HST/WFC3 transmission spectroscopy of the cold rocky planet TRAPPIST-1h

TRAPPIST-1 is a nearby ultra-cool dwarf star transited by seven rocky planets. We observed three transits of its outermost planet, TRAPPIST-1h, using the G141 grism of the Wide Field Camera 3 instrument aboard the Hubble Space Telescope to place constraints on its potentially cold atmosphere. In order to deal with the effect of stellar contamination, we model TRAPPIST-1 active regions as portions of a cooler and a hotter photosphere, and generate multi-temperature models that we compare to the out-of-transit spectrum of the star. Using the inferred spot parameters, we produce corrected transmission spectra for planet h under five transit configurations and compare these data to planetary atmospheric transmission models using the forward model CHIMERA. Our analysis reveals that TRAPPIST-1h is unlikely to host an aerosol-free H/He-dominated atmosphere. While the current data precision limits the constraints we can put on the planetary atmosphere, we find that the likeliest scenario is that of a flat, featureless transmission spectrum in the WFC3/G141 bandpass due to a high mean molecular weight atmosphere (>1000x solar), no atmosphere, or an opaque aerosol layer, all in absence of stellar contamination. This work outlines the limitations of modeling active photospheric regions with theoretical stellar spectra, and those brought by our lack of knowledge of the photospheric structure of ultracool dwarf stars. Further characterization of the planetary atmosphere of TRAPPIST-1h would require higher precision measurements over wider wavelengths, which will be possible with the James Webb Space Telescope

The effects of stand characteristics on the understory vegetation in Quercus petraea and Q. cerris dominated forests

The shelterwood system used in Hungary has many effects on the composition and structure of the herb layer. The aim of our study was to identify the main variables that affect the occurence of herbs and seedlings in Turkey oak-sessile oak (Quercus cerris and Q. petraea) stands. The study was carried out in the Bükk mountains, Hungary. 122 sampling plots were established in 50-150 year old oak forests, where we studied the species composition and structure of the understorey and overstorey. The occurence of herbs was affected by canopy closure, the heterogenity and patchiness of the stand, the slope and the east-west component of the aspect. The composition of saplings was significantly explained by the ratio of the two major oak species in the stand and the proximity of the adult plants. An important result for forest management was that sessile oaks were able to regenerate almost only where they were dominant in the overstorey

A Bayesian Approach for Analysis of Whole-Genome Bisulphite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation

DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulphite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome whilst taking into account the distance between CpG sites as a covariate. Our simulation study shows that ABBA has greater power to detect DMRs than existing methods, providing an accurate identification of DMRs in the large majority of simulated cases. To empirically demonstrate the method's efficacy in generating biological hypotheses, we performed WGBS of primary macrophages derived from an experimental rat system of glomerulonephritis and used ABBA to identify >1,000 disease-associated DMRs. Investigation of these DMRs revealed differential DNA methylation localized to a 600bp region in the promoter of the Ifitm3 gene. This was confirmed by ChIP-seq and RNA-seq analyses, showing differential transcription factor binding at the Ifitm3 promoter by JunD (an established determinant of glomerulonephritis) and a consistent change in Ifitm3 expression. Our ABBA analysis allowed us to propose a new role for Ifitm3 in the pathogenesis of glomerulonephritis via a mechanism involving promoter hypermethylation that is associated with Ifitm3 repression in the rat strain susceptible to glomerulonephritis.This research was funded by Engineering and Physical Sciences Research Council Grant EP/K030760/1 (L.B.), The Alan Turing Institute under the EPSRC grant EP/N510129/1 (L.B., P.D.), Royal Society IE110977 (L.B., P.D.), European Union (European Social Fund - ESF), Greek national funds through the Operational Program "Education and Lifelong Learning'' of the National Strategic Reference Framework (NSRF), project ARISTEIA (P.D.), Duke-NUS Medical School and Singapore Ministry of Health (O.J.L.R., E.P.), a Medical Research Council Chain-Florey fellowship (T.O.), the Medical Research Council (MR/M004716/1 to J.B. and E.P.) and by Kidney Research UK - RP9/2013 (J.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The Human Mitochondrial Transcriptome

SummaryThe human mitochondrial genome comprises a distinct genetic system transcribed as precursor polycistronic transcripts that are subsequently cleaved to generate individual mRNAs, tRNAs, and rRNAs. Here, we provide a comprehensive analysis of the human mitochondrial transcriptome across multiple cell lines and tissues. Using directional deep sequencing and parallel analysis of RNA ends, we demonstrate wide variation in mitochondrial transcript abundance and precisely resolve transcript processing and maturation events. We identify previously undescribed transcripts, including small RNAs, and observe the enrichment of several nuclear RNAs in mitochondria. Using high-throughput in vivo DNaseI footprinting, we establish the global profile of DNA-binding protein occupancy across the mitochondrial genome at single-nucleotide resolution, revealing regulatory features at mitochondrial transcription initiation sites and functional insights into disease-associated variants. This integrated analysis of the mitochondrial transcriptome reveals unexpected complexity in the regulation, expression, and processing of mitochondrial RNA and provides a resource for future studies of mitochondrial function (accessed at http://mitochondria.matticklab.com)

