Disentangling the effect of host-genotype and environment on the microbiome of the coral Acropora tenuis

Genotype-specific contributions to the environmental tolerance and disease susceptibility of corals are widely accepted. Yet our understanding of how host genotype influences the composition and stability of the coral microbiome subjected to environmental fluctuations is limited. To gain insight into the community dynamics and environmental stability of microbiomes associated with distinct coral genotypes, we assessed the microbial community associated with Acropora tenuis under single and cumulative pressure experiments. Experimental treatments comprised either a single pulse of reduced salinity (minimum of 28 psu) or exposure to the cumulative pressures of reduced salinity (minimum of 28 psu), elevated seawater temperature (+2°C), elevated pCO2(900 ppm), and the presence of macroalgae. Analysis of 16S rRNA gene amplicon sequence data revealed that A. tenuis microbiomes were highly host-genotype specific and maintained high compositional stability irrespective of experimental treatment. On average, 48% of the A. tenuis microbiome was dominated by Endozoicomonas. Amplicon sequence variants (ASVs) belonging to this genus were significantly different between host individuals. Although no signs of stress were evident in the coral holobiont and the vast majority of ASVs remained stable across treatments, a microbial indicator approach identified 26 ASVs belonging to Vibrionaceae, Rhodobacteraceae, Hahellaceae, Planctomycetes, Phylobacteriaceae, Flavobacteriaceae, and Cryomorphaceae that were significantly enriched in corals exposed to single and cumulative stressors. While several recent studies have highlighted the efficacy of microbial indicators as sensitive markers for environmental disturbance, the high host-genotype specificity of coral microbiomes may limit their utility and we therefore recommend meticulous control of host-genotype effects in coral microbiome research

Soil Microbial Networks Shift Across a High-Elevation Successional Gradient.

While it is well established that microbial composition and diversity shift along environmental gradients, how interactions among microbes change is poorly understood. Here, we tested how community structure and species interactions among diverse groups of soil microbes (bacteria, fungi, non-fungal eukaryotes) change across a fundamental ecological gradient, succession. Our study system is a high-elevation alpine ecosystem that exhibits variability in successional stage due to topography and harsh environmental conditions. We used hierarchical Bayesian joint distribution modeling to remove the influence of environmental covariates on species distributions and generated interaction networks using the residual species-to-species variance-covariance matrix. We hypothesized that as ecological succession proceeds, diversity will increase, species composition will change, and soil microbial networks will become more complex. As expected, we found that diversity of most taxonomic groups increased over succession, and species composition changed considerably. Interestingly, and contrary to our hypothesis, interaction networks became less complex over succession (fewer interactions per taxon). Interactions between photosynthetic microbes and any other organism became less frequent over the gradient, whereas interactions between plants or soil microfauna and any other organism were more abundant in late succession. Results demonstrate that patterns in diversity and composition do not necessarily relate to patterns in network complexity and suggest that network analyses provide new insight into the ecology of highly diverse, microscopic communities

Fellowships in Community Pharmacy Research: Experiences of Five Schools and Colleges of Pharmacy

Objective To describe common facilitators, challenges, and lessons learned in 5 schools and colleges of pharmacy in establishing community pharmacy research fellowships. Setting: Five schools and colleges of pharmacy in the United States. Practice description: Schools and colleges of pharmacy with existing community partnerships identified a need and ability to develop opportunities for pharmacists to engage in advanced research training. Practice innovation: Community pharmacy fellowships, each structured as 2 years long and in combination with graduate coursework, have been established at the University of Pittsburgh, Purdue University, East Tennessee State University, University of North Carolina at Chapel Hill, and The Ohio State University. Evaluation: Program directors from each of the 5 community pharmacy research fellowships identified common themes pertaining to program structure, outcomes, and lessons learned to assist others planning similar programs. Results: Common characteristics across the programs include length of training, prerequisites, graduate coursework, mentoring structure, and immersion into a pharmacist patient care practice. Common facilitators have been the existence of strong community pharmacy partnerships, creating a fellowship advisory team, and networking. A common challenge has been recruitment, with many programs experiencing at least one year without filling the fellowship position. All program graduates (n = 4) have been successful in securing pharmacy faculty positions. Conclusion: Five schools and colleges of pharmacy share similar experiences in implementing community pharmacy research fellowships. Early outcomes show promise for this training pathway in growing future pharmacist-scientists focused on community pharmacy practice

Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia

Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia

Comparative genomic and phylogenetic approaches to characterize the role of genetic recombination in mycobacterial evolution

The genus Mycobacterium encompasses over one hundred named species of environmental and pathogenic organisms, including the causative agents of devastating human diseases such as tuberculosis and leprosy. The success of these human pathogens is due in part to their ability to rapidly adapt to their changing environment and host. Recombination is the fastest way for bacterial genomes to acquire genetic material, but conflicting results about the extent of recombination in the genus Mycobacterium have been reported. We examined a data set comprising 18 distinct strains from 13 named species for evidence of recombination. Genomic regions common to all strains (accounting for 10% to 22% of the full genomes of all examined species) were aligned and concatenated in the chromosomal order of one mycobacterial reference species. The concatenated sequence was screened for evidence of recombination using a variety of statistical methods, with each proposed event evaluated by comparing maximum-likelihood phylogenies of the recombinant section with the non-recombinant portion of the dataset. Incongruent phylogenies were identified by comparing the site-wise log-likelihoods of each tree using multiple tests. We also used a phylogenomic approach to identify genes that may have been acquired through horizontal transfer from non-mycobacterial sources. The most frequent associated lineages (and potential gene transfer partners) in the Mycobacterium lineage-restricted gene trees are other members of suborder Corynebacterinae, but more-distant partners were identified as well. In two examined cases of potentially frequent and habitat-directed transfer ( M. abscessus to Segniliparus and M. smegmatis to Streptomyces ), observed sequence distances were small and consistent with a hypothesis of transfer, while in a third case ( M. vanbaalenii to Streptomyces ) distances were larger. The analyses described here indicate that whereas evidence of recombination in core regions within the genus is relatively sparse, the acquisition of genes from non-mycobacterial lineages is a significant feature of mycobacterial evolution

Tuberculosis susceptibility and vaccine protection are independently controlled by host genotype

The outcome of Mycobacterium tuberculosis infection and the immunological response to the bacillus Calmette-Guerin (BCG) vaccine are highly variable in humans. Deciphering the relative importance of host genetics, environment, and vaccine preparation for the efficacy of BCG has proven difficult in natural populations. We developed a model system that captures the breadth of immunological responses observed in outbred individual mice, which can be used to understand the contribution of host genetics to vaccine efficacy. This system employs a panel of highly diverse inbred mouse strains, consisting of the founders and recombinant progeny of the "Collaborative Cross" project. Unlike natural populations, the structure of this panel allows the serial evaluation of genetically identical individuals and the quantification of genotype-specific effects of interventions such as vaccination. When analyzed in the aggregate, our panel resembled natural populations in several important respects: the animals displayed a broad range of susceptibility to M. tuberculosis, differed in their immunological responses to infection, and were not durably protected by BCG vaccination. However, when analyzed at the genotype level, we found that these phenotypic differences were heritable. M. tuberculosis susceptibility varied between lines, from extreme sensitivity to progressive M. tuberculosis clearance. Similarly, only a minority of the genotypes was protected by vaccination. The efficacy of BCG was genetically separable from susceptibility to M. tuberculosis, and the lack of efficacy in the aggregate analysis was driven by nonresponsive lines that mounted a qualitatively distinct response to infection. These observations support an important role for host genetic diversity in determining BCG efficacy and provide a new resource to rationally develop more broadly efficacious vaccines. IMPORTANCE Tuberculosis (TB) remains an urgent global health crisis, and the efficacy of the currently used TB vaccine, M. bovis BCG, is highly variable. The design of more broadly efficacious vaccines depends on understanding the factors that limit the protection imparted by BCG. While these complex factors are difficult to disentangle in natural populations, we used a model population of mice to understand the role of host genetic composition in BCG efficacy. We found that the ability of BCG to protect mice with different genotypes was remarkably variable. The efficacy of BCG did not depend on the intrinsic susceptibility of the animal but, instead, correlated with qualitative differences in the immune responses to the pathogen. These studies suggest that host genetic polymorphism is a critical determinant of vaccine efficacy and provide a model system to develop interventions that will be useful in genetically diverse populations.This work, including the efforts of Hardy Kornfeld, was funded by HHS | National Institutes of Health (NIH) (HL081149). This work, including the efforts of Sam Behar, was funded by HHS | National Institutes of Health (NIH) (AI123286-01). This work, including the efforts of Clare Margaret Smith and Christopher Sassetti, was funded by Howard Hughes Medical Institute (HHMI)

