The composition of the zebrafish intestinal microbial community varies across development

The assembly of resident microbial communities is an important event in animal development; however, the extent to which this process mirrors the developmental programs of host tissues is unknown. Here we surveyed the intestinal bacteria at key developmental time points in a sibling group of 135 individuals of a model vertebrate, the zebrafish (Danio rerio). Our survey revealed stage-specific signatures in the intestinal microbiota and extensive interindividual variation, even within the same developmental stage. Microbial community shifts were apparent during periods of constant diet and environmental conditions, as well as in concert with dietary and environmental change. Interindividual variation in the intestinal microbiota increased with age, as did the difference between the intestinal microbiota and microbes in the surrounding environment. Our results indicate that zebrafish intestinal microbiota assemble into distinct communities throughout development, and that these communities are increasingly different from the surrounding environment and from one another

Contribution of neutral processes to the assembly of gut microbial communities in the zebrafish over host development

Despite their importance to host health and development, the communities of microorganisms associated with humans and other animals are characterized by a large degree of unexplained variation across individual hosts. The processes that drive such inter-individual variation are not well understood. To address this, we surveyed the microbial communities associated with the intestine of the zebrafish, Danio rerio, over developmental time. We compared our observations of community composition and distribution across hosts with that predicted by a neutral assembly model, which assumes that community assembly is driven solely by chance and dispersal. We found that as hosts develop from larvae to adults, the fit of the model to observed microbial distributions decreases, suggesting that the relative importance of non-neutral processes, such as microbe-microbe interactions, active dispersal, or selection by the host, increases as hosts mature. We also observed that taxa which depart in their distributions from the neutral prediction form ecologically distinct sub-groups, which are phylogenetically clustered with respect to the full metacommunity. These results demonstrate that neutral processes are sufficient to generate substantial variation in microbiota composition across individual hosts, and suggest that potentially unique or important taxa may be identified by their divergence from neutral distributions

Synthetic protein-conductive membrane nanopores built with DNA

Nanopores are key in portable sequencing and research given their ability to transport elongated DNA or small bioactive molecules through narrow transmembrane channels. Transport of folded proteins could lead to similar scientific and technological benefits. Yet this has not been realised due to the shortage of wide and structurally defined natural pores. Here we report that a synthetic nanopore designed via DNA nanotechnology can accommodate folded proteins. Transport of fluorescent proteins through single pores is kinetically analysed using massively parallel optical readout with transparent silicon-on-insulator cavity chips vs. electrical recordings to reveal an at least 20-fold higher speed for the electrically driven movement. Pores nevertheless allow a high diffusive flux of more than 66 molecules per second that can also be directed beyond equillibria. The pores may be exploited to sense diagnostically relevant proteins with portable analysis technology, to create molecular gates for drug delivery, or to build synthetic cells

A Joint Fermi-GBM and LIGO/Virgo Analysis of Compact Binary Mergers from the First and Second Gravitational-wave Observing Runs

We present results from offline searches of Fermi Gamma-ray Burst Monitor (GBM) data for gamma-ray transients coincident with the compact binary coalescences observed by the gravitational-wave (GW) detectors Advanced LIGO and Advanced Virgo during their first and second observing runs. In particular, we perform follow-up for both confirmed events and low significance candidates reported in the LIGO/Virgo catalog GWTC-1. We search for temporal coincidences between these GW signals and GBM-triggered gamma-ray bursts (GRBs). We also use the GBM Untargeted and Targeted subthreshold searches to find coincident gamma-rays below the onboard triggering threshold. This work implements a refined statistical approach by incorporating GW astrophysical source probabilities and GBM visibilities of LIGO/Virgo sky localizations to search for cumulative signatures of coincident subthreshold gamma-rays. All search methods recover the short gamma-ray burst GRB 170817A occurring ~1.7 s after the binary neutron-star merger GW170817. We also present results from a new search seeking GBM counterparts to LIGO single-interferometer triggers. This search finds a candidate joint event, but given the nature of the GBM signal and localization, as well as the high joint false alarm rate of 1.1 × 10−6 Hz, we do not consider it an astrophysical association. We find no additional coincidences

