ALBERT

Description: Eccentric millisecond pulsars (eMSPs) with white dwarf companions exhibit orbital eccentricities orders of magnitude larger than predicted by turbulent convection in the white dwarfs’ red giant progenitors. The orbital periods of eMSPs cluster around P = 20–30 d, remarkably close to the red giant convective eddy turnover time teddy. We propose that the anomalously large eccentricities are resonantly driven by convective flows somehow made coherent when the turnover time matches the tidally locked red giant’s spin period, which is also the tidal forcing period. Numerical simulations of rotating red giants and magnetic field studies of stars show some evidence for especially ordered flow patterns when the convective Rossby number P/teddy is of order unity. We show that resonant convection boosts eccentricities by a factor of (tnuc/P)1/2 ≈ 3 × 103 over the random-walk values that characterize conventional MSPs, in good agreement with observations (tnuc is the giant’s nuclear burning time-scale). We also show how variations in the eddy turnover time arising from red giant metallicity variations can reproduce the observed effective width of the resonance, ΔP/P ≈ 0.4.

Description: The long-term evolutionary impacts of whole genome duplication (WGD) are strongly influenced by the ensuing rediploidization process. Following autopolyploidization, rediploidization involves a transition from tetraploid to diploid meiotic pairing, allowing duplicated genes (ohnologues) to diverge genetically and functionally. Our understanding of autopolyploid rediploidization has been informed by a WGD event ancestral to salmonid fishes, where large genomic regions are characterized by temporally delayed rediploidization, allowing lineage-specific ohnologue sequence divergence in the major salmonid clades. Here, we investigate the long-term outcomes of autopolyploid rediploidization at genome-wide resolution, exploiting a recent ‘explosion’ of salmonid genome assemblies, including a new genome sequence for the huchen (Hucho hucho). We developed a genome alignment approach to capture duplicated regions across multiple species, allowing us to create 121,864 phylogenetic trees describing genome-wide ohnologue divergence across salmonid evolution. Using molecular clock analysis, we show that 61% of the ancestral salmonid genome experienced an initial ‘wave’ of rediploidization in the late Cretaceous (85-106 Mya). This was followed by a period of relative genomic stasis lasting 17-39 My, where much of the genome remained tetraploid. A second rediploidization wave began in the early Eocene and proceeded alongside species diversification, generating predictable patterns of lineage-specific ohnologue divergence, scaling in complexity with the number of speciation events. Using gene set enrichment, gene expression, and codon-based selection analyses, we provide insights into potential functional outcomes of delayed rediploidization. This study enhances our understanding of delayed autopolyploid rediploidization and has broad implications for future studies of WGD events.

Description: To assess the number of life-bearing worlds in astrophysical environments, it is necessary to take the intertwined processes of abiogenesis (birth), extinction (death), and transfer of life (migration) into account. We construct a mathematical model that incorporates this trio of mechanisms and accordingly derive the probability distribution function and other statistical properties (e.g. mean) for the number of worlds with biospheres. We show that a given astrophysical setting may become eventually saturated with life if the rate of successful transfers of organisms is higher than the extinction rate of biospheres. Based on the available data, we suggest that this criterion might be fulfilled for star-forming clusters (and perhaps the Galactic bulge under optimal circumstances), thereby indicating that such regions could constitute promising abodes for hosting and detecting life.

Description: We present a search for disturbed, candidate ram pressure stripping galaxies across more than 50 spectroscopically selected SDSS groups and clusters. Forty-eight ram pressure candidates are visually identified in these systems using high quality UNIONS imaging from the Canada-France Hawaii Telescope, covering ∼6200 deg2 and ∼2800 deg2 in the u- and r-bands respectively. Ram pressure candidates are found in groups and clusters spanning a wide range in halo mass and include ∼30 ram pressure candidates in the group regime (Mh 〈 1014). The observed frequency of ram pressure candidates shows substantial scatter with group/cluster mass, but on average is larger in clusters (Mh ≥ 1014 M⊙) than groups (Mh 〈 1014 M⊙) by a factor of ∼2. We find that ram pressure candidates are most commonly low-mass galaxies and have enhanced star formation rates relative to star-forming field galaxies. The enhancement in star formation is largely independent of galaxy mass and strongest for galaxies in clusters. As a result of the large survey footprint and excellent image quality from UNIONS, we are able to identify disturbed galaxies, potentially affected by ram pressure stripping, across a wide range of host environment.

Description: We present a comprehensive study of three large long-duration flares detected on an active M-dwarf binary EQ Peg using the Soft X-Ray Telescope of the AstroSat observatory. The peak X-ray luminosities of the flares in the 0.3–7 keV band are found to be within ∼5–10 ×  1030 $ m {erg}~ m {s}^{-1}$. The e-folding rise- and decay-times of the flares are derived to be in the range of 3.4–11 and 1.6–24 ks, respectively. Spectral analysis indicates the presence of three temperature corona with the first two plasma temperatures remain constant during all the flares and the post-flare observation at ∼3 and ∼9 MK. The flare temperature peaked at 26, 16, and 17 MK, which are 2, 1.3, and 1.4 times more than the minimum value, respectively. The peak emission measures are found to be 3.9–7.1 ×  1053 cm−3, whereas the abundances peaked at 0.16–0.26 times the solar abundances. Using quasi-static loop modelling, we derive loop-lengths for all the flares as 2.5±0.5 ×  1011, 2.0 ± 0.5 ×  1011, and 2.5 ± 0.9 ×  1011 cm, respectively. The density of the flaring plasma is estimated to be 4.2 ± 0.8 ×  1010, 3.0 ± 0.7 ×  1010, 2.2 ± 0.8 ×  1010 cm−3 for flares F1, F2, and F3, respectively. Whereas the magnetic field for all three flares is estimated to be

Description: Summary We have studied the active and recent tectonics of New Guinea, using earthquake source modelling, analysis of gravity anomalies, seismic reflection profiles, and thermal and mechanical models. Our aim is to investigate the behaviour and evolution of a young continental deformation belt, and to explore the effects of lateral variations in foreland rheology on the deformation. We find that along-strike gradients in the lithosphere thickness of the southern foreland have resulted in correlated changes in seismogenic thickness, likely due to the effects on the temperature structure of the crust. The resulting variation in the strength of the foreland means that in the east, the foreland is broken through on thrust faults, whereas in the west it is relatively intact. The lack of correlation between the elevation of the mountain belt and the seismogenic thickness of the foreland is likely to be due to the time taken to thicken the crust in the mountains following changes in the rheology of the underthrusting foreland, as the thinned passive margin of northern Australia is consumed. The along-strike variation in whether the force exerted between the mountains and the lowlands is able to break the foreland crust enables us to estimate the effective coefficient of friction on foreland faults to be in the range of 0.01-0.28. We use force-balance calculations to show that the recent tectonic re-organisation in western New Guinea is likely to be due to the development of increasing curvature in the Banda Arc, and that the impingement of continental material on the subduction zone may explain the unusually low force it exerts on western New Guinea.

Description: Almost twenty years after its initial release, the Eukaryotic Linear Motif (ELM) resource remains an invaluable source of information for the study of motif-mediated protein-protein interactions. ELM provides a comprehensive, regularly updated and well-organised repository of manually curated, experimentally validated short linear motifs (SLiMs). An increasing number of SLiM-mediated interactions are discovered each year and keeping the resource up-to-date continues to be a great challenge. In the current update, 30 novel motif classes have been added and five existing classes have undergone major revisions. The update includes 411 new motif instances mostly focused on cell-cycle regulation, control of the actin cytoskeleton, membrane remodelling and vesicle trafficking pathways, liquid-liquid phase separation and integrin signalling. Many of the newly annotated motif-mediated interactions are targets of pathogenic motif mimicry by viral, bacterial or eukaryotic pathogens, providing invaluable insights into the molecular mechanisms underlying infectious diseases. The current ELM release includes 317 motif classes incorporating 3934 individual motif instances manually curated from 3867 scientific publications. ELM is available at: http://elm.eu.org.

Description: Summary On 2020 December 29, the Mw 6.4 Petrinja earthquake hit the Kupa Valley region and set a record for the largest earthquake in northwestern (NW) Croatia. The coseismic surface displacements are well obtained on three pairs of interferometric synthetic aperture radar (InSAR) images from Sentinel-1 satellites. The interferograms exhibit coseismic ground deformation with a maximum line-of-sight (LOS) displacement of 0.4 m. Based on the coseismic deformation field, we investigate both the fault geometry and the coseismic slip distribution. The results show a dextral event with a peak slip of 3.50 m at a depth of 3.47 km. The shallow depth and unusually large coseismic slip correspond to obvious ground deformation and serious damage in the epicentral zone. The 2020 earthquake highlights an unmapped, steeply dipping strike-slip fault, which possibly enabled a potential ‘curve cut-off’ process on the bending segment of the Pokupsko fault in the context of ∼N-S compression in NW Croatia. The large coseismic slip and high stress drop associated with the Mw 6.4 Petrinja earthquake are likely products of the geometrically complex fault zones and immature seismotectonic environment in NW Croatia.

