Showing papers by "DSM published in 2018"

The role of the microbiome for human health: from basic science to clinical applications

Abstract: The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health and disease, the development of the microbiome in early-life and the role of the microbiome on the gut-brain axis. The gut microbiota changes dramatically during pregnancy and intrinsic factors (such as stress), in addition to extrinsic factors (such as diet, and drugs) influence the composition and activity of the gut microbiome throughout life. Microbial metabolites, e.g. short-chain fatty acids affect gut-brain signaling and the immune response. The gut microbiota has a regulatory role on anxiety, mood, cognition and pain which is exerted via the gut-brain axis. Ingestion of prebiotics or probiotics has been used to treat a range of conditions including constipation, allergic reactions and infections in infancy, and IBS. Fecal microbiota transplantation (FMT) highly effective for treating recurrent Clostridium difficile infections. The gut microbiome affects virtually all aspects of human health, but the degree of scientific evidence, the models and technologies and the understanding of mechanisms of action vary considerably from one benefit area to the other. For a clinical practice to be broadly accepted, the mode of action, the therapeutic window, and potential side effects need to thoroughly be investigated. This calls for further coordinated state-of-the art research to better understand and document the human gut microbiome's effects on human health.

Relationship between the gut microbiome and brain function.

Abstract: It has become increasingly evident in recent years that the gut microbiome and the brain communicate in a bidirectional manner, with each possibly affecting the other's functions. Substantial research has aimed to understand the mechanisms of this interaction and to outline strategies for preventing or treating nervous system-related disturbances. This review explores the evidence demonstrating how the gut microbiome may affect brain function in adults, thereby having an impact on stress, anxiety, depression, and cognition. In vitro, in vivo, and human studies reporting an association between a change in the gut microbiome and functional changes in the brain are highlighted, as are studies outlining the mechanisms by which the brain affects the microbiome and the gastrointestinal tract. Possible modes of action to explain how the gut microbiome and the brain functionally affect each other are proposed. Supplemental probiotics to combat brain-related dysfunction offer a promising approach, provided future research elucidates their mode of action and possible side effects. Further studies are warranted to establish how pre- and probiotic interventions may help to balance brain function in healthy and diseased individuals.

Probiotics and the Gut Immune System: Indirect Regulation.

Abstract: The gastrointestinal tract (GIT) represents the largest interface between the human organism and the external environment. In the lumen and upper part of the mucus layer, this organ hosts an enormous number of microorganisms whose composition affects the functions of the epithelial barrier and the gut immune system. Consequentially, the microorganisms in the GIT influence the health status of the organism. Probiotics are living microorganisms which, in specific conditions, confer a health benefit to the host. Among others, probiotics have immunomodulatory properties that usually act directly by (a) increasing the activity of macrophages or natural killer cells, (b) modulating the secretion of immunoglobulins or cytokines, or indirectly by (c) enhancing the gut epithelial barrier, (d) altering the mucus secretion, and (e) competitive exclusion of other (pathogenic) bacteria. This review focuses on specific bacteria strains with indirect immunomodulatory properties. Particularly, we describe here the mechanisms through which specific probiotics enhance the gut epithelial barrier and modulate mucus production. Moreover, we describe the antimicrobial properties of specific bacteria strains. Recent data suggest that multiple pathologies are associated with an unbalanced gut microflora (dysbiosis). Although the cause-effect relationship between pathology and gut microflora is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health.

Toll-Like Receptors: Regulators of the Immune Response in the Human Gut.

Abstract: Toll-like receptors (TLRs) are powerful molecular regulators by which the immune system may “sense” the environment and protect the host from pathogens or endogenous threats. In mammalian cells, several TLRs were identified with a tissue and cell type-specific distribution. Understanding the functions of specific TLRs is crucial for the development and discovery of compounds useful to maintaining or re-establishing homeostasis in the gastrointestinal tract (GIT). Due to their relevance in regulating the inflammatory response in the GIT, we will focus here on TLR2, TLR4, and TLR5. In particular, we describe (a) the molecular pathways activated by the stimulation of these receptors with their known bacterial ligands; (b) the non-bacterial ligands known to interact directly with TLR2 and TLR4 and their soluble forms. The scope of this minireview is to highlight the importance of bacterial and non-bacterial compounds in affecting the gut immune functions via the activation of the TLRs.