Feeding melancholic microbes: MyNewGut recommendations on diet and mood

Summary: Depression is a highly prevalent disorder which exerts a major economic impact in all European countries. The brain-gut-microbiota axis has been described as a new paradigm for advancing understanding and treatment of the disorder. There is now over-whelming evidence to support the fact that gut microbes have a major impact on central neurochemistry and behaviour, especially stress related disorders such as depression. Recent studies indicate that patients with depression have a gut dysbiosis. The reason for this dysbiosis is uncertain. Over recent decades, dietary patterns in Europe and elsewhere have undergone major compositional changes, with increased intakes of red meat, high fat foods, and refined sugars. Individuals who consume a Mediterranean diet have lower rates of depression and a recent study suggests that a Mediterranean diet may have antidepressant properties. Assuming this to be the case, which components of the Mediterranean diet mediate the effects? Highly levels of polyphenols or polyunsaturated fatty acids are obvious candidates. We in the MyNewGut consortium recommend that patients with depression or vulnerability to depression should be encouraged to enhance a plant-based diet with a high content of grains/fibres and fish

Observational constraints on the physical nature of submillimetre source multiplicity : chance projections are common

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2018 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Interferometric observations have demonstrated that a significant fraction of single-dish submillimetre (submm) sources are blends of multiple submm galaxies (SMGs), but the nature of this multiplicity, i.e. whether the galaxies are physically associated or chance projections, has not been determined.We performed spectroscopy of 11 SMGs in six multicomponent submm sources, obtaining spectroscopic redshifts for nine of them. For an additional two component SMGs, we detected continuum emission but no obvious features.We supplement our observed sources with four single-dish submm sources from the literature. This sample allows us to statistically constrain the physical nature of single-dish submm source multiplicity for the first time. In three (3/7, or 43 -33 +39 per cent at 95 per cent confidence) of the single-dish sources for which the nature of the blending is unambiguous, the components for which spectroscopic redshifts are available are physically associated, whereas 4/7 (57 -39 +33 per cent) have at least one unassociated component. When components whose spectra exhibit continuum but no features and for which the photometric redshift is significantly different from the spectroscopic redshift of the other component are also considered, 6/9 (67 -37 +26 per cent) of the single-dish sources are comprised of at least one unassociated component SMG. The nature of the multiplicity of one single-dish source is ambiguous. We conclude that physically associated systems and chance projections both contribute to the multicomponent single-dish submm source population. This result contradicts the conventional wisdom that bright submm sources are solely a result of merger-induced starbursts, as blending of unassociated galaxies is also important.Peer reviewe

Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course

Rationale: We aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course. Methods: We meta-analysed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio and forced expiratory flow at 75% of FVC at ages 7-13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes. Results: We identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and nine with COPD in adulthood. Genes annotated to the top 10 identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways. Interpretation: Our findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course