Description: Pathogenic variants that disrupt human mitochondrial protein synthesis are associated with a clinically heterogenous group of diseases. Despite an impairment in oxidative phosphorylation being a common phenotype, the underlying molecular pathogenesis is more complex than simply a bioenergetic deficiency. Currently, we have limited mechanistic understanding on the scope by which a primary defect in mitochondrial protein synthesis contributes to organelle dysfunction. Since the proteins encoded in the mitochondrial genome are hydrophobic and need co-translational insertion into a lipid bilayer, responsive quality control mechanisms are required to resolve aberrations that arise with the synthesis of truncated and misfolded proteins. Here, we show that defects in the OXA1L-mediated insertion of MT-ATP6 nascent chains into the mitochondrial inner membrane are rapidly resolved by the AFG3L2 protease complex. Using pathogenic MT-ATP6 variants, we then reveal discrete steps in this quality control mechanism and the differential functional consequences to mitochondrial gene expression. The inherent ability of a given cell type to recognize and resolve impairments in mitochondrial protein synthesis may in part contribute at the molecular level to the wide clinical spectrum of these disorders.

Description: Motivation Coiled-coil is composed of two or more helices that are wound around each other. It widely exists in proteins and has been discovered to play a variety of critical roles in biology processes. Generally, there are three types of structural features in coiled-coil: coiled-coil domain (CCD), oligomeric state, and register. However, most of the existing computational tools only focus on one of them. Results Here, we describe a new deep learning model, CoCoPRED, which is based on convolutional layers, bidirectional long short-term memory, and attention mechanism. It has three networks, i.e., CCD network, oligomeric state network, and register network, corresponding to the three types of structural features in coiled-coil. This means CoCoPRED has the ability of fulfilling comprehensive prediction for coiled-coil proteins. Through the 5-fold cross-validation experiment, we demonstrate that CoCoPRED can achieve better performance than the state-of-the-art models on both CCD prediction and oligomeric state prediction. Further analysis suggests the CCD prediction may be a performance indicator of the oligomeric state prediction in CoCoPRED. The attention heads in CoCoPRED indicate that registers a, b, and e are more crucial for the oligomeric state prediction. Availability CoCoPRED is available at http://www.csbio.sjtu.edu.cn/bioinf/CoCoPRED. Supplementary information Supplementary data are available at Bioinformatics online.

Description: Studies of planetary systems of stars in star-forming regions and young clusters open a window on the formative stages of planetary evolution. We obtained high-cadence high-resolution infrared spectroscopy of the solar-mass Taurus association-member V1298 Tau during a transit of its 10R⊕-size ‘b’ planet. We measured the systemic radial velocity and find that the kinematics of V1298 Tau suggest an affiliation with a ≳6 Myr-old subgroup. A comparison of V1298 Tau and the nearby, co-moving star 2M0405 with stellar evolution models suggests an age of ∼10-25 Myr. We measured the projected spin-orbit angle of ‘b’ as $lambda =15_{-16}^{+15}$ and $lambda = 2_{-4}^{+12}$ degrees using the apparent RV shift and change in line profile, respectively, induced by the transient occultation of the rotating star by the planet. These values indicate a prograde orbit like that of the interior ‘c’ planet of V1298 Tau and point to a co-planar multi-planet system that formed within a disk. We also measured variation in the strength of the 1083 nm triplet of neutral orthohelium as a probe of any extended/escaping atmosphere around ‘b’. We detect a steady decrease in absorption over the transit which appears to arise from the star or its planetary system. While this variation could be ascribed to ‘b’ or possibly to the immediately preceding transit of ‘d’, we cannot rule out that this is due to rapid variation in the stellar disk-integrated flux in the triplet. The amplitude of variation (∼0.04 nm) is consistent with moderate estimates of atmospheric escape driven by XUV radiation from the central star.

Description: We present light curve analyses of two newly identified detached eclipsing binaries, HD 96609 and HD 303734, in the region of the richly populated open cluster NGC 3532. HD 96609 is composed of two main sequence stars (B9-A0V + A2V) with masses and radii of M1 = 2.66 ± 0.02M⊙, M2 = 1.84 ± 0.01M⊙, R1 = 2.740 ± 0.006R⊙, R2 = 1.697 ± 0.005R⊙. The positions of the components on log M − log R plane suggests log(age/yr) 8.55, corresponding 350 ± 40 Myr of age, which agrees with the 300 ± 100 Myr age of NGC 3532 estimated in previous studies. We find the distance of HD 96609 as 460 ± 17 pc, which is consistent with the $484^{+35}_{-30}$ pc distance of NGC 3532, estimated from GAIA parallaxes. HD 303734 is an interesting totally eclipsing binary with a quite shallow secondary eclipse. Using photometric properties of the system in conjunction with theoretical calibrations, we estimate that HD 303734 consists of A6V + K3V components. HD 96609 and HD 303734 are the second and third eclipsing binaries discovered in the region of NGC 3532, after the first one, GV Car.

Description: We propose a novel approach to obtain the growth rate of cosmic structures, f(z), from the evolution of the cosmic homogeneity scale, RH(z). Our methodology needs two ingredients in a specific functional form: RH(z) data and the matter two-point correlation function today, i.e., ξ(r, z = 0). We use a Gaussian Process approach to reconstruct the function RH. In the absence of suitable observational information of the matter correlation function in the local Universe, z ≃ 0, we assume a fiducial cosmology to obtain ξ(r, z = 0). For this reason, our final result turns out to be a consistency test of the cosmological model assumed. Our results show a good agreement between: (i) the growth rate $f^{R_{ext{H}}}(z)$ obtained through our approach, (ii) the fΛCDM(z) expected in the fiducial model, and (iii) the best-fit f(z) from data compiled in the literature. Moreover, using this data compilation, we perform a Gaussian Process to reconstruct the growth rate function fdata(z) and compare it with the function $f^{R_{ext{H}}}(z)$ finding a concordance of

Description: Motivation Adverse Outcome Pathways (AOPs) are a conceptual framework developed to support the use of alternative toxicology approaches in the risk assessment. AOPs are structured linear organizations of existing knowledge illustrating causal pathways from the initial molecular perturbation triggered by various stressors, through key events (KEs) at different levels of biology, to the ultimate health or ecotoxicological adverse outcome. Results Artificial intelligence can be used to systematically explore available toxicological data that can be parsed in the scientific literature. Recently a tool called AOP-helpFinder was developed to identify associations between stressors and KEs supporting thus documentation of AOPs. To facilitate the utilization of this advanced bioinformatics tool by the scientific and the regulatory community, a webserver was created. The proposed AOP-helpFinder webserver uses better performing version of the tool which reduces the need for manual curation of the obtained results. As an example, the server was successfully applied to explore relationships of a set of endocrine disruptors with metabolic-related events. The AOP-helpFinder webserver assists in a rapid evaluation of existing knowledge stored in the PubMed database, a global resource of scientific information, to build AOPs and Adverse Outcome Networks (AONs) supporting the chemical risk assessment. Availability and implementation AOP-helpFinder is available at http://aop-helpfinder.u-paris-sciences.fr/index.php

Description: Motivation Differential network inference is a fundamental and challenging problem to reveal gene interactions and regulation relationships under different conditions. Many algorithms have been developed for this problem; however, they do not consider the differences between the importance of genes, which may not fit the real-world situation. Different genes have different mutation probabilities, and the vital genes associated with basic life activities have less fault tolerance to mutation. Equally treating all genes may bias the results of differential network inference. Thus, it is necessary to consider the importance of genes in the models of differential network inference. Results Based on the Gaussian graphical model with adaptive gene importance regularization, we develop a novel importance-penalized joint graphical Lasso method, IPJGL, for differential network inference. The presented method is validated by the simulation experiments as well as the real datasets. Furthermore, to precisely evaluate the results of differential network inference, we propose a new metric named APC2 for the differential levels of gene pairs. We apply IPJGL to analyze the TCGA colorectal and breast cancer datasets and find some candidate cancer genes with significant survival analysis results, including SOST for colorectal cancer and RBBP8 for breast cancer. We also conduct further analysis based on the interactions in the Reactome database and confirm the utility of our method. Availability R source code of importance-penalized joint graphical lasso is freely available at https://github.com/Wu-Lab/IPJGL. Supplementary information Supplementary materials are available at Bioinformatics online.

Description: Evolutionary radiation is a widely recognized mode of species diversification, but its underlying mechanisms have not been unambiguously resolved for species-rich cosmopolitan plant genera. In particular, it remains largely unknown how biological and environmental factors have jointly driven its occurrence in specific regions. Here we use Rhododendron, the largest genus of woody plants in the Northern Hemisphere, to investigate how geographic and climatic factors, as well as functional traits, worked together to trigger plant evolutionary radiations and shape the global patterns of species richness based on a solid species phylogeny. Using 3437 orthologous nuclear genes, we reconstructed the first highly supported and dated backbone phylogeny of Rhododendron comprising 200 species that represent all subgenera, sections, and nearly all multi-species subsections, and found that most extant species originated by evolutionary radiations when the genus migrated southwards from circumboreal areas to tropical/subtropical mountains, showing rapid increases of both net diversification rate and evolutionary rate of environmental factors in the Miocene. We also found that the geographically uneven diversification of Rhododendron led to a much higher diversity in Asia than in other continents, which was mainly driven by two environmental variables, i.e., elevation range and annual precipitation, and were further strengthened by the adaptation of leaf functional traits. Our study provides a good example of integrating phylogenomic and ecological analyses in deciphering the mechanisms of plant evolutionary radiations, and sheds new light on how the intensification of the Asian monsoon has driven evolutionary radiations in large plant genera of the Himalaya-Hengduan Mountains.