In Vitro Fermentation of Selected Prebiotics and Their Effects on the Composition and Activity of the Adult Gut Microbiota

Abstract: Recently, the concept of prebiotics has been revisited to expand beyond non-digestible oligosaccharides, and the requirements for selective stimulation were extended to include microbial groups other than, and additional to, bifidobacteria and lactobacilli. Here, the gut microbiota-modulating effects of well-known and novel prebiotics were studied. An in vitro fermentation screening platform (i-screen) was inoculated with adult fecal microbiota, exposed to different dietary fibers that had a range of concentrations (inulin, alpha-linked galacto-oligosaccharides (alpha-GOS), beta-linked GOS, xylo-oligosaccharides (XOS) from corn cobs and high-fiber sugar cane, and beta-glucan from oats), and compared to a positive fructo-oligosaccharide (FOS) control and a negative control (no fiber addition). All dietary fibers displayed prebiotic activity, with beta-glucan showing more distinct effects on the microbial composition and metabolism compared to the other fibers. Beta-glucan induced the growth of Prevotella and Roseburia with a concomitant increase in propionate production. Inulin and both forms of GOS and XOS had a strong bifidogenic effect on the microbial composition. A dose-response effect was observed for butyrate when exposed to beta-glucan and inulin. The findings of this study support the potential for alpha-GOS, XOS, and oat beta-glucan to serve as novel prebiotics, due to their association with the positive shifts in microbiome composition and short-chain fatty acid production that point to potential health benefits.

Understanding the prebiotic potential of different dietary fibers using an in vitro continuous adult fermentation model (PolyFermS)

Abstract: Consumption of fermentable dietary fibers (DFs), which can induce growth and/or activity of specific beneficial populations, is suggested a promising strategy to modulate the gut microbiota and restore health in microbiota-linked diseases. Until today, inulin and fructo-oligosaccharides (FOS) are the best studied DFs, while little is known about the gut microbiota-modulating effects of β-glucan, α-galactooligosaccharide (α-GOS) and xylo-oligosaccharide (XOS). Here, we used three continuous in vitro fermentation PolyFermS model to study the modulating effect of these DFs on two distinct human adult proximal colon microbiota, independently from the host. Supplementation of DFs, equivalent to a 9 g daily intake, induced a consistent metabolic response depending on the donor microbiota. Irrespective to the DF supplemented, the Bacteroidaceae-Ruminococcaceae dominated microbiota produced more butyrate (up to 96%), while the Prevotellaceae-Ruminococcaceae dominated microbiota produced more propionate (up to 40%). Changes in abundance of specific bacterial taxa upon DF supplementation explained the observed changes in short-chain fatty acid profiles. Our data suggest that the metabolic profile of SCFA profile may be the most suitable and robust read-out to characterize microbiota-modulating effects of a DF and highlights importance to understand the inter-individual response to a prebiotic treatment for mechanistic understanding and human application.

Dietary Fiber Pectin Directly Blocks Toll-Like Receptor 2–1 and Prevents Doxorubicin-Induced Ileitis

Abstract: Dietary carbohydrate fibers are known to prevent immunological diseases common in Western countries such as allergy and asthma but the underlying mechanisms are largely unknown. Until now beneficial effects of dietary fibers are mainly attributed to fermentation products of the fibers such as anti-inflammatory short-chain fatty acids (SCFAs). Here, we found and present a new mechanism by which dietary fibers can be anti-inflammatory: a commonly consumed fiber, pectin, blocks innate immune receptors. We show that pectin binds and inhibits, toll-like receptor 2 (TLR2) and specifically inhibits the proinflammatory TLR2-TLR1 pathway while the tolerogenic TLR2-TLR6 pathway remains unaltered. This effect is most pronounced with pectins having a low degree of methyl esterification (DM). Low-DM pectin interacts with TLR2 through electrostatic forces between non-esterified galacturonic acids on the pectin and positive charges on the TLR2 ectodomain, as confirmed by testing pectin binding on mutated TLR2. The anti-inflammatory effect of low-DM pectins was first studied in human dendritic cells and mouse macrophages in vitro and was subsequently tested in vivo in TLR2-dependent ileitis in a mouse model. In these mice, ileitis was prevented by pectin administration. Protective effects were shown to be TLR2-TLR1 dependent and independent of the SCFAs produced by the gut microbiota. These data suggest that low-DM pectins as a source of dietary fiber can reduce inflammation through direct interaction with TLR2-TLR1 receptors.

