The Transit Light Source Effect: False Spectral Features and Incorrect Densities for M-dwarf Transiting Planets

Transmission spectra are differential measurements that utilize stellar illumination to probe transiting exoplanet atmospheres. Any spectral difference between the illuminating light source and the disk-integrated stellar spectrum due to starspots and faculae will be imprinted in the observed transmission spectrum. However, few constraints exist for the extent of photospheric heterogeneities in M dwarfs. Here, we model spot and faculae covering fractions consistent with observed photometric variabilities for M dwarfs and the associated 0.3-5.5 $\mu$m stellar contamination spectra. We find that large ranges of spot and faculae covering fractions are consistent with observations and corrections assuming a linear relation between variability amplitude and covering fractions generally underestimate the stellar contamination. Using realistic estimates for spot and faculae covering fractions, we find stellar contamination can be more than $10 \times$ larger than transit depth changes expected for atmospheric features in rocky exoplanets. We also find that stellar spectral contamination can lead to systematic errors in radius and therefore the derived density of small planets. In the case of the TRAPPIST-1 system, we show that TRAPPIST-1's rotational variability is consistent with spot covering fractions $f_{spot} = 8^{+18}_{-7}\%$ and faculae covering fractions $f_{fac} = 54^{+16}_{-46}\%$. The associated stellar contamination signals alter transit depths of the TRAPPIST-1 planets at wavelengths of interest for planetary atmospheric species by roughly 1-15 $\times$ the strength of planetary features, significantly complicating $JWST$ follow-up observations of this system. Similarly, we find stellar contamination can lead to underestimates of bulk densities of the TRAPPIST-1 planets of $\Delta(\rho) = -3^{+3}_{-8} \%$, thus leading to overestimates of their volatile contents.Comment: accepted for publication in Ap

Web-based Gene Pathogenicity Analysis (WGPA): a web platform to interpret gene pathogenicity from personal genome data

UNLABELLED: As the volume of patient-specific genome sequences increases the focus of biomedical research is switching from the detection of disease-mutations to their interpretation. To this end a number of techniques have been developed that use mutation data collected within a population to predict whether individual genes are likely to be disease-causing or not. As both sequence data and associated analysis tools proliferate, it becomes increasingly difficult for the community to make sense of these data and their implications. Moreover, no single analysis tool is likely to capture all relevant genomic features that contribute to the gene's pathogenicity. Here, we introduce Web-based Gene Pathogenicity Analysis (WGPA), a web-based tool to analyze genes impacted by mutations and rank them through the integration of existing prioritization tools, which assess different aspects of gene pathogenicity using population-level sequence data. Additionally, to explore the polygenic contribution of mutations to disease, WGPA implements gene set enrichment analysis to prioritize disease-causing genes and gene interaction networks, therefore providing a comprehensive annotation of personal genomes data in disease. AVAILABILITY AND IMPLEMENTATION: wgpa.systems-genetics.net

The legacy of 20th Century landscape change on today’s woodland carabid communities

Aim For many species, the effects of landscape change can involve a time lag and result in an extinction debt. The landscape matrix plays a vital role in supporting species populations. However, the importance of the historical composition and configuration of landscape mosaics has received little attention, with studies focusing on the effects of loss and fragmentation of single (focal) habitat over time. We investigated the importance of historical and contemporary landscape heterogeneity (composition and configuration) to identify how landscape change has, and is continuing to have, an effect on current woodland carabid communities. Location Lowland Britain. Methods Carabids were sampled from woodlands in 36 tetrads of 4 km2. Ordination methods analysed current community response to representations of contemporary and historical (1930’s) landscape heterogeneity. The effects of 80 years of landscape change on current carabid assemblages were compared among tetrads. Results Results are consistent with an extinction debt; carabid communities correlated significantly with the historical composition and configuration of the landscape, but not contemporary landscape configuration. Community assemblages have been shaped, and many species remain affiliated with landscape conditions that no longer exist, notably, large patches of broadleaf woodland and semi-natural grassland. Recent introduction of conifer plantations has had a negative effect on the abundance of many woodland species. For many common, slow-dispersing species, contemporary and historical landscapes offered sub-optimum woodland coverage indicating a lag effect that exceeds 80 years. Increased arable landcover and loss of semi-natural grassland and heathland points towards an ongoing detrimental impact on carabid populations. Main conclusions Compared with focal-habitat studies, the landscape mosaic approach provides a more comprehensive understanding of the effects of widespread landscape change on species communities. Conservation guidance includes new planting, maintenance and restoration of semi-natural habitats, implemented across multiple spatial scales and where feasible, considering both historical and contemporary landscape heterogeneity

Discovery of a family of γ-aminobutyrate ureas via rational derepression of a silent bacterial gene cluster

Gaburedins, a family of γ-aminobutyrate (GABA)-derived ureas, have been discovered by deletion of gbnR, an arpA-like putative transcriptional repressor in Streptomyces venezuelae ATCC 10712. Comparison of metabolite profiles in the wild type and mutant strains revealed six metabolites in the mutant that are lacking from the wild type. The structure of gaburedin A was established by HRMS combined with 1- and 2-D NMR spectroscopy and was confirmed by total synthesis. The other metabolites were confirmed as congeners using HRMS, MS/MS and feeding of putative biosynthetic precursors. Two genes, gbnA and gbnB, are proposed to be involved in gaburedin biosynthesis. Consistent with this hypothesis, deletion of gbnB in the gbnR mutant abolished gaburedin production. This is the first report to disclose the discovery of novel natural products via rational deletion of a putative pathway-specific regulatory gene

Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins

Human mitochondrial long noncoding RNAs (lncRNAs) have not been described to date. By analysis of deep-sequencing data we have identified three lncRNAs generated from the mitochondrial genome and confirmed their expression by Northern blotting and strand-specific qRT-PCR. We show that the abundance of these lncRNAs is comparable to their complementary mRNAs and that nuclear-encoded mitochondrial proteins involved in RNA processing regulate their expression. We also identify the 5′ and 3′ transcript ends of the three lncRNAs and show that mitochondrial RNase P protein 1 (MRPP1) is important for the processing of these transcripts. Finally, we show that mitochondrial lncRNAs form intermolecular duplexes and that their abundance is cell- and tissue-specific, suggesting a functional role in the regulation of mitochondrial gene expression. Published by Cold Spring Harbor Laboratory Press

Diverse modes of binding in structures of Leishmania major N-myristoyltransferase with selective inhibitors

The leishmaniases are a spectrum of global diseases of poverty associated with immune dysfunction and are the cause of high morbidity. Despite the long history of these diseases, no effective vaccine is available and the currently used drugs are variously compromised by moderate efficacy, complex side effects and the emergence of resistance. It is therefore widely accepted that new therapies are needed. N-Myristoyltransferase (NMT) has been validated pre-clinically as a target for the treatment of fungal and parasitic infections. In a previously reported high-throughput screening program, a number of hit compounds with activity against NMT from Leishmania donovani have been identified. Here, high-resolution crystal structures of representative compounds from four hit series in ternary complexes with myristoyl-CoA and NMT from the closely related L. major are reported. The structures reveal that the inhibitors associate with the peptide-binding groove at a site adjacent to the bound myristoyl-CoA and the catalytic -carboxylate of Leu421. Each inhibitor makes extensive apolar contacts as well as a small number of polar contacts with the protein. Remarkably, the compounds exploit different features of the peptide-binding groove and collectively occupy a substantial volume of this pocket, suggesting that there is potential for the design of chimaeric inhibitors with significantly enhanced binding. Despite the high conservation of the active sites of the parasite and human NMTs, the inhibitors act selectively over the host enzyme. The role of conformational flexibility in the side chain of Tyr217 in conferring selectivity is discussed