Description: Motivation The adoption of current single-cell DNA methylation sequencing protocols is hindered by incomplete coverage, outlining the need for effective imputation techniques. The task of imputing single-cell (methylation) data requires models to build an understanding of underlying biological processes. Results We adapt the transformer neural network architecture to operate on methylation matrices through combining axial attention with sliding window self-attention. The obtained CpG Transformer displays state-of-the-art performances on a wide range of scBS-seq and scRRBS-seq datasets. Furthermore, we demonstrate the interpretability of CpG Transformer and illustrate its rapid transfer learning properties, allowing practitioners to train models on new datasets with a limited computational and time budget. Availability and Implementation CpG Transformer is freely available at https://github.com/gdewael/cpg-transformer. Supplementary information Supplementary data are available at Bioinformatics online.

Description: High mass proto-stars create Ultra-Compact H ii regions (UCHII) at the stage of evolution when most of the accretion is finished but the star is still heavily embedded in molecular material. The morphologies of UCHII regions reflect the interactions of stellar winds, stellar motions, and density structure in the molecular cloud; they are complex and it has been very difficult to interpret them. We here present data obtained with TEXES on the NASA IRTF of the [Nei,ii] emission line in the proto-cluster of young OB stars in W33 Main. The data cube has a spatial resolution of ∼1.4 arcsec and true velocity resolution ∼5 km s-1; with Aλ ∼ 0.02AV it is relatively unaffected by extinction. We have run 3D hydrodynamic and line profile simulations, using PLUTO and RADMC-3D, of the gas structures created by multiple windy stars moving relative to each other through the ambient cloud. By iterative comparison of the data cube and the simulations, we arrive at models that reproduce the different morphology and kinematic structure of each UCHII region in W33 Main. The results indicate that each sub-source probably holds multiple exciting stars, permitting an improved view of the stellar population, and finds the stellar trajectories, which may determine the dynamical development of the proto-cluster.

Description: Bayesian evidence ratios are widely used to quantify the statistical consistency between different experiments. However, since the evidence ratio is prior dependent, the precise translation between its value and the degree of concordance/discordance requires additional information. The most commonly adopted metric, the Jeffreys scale, can falsely suggest agreement between datasets when priors are chosen to be sufficiently wide. This work examines evidence ratios in a DES-Y1 simulated analysis, focusing on the internal consistency between weak lensing and galaxy clustering. We study two scenarios using simulated data in controlled experiments. First, we calibrate the expected evidence ratio distribution given noise realizations around the best fit DES-Y1 ΛCDM cosmology. Second, we show the behavior of evidence ratios for noiseless fiducial data vectors simulated using a modified gravity model, which generates internal tension in the LCDM analysis. We find that the evidence ratio of noise realizations generated at all confidence levels was biased towards agreement and show, with a modified gravity model, that the choice of prior could conceal the discrepancies between weak lensing and galaxy clustering induced by prior effects in unlike cosmological models, concluding that the evidence ratio in a DES-Y1 study is, indeed, biased towards agreement. Boundary effects can also influence conclusions about the inconsistency induced by modified gravity, even in a noiseless data vector simulation.

Description: Detailed spectropolarimetric studies may hold the key to probing the explosion mechanisms and the progenitor scenarios of Type Ia supernovae (SNe Ia). We present multi-epoch spectropolarimetry and imaging polarimetry of SN 2019ein, an SN Ia showing high expansion velocities at early phases. The spectropolarimetry sequence spans from ∼−11 to +10 days relative to peak brightness in the B-band. We find that the level of the continuum polarization of SN 2019ein, after subtracting estimated interstellar polarization, is in the range 0.0–0.3%, typical for SNe Ia. The polarization position angle remains roughly constant before and after the SN light-curve peak, implying that the inner regions share the same axisymmetry as the outer layers. We observe high polarization ($sim 1\%$) across both the Si ii λ6355 and Ca ii near-infrared triplet features. These two lines also display complex polarization modulations. The spectropolarimetric properties of SN 2019ein rule out a significant departure from spherical symmetry of the ejecta for up to a month after the explosion. These observations disfavour merger-induced and double-detonation models for SN 2019ein. The imaging polarimetry shows weak evidence for a modest increase in polarization after ∼20 days since the B-band maximum. If this rise is real and is observed in other SNe Ia at similar phases, we may have seen, for the first time, an aspherical interior similar to what has been previously observed for SNe IIP. Future polarization observations of SNe Ia extending to post-peak epochs will help to examine the inner structure of the explosion.

Description: Summary We deployed a seismic network near the source region of the 2017 Mw 6.5 Jiuzhaigou earthquake to monitor aftershock activity and to investigate the local fault structure. An aftershock deployment of Array of small Arrays (AsA) and a Geometric Mean Envelop (GME) algorithm are adopted to enhance detection performance. We also adopt a set of association, relocation, and matched-filter techniques to obtain a detailed regional catalog. 16,742 events are detected and relocated, including 1,279 aftershocks following the Mw 4.8 aftershock. We develop a joint inversion algorithm utilizing locations of event clusters and focal mechanisms to determine the geometry of planar faults. Six segments were finally determined, in which three segments are related to the Huya fault reflecting a change in fault dip direction near the mainshock hypocenter, while the other segments reflect branches showing orthogonal and conjugate geometries with the Huya fault. Aftershocks were active on branching faults between the Huya and Minjiang faults indicating that the mainshock may have ruptured both major faults. We also resolve a fault portion with ‘weak strength’ near the mainshock hypocenter, which is characterized by limited co-seismic slips, concentrated afterslip, low aftershock activities, high b-value, and high sensitivity to stress changes. These phenomena can be explained by fault frictional properties at conditional stable sliding status, which may be related to the localized high pore-fluid pressure produced by the fluid intrusion.

Description: We study gravitational lensing of gravitational waves from compact object binaries as a probe of compact dark matter (DM) objects such as primordial black holes. Assuming a point mass lens, we perform parameter estimation of lensed gravitational wave signals from compact object binaries to determine the detectability of the lens with ground based laser interferometers. Then, considering binary populations that LIGO-Virgo has been probing, we derive a constraint on the abundance of compact DM from non-observation of lensed events. We find that the LIGO-Virgo observations imply that compact objects heavier than Ml = 200 M⊙ can not constitute all DM and less than $40{{ m per cent}}$ of DM can be in compact objects heavier than Ml = 400 M⊙. We also show that the DM fraction in compact objects can be probed by LIGO in its final sensitivity for Ml 〉 40 M⊙ reaching $2{{ m per cent}}$ of the DM abundance at Ml 〉 200 M⊙, and by ET for Ml 〉 1 M⊙ reaching DM fraction as low as 7 × 10−5 at Ml 〉 40 M⊙.

Description: Genetic variation and phenotypic plasticity are both important to adaptive evolution. However, how they act together on particular traits remains poorly understood. Here, we integrated phenotypic, genomic, and transcriptomic data from two allopatric but closely related congeneric oyster species, Crassostrea angulata from southern/warm environments and Crassostrea gigas from northern/cold environments, to investigate the roles of genetic divergence and plasticity in thermal adaptation. Reciprocal transplantation experiments showed that both species had higher fitness in their native habitats than in nonnative environments, indicating strong adaptive divergence. The southern species evolved higher transcriptional plasticity, and the plasticity was adaptive, suggesting that increased plasticity is important for thermal adaptation to warm climates. Genome-wide comparisons between the two species revealed that genes under selection tended to respond to environmental changes and showed higher sequence divergence in noncoding regions. All genes under selection and related to energy metabolism exhibited habitat-specific expression with genes involved in ATP production and lipid catabolism highly expressed in warm/southern habitats, and genes involved in ATP consumption and lipid synthesis were highly expressed in cold/northern habitats. The gene for acyl-CoA desaturase, a key enzyme for lipid synthesis, showed strong selective sweep in the upstream noncoding region and lower transcription in the southern species. These results were further supported by the lower free fatty acid (FFA) but higher ATP content in southern species and habitat, pointing to significance of ATP/FFA trade-off. Our findings provide evidence that noncoding variation and transcriptional plasticity play important roles in shaping energy metabolism for thermal adaptation in oysters.