The XXL Survey : XX : the 365 cluster catalogue

Abstract: Context. In the currently debated context of using clusters of galaxies as cosmological probes, the need for well-defined cluster samples is critical.Aims. The XXL Survey has been specifically designed to provide a well characterised sample of some 500 X-ray detected clusters suitable for cosmological studies. The main goal of present article is to make public and describe the properties of the cluster catalogue in its present state, as well as of associated catalogues of more specific objects such as super-clusters and fossil groups.Methods. Following from the publication of the hundred brightest XXL clusters, we now release a sample containing 365 clusters in total, down to a flux of a few 10−15 erg s−1 cm−2 in the [0.5–2] keV band and in a 1′ aperture. This release contains the complete subset of clusters for which the selection function is well determined plus all X-ray clusters which are, to date, spectroscopically confirmed. In this paper, we give the details of the follow-up observations and explain the procedure adopted to validate the cluster spectroscopic redshifts. Considering the whole XXL cluster sample, we have provided two types of selection, both complete in a particular sense: one based on flux-morphology criteria, and an alternative based on the [0.5–2] keV flux within 1 arcmin of the cluster centre. We have also provided X-ray temperature measurements for 80% of the clusters having a flux larger than 9 × 10−15 erg s−1 cm−2 .Results. Our cluster sample extends from z ~ 0 to z ~ 1.2, with one cluster at z ~ 2. Clusters were identified through a mean number of six spectroscopically confirmed cluster members. The largest number of confirmed spectroscopic members in a cluster is 41. Our updated luminosity function and luminosity–temperature relation are compatible with our previous determinations based on the 100 brightest clusters, but show smaller uncertainties. We also present an enlarged list of super-clusters and a sample of 18 possible fossil groups.Conclusions. This intermediate publication is the last before the final release of the complete XXL cluster catalogue when the ongoing C2 cluster spectroscopic follow-up is complete. It provides a unique inventory of medium-mass clusters over a 50 deg2 area out to z ~ 1.

Search for heavy particles decaying into top-quark pairs using lepton-plus-jets events in proton-proton collisions at s√=13 TeV with the ATLAS detector

Abstract: A search for new heavy particles that decay into top-quark pairs is performed using data collected from proton-proton collisions at a centre-of-mass energy of 13 TeV by the ATLAS detector at the La ...

CRISPR/Cpf1 enables fast and simple genome editing of Saccharomyces cerevisiae

Abstract: Cpf1 represents a novel single RNA-guided CRISPR/Cas endonuclease system suitable for genome editing with distinct features compared with Cas9. We demonstrate the functionality of three Cpf1 orthologues - Acidaminococcus spp. BV3L6 (AsCpf1), Lachnospiraceae bacterium ND2006 (LbCpf1) and Francisella novicida U112 (FnCpf1) - for genome editing of Saccharomyces cerevisiae. These Cpf1-based systems enable fast and reliable introduction of donor DNA on the genome using a two-plasmid-based editing approach together with linear donor DNA. LbCpf1 and FnCpf1 displayed editing efficiencies comparable with the CRISPR/Cas9 system, whereas AsCpf1 editing efficiency was lower. Further characterization showed that AsCpf1 and LbCpf1 displayed a preference for their cognate crRNA, while FnCpf1-mediated editing with similar efficiencies was observed using non-cognate crRNAs of AsCpf1 and LbCpf1. In addition, multiplex genome editing using a single LbCpf1 crRNA array is shown to be functional in yeast. This work demonstrates that Cpf1 broadens the genome editing toolbox available for Saccharomyces cerevisiae. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd.

