Identification of KasA as the cellular target of an anti-tubercular scaffold

Phenotypic screens for bactericidal compounds are starting to yield promising hits against tuberculosis. In this regard, whole-genome sequencing of spontaneous resistant mutants generated against an indazole sulfonamide (GSK3011724A) identifies several specific single-nucleotide polymorphisms in the essential Mycobacterium tuberculosis β-ketoacyl synthase (kas) A gene. Here, this genomic-based target assignment is confirmed by biochemical assays, chemical proteomics and structural resolution of a KasA-GSK3011724A complex by X-ray crystallography. Finally, M. tuberculosis GSK3011724A-resistant mutants increase the in vitro minimum inhibitory concentration and the in vivo 99% effective dose in mice, establishing in vitro and in vivo target engagement. Surprisingly, the lack of target engagement of the related β-ketoacyl synthases (FabH and KasB) suggests a different mode of inhibition when compared with other Kas inhibitors of fatty acid biosynthesis in bacteria. These results clearly identify KasA as the biological target of GSK3011724A and validate this enzyme for further drug discovery efforts against tuberculosis

Remodelling of the angular collagen fiber distribution in cardiovascular tissues

Understanding collagen fiber remodelling is desired to optimize the mechanical conditioning protocols in tissue-engineering of load-bearing cardiovascular structures. Mathematical models offer strong possibilities to gain insight into the mechanisms and mechanical stimuli involved in these remodelling processes. In this study, a framework is proposed to investigate remodelling of angular collagen fiber distribution in cardiovascular tissues. A structurally based model for collagenous cardiovascular tissues is extended with remodelling laws for the collagen architecture, and the model is subsequently applied to the arterial wall and aortic valve. For the arterial wall, the model predicts the presence of two helically arranged families of collagen fibers. A branching, diverging hammock-type fiber architecture is predicted for the aortic valve. It is expected that the proposed model may be of great potential for the design of improved tissue engineering protocols and may give further insight into the pathophysiology of cardiovascular diseases

Unmanned aircraft systems as a new source of disturbance for wildlife: A systematic review.

The use of small Unmanned Aircraft Systems (UAS; also known as "drones") for professional and personal-leisure use is increasing enormously. UAS operate at low altitudes (<500 m) and in any terrain, thus they are susceptible to interact with local fauna, generating a new type of anthropogenic disturbance that has not been systematically evaluated. To address this gap, we performed a review of the existent literature about animals' responses to UAS flights and conducted a pooled analysis of the data to determine the probability and intensity of the disturbance, and to identify the factors influencing animals' reactions towards the small aircraft. We found that wildlife reactions depended on both the UAS attributes (flight pattern, engine type and size of aircraft) and the characteristics of animals themselves (type of animal, life-history stage and level of aggregation). Target-oriented flight patterns, larger UAS sizes, and fuel-powered (noisier) engines evoked the strongest reactions in wildlife. Animals during the non-breeding period and in large groups were more likely to show behavioral reactions to UAS, and birds are more prone to react than other taxa. We discuss the implications of these results in the context of wildlife disturbance and suggest guidelines for conservationists, users and manufacturers to minimize the impact of UAS. In addition, we propose that the legal framework needs to be adapted so that appropriate actions can be undertaken when wildlife is negatively affected by these emergent practices

Carcass persistence and detectability : reducing the uncertainty surrounding wildlife-vehicle collision surveys

Carcass persistence time and detectability are two main sources of uncertainty on roadkill surveys. In this study, we evaluate the influence of these uncertainties on roadkill surveys and estimates. To estimate carcass persistence time, three observers (including the driver) surveyed 114km by car on a monthly basis for two years, searching for wildlife-vehicle collisions (WVC). Each survey consisted of five consecutive days. To estimate carcass detectability, we randomly selected stretches of 500m to be also surveyed on foot by two other observers (total 292 walked stretches, 146 km walked). We expected that body size of the carcass, road type, presence of scavengers and weather conditions to be the main drivers influencing the carcass persistence times, but their relative importance was unknown. We also expected detectability to be highly dependent on body size. Overall, we recorded low median persistence times (one day) and low detectability (<10%) for all vertebrates. The results indicate that body size and landscape cover (as a surrogate of scavengers' presence) are the major drivers of carcass persistence. Detectability was lower for animals with body mass less than 100g when compared to carcass with higher body mass. We estimated that our recorded mortality rates underestimated actual values of mortality by 2±10 fold. Although persistence times were similar to previous studies, the detectability rates here described are very different from previous studies. The results suggest that detectability is the main source of bias across WVC studies. Therefore, more than persistence times, studies should carefully account for differing detectability when comparing WVC studies

Ecological connectivity in the three-dimensional urban green volume using waveform airborne lidar