Description: Domestication and breeding have reshaped the genomic architecture of chicken, but the retention and loss of genomic elements during these evolutionary processes remain unclear. We present the first chicken pan-genome constructed using 664 individuals, which identified an additional approximately 66.5-Mb sequences that are absent from the reference genome (GRCg6a). The constructed pan-genome encoded 20,491 predicated protein-coding genes, of which higher expression levels are observed in conserved genes relative to dispensable genes. Presence/absence variation (PAV) analyses demonstrated that gene PAV in chicken was shaped by selection, genetic drift, and hybridization. PAV-based genome-wide association studies identified numerous candidate mutations related to growth, carcass composition, meat quality, or physiological traits. Among them, a deletion in the promoter region of IGF2BP1 affecting chicken body size is reported, which is supported by functional studies and extra samples. This is the first time to report the causal variant of chicken body size quantitative trait locus located at chromosome 27 which was repeatedly reported. Therefore, the chicken pan-genome is a useful resource for biological discovery and breeding. It improves our understanding of chicken genome diversity and provides materials to unveil the evolution history of chicken domestication.

Description: Aspect sentiment classification is an important research topic in natural language processing and computational linguistics, assisting in automatically review analysis and emotional tendency judgement. Different from extant methods that focus on text sequence representations, this paper presents a network framework to learn representation from concurrence-words relation graph (LRCWG), so as to improve the Macro-F1 and accuracy. The LRCWG first employs the multi-head attention mechanism to capture the sentiment representation from the sentences which can learn the importance of text sequence representation. And then, it leverages the priori sentiment dictionary information to construct the concurrence relations of sentiment words with Graph Convolution Network (GCN). This assists in that the learnt context representation can keep both the semantics integrity and the features of sentiment concurrence-words relations. The designed algorithm is experimentally evaluated with all the five benchmark datasets and demonstrated that the proposed aspect sentiment classification can significantly improve the prediction performance of learning task.

Description: Penelope-like elements (PLEs) are an enigmatic clade of retrotransposons whose reverse transcriptases (RTs) share a most recent common ancestor with telomerase RTs. The single ORF of canonical endonuclease (EN)+ PLEs encodes RT and a C-terminal GIY–YIG EN that enables intrachromosomal integration, whereas EN− PLEs lack EN and are generally restricted to chromosome termini. EN+ PLEs have only been found in animals, except for one case of horizontal transfer to conifers, whereas EN− PLEs occur in several kingdoms. Here, we report a new, deep-branching PLE clade with a permuted domain order, whereby an N-terminal GIY–YIG EN is linked to a C-terminal RT by a short domain with a characteristic CxC motif. These N-terminal EN+ PLEs share a structural organization, including pseudo-LTRs and complex tandem/inverted insertions, with canonical EN+ PLEs from Penelope/Poseidon, Neptune, and Nematis clades, and show insertion bias for microsatellites, but lack canonical hammerhead ribozyme motifs. However, their phylogenetic distribution is much broader. The Naiads, found in numerous invertebrate phyla, can reach tens of thousands of copies per genome. In spiders and clams, Naiads independently evolved to encode selenoproteins containing multiple selenocysteines. Chlamys, which lack the CCHH motif universal to PLE ENs, occur in green algae, spike mosses (targeting ribosomal DNA), and slime molds. Unlike canonical PLEs, RTs of N-terminal EN+ PLEs contain the insertion-in-fingers domain (IFD), strengthening the link between PLEs and telomerases. Additionally, we describe Hydra, a novel metazoan C-terminal EN+ clade. Overall, we conclude that PLE diversity, taxonomic distribution, and abundance are comparable with non-LTR and LTR-retrotransposons.

Description: In mammals, the placenta mediates maternal–fetal nutrient and waste exchange and acts in an immunomodulatory way to facilitate maternal–fetal tolerance. The placenta is highly diverse across mammalian species, yet the molecular mechanisms that distinguish the placenta of human from other mammals are not fully understood. Using an interspecies transcriptomic comparison of human, macaque, and mouse late-gestation placentae, we identified hundreds of genes with lineage-specific expression—including dozens that are placentally enriched and potentially related to pregnancy. We further annotated the enhancers for different human tissues using epigenomic data and demonstrate that the placenta and chorion are unique in that their enhancers display the least conservation. We identified numerous lineage-specific human placental enhancers and found they highly overlap with specific families of endogenous retroviruses (ERVs), including MER21A, MER41A/B, and MER39B that were previously linked to immune response and placental function. Among these ERV families, we further demonstrate that MER41A/B insertions create dozens of lineage-specific serum response factor-binding loci in human, including one adjacent to FBN2, a placenta-specific gene with increased expression in humans that produces the peptide hormone placensin to stimulate glucose secretion and trophoblast invasion. Overall, our results demonstrate the prevalence of lineage-specific placental enhancers which are frequently associated with ERV insertions and likely facilitate the lineage-specific evolution of the mammalian placenta.

Description: True sea snakes (Hydrophiini) are among the last and most successful clades of vertebrates that show secondary marine adaptation, exhibiting diverse phenotypic traits and lethal venom systems. To better understand their evolution, we generated the first chromosome-level genomes of two representative Hydrophiini snakes, Hydrophis cyanocinctus and H. curtus. Through comparative genomics we identified a great expansion of the underwater olfaction-related V2R gene family, consisting of more than 1,000 copies in both snakes. A series of chromosome rearrangements and genomic structural variations were recognized, including large inversions longer than 30 megabase (Mb) on sex chromosomes which potentially affect key functional genes associated with differentiated phenotypes between the two species. By integrating multiomics we found a significant loss of the major weapon for elapid predation, three-finger toxin genes, which displayed a dosage effect in H. curtus. These genetic changes may imply mechanisms that drove the divergent evolution of adaptive traits including prey preferences between the two closely related snakes. Our reference-quality sea snake genomes also enrich the repositories for addressing important issues on the evolution of marine tetrapods, and provide a resource for discovering marine-derived biological products.

Description: The recent and exclusively in humans and a few other higher primates expressed APOL1 (apolipoprotein L1) gene is linked to African human trypanosomiasis (also known as African sleeping sickness) as well as to different forms of kidney diseases. Whereas APOL1’s role as a trypanolytic factor is well established, pathobiological mechanisms explaining its cytotoxicity in renal cells remain unclear. In this study, we compared the APOL family members using a combination of evolutionary studies and cell biological experiments to detect unique features causal for APOL1 nephrotoxic effects. We investigated available primate and mouse genome and transcriptome data to apply comparative phylogenetic and maximum likelihood selection analyses. We suggest that the APOL gene family evolved early in vertebrates and initial splitting occurred in ancestral mammals. Diversification and differentiation of functional domains continued in primates, including developing the two members APOL1 and APOL2. Their close relationship could be diagnosed by sequence similarity and a shared ancestral insertion of an AluY transposable element. Live-cell imaging analyses showed that both expressed proteins show a strong preference to localize at the endoplasmic reticulum (ER). However, glycosylation and secretion assays revealed that—unlike APOL2—APOL1 membrane insertion or association occurs in different orientations at the ER, with the disease-associated mutants facing either the luminal (cis) or cytoplasmic (trans) side of the ER. The various pools of APOL1 at the ER offer a novel perspective in explaining the broad spectrum of its observed toxic effects.

Description: Sexually dimorphic development is responsible for some of the most remarkable phenotypic variation found in nature. Alternative splicing of the transcription factor gene doublesex (dsx) is a highly conserved developmental switch controlling the expression of sex-specific pathways. Here, we leverage sex-specific differences in butterfly wing color pattern to characterize the genetic basis of sexually dimorphic development. We use RNA-seq, immunolocalization, and motif binding site analysis to test specific predictions about the role of dsx in the development of structurally based ultraviolet (UV) wing patterns in Zerene cesonia (Southern Dogface). Unexpectedly, we discover a novel duplication of dsx that shows a sex-specific burst of expression associated with the sexually dimorphic UV coloration. The derived copy consists of a single exon that encodes a DNA binding but no protein-binding domain and has experienced rapid amino-acid divergence. We propose the novel dsx paralog may suppress UV scale differentiation in females, which is supported by an excess of Dsx-binding sites at cytoskeletal and chitin-related genes with sex-biased expression. These findings illustrate the molecular flexibility of the dsx gene in mediating the differentiation of secondary sexual characteristics.

Description: The fishery for Northern Atlantic cod (Gadus morhua) off Newfoundland and Labrador, Eastern Canada, presents the most spectacular case of an exploited stock crashed in a few decades by an industrial bottom trawl fishery under a seemingly sophisticated management regime after half a millennium of sustainable fishing. The fishery, which had generated annual catches of 100000 to 200000 tonnes from the beginning of the 16th century to the 1950s,  peaked in 1968 at 810000 tonnes, followed by a devastating collapse and closure 24 years later. Since then, stock recovery may have been hindered by premature openings, with vessels targeting the remains of the cod population. Previous research paid little attention towards using multicentury time series to inform sustainable catches and recovery plans. Here, we show that a simple stock assessment model can be used to model the cod population trajectory for the entire period from 1508 to 2019 for which catch estimates are available. The model suggests that if fishing effort and mortality had been stabilized in the 1980s,  precautionary annual yields of about 200000 tonnes could have been sustained. Our analysis demonstrates the value of incorporating prior knowledge to counteract shifting baseline effects on reference points and contemporary perceptions of historical stock status.