Search for pair production of up-type vector-like quarks and for four-top-quark events in final states with multiple b-jets with the ATLAS detector

Abstract: A search for pair production of up-type vector-like quarks (T) with a significant branching ratio into a top quark and either a Standard Model Higgs boson or a Z boson is presented. The same analys ...

Protein fermentation in the gut; implications for intestinal dysfunction in humans, pigs, and poultry.

Abstract: The amount of dietary protein is associated with intestinal disease in different vertebrate species. In humans, this is exemplified by the association between high-protein intake and fermentation metabolite concentrations in patients with inflammatory bowel disease. In production animals, dietary protein intake is associated with postweaning diarrhea in piglets and with the occurrence of wet litter in poultry. The underlying mechanisms by which dietary protein contributes to intestinal problems remain largely unknown. Fermentation of undigested protein in the hindgut results in formation of fermentation products including short-chain fatty acids, branched-chain fatty acids, ammonia, phenolic and indolic compounds, biogenic amines, hydrogen sulfide, and nitric oxide. Here, we review the mechanisms by which these metabolites may cause intestinal disease. Studies addressing how different metabolites induce epithelial damage rely mainly on cell culture studies and occasionally on mice or rat models. Often, contrasting results were reported. The direct relevance of such studies for human, pig, and poultry gut health is therefore questionable and does not suffice for the development of interventions to improve gut health. We discuss a roadmap to improve our understanding of gut metabolites and microbial species associated with intestinal health in humans and production animals and to determine whether these metabolite/bacterial networks cause epithelial damage. The outcomes of these studies will dictate proof-of-principle studies to eliminate specific metabolites and or bacterial strains and will provide the basis for interventions aiming to improve gut health.

Bridging the Gap between the Direct and Hydrocarbon Pool Mechanisms of the Methanol-to-Hydrocarbons Process

Abstract: After a prolonged effort over many years, the route for the formation of a direct carbon-carbon (C-C) bond during the methanol-to-hydrocarbon (MTH) process has very recently been unveiled. However, the relevance of the "direct mechanism"-derived molecules (that is, methyl acetate) during MTH, and subsequent transformation routes to the conventional hydrocarbon pool (HCP) species, are yet to be established. This important piece of the MTH chemistry puzzle is not only essential from a fundamental perspective, but is also important to maximize catalytic performance. The MTH process was probed over a commercially relevant H-SAPO-34 catalyst, using a combination of advanced solid-state NMR spectroscopy and operando UV/Vis diffuse reflectance spectroscopy coupled to an on-line mass spectrometer. Spectroscopic evidence is provided for the formation of (olefinic and aromatic) HCP species, which are indeed derived exclusively from the direct C-C bond-containing acetyl group of methyl acetate. New mechanistic insights have been obtained from the MTH process, including the identification of hydrocarbon-based co-catalytic organic reaction centers.

DustPedia: Multiwavelength photometry and imagery of 875 nearby galaxies in 42 ultraviolet-microwave bands

Abstract: The DustPedia project is capitalising on the legacy of the Herschel Space Observatory, using cutting-edge modelling techniques to study dust in the 875 DustPedia galaxies - representing the vast majority of extended galaxies within 3000 km s^−1 that were observed by Herschel. This work requires a database of multiwavelength imagery and photometry that greatly exceeds the scope (in terms of wavelength coverage and number of galaxies) of any previous local-Universe survey. We constructed a database containing our own custom Herschel reductions, along with standardised archival observations from GALEX, SDSS, DSS, 2MASS, WISE, Spitzer, and Planck. Using these data, we performed consistent aperture-matched photometry, which we combined with external supplementary photometry from IRAS and Planck. We present our multiwavelength imagery and photometry across 42 UV-microwave bands for the 875 DustPedia galaxies. Our aperture-matched photometry, combined with the external supplementary photometry, represents a total of 21,857 photometric measurements. A typical DustPedia galaxy has multiwavelength photometry spanning 25 bands. We also present the Comprehensive & Adaptable Aperture Photometry Routine (CAAPR), the pipeline we developed to carry out our aperture-matched photometry. CAAPR is designed to produce consistent photometry for the enormous range of galaxy and observation types in our data. In particular, CAAPR is able to determine robust cross-compatible uncertainties, thanks to a novel method for reliably extrapolating the aperture noise for observations that cover a very limited amount of background. Our rich database of imagery and photometry is being made available to the community

Characterising the VHE diffuse emission in the central 200 parsecs of our Galaxy with H.E.S.S.