Fair game: exploring the dynamics, perception and environmental impact of ‘surplus’ wild foods in England 10kya-present

This paper brings together zooarchaeological data from Neolithic to Post-medieval sites in England to explore the plasticity of cultural attitudes to the consumption of wild animals. It shows how, through time, game has been considered variously as ‘tabooed’ and ‘edible’, each having implications for patterns of biodiversity and wildlife management. The essential points being made are that deeper-time studies can reveal how human perceptions of ‘surplus foods’ have the potential to both create and remedy problems of environmental sustainability and food security. Perhaps more significantly, this paper argues that understanding the bio-cultural past of edible wild animal species has the potential to transform human attitudes to game in the present. This is important at a time when food security and the production of surplus are pressing national and global concerns

Development of the SPECULOOS exoplanet search project

SPECULOOS (Search for habitable Planets EClipsing ULtra-cOOl Stars) aims to perform a transit search on the nearest ($<40$pc) ultracool ($<3000$K) dwarf stars. The project's main motivation is to discover potentially habitable planets well-suited for detailed atmospheric characterisation with upcoming giant telescopes, like the James Webb Space Telescope (JWST) and European Large Telescope (ELT). The project is based on a network of 1m robotic telescopes, namely the four ones of the SPECULOOS-Southern Observatory (SSO) in Cerro Paranal, Chile, one telescope of the SPECULOOS-Northern Observatory (SNO) in Tenerife, and the SAINT-Ex telescope in San Pedro M\'artir, Mexico. The prototype survey of the SPECULOOS project on the 60~cm TRAPPIST telescope (Chile) discovered the TRAPPIST-1 system, composed of seven temperate Earth-sized planets orbiting a nearby (12~pc) Jupiter-sized star. In this paper, we review the current status of SPECULOOS, its first results, the plans for its development, and its connection to the Transiting Exoplanet Survey Satellite (TESS) and JWST

Design and Synthesis of High Affinity Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferases Directed by Ligand Efficiency Dependent Lipophilicity (LELP)

N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model. Here we describe the discovery of 34c through optimization of a previously described series. Development, guided by targeting a ligand efficiency dependent lipophilicity (LELP) score of less than 10, yielded a 100-fold increase in enzyme affinity and a 100-fold drop in lipophilicity with the addition of only two heavy atoms. 34c was found to be equipotent on chloroquine-sensitive and -resistant cell lines and on both blood and liver stage forms of the parasite. These data further validate NMT as an exciting drug target in malaria and support 34c as an attractive tool for further optimization

Widespread translational control of fibrosis in the human heart by RNA-binding proteins

BACKGROUND: Fibrosis is a common pathology in many cardiac disorders and is driven by the activation of resident fibroblasts. The global post-transcriptional mechanisms underlying fibroblast-to-myofibroblast conversion in the heart have not been explored. METHODS: Genome-wide changes of RNA transcription and translation during human cardiac fibroblast activation were monitored with RNA sequencing and ribosome profiling. We then used an RNA-binding protein-based analyses to identify translational regulators of fibrogenic genes. The integration with cardiac ribosome occupancy levels of 30 dilated cardiomyopathy patients demonstrates that these post-transcriptional mechanisms are also active in the diseased fibrotic human heart. RESULTS: We generated nucleotide-resolution translatome data during the TGFβ1-driven cellular transition of human cardiac fibroblasts to myofibroblasts. This identified dynamic changes of RNA transcription and translation at several time points during the fibrotic response, revealing transient and early-responder genes. Remarkably, about one-third of all changes in gene expression in activated fibroblasts are subject to translational regulation and dynamic variation in ribosome occupancy affects protein abundance independent of RNA levels. Targets of RNA-binding proteins were strongly enriched in post-transcriptionally regulated genes, suggesting genes such as MBNL2 can act as translational activators or repressors. Ribosome occupancy in the hearts of patients with dilated cardiomyopathy suggested the same post-transcriptional regulatory network was underlying cardiac fibrosis. Key network hubs include RNA-binding proteins such as PUM2 and QKI that work in concert to regulate the translation of target transcripts in human diseased hearts. Furthermore, silencing of both PUM2 and QKI inhibits the transition of fibroblasts toward pro-fibrotic myofibroblasts in response to TGFβ1. CONCLUSIONS: We reveal widespread translational effects of TGFβ1 and define novel post-transcriptional regulatory networks that control the fibroblast-to-myofibroblast transition. These networks are active in human heart disease and silencing of hub genes limits fibroblast activation. Our findings show the central importance of translational control in fibrosis and highlight novel pathogenic mechanisms in heart failure

From icon of empire to national emblem: new evidence for the fallow deer of Barbuda

Barbuda and Antigua's national animal is the fallow deer, Dama dama dama, a species native to the eastern Mediterranean that has been transported around the world by people during the last 8,000 years. The timing and circumstances by which fallow deer came to be established on Barbuda are currently uncertain but, by examining documentary, osteological and genetic evidence, this paper will consider the validity of existing theories. It will review the dynamics of human-Dama relationships from the 1500s AD to the present day and consider how the meaning attached to this species has changed through time: from a symbol of colonial authority and dominance, to a 'walking larder' after the slave emancipation of 1834, and now an important part of the island's economy and cultural heritage that requires careful management