Description: Since 1996, the European Union has required that fishery products of 35 fish species or groups of species, including crustaceans and cephalopods, be graded before being landed on the basis of commercial size-categories. A multi-stage sampling scheme to estimate catch-at-length and catch-at-age compositions of total annual landings has been conducted in Portuguese waters since 2009. All species and their size-categories are sampled concurrently from random trips within representatively selected site-days annually. In an effort to improve cost-efficiency of the biological catch sampling of commercial landings in Portugal, a size- category sampling scheme was tested during 2017, taking advantage of the stratification of horse mackerel landings, induced by the mandatory grading of landings by size-category. The total number of site-days (primary sampling units), fish boxes sampled, and specimens of horse mackerel sampled for length and age across strata during the pilot study were 30%, 57%, and 12% of the sampling carried out under the standard concurrent scheme, respectively. The assignment of horse mackerel length to the six commercial size-categories was highly consistent across site-days. Our study shows that the concurrent sampling, where trips are subsampled within site-days, could miss some size-categories by chance, resulting in poor estimates of catch-at-length especially for small fish present at the market during a site-day. The size-category sampling scheme ensured subsamples of fish from all size-categories within a site-day, and achieved data on catch-at-age that are fit-for purpose at 24% of the total cost for the standard concurrent sampling. The effect of sampling designs and sample sizes on horse mackerel stock assessment outputs showed that the onshore biological sampling to estimate catch-at-age compositions for stock assessment is optimized with the size-category sampling scheme. Pilot field experiments should be carried out for selected species that evidence consistent size grading among commercial categories.

Description: The mechanisms by which transposable elements (TEs) can be horizontally transferred between animals are unknown, but viruses are possible candidate vectors. Here, we surveyed the presence of host-derived TEs in viral genomes in 35 deep sequencing data sets produced from 11 host–virus systems, encompassing nine arthropod host species (five lepidopterans, two dipterans, and two crustaceans) and six different double-stranded (ds) DNA viruses (four baculoviruses and two iridoviruses). We found evidence of viral-borne TEs in 14 data sets, with frequencies of viral genomes carrying a TE ranging from 0.01% to 26.33% for baculoviruses and from 0.45% to 7.36% for iridoviruses. The analysis of viral populations separated by a single replication cycle revealed that viral-borne TEs originating from an initial host species can be retrieved after viral replication in another host species, sometimes at higher frequencies. Furthermore, we detected a strong increase in the number of integrations in a viral population for a TE absent from the hosts’ genomes, indicating that this TE has undergone intense transposition within the viral population. Finally, we provide evidence that many TEs found integrated in viral genomes (15/41) have been horizontally transferred in insects. Altogether, our results indicate that multiple large dsDNA viruses have the capacity to shuttle TEs in insects and they underline the potential of viruses to act as vectors of horizontal transfer of TEs. Furthermore, the finding that TEs can transpose between viral genomes of a viral species sets viruses as possible new niches in which TEs can persist and evolve.

Description: In higher plants, whole-genome duplication (WGD) is thought to facilitate the evolution of C4 photosynthesis from C3 photosynthesis. To understand this issue, we used new and existing leaf-development transcriptomes to construct two coding sequence databases for C4Gynandropsis gynandra and C3Tarenaya hassleriana, which shared a WGD before their divergence. We compared duplicated genes in the two species and found that the WGD contributed to four aspects of the evolution of C4 photosynthesis in G. gynandra. First, G. gynandra has retained the duplicates of ALAAT (alanine aminotransferase) and GOGAT (glutamine oxoglutarate aminotransferase) for nitrogen recycling to establish a photorespiratory CO2 pump in bundle sheath (BS) cells for increasing photosynthesis efficiency, suggesting that G. gynandra experienced a C3–C4 intermediate stage during the C4 evolution. Second, G. gynandra has retained almost all known vein-development-related paralogous genes derived from the WGD event, likely contributing to the high vein complexity of G. gynandra. Third, the WGD facilitated the evolution of C4 enzyme genes and their recruitment into the C4 pathway. Fourth, several genes encoding photosystem I proteins were derived from the WGD and are upregulated in G. gynandra, likely enabling the NADH dehydrogenase-like complex to produce extra ATPs for the C4 CO2 concentration mechanism. Thus, the WGD apparently played an enabler role in the evolution of C4 photosynthesis in G. gynandra. Importantly, an ALAAT duplicate became highly expressed in BS cells in G. gynandra, facilitating nitrogen recycling and transition to the C4 cycle. This study revealed how WDG may facilitate C4 photosynthesis evolution.

Description: We report the discovery of large amounts of previously undetected cold neutral atomic hydrogen (H i) around the core triplet galaxies in the nearby NGC 7232 galaxy group with MeerKAT. With a physical resolution of ∼1 kpc, we detect a complex web of low-surface-brightness H i emission down to a 4σ column density level of ∼1 × 1019 cm−2 (over 44  km s−1). The newly discovered H i streams extend over ∼20 arcmin corresponding to 140 kpc in projection. This is approximately three times the H i extent of the galaxy triplet (52 kpc). The H i debris has an H i mass of ∼6.6 × 109 M⊙, more than 50 per cent of the total H i mass of the triplet. Within the galaxy triplet, NGC 7233 and NGC 7232 have lost a significant amount of H i while NGC 7232B appears to have an excess of H i. The H i deficiency in NGC 7232 and NGC 7233 indicates that galaxy–galaxy interaction in the group concentrates on this galaxy pair while the other disc galaxies have visited them over time. In comparison to the AMIGA sample of isolated galaxies, we find that with regards to its total H i mass the NGC 7232/3 galaxy triplet is not H i-deficient. Despite the many interactions associated to the triplet galaxies, no H i seems to have been lost from the group (yet).

Description: Clustering is a widely used technique in data mining applications and various pattern recognition applications, in which data objects are divided into groups. K-means algorithm is one of the most classical clustering algorithms. In this algorithm, the initial clustering centers are randomly selected, this results in unstable clustering results. To solve this problem, an optimized algorithm to select the initial centers is proposed. In the proposed algorithm, dispersion degree is defined, which is based on entropy. In the algorithm, all the objects are firstly grouped into a big cluster, and the object that has the maximum dispersion degree and the object that has the minimum dispersion degree are selected as the initial clustering centers from the initial big cluster. And then other objects in the biggest cluster are partitioned to the initial clusters to which the objects are nearest. The partition process will be repeated until the cluster number is equal to the specified value k. Finally, the partitioned k clusters and their cluster centers are applied to k-means algorithm as initial clusters and centers. Several experiments are conducted on real data sets to evaluate the proposed algorithm. The proposed algorithm is compared with traditional k-means algorithm and max-min distance clustering algorithm, and experimental results show that the improved k-means algorithm is stable in selecting initial clustering, because it can select unique initial clustering centers. The optimized algorithm’s effectiveness and feasibility are also verified by experiments, and the algorithm can reduce the times of iterations and has more stable clustering results and higher accuracy.

Description: Pathogens and associated outbreaks of infectious disease exert selective pressure on human populations, and any changes in allele frequencies that result may be especially evident for genes involved in immunity. In this regard, the 1346-1353 Yersinia pestis-caused Black Death pandemic, with continued plague outbreaks spanning several hundred years, is one of the most devastating recorded in human history. To investigate the potential impact of Y. pestis on human immunity genes, we extracted DNA from 36 plague victims buried in a mass grave in Ellwangen, Germany in the 16th century. We targeted 488 immune-related genes, including HLA, using a novel in-solution hybridization capture approach. In comparison with 50 modern native inhabitants of Ellwangen, we find differences in allele frequencies for variants of the innate immunity proteins Ficolin-2 and NLRP14 at sites involved in determining specificity. We also observed that HLA-DRB1*13 is more than twice as frequent in the modern population, whereas HLA-B alleles encoding an isoleucine at position 80 (I-80+), HLA C*06:02 and HLA-DPB1 alleles encoding histidine at position 9 are half as frequent in the modern population. Simulations show that natural selection has likely driven these allele frequency changes. Thus, our data suggest that allele frequencies of HLA genes involved in innate and adaptive immunity responsible for extracellular and intracellular responses to pathogenic bacteria, such as Y. pestis, could have been affected by the historical epidemics that occurred in Europe.

Description: Advances in phylogenomics contribute toward resolving long-standing evolutionary questions. Notwithstanding, genetic diversity contained within more than a billion biological specimens deposited in natural history museums remains recalcitrant to analysis owing to challenges posed by its intrinsically degraded nature. Yet that tantalizing resource could be critical in overcoming taxon sampling constraints hindering our ability to address major evolutionary questions. We addressed this impediment by developing phyloHyRAD, a new bioinformatic pipeline enabling locus recovery at a broad evolutionary scale from HyRAD-X exome capture of museum specimens of low DNA integrity using a benchtop RAD-derived exome-complexity-reduction probe set developed from high DNA integrity specimens. Our new pipeline can also successfully align raw RNAseq transcriptomic and ultraconserved element reads with the RAD-derived probe catalog. Using this method, we generated a robust timetree for Carabinae beetles, the lack of which had precluded study of macroevolutionary trends pertaining to their biogeography and wing-morphology evolution. We successfully recovered up to 2,945 loci with a mean of 1,788 loci across the exome of specimens of varying age. Coverage was not significantly linked to specimen age, demonstrating the wide exploitability of museum specimens. We also recovered fragmentary mitogenomes compatible with Sanger-sequenced mtDNA. Our phylogenomic timetree revealed a Lower Cretaceous origin for crown group Carabinae, with the extinct Aplothorax Waterhouse, 1841 nested within the genus Calosoma Weber, 1801 demonstrating the junior synonymy of Aplothorax syn. nov., resulting in the new combination Calosomaburchellii (Waterhouse, 1841) comb. nov. This study compellingly illustrates that HyRAD-X and phyloHyRAD efficiently provide genomic-level data sets informative at deep evolutionary scales.