Abstract: The diffuse very high-energy (VHE; >100 GeV) γ -ray emission observed in the central 200 pc of the Milky Way by H.E.S.S. was found to follow dense matter distribution in the central molecular zone (CMZ) up to a longitudinal distance of about 130 pc to the Galactic centre (GC), where the flux rapidly decreases. This was initially interpreted as the result of a burst-like injection of energetic particles 104 yr ago, but a recent more sensitive H.E.S.S. analysis revealed that the cosmic-ray (CR) density profile drops with the distance to the centre, making data compatible with a steady cosmic PeVatron at the GC. In this paper, we extend this analysis to obtain, for the first time, a detailed characterisation of the correlation with matter and to search for additional features and individual γ -ray sources in the inner 200 pc. Taking advantage of 250 h of H.E.S.S. data and improved analysis techniques, we perform a detailed morphology study of the diffuse VHE emission observed from the GC ridge and reconstruct its total spectrum. To test the various contributions to the total γ -ray emission, we used an iterative 2D maximum-likelihood approach that allows us to build a phenomenological model of the emission by summing a number of different spatial components. We show that the emission correlated with dense matter covers the full CMZ and that its flux is about half the total diffuse emission flux. We also detect some emission at higher latitude that is likely produced by hadronic collisions of CRs in less dense regions of the GC interstellar medium. We detect an additional emission component centred on the GC and extending over about 15 pc that is consistent with the existence of a strong CR density gradient and confirms the presence of a CR accelerator at the very centre of our Galaxy. We show that the spectrum of full ridge diffuse emission is compatible with that previously derived from the central regions, suggesting that a single population of particles fills the entire CMZ. Finally, we report the discovery of a VHE γ -ray source near the GC radio arc and argue that it is produced by the pulsar wind nebula candidate G0.13−0.11.

The application of in vitro human intestinal models on the screening and development of pre- and probiotics.

Abstract: The importance of the gut microbiota community on host's health and disease has long been recognised and is well documented. The development of pro- and prebiotic interventions offers an opportunity for the modulation of the gut microbiota towards long lasting health. In vitro fermentation models were developed as a powerful tool to study the impact of pro- and prebiotics on the gut microbiota under tightly controlled conditions, which allow dynamic sampling over time in reactors mimicking different colon regions. These models have been further evolved to suit specific experimental purposes, e.g. including immobilised faecal microbiota, peristaltic movement, mucin microcosm and the ability to perform treatments in parallel. In this review we discuss the advantages, disadvantages and technical considerations of the most frequently used models. We further focus on recent advances in the application of these models in prebiotics and probiotics research and outline their predictability for clinical research.

Mechanics of elastomeric molecular composites

Abstract: A classic paradigm of soft and extensible polymer materials is the difficulty of combining reversible elasticity with high fracture toughness, in particular for moduli above 1 MPa Our recent discovery of multiple network acrylic elastomers opened a pathway to obtain precisely such a combination We show here that they can be seen as true molecular composites with a well–cross-linked network acting as a percolating filler embedded in an extensible matrix, so that the stress–strain curves of a family of molecular composite materials made with different volume fractions of the same cross-linked network can be renormalized into a master curve For low volume fractions (

Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural Products.

Abstract: Penicillium chrysogenum (renamed P. rubens) is the most studied member of a family of more than 350 Penicillium species that constitute the genus. Since the discovery of penicillin by Alexander Fleming, this filamentous fungus is used as a commercial β-lactam antibiotic producer. For several decades, P. chrysogenum was subjected to a classical strain improvement (CSI) program to increase penicillin titers. This resulted in a massive increase in the penicillin production capacity, paralleled by the silencing of several other biosynthetic gene clusters (BGCs), causing a reduction in the production of a broad range of BGC encoded natural products (NPs). Several approaches have been used to restore the ability of the penicillin production strains to synthetize the NPs lost during the CSI. Here, we summarize various re-activation mechanisms of BGCs, and how interference with regulation can be used as a strategy to activate or silence BGCs in filamentous fungi. To further emphasize the versatility of P. chrysogenum as a fungal production platform for NPs with potential commercial value, protein engineering of biosynthetic enzymes is discussed as a tool to develop de novo BGC pathways for new NPs.