Biotechnologies as catalysts for driving net zero

R&D impact delivered by this work extends to policy development and to the benefits derived from delivering circularity, green growth and reducing carbon emissions by anaerobic digestion that (1) recovers a variety of organic wastes and low value biomass and (2) produces bioenergy and fertiliser. Other biotechnologies being developed can recover resources for the production of fuels (CH4, H2 and NH3), chemicals e.g. volatile fatty acids, biopolymers e.g. polyhydroxyalkanoates and single-cell proteins that can be used for animal feed. Biotechnologies delivering solutions for Power to X, for energy storage and for the capture and use of carbon have also been a focus of our research. Monitoring and control methodologies for the biotechnologies have been developed, including the use of analytical technologies such as FTNIR, GC-IMS and qPCR. Work continues on the valorisation of digestates as microbial and algae growth media, and the recovery of nutrients (NPK). Evaluations of the fate of polymers in the environment, their biochemical recycling and the production of biostimulants for soil and crop improvements, nitrogen fixing and emissions’ reduction are all in progress. Technologies are currently across the TRL 3-6 range and require further R&D to progress them to commercialisation. Deploying industrial biotechnologies is essential to act as sustainable catalysts for change and for delivering net zero, circular economy and green growth. Biotechnologies can impact beneficially on the sustainability of cities and benefit their relationship and integration with surrounding rural areas

The 3rd Fermi GBM Gamma-Ray Burst Catalog: The First Six Years

Since its launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has triggered and located on average approximately two gamma-ray bursts (GRB) every three days. Here we present the third of a series of catalogs of GRBs detected by GBM, extending the second catalog by two more years, through the middle of July 2014. The resulting list includes 1405 triggers identified as GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM detected GRBs. For each GRB the location and main characteristics of the prompt emission, the duration, peak flux and fluence are derived. The latter two quantities are calculated for the 50-300~keV energy band, where the maximum energy release of GRBs in the instrument reference system is observed, and also for a broader energy band from 10-1000 keV, exploiting the full energy range of GBM's low-energy NaI(Tl) detectors. Using statistical methods to assess clustering, we find that the hardness and duration of GRBs are better fitted by a two-component model with short-hard and long-soft bursts, than by a model with three components. Furthermore, information is provided on the settings and modifications of the triggering criteria and exceptional operational conditions during years five and six in the mission. This third catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center (HEASARC).Comment: 225 pages, 13 figures and 8 tables. Accepted for publication in Astrophysical Journal Supplement 201

Vitamin C activates young LINE-1 elements in mouse embryonic stem cells via H3K9me3 demethylation

Background Vitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells. Results Here we show that vitC increases the expression of several TE families, including evolutionarily young LINE-1 (L1) elements, in mouse ESCs. We find that TET activity is dispensable for L1 upregulation, and that instead it occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we did not detect increased somatic insertion rates in vitC-treated cells. Notably, treatment of human ESCs with vitC also increases L1 protein levels, albeit through a distinct, post-transcriptional mechanism. Conclusion VitC directly modulates the expression of mouse L1s and other TEs through epigenetic mechanisms, with potential for downstream effects related to the multiple emerging roles of L1s in cellular function.This work was supported by grants from the Wellcome Trust/Royal Society (101225/Z/13/Z) and MRC (MR/X008487/1) to M.R.B.; and BBSRC (BB/T000031/1) to M.R.B. and J.M.F.Peer reviewe

Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer.

The somatic mutations in a cancer genome are the aggregate outcome of one or more mutational processes operative through the lifetime of the individual with cancer. Each mutational process leaves a characteristic mutational signature determined by the mechanisms of DNA damage and repair that constitute it. A role was recently proposed for the APOBEC family of cytidine deaminases in generating particular genome-wide mutational signatures and a signature of localized hypermutation called kataegis. A germline copy number polymorphism involving APOBEC3A and APOBEC3B, which effectively deletes APOBEC3B, has been associated with modestly increased risk of breast cancer. Here we show that breast cancers in carriers of the deletion show more mutations of the putative APOBEC-dependent genome-wide signatures than cancers in non-carriers. The results suggest that the APOBEC3A-APOBEC3B germline deletion allele confers cancer susceptibility through increased activity of APOBEC-dependent mutational processes, although the mechanism by which this increase in activity occurs remains unknown.We would like to thank the Wellcome Trust for support (grant reference 098051). SN-Z is a Wellcome-Beit Prize Fellow and is supported through a Wellcome Trust Intermediate Fellowship (grant reference WT100183MA). PJC is personally funded through a Wellcome Trust Senior Clinical Research Fellowship (grant reference WT088340MA). NB is an EHA fellow and is supported by a Lady Tata Memorial Trust award. The H.L. Holmes Award from the National Research Council Canada and an EMBO Fellowship supports AS

Ontogenetic Differences in Dietary Fat Influence Microbiota Assembly in the Zebrafish Gut

ABSTRACT Gut microbiota influence the development and physiology of their animal hosts, and these effects are determined in part by the composition of these microbial communities. Gut microbiota composition can be affected by introduction of microbes from the environment, changes in the gut habitat during development, and acute dietary alterations. However, little is known about the relationship between gut and environmental microbiotas or about how host development and dietary differences during development impact the assembly of gut microbiota. We sought to explore these relationships using zebrafish, an ideal model because they are constantly immersed in a defined environment and can be fed the same diet for their entire lives. We conducted a cross-sectional study in zebrafish raised on a high-fat, control, or low-fat diet and used bacterial 16S rRNA gene sequencing to survey microbial communities in the gut and external environment at different developmental ages. Gut and environmental microbiota compositions rapidly diverged following the initiation of feeding and became increasingly different as zebrafish grew under conditions of a constant diet. Different dietary fat levels were associated with distinct gut microbiota compositions at different ages. In addition to alterations in individual bacterial taxa, we identified putative assemblages of bacterial lineages that covaried in abundance as a function of age, diet, and location. These results reveal dynamic relationships between dietary fat levels and the microbial communities residing in the intestine and the surrounding environment during ontogenesis. IMPORTANCE The ability of gut microbiota to influence host health is determined in part by their composition. However, little is known about the relationship between gut and environmental microbiotas or about how ontogenetic differences in dietary fat impact gut microbiota composition. We addressed these gaps in knowledge using zebrafish, an ideal model organism because their environment can be thoroughly sampled and they can be fed the same diet for their entire lives. We found that microbial communities in the gut changed as zebrafish aged under conditions of a constant diet and became increasingly different from microbial communities in their surrounding environment. Further, we observed that the amount of fat in the diet had distinct age-specific effects on gut community assembly. These results reveal the complex relationships between microbial communities residing in the intestine and those in the surrounding environment and show that these relationships are shaped by dietary fat throughout the life of animal hosts

The Carnegie Supernova Project: First Near-Infrared Hubble Diagram to z~0.7

The Carnegie Supernova Project (CSP) is designed to measure the luminosity distance for Type Ia supernovae (SNe Ia) as a function of redshift, and to set observational constraints on the dark energy contribution to the total energy content of the Universe. The CSP differs from other projects to date in its goal of providing an I-band {rest-frame} Hubble diagram. Here we present the first results from near-infrared (NIR) observations obtained using the Magellan Baade telescope for SNe Ia with 0.1 < z < 0.7. We combine these results with those from the low-redshift CSP at z <0.1 (Folatelli et al. 2009). We present light curves and an I-band Hubble diagram for this first sample of 35 SNe Ia and we compare these data to 21 new SNe Ia at low redshift. These data support the conclusion that the expansion of the Universe is accelerating. When combined with independent results from baryon acoustic oscillations (Eisenstein et al. 2005), these data yield Omega_m = 0.27 +/- 0.0 (statistical), and Omega_DE = 0.76 +/- 0.13 (statistical) +/- 0.09 (systematic), for the matter and dark energy densities, respectively. If we parameterize the data in terms of an equation of state, w, assume a flat geometry, and combine with baryon acoustic oscillations, we find that w = -1.05 +/- 0.13 (statistical) +/- 0.09 (systematic). The largest source of systematic uncertainty on w arises from uncertainties in the photometric calibration, signaling the importance of securing more accurate photometric calibrations for future supernova cosmology programs. Finally, we conclude that either the dust affecting the luminosities of SNe Ia has a different extinction law (R_V = 1.8) than that in the Milky Way (where R_V = 3.1), or that there is an additional intrinsic color term with luminosity for SNe Ia independent of the decline rate.Comment: 44 pages, 23 figures, 9 tables; Accepted for publication in the Astrophysical Journa