Description: Laplacian support vector machine (LapSVM) is an extremely popular classification method and relies on a small number of labels and a Laplacian regularization to complete the training of the support vector machine (SVM). However, the training of SVM model and Laplacian matrix construction are usually two independent process. Therefore, In this paper, we propose a new adaptive LapSVM method to realize semi-supervised learning with a primal solution. Specifically, the hinge loss of unlabelled data is considered to maximize the distance between unlabelled samples from different classes and the process of dealing with labelled data are similar to other LapSVM methods. Besides, the proposed method embeds the Laplacian matrix acquisition into the SVM training process to improve the effectiveness of Laplacian matrix and the accuracy of new SVM model. Moreover, a novel optimization algorithm considering primal solver is proposed to our adaptive LapSVM model. Experimental results showed that our method outperformed all comparison methods in terms of different evaluation metrics on both real datasets and synthetic datasets.

Description: Spectral clustering is widely applied in real applications, as it utilizes a graph matrix to consider the similarity relationship of subjects. The quality of graph structure is usually important to the robustness of the clustering task. However, existing spectral clustering methods consider either the local structure or the global structure, which can not provide comprehensive information for clustering tasks. Moreover, previous clustering methods only consider the simple similarity relationship, which may not output the optimal clustering performance. To solve these problems, we propose a novel clustering method considering both the local structure and the global structure for conducting nonlinear clustering. Specifically, our proposed method simultaneously considers (i) preserving the local structure and the global structure of subjects to provide comprehensive information for clustering tasks, (ii) exploring the nonlinear similarity relationship to capture the complex and inherent correlation of subjects and (iii) embedding dimensionality reduction techniques and a low-rank constraint in the framework of adaptive graph learning to reduce clustering biases. These constraints are considered in a unified optimization framework to result in one-step clustering. Experimental results on real data sets demonstrate that our method achieved competitive clustering performance in comparison with state-of-the-art clustering methods.

Description: Summary We describe improvements to BAli-Phy, a Markov chain Monte Carlo (MCMC) program that jointly estimates phylogeny, alignment and other parameters from unaligned sequence data. Version 3 is substantially faster for large trees, and implements covarion models, additional codon models and other new models. It implements ancestral state reconstruction, allows prior selection for all model parameters, and can also analyze multiple genes simultaneously. Availability and implementation Software is available for download at http://www.bali-phy.org. C++ source code is freely available on Github under the GPL2 License. Supplementary information Supplementary data are available at Bioinformatics online.

Description: Thermoacidophilic archaea belonging to the order Sulfolobales thrive in extreme biotopes, such as sulfuric hot springs and ore deposits. These microorganisms have been model systems for understanding life in extreme environments, as well as for probing the evolution of both molecular genetic processes and central metabolic pathways. Thermoacidophiles, such as the Sulfolobales, use typical microbial responses to persist in hot acid (e.g. motility, stress response, biofilm formation), albeit with some unusual twists. They also exhibit unique physiological features, including iron and sulfur chemolithoautotrophy, that differentiate them from much of the microbial world. Although first discovered 〉50 years ago, it was not until recently that genome sequence data and facile genetic tools have been developed for species in the Sulfolobales. These advances have not only opened up ways to further probe novel features of these microbes but also paved the way for their potential biotechnological applications. Discussed here are the nuances of the thermoacidophilic lifestyle of the Sulfolobales, including their evolutionary placement, cell biology, survival strategies, genetic tools, metabolic processes and physiological attributes together with how these characteristics make thermoacidophiles ideal platforms for specialized industrial processes.

Description: Summary Stoneley modes are a special subset of normal modes whose energy is confined along the core-mantle boundary. As such, they offer a unique glimpse into Earth structure at the base of the mantle. They are often observed through coupling with mantle modes due to rotation, ellipticity and lateral heterogeneity, though they can be detected without such coupling. In this study, we explore the relative sensitivities of seismic spectra of two low-frequency Stoneley modes to several factors, taking as reference the fully coupled computation up to 3 mHz in model S20RTS. The factors considered are (i) theoretical, by exploring the extent to which various coupling approximations can accurately reproduce reference spectra; and (ii) model-based, by exploring how various Earth parameters such as core-mantle boundary topography, attenuation, and S-wave and P-wave structures, and the seismic source solution may influence the spectra. We find that mode-pair coupling is insufficiently accurate, but coupling modes within a range of ±0.1 mHz produces acceptable spectra, compared to full coupling. This has important implications for splitting function measurements, which are computed under the assumption of isolated modes or at best, mode-pair or group coupling. We find that uncertainties in the P-wave velocity mantle model dominate compared to other model parameters. In addition, we also test several hypothetical models of mantle density structure against real data. These tests indicate that, with the low-frequency Stoneley mode spectral data considered here, it is difficult to make any firm statement on whether the large-low-shear-velocity-provinces are denser or lighter than their surroundings. We conclude that better constraints on long wavelength elastic mantle structure, particularly P-wave velocity, need to be obtained, before making further statements on deep mantle density heterogeneity. In particular, a dense anomaly confined to a thin layer at the base of the mantle (less than ∼100-200 km) may not be resolvable using the two Stoneley modes tested here, while the ability of higher frequency Stoneley modes to resolve it requires further investigations.

Description: Using the recent GAIA eDR3 catalogue we construct a sample of solar neighbourhood isolated wide binaries satisfying a series of strict signal-to-noise data cuts, exclusion of random association criteria and detailed colour-magnitude diagram selections, to minimize the presence of any kinematic contaminating effects having been discussed in the literature to date. Our final high-purity sample consists of 423 binary pairs within 130 pc of the sun and in all cases high-quality GAIA single-stellar fits for both components of each binary (final average RUWE values of 0.99), both also restricted to the cleanest region of the main sequence. We find kinematics fully consistent with Newtonian expectations for separations, s, below 0.009 pc, with relative velocities scaling with ΔV∝s−1/2 and a total binary mass, Mb, velocity scaling consistent with $Delta V propto M_{b}^{1/2}$. For the separation region of s 〉 0.009 pc we obtain significantly different results, with a separation independent ΔV ≈ 0.5 km/s and a $Delta V propto M_{b}^{0.24 pm 0.21}$. This situation is reminiscent of the low acceleration galactic baryonic Tully-Fisher phenomenology, and indeed, the change from the two regimes we find closely corresponds to the a ≲ a0 transition. These results are at odds not only with Newtonian expectations, but also with MOND predictions, where the presence of an external field effect implies only small deviations from Newtonian dynamics are expected for Solar Neighbourhood wide binaries.

Description: Understanding the spatial distribution of metals within galaxies allows us to study the processes of chemical enrichment and mixing in the interstellar medium (ISM). In this work, we map the two-dimensional distribution of metals using a Gaussian Process Regression (GPR) for 19 star-forming galaxies observed with the Very Large Telescope/Multi Unit Spectroscopic Explorer (VLT–MUSE) as part of the PHANGS–MUSE survey. We find that 12 of our 19 galaxies show significant two-dimensional metallicity variation. Those without significant variations typically have fewer metallicity measurements, indicating this is due to the dearth of H ii regions in these galaxies, rather than a lack of higher-order variation. After subtracting a linear radial gradient, we see no enrichment in the spiral arms versus the disc. We measure the 50 per cent correlation scale from the two-point correlation function of these radially-subtracted maps, finding it to typically be an order of magnitude smaller than the fitted GPR kernel scale length. We study the dependence of the two-point correlation scale length with a number of global galaxy properties. We find no relationship between the 50 per cent correlation scale and the overall gas turbulence, in tension with existing theoretical models. We also find more actively star forming galaxies, and earlier type galaxies have a larger 50 per cent correlation scale. The size and stellar mass surface density do not appear to correlate with the 50 per cent correlation scale, indicating that perhaps the evolutionary state of the galaxy and its current star formation activity is the strongest indicator of the homogeneity of the metal distribution.

Description: Summary Whole genome assembly (WGA) of bacterial genomes with short reads is a quite common task as DNA sequencing has become cheaper with the advances of its technology. The process of assembling a genome has no absolute golden standard and it requires to perform a sequence of steps each of which can involve combinations of many different tools. However, the quality of the final assembly is always strongly related to the quality of the input data. With this in mind we built WGA-LP, a package that connects state-of-the-art programs for microbial analysis and novel scripts to check and improve the quality of both samples and resulting assemblies. WGA-LP, with its conservative decontamination approach, has shown to be capable of creating high quality assemblies even in the case of contaminated reads. Availability and implementation WGA-LP is available on GitHub (https://github.com/redsnic/WGA-LP) and Docker Hub (https://hub.docker.com/r/redsnic/wgalp). The web app for node visualization is hosted by shinyapps.io (https://redsnic.shinyapps.io/ContigCoverageVisualizer/). Supplementary information Supplementary data are available at Bioinformatics online.