Effects of resveratrol supplementation on liver fat content in overweight and insulin‐resistant subjects: A randomized, double‐blind, placebo‐controlled clinical trial

Abstract: We performed the largest randomized, placebo-controlled clinical trial to date (N = 112, 12-week intervention) to investigate the effects and safety of resveratrol supplementation on liver fat content and cardiometabolic risk parameters in overweight and obese and insulin-resistant subjects. At baseline the variability in liver fat content was very large, ranging from 0.09% to 37.55% (median, 7.12%; interquartile range, 3.85%-12.94%). Mean (SD) liver fat content was 9.22 (6.85) % in the placebo group and 9.91 (7.76) % in the resveratrol group. During the study liver fat content decreased in the placebo group (-0.7%) but not in the resveratrol group (-0.03%) (differences between groups: P = .018 for the intention-to-treat [ITT] population; N = 54, resveratrol, N = 54, placebo and P = .0077 for the per protocol [PP] population). No effects of resveratrol supplementation on cardiometabolic risk parameters were observed. Resveratrol supplementation was well tolerated and safe. In conclusion, these data suggest that resveratrol supplementation is safe and that it does not considerably impact liver fat content or cardiometabolic risk parameters in humans.

The combined effects of supplementing monensin and 3-nitrooxypropanol on methane emissions, growth rate, and feed conversion efficiency in beef cattle fed high-forage and high-grain diets.

Abstract: The study objective was to evaluate the combined effects of supplementing monensin (MON) and the methane (CH4) inhibitor 3-nitrooxypropanol (NOP) on enteric CH4 emissions, growth rate, and feed conversion efficiency of backgrounding and finishing beef cattle. Two hundred and forty crossbred steers were used in a 238-d feeding study and fed a backgrounding diet for the first 105 d (backgrounding phase), transition diets for 28 d, followed by a finishing diet for 105 d (finishing phase). Treatments were as follows: 1) control (no additive); 2) MON (monensin supplemented at 33 mg/kg DM; 3) NOP (3-nitrooxypropanol supplemented at 200 mg/kg DM for backgrounding or 125 mg/kg DM for finishing phase); and 4) MONOP (33 mg/kg DM MON supplemented with either 200 mg/kg DM or 125 mg/kg DM NOP). The experiment was a randomized complete block (weight: heavy and light) design with 2 (NOP) × 2 (MON) factorial arrangement of treatments using 24 pens (8 cattle/pen; 6 pens/treatment) at the main feedlot and 8 pens (6 cattle/pen; 2 pens/treatment) at the controlled environment building (CEB) feedlot. Five animals per treatment were moved to chambers for CH4 measurements during both phases. Data were analyzed using a Mixed procedure of SAS with pen as experimental unit (except CH4). Location (Main vs. CEB) had no significant effect and was thus omitted from the final model. Overall, there were few interactions between MON and NOP indicating that the effects of the 2 compounds were independent. When cattle were fed the backgrounding diet, pen DMI was decreased by 7%, whereas gain-to-feed ratio (G:F) was improved by 5% with NOP supplementation (P < 0.01). Similarly, MON improved G:F ratio by 4% (P < 0.01), but without affecting DMI. During the finishing phase, DMI tended (P = 0.06) to decrease by 5% with both MON (5%) and NOP (5%), whereas ADG tended (P = 0.08) to decrease by 3% with MON. Gain-to-feed ratio for finishing cattle was improved with NOP by 3% (P < 0.01); however, no effects were observed with MON. 3-Nitrooxypropanol decreased CH4 yield (g/kg DMI) by 42% and 37% with backgrounding and finishing diets (P ≤ 0.01), respectively, whereas MON did not lower CH4 yield. Overall, these results demonstrate efficacy of NOP in reducing enteric CH4 emissions and subsequently improving feed conversion efficiency in cattle fed high-forage and high-grain diets. Furthermore, effects of NOP did not depend on whether MON was included in the diet.