This is the final version. Available on open access from Nature Research via the DOI in this record.The movements of organisms and the resultant flows of ecosystem services are strongly shaped by landscape connectivity. Studies of urban ecosystems have relied on two-dimensional (2D) measures of greenspace structure to calculate connectivity. It is now possible to explore three-dimensional (3D) connectivity in urban vegetation using waveform lidar technology that measures the full 3D structure of the canopy. Making use of this technology, here we evaluate urban greenspace 3D connectivity, taking into account the full vertical stratification of the vegetation. Using three towns in southern England, UK, all with varying greenspace structures, we describe and compare the structural and functional connectivity using both traditional 2D greenspace models and waveform lidar-generated vegetation strata (namely, grass, shrubs and trees). Measures of connectivity derived from 3D greenspace are lower than those derived from 2D models, as the latter assumes that all vertical vegetation strata are connected, which is rarely true. Fragmented landscapes that have more complex 3D vegetation showed greater functional connectivity and we found highest 2D to 3D functional connectivity biases for short dispersal capacities of organisms (6 m to 16 m). These findings are particularly pertinent in urban systems where the distribution of greenspace is critical for delivery of ecosystem services.This work was funded under the NERC Biodiversity and Ecosystem Services Sustainability (BESS) thematic programme for the ‘Fragments Functions and Flows in Urban Ecosystems’ project (Reference: NE/J015237/1; http://bess-urban.group.shef.ac.uk/). The waveform ALS data were acquired by the NERC Airborne Research and Survey Facility (ARSF) and the team from the ARSF Data Analysis Node at Plymouth Marine Laboratory is acknowledged for undertaking initial ALS processing

Observation of Electroweak Production of a Same-Sign W Boson Pair in Association with Two Jets in pp Collisions root s=13 TeV with the ATLAS Detector

This Letter presents the observation and measurement of electroweak production of a same-sign W boson pair in association with two jets using 36.1     fb − 1 of proton-proton collision data recorded at a center-of-mass energy of √ s = 13     TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed in the detector fiducial phase-space region, defined by the presence of two same-sign leptons, electron or muon, and at least two jets with a large invariant mass and rapidity difference. A total of 122 candidate events are observed for a background expectation of 69 ± 7 events, corresponding to an observed signal significance of 6.5 standard deviations. The measured fiducial signal cross section is σ fid = 2.89 + 0.51 − 0.48 ( stat ) + 0.29 − 0.28 ( syst )     fb

A search for pair-produced resonances in four-jet final states at root s=13 TeV with the ATLAS detector

A search for massive coloured resonances which are pair-produced and decay into two jets is presented. The analysis uses 36.7 fb−1 − 1 of √ s = 13 TeV pp collision data recorded by the ATLAS experiment at the LHC in 2015 and 2016. No significant deviation from the background prediction is observed. Results are interpreted in a SUSY simplified model where the lightest supersymmetric particle is the top squark, ̃ t ~ , which decays promptly into two quarks through R-parity-violating couplings. Top squarks with masses in the range 100 GeV<̃<410 100 GeV < m t ~ < 410 GeV GeV are excluded at 95% confidence level. If the decay is into a b-quark and a light quark, a dedicated selection requiring two b-tags is used to exclude masses in the ranges 100 GeV<̃<470 100 GeV < m t ~ < 470 GeV GeV and 480 GeV<̃<610 480 GeV < m t ~ < 610 GeV GeV . Additional limits are set on the pair-production of massive colour-octet resonances

Determination of the strong coupling constant αs from transverse energy–energy correlations in multijet events at s√=8 TeV using the ATLAS detector

Measurements of transverse energy–energy correlations and their associated asymmetries in multi-jet events using the ATLAS detector at the LHC are presented. The data used correspond to s√=8 TeV proton–proton collisions with an integrated luminosity of 20.2 fb−1 . The results are presented in bins of the scalar sum of the transverse momenta of the two leading jets, unfolded to the particle level and compared to the predictions from Monte Carlo simulations. A comparison with next-to-leading-order perturbative QCD is also performed, showing excellent agreement within the uncertainties. From this comparison, the value of the strong coupling constant is extracted for different energy regimes, thus testing the running of αs(μ) predicted in QCD up to scales over 1 TeV . A global fit to the transverse energy–energy correlation distributions yields αs(mZ)=0.1162±0.0011(exp.) +0.0084−0.0070(theo.) , while a global fit to the asymmetry distributions yields a value of αs(mZ)=0.1196±0.0013(exp.) +0.0075−0.0045(theo.)

Search for new phenomena in high-mass diphoton final states using 37 fb−1 of proton–proton collisions collected at √s = 13 TeV with the ATLAS detector

Searches for new phenomena in high-mass diphoton final states with the ATLAS experiment at the LHC are presented. The analysis is based on pp collision data corresponding to an integrated luminosity of 36.7 fb−1 at a centre-of-mass energy √s = 13 TeV recorded in 2015 and 2016. Searches are performed for resonances with spin 0, as predicted by theories with an extended Higgs sector, and for resonances with spin 2, using a warped extra-dimension model as a benchmark model, as well as for non-resonant signals, assuming a large extra-dimension scenario. No significant deviation from the Standard Model is observed. Upper limits are placed on the production cross section times branching ratio to two photons as a function of the resonance mass. In addition, lower limits are set on the ultraviolet cutoff scale in the large extra-dimensions model

Search for dark matter in association with a Higgs boson decaying to two photons at root s=13 TeV with the ATLAS detector

A search for dark matter in association with a Higgs boson decaying to two photons is presented. This study is based on data collected with the ATLAS detector, corresponding to an integrated luminosity of 36.1     fb − 1 of proton-proton collisions at the LHC at a center-of-mass energy of 13 TeV in 2015 and 2016. No significant excess over the expected background is observed. Upper limits at 95% confidence level are set on the visible cross section for beyond the Standard Model physics processes, and the production cross section times branching fraction of the Standard Model Higgs boson decaying into two photons in association with missing transverse momentum in three different benchmark models. Limits at 95% confidence level are also set on the observed signal in two-dimensional mass planes. Additionally, the results are interpreted in terms of 90% confidence-level limits on the dark-matter–nucleon scattering cross section, as a function of the dark-matter particle mass, for a spin-independent scenario