Description: An exomoon on a non-perfectly circular orbit experiences tidal heating that is capable to significantly contribute to the thermal brightness of the moon. Here we argue that the thermal heat is unevenly distributed on the moon’s surface, the emission of the tidal heat is limited to a few hotspots on the surface. A well-known example is the tidally heated Io. Due to their significantly increased temperature, the hotspots enhance the energy emission in thermal wavelengths. We made simulations using Monte Carlo method to examine this contribution, and to predict about the possible detectability of such a spotted exomoon. We found that in the case of large, Earth-sized companions to Jupiters around red dwarf stars exhibit a thermal flux that enables the direct detection of the moon, due to its photometric signal that can exceed ≈100 ppm in the most favourable configurations.

Description: Nephrops (Nephrops norvegicus) is an economically valuable target species in the North Sea. Although individual Nephrops populations are scattered, the crustacean is managed regionally by the European Union (EU). The spatial competition for fisheries in the North Sea is growing especially due to expanding offshore wind farms (OWF) and newly implemented marine protected areas (MPA). Moreover, the Brexit affects the availability of EU fishing quotas and adds to the overall uncertainty EU fishers face. We compare landings and catches to scientifically advised quantities and perform an overlap analysis of fishing grounds with current and future OWFs and MPAs. Furthermore, we explore the German Nephrops fleet using high-resolution spatial fishing effort and catch data. Our results confirm earlier studies showing that Nephrops stocks have been fished above scientific advice. Present OWFs and MPAs marginally overlap with Nephrops fishing grounds, whereas German fishing grounds are covered up to 45% in future scenarios. Co-use strategies with OWFs could mitigate the loss of fishing opportunities. Decreased cod quotas due to Brexit and worse stock conditions, lowers Germany's capability to swap Nephrops quotas with the UK. We support the call for a new management strategy of individual Nephrops populations and the promotion of selective fishing gears.

Description: Assessment of zooplankton abundance, distribution, community composition, and temporal variability is critical to understanding the effects of climate variability and change on lower trophic level production and availability for consumption by larger consumers. Zooplankton sampling is performed across the Canadian continental shelf system by Fisheries and Oceans Canada's Atlantic Zone Monitoring Programme (AZMP). Sampling includes semi-monthly to monthly collection of zooplankton using vertical net tows (VNTs) deployed from near-bottom to surface at stations on the central Scotian Shelf (Stn 2, 150 m depth) and Newfoundland Shelf (Stn 27, 175 m depth), and by Continuous Plankton Recorders (CPRs) in the near-surface layers along routes over the Scotian and Newfoundland shelves (0–10 m depth). Here, we compare abundance metrics for 11 copepod taxa collected using both gear types in both regions between 1999 and 2015. Seasonal cycles of VNT and CPR abundance were similar for near-surface residents. VNT: CPR abundance ratios varied year-round for vertical migrants, as ontogenetic migrants shifted their vertical distribution, and as diel migrants changed their migratory behaviour. For some taxa, differences in annual average VNT: CPR abundance ratios between regions suggest differences in vertical distribution, while for others differences in inter-annual variability for VNT and CPR abundances suggest differences in the dynamics of the near- and sub-surface components of the populations.

Description: Mitigating bycatch of non-target fish species is a common objective in fisheries management that may be supported by the gathering of data from fishery observer programs and quantitative analysis of bycatch risk factors. We build three GLM models based on Chinese tuna longline fishery observer data in terms of analysis of total bycatch rate (TB rate), total bycatch ratio (TB ratio), and species-specific bycatch rate, respectively. The positive log-linear models assumed a Gaussian observation error model and a linear combination of categorical independent variables, including area, year, month, depth, and bycatch species. Results show that distributions of TB rate and TB ratio followed different trends and a latitudinal decrease was observed from both the northern and southern hemisphere of the equator. Comprehensively, the Pacific is a better place to fish compared to the Indian and Atlantic Oceans in terms of relatively lower TB rate and TB ratio. Fishing in open oceans can somehow avoid a high TB ratio than fishing in coastal waters. As a result, we recommend area 2SW, 2SE, 2 NW, 14SW, 14SE, and 14 NW as appropriate fishing ground for Albacore (Thunnus alalunga) while area 11N,  11S, 18SW, and 18SE to be appropriate fishing ground for fishing bigeye tuna (Thunnus obesus). Setting fishing gears deeper than 500 m would also help to get a low TB rate and TB ratio.

Description: The European Variation Archive (EVA; https://www.ebi.ac.uk/eva/) is a resource for sharing all types of genetic variation data (SNPs, indels, and structural variants) for all species. The EVA was created in 2014 to provide FAIR access to genetic variation data and has since grown to be a primary resource for genomic variants hosting 〉3 billion records. The EVA and dbSNP have established a compatible global system to assign unique identifiers to all submitted genetic variants. The EVA is active within the Global Alliance of Genomics and Health (GA4GH), maintaining, contributing and implementing standards such as VCF, Refget and Variant Representation Specification (VRS). In this article, we describe the submission and permanent accessioning services along with the different ways the data can be retrieved by the scientific community.

Description: The DMASS sample is a photometric sample from the DES Year 1 data set designed to replicate the properties of the CMASS sample from BOSS, in support of a joint analysis of DES and BOSS beyond the small overlapping area. In this paper, we present the measurement of galaxy-galaxy lensing using the DMASS sample as gravitational lenses in the DES Y1 imaging data. We test a number of potential systematics that can bias the galaxy-galaxy lensing signal, including those from shear estimation, photometric redshifts, and observing conditions. After careful systematic tests, we obtain a highly significant detection of the galaxy-galaxy lensing signal, with total S/N = 25.7. With the measured signal, we assess the feasibility of using DMASS as gravitational lenses equivalent to CMASS, by estimating the galaxy-matter cross-correlation coefficient rcc. By jointly fitting the galaxy-galaxy lensing measurement with the galaxy clustering measurement from CMASS, we obtain $r_{ m cc}=1.09^{+0.12}_{-0.11}$ for the scale cut of 4h−1 Mpc and $r_{ m cc}=1.06^{+0.13}_{-0.12}$ for 12h−1 Mpc in fixed cosmology. By adding the angular galaxy clustering of DMASS, we obtain rcc = 1.06 ± 0.10 for the scale cut of 4h−1 Mpc and rcc = 1.03 ± 0.11 for 12h−1 Mpc. The resulting values of rcc indicate that the lensing signal of DMASS is statistically consistent with the one that would have been measured if CMASS had populated the DES region within the given statistical uncertainty. The measurement of galaxy-galaxy lensing presented in this paper will serve as part of the data vector for the forthcoming cosmology analysis in preparation.

Description: Eukaryotic genome and methylome encode DNA fragments’ propensity to form nucleosome particles. Although the mechanical properties of DNA possibly orchestrate such encoding, the definite link between ‘omics’ and DNA energetics has remained elusive. Here, we bridge the divide by examining the sequence-dependent energetics of highly bent DNA. Molecular dynamics simulations of 42 intact DNA minicircles reveal that each DNA minicircle undergoes inside-out conformational transitions with the most likely configuration uniquely prescribed by the nucleotide sequence and methylation of DNA. The minicircles’ local geometry consists of straight segments connected by sharp bends compressing the DNA’s inward-facing major groove. Such an uneven distribution of the bending stress favors minimum free energy configurations that avoid stiff base pair sequences at inward-facing major grooves. Analysis of the minicircles’ inside-out free energy landscapes yields a discrete worm-like chain model of bent DNA energetics that accurately account for its nucleotide sequence and methylation. Experimentally measuring the dependence of the DNA looping time on the DNA sequence validates the model. When applied to a nucleosome-like DNA configuration, the model quantitatively reproduces yeast and human genomes’ nucleosome occupancy. Further analyses of the genome-wide chromatin structure data suggest that DNA bending energetics is a fundamental determinant of genome architecture.

Description: The question of what determines the width of Kuiper belt analogues (exoKuiper belts) is an open one. If solved, this understanding would provide valuable insights into the architecture, dynamics, and formation of exoplanetary systems. Recent observations by ALMA have revealed an apparent paradox in this field, the presence of radially narrow belts in protoplanetary discs that are likely the birthplaces of planetesimals, and exoKuiper belts nearly four times as wide in mature systems. If the parent planetesimals of this type of debris disc indeed form in these narrow protoplanetary rings via streaming instability where dust is trapped, we propose that this width dichotomy could naturally arise if these dust traps form planetesimals whilst migrating radially, e.g. as caused by a migrating planet. Using the dust evolution software dustpy, we find that if the initial protoplanetary disc and trap conditions favour planetesimal formation, dust can still effectively accumulate and form planetesimals as the trap moves. This leads to a positive correlation between the inward radial speed and final planetesimal belt width, forming belts up to ∼100au over 10 Myr of evolution. We show that although planetesimal formation is most efficient in low-viscosity (α = 10−4) discs with steep dust traps to trigger the streaming instability, the large widths of most observed planetesimal belts constrain α to values ≥4 × 10−4 at tens of au, otherwise the traps cannot migrate far enough. Additionally, the large spread in the widths and radii of exoKuiper belts could be due to different trap migration speeds (or protoplanetary disc lifetimes) and different starting locations, respectively. Our work serves as a first step to link exoKuiper belts and rings in protoplanetary discs.

Description: The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb; www.guidetopharmacology.org) is an open-access, expert-curated database of molecular interactions between ligands and their targets. We describe expansion in content over nine database releases made during the last two years, which has focussed on three main areas of infection. The COVID-19 pandemic continues to have a major impact on health worldwide. GtoPdb has sought to support the wider research community to understand the pharmacology of emerging drug targets for SARS-CoV-2 as well as potential targets in the host to block viral entry and reduce the adverse effects of infection in patients with COVID-19. We describe how the database rapidly evolved to include a new family of Coronavirus proteins. Malaria remains a global threat to half the population of the world. Our database content continues to be enhanced through our collaboration with Medicines for Malaria Venture (MMV) on the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY (www.guidetomalariapharmacology.org). Antibiotic resistance is also a growing threat to global health. In response, we have extended our coverage of antibacterials in partnership with AntibioticDB.

Description: We have carried out relativistic three-dimensional simulations of high-power radio sources propagating i,nto asymmetric cluster environments. We offset the environment by 0 or 1 core radii (equal to 144 kpc), and incline the jets by 0, 15, or 45° away from the environment centre. The different environment encountered by each radio lobe provides a unique opportunity to study the effect of environment on otherwise identical jets. We find that the jets become unstable towards the end of the simulations, even with a Lorentz factor of 5; they nevertheless develop typical Fanaroff–Riley class II radio morphology. The jets propagating into denser environments have consistently shorter lobe lengths and brighter hotspots, while the axial ratio of the two lobes is similar. We reproduce the recently reported observational anticorrelation between lobe length asymmetry and environment asymmetry, corroborating the notion that observed large-scale radio lobe asymmetry can be driven by differences in the underlying environment.

Description: Background To observe a long-term prognosis in late-onset multiple acyl-coenzyme-A dehydrogenation deficiency(MADD) patients and to determine whether riboflavin should be administrated in the long-term and high-dosage manner. Methods We studied the clinical, pathological and genetic features of 110 patients with late-onset MADD in a single neuromuscular center. The plasma riboflavin levels and a long-term follow-up were performed. Results Fluctuating proximal muscle weakness, exercise intolerance and dramatic responsiveness to riboflavin treatment were essential clinical features for all 110 MADD patients. Among them, we identified 106 cases with ETFDH variants, 1 case with FLAD1 variants and 3 cases without causal variants. On muscle pathology, fibers with cracks, atypical ragged red fibers(aRRFs) and diffuse decrease of SDH activity were the distinctive features of these MADD patients. The plasma riboflavin levels before treatment were significantly decreased in these patients as compared to healthy controls. Among 48 MADD patients with a follow-up of 6.1 years on average, 31 patients were free of muscle weakness recurrence, while 17 patients had episodes of slight muscle weakness upon riboflavin withdrawal, but recovered after retaking a small-dose of riboflavin for a short-term. Multivariate Cox regression analysis showed vegetarian diet and masseter weakness were independent risk factors for muscle weakness recurrence. Conclusion Fibers with cracks, aRRFs and diffuse decreased SDH activity distinguish MADD from other genotypes of lipid storage myopathy. For late-onset MADD, increased fatty acid oxidation and reduced riboflavin levels can induce episodes of muscle symptoms, which can be treated by short-term and small-dose of riboflavin therapy.

Description: We describe a modified version of the nbody6 code for simulating star clusters which greatly improves computational efficiency while sacrificing little in the way of accuracy. The distant force calculator is replaced by a GPU-enabled Barnes-Hut code, and integration is done with a standard leap frog scheme. Short-range forces continue to use the CPU-based fourth-order Hermite predictor-corrector scheme of nbody6. Our code outperforms nbody6 for systems with more than 3 × 105 particles and runs more than a factor 2 faster for systems of 106 particles with similar energy conservation. Our code should be useful for simulating realistic dense stellar clusters, such as globular clusters or galactic nuclei.

Description: Light and water availability are likely to vary over the lifespan of closed-canopy forest trees with understory trees experiencing greater limitations to growth by light and canopy trees greater limitation due to drought. As drought and shade have opposing effects on isotope discrimination (Δ13C), paired measurement of ring width and Δ13C can potentially be used to differentiate between water and light limitations on tree growth. We tested this approach for Cedrela trees from three tropical forests in Bolivia and Mexico that differ in rainfall and canopy structure. Using lifetime ring width and Δ13C data for trees of up to and over 200 years old, we assessed how controls on tree growth changed from understory to the canopy. Growth and Δ13C are mostly anti-correlated in the understory but this anti-correlation disappeared or weakened when trees reached the canopy, especially at the wettest site. This indicates that understory growth variation is controlled by photosynthetic carbon assimilation (A) due to variation in light levels. Once trees reached the canopy, inter-annual variation in growth and Δ13C at one of the dry sites showed positive correlations, indicating inter-annual variation in growth is driven by variation in water stress affecting stomatal conductance (gs). Paired analysis of ring widths and carbon isotopes provides significant insight to discerning between environmental factors controlling growth over trees’ life; strong light limitations for understory trees in closed-canopy moist forests switched to drought stress for (sub)canopy trees in dry forests. We show that combined isotope and ring width measurements can significantly improve our insights in tree functioning and be used to disentangle limitations due to shade from those due to drought.

Description: Summary The numerical simulation of seismic wave propagation in realistic heterogeneous media, as sedimentary basins, is a key element of seismic hazard estimation. Many numerical methods in two dimensions are based on unstructured triangular meshes and explicit time schemes. However, the presence of thin layers and tangential stratigraphic contacts in sedimentary basins entails poorly shaped mesh elements: some triangle heights are extremely small compared to the edge lengths, which requires small time steps in the simulations and thus leads to prohibitive computation times. We compare manual and automatic geological model simplification techniques to modify problematic areas of the domain, so as to improve the quality of the triangulated mesh. We modify the shape and the connectivity between rock units in the basin, with the objective to reduce the computation time without significantly changing the physical response of the geological medium. These simplification techniques are applied in an investigation of site effects in the lower Var valley, a densely urbanized area located near the city of Nice (South-East of France). Numerical simulations of plane wave propagation in a heterogeneous 2D profile are carried out with a discontinuous Galerkin finite element method. Five simplified meshes are generated and the impacts of the simplifications are analyzed in comparison to the reference model. We compare the time solutions and the transfer functions obtained on the surface of the basin. The results show that the simplification procedures, in particular automatic modifications of the model, yield a significant performance gain, with a ratio higher than 55, while having a negligible impact on the ground motion response.

Description: The invasive Japanese stiltgrass (Microstegium vimineum) affects a wide range of ecosystems and threatens biodiversity across the eastern USA. However, the mechanisms underlying rapid adaptation, plasticity, and epigenetics in the invasive range are largely unknown. We present a chromosome-level assembly for M. vimineum to investigate genome dynamics, evolution, adaptation, and the genomics of phenotypic plasticity. We generated a 1.12 Gb genome with scaffold N50 length of 53.44 Mb respectively, taking a de novo assembly approach that combined PacBio and Dovetail Genomics Omni-C sequencing. The assembly contains 23 pseudochromosomes, representing 99.96% of the genome. BUSCO assessment indicated that 80.3% of Poales gene groups are present in the assembly. The genome is predicted to contain 39,604 protein-coding genes, of which 26,288 are functionally annotated. Furthermore, 66.68% of the genome is repetitive, of which unclassified (35.63%) and long terminal repeat (LTR) retrotransposons (26.90%) are predominant. Similar to other grasses, Gypsy (41.07%) and Copia (32%) are the most abundant LTR-retrotransposon families. The majority of LTR-retrotransposons are derived from a significant expansion in the past 1-2 million years, suggesting the presence of relatively young LTR-retrotransposon lineages. We find corroborating evidence from Ks plots for a stiltgrass-specific duplication event, distinct from the more ancient grass-specific duplication event. The assembly and annotation of M. vimineum will serve as an essential genomic resource facilitating studies of the invasion process, the history and consequences of polyploidy in grasses, and provides a crucial tool for natural resource managers.

Description: To reduce and analyse astronomical images, astronomers can rely on a wide range of libraries providing low-level implementations of legacy algorithms. However, combining these routines into robust and functional pipelines requires a major effort which often ends up in instrument-specific and poorly maintainable tools, yielding products that suffer from a low-level of reproducibility and portability. In this context, we present prose, a Python framework to build modular and maintainable image processing pipelines. Built for astronomy, it is instrument-agnostic and allows the construction of pipelines using a wide range of building blocks, pre-implemented or user-defined. With this architecture, our package provides basic tools to deal with common tasks such as automatic reduction and photometric extraction. To demonstrate its potential, we use its default photometric pipeline to process 26 TESS candidates follow-up observations and compare their products to the ones obtained with AstroImageJ, the reference software for such endