH maser emission are warmer than sources showing any of the other three maser types. We further find that sources exhibiting both 6.7-GHz and 12.2-GHz methanol masers are warmer than sources exhibiting just 6.7-GHz methanol maser emission. These findings are consistent with previously made suggestions that both OH and 12.2-GHz methanol masers generally trace a later stage of star formation compared to other common maser types

Intermittent maser flare around the high mass young stellar object G353.273+0.641 I: data & overview

We have performed VLBI and single-dish monitoring of 22 GHz H$_{2}$O maser emission from the high mass young stellar object G353.273+0.641 with VERA (VLBI Exploration of Radio Astrometry) and Tomakamai 11-m radio telescope. Two maser flares have been detected, separated almost two years. Frequent VLBI monitoring has revealed that these flare activities have been accompanied by structural change of the prominent shock front traced by H2O maser alignments. We have detected only blue-shifted emissions and all maser features have been distributed within very small area of 200 $\times$ 200 au$^{2}$ in spite of wide velocity range (> 100 km s$^{-1}$). The light curve shows notably intermittent variation and suggests that the H$_{2}$O masers in G353.273+0.641 are excited by episodic radio jet. The time-scale of \sim2 yr and characteristic velocity of \sim500 km s$^{-1}$ also support this interpretation. Two isolated velocity components of C50 (-53 \pm 7 km s$^{-1}$) and C70 (-73 \pm 7 km s$^{-1}$) have shown synchronised linear acceleration of the flux weighted V_{\rmn{LSR}} values (\sim-5 km s$^{-1}$ yr$^{-1}$) during the flare phase. This can be converted to the lower-limit momentum rate of 1.1 \times 10$^{-3}$ M_{\sun} km s$^{-1}$ yr$^{-1}$. Maser properties are quite similar to that of IRAS 20126+4104 especially. This corroborates the previous suggestion that G353.273+0.641 is a candidate of high mass protostellar object. The possible pole-on geometry of disc-jet system can be suitable for direct imaging of the accretion disc in this case.Comment: 13 pages, 5 figures accepted for publication in MNRA

A new framework to enable equitable outcomes: resilience and nexus approaches combined

Managing integrated social-ecological systems to reduce risks to human and environmental well-being remains challenging in light of the rate and extent of undesirable changes that are occurring. Developing frameworks that are sufficiently integrative to guide research to deliver the necessary insights into all key system aspects is an important outstanding task. Among existing approaches, resilience and nexus framings both allow focus on unpacking relationships across scales and levels in a system and emphasize the involvement of different groups in decision making to different extents. They also suffer weaknesses and neither approach puts social justice considerations explicitly at its core. This has important implications for understanding who wins and loses out from different decisions and how social and ecological risks and trade-offs are shared and distributed, temporally and spatially. This paper conceptually integrates resilience and nexus approaches, developing a combined framework and indicating how it could effectively be operationalized in cases from mountain and mangrove social-ecological systems. In doing so, it advances understanding of complex social-ecological systems framings for risk-based decision making beyond that which could be achieved through use of either resilience or nexus approaches alone. Important next steps in testing the framework involve empirical and field operationalization, requiring interdisciplinary, mixed method approache

A small dose of whey protein co-ingested with mixed-macronutrient breakfast and lunch meals improves postprandial glycemia and suppresses appetite in men with type 2 diabetes: a randomized controlled trial.

Background: Large doses of whey protein consumed as a preload before single high-glycemic load meals has been shown to improve postprandial glycemia in type 2 diabetes. It is unclear if this effect remains with smaller doses of whey co-ingested at consecutive mixed-macronutrient meals. Moreover, whether hydrolyzed whey offers further benefit under these conditions is unclear. Objective: The aim of this study was to investigate postprandial glycemic and appetite responses after small doses of intact and hydrolyzed whey protein co-ingested with mixed-nutrient breakfast and lunch meals in men with type 2 diabetes. Design: In a randomized, single-blind crossover design, 11 men with type 2 diabetes [mean ± SD age: 54.9 ± 2.3 y; glycated hemoglobin: 6.8% ± 0.3% (51.3 ± 3.4 mmol/mol)] attended the laboratory on 3 mornings and consumed 1) intact whey protein (15 g), 2) hydrolyzed whey protein (15 g), or 3) placebo (control) immediately before mixed-macronutrient breakfast and lunch meals, separated by 3 h. Blood samples were collected periodically and were processed for insulin, intact glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), leptin, peptide tyrosine tyrosine (PYY3-36), and amino acid concentrations. Interstitial glucose was measured during and for 24 h after each trial. Subjective appetite was assessed with the use of visual analog scales. Results: Total postprandial glycemia area under the curve was reduced by 13% ± 3% after breakfast following the intact whey protein when compared with control (P  0.05). Conclusions: The consumption of a small 15-g dose of intact whey protein immediately before consecutive mixed-macronutrient meals improves postprandial glycemia, stimulates insulin release, and increases satiety in men with type 2 diabetes. This trial was registered at www.clinicialtrials.gov as NCT02903199

Proportional lumbar spine inter-vertebral motion patterns: a comparison of patients with chronic, non-specific low back pain and healthy controls

Introduction: Identifying biomechanical subgroups in chronic, non-specific low back pain (CNSLBP) populations from inter-vertebral displacements has proven elusive. Quantitative fluoroscopy (QF) has excellent repeatability and provides continuous standardised inter-vertebral kinematic data from fluoroscopic sequences allowing assessment of mid-range motion. The aim of this study was to determine whether proportional continuous IV rotational patterns were different in patients and controls. A secondary aim was to update the repeatability of QF measurement of range of motion (RoM) for inter-vertebral (IV) rotation

Properties of local interactions and their potential value in complementing genome-wide association studies

Local interactions between neighbouring SNPs are hypothesized to be able to capture variants missing from genome-wide association studies (GWAS) via haplotype effects but have not been thoroughly explored. We have used a new high-throughput analysis tool to probe this underexplored area through full pair-wise genome scans and conventional GWAS in diastolic and systolic blood pressure and six metabolic traits in the Northern Finland Birth Cohort 1966 (NFBC1966) and the Atherosclerosis Risk in Communities study cohort (ARIC). Genome-wide significant interactions were detected in ARIC for systolic blood pressure between PLEKHA7 (a known GWAS locus for blood pressure) and GPR180 (which plays a role in vascular remodelling), and also for triglycerides as local interactions within the 11q23.3 region (replicated significantly in NFBC1966), which notably harbours several loci (BUD13, ZNF259 and APOA5) contributing to triglyceride levels. Tests of the local interactions within the 11q23.3 region conditional on the top GWAS signal suggested the presence of two independent functional variants, each with supportive evidence for their roles in gene regulation. Local interactions captured 9 additional GWAS loci identified in this study (3 significantly replicated) and 73 from previous GWAS (24 in the eight traits and 49 in related traits). We conclude that the detection of local interactions requires adequate SNP coverage of the genome and that such interactions are only likely to be detectable between SNPs in low linkage disequilibrium. Analysing local interactions is a potentially valuable complement to GWAS and can provide new insights into the biology underlying variation in complex traits

Immune signatures and disorder-specific patterns in a cross-disorder gene expression analysis

BACKGROUND: Recent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology. AIMS: To systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD). METHOD: Analysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD-ASD (n = 16) and healthy controls (n = 78). RESULTS: Weighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures. CONCLUSIONS: Our results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors

Potential causal association between gut microbiome and posttraumatic stress disorder

BackgroundThe causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). MethodsThe summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. ResultsIn Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P &lt; 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. ConclusionOur study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.</p