Genetic Competence Drives Genome Diversity in Bacillus subtilis.

Abstract: Prokaryote genomes are the result of a dynamic flux of genes, with increases achieved via horizontal gene transfer and reductions occurring through gene loss. The ecological and selective forces that drive this genomic flexibility vary across species. Bacillus subtilis is a naturally competent bacterium that occupies various environments, including plant-associated, soil, and marine niches, and the gut of both invertebrates and vertebrates. Here, we quantify the genomic diversity of B. subtilis and infer the genome dynamics that explain the high genetic and phenotypic diversity observed. Phylogenomic and comparative genomic analyses of 42 B. subtilis genomes uncover a remarkable genome diversity that translates into a core genome of 1,659 genes and an asymptotic pangenome growth rate of 57 new genes per new genome added. This diversity is due to a large proportion of low-frequency genes that are acquired from closely related species. We find no gene-loss bias among wild isolates, which explains why the cloud genome, 43% of the species pangenome, represents only a small proportion of each genome. We show that B. subtilis can acquire xenologous copies of core genes that propagate laterally among strains within a niche. While not excluding the contributions of other mechanisms, our results strongly suggest a process of gene acquisition that is largely driven by competence, where the long-term maintenance of acquired genes depends on local and global fitness effects. This competence-driven genomic diversity provides B. subtilis with its generalist character, enabling it to occupy a wide range of ecological niches and cycle through them.

Cosmological simulations of black hole growth II: how (in)significant are merger events for fuelling nuclear activity?

Abstract: Which mechanism(s) are mainly driving nuclear activity in the centres of galaxies is a major unsettled question. In this study, we investigate the statistical relevance of galaxy mergers for fuelling gas onto the central few kpc of a galaxy, potentially resulting in an active galactic nucleus (AGN). To robustly address that, we employ large-scale cosmological hydrodynamic simulations from the Magneticum Pathfinder set, including models for black hole accretion and AGN feedback. Our simulations predict that for luminous AGN (LAGN > 1045 erg s(-1)) at z = 2, more than 50 per cent of their host galaxies have experienced a merger in the last 0.5 Gyr. These high merger fractions, however, merely reflect the intrinsically high merger fractions of massive galaxies at z = 2, in which luminous AGN preferentially occur. Apart from that, our simulations suggest that merger events are not the statistically dominant fuelling mechanism for nuclear activity over a redshift range z = 0-2: irrespective ofAGNluminosity, less than 20 per cent of AGN hosts have on average undergone a recent merger, in agreement with a number of observational studies. The central interstellar medium conditions required for inducing AGN activity can be, but are not necessarily caused by a merger. Despite the statistically minor relevance of mergers, at a given AGN luminosity and stellar mass, the merger fractions of AGN hosts can be by up to three times higher than that of inactive galaxies. Such elevated merger fractions still point towards an intrinsic connection between AGN and mergers, consistent with our traditional expectation.

The Role of n-3 Long Chain Polyunsaturated Fatty Acids in Cardiovascular Disease Prevention, and Interactions with Statins.

Abstract: Decreases in global cardiovascular disease (CVD) mortality and morbidity in recent decades can be partly attributed to cholesterol reduction through statin use. n-3 long chain polyunsaturated fatty acids are recommended by some authorities for primary and secondary CVD prevention, and for triglyceride reduction. The residual risk of CVD that remains after statin therapy may potentially be reduced by n-3 long chain polyunsaturated fatty acids. However, the effects of concomitant use of statins and n-3 long chain polyunsaturated fatty acids are not well understood. Pleiotropic effects of statins and n-3 long chain polyunsaturated fatty acids overlap. For example, cytochrome P450 enzymes that metabolize statins may affect n-3 long chain polyunsaturated fatty acid metabolism and vice versa. Clinical and mechanistic study results show both synergistic and antagonistic effects of statins and n-3 long chain polyunsaturated fatty acids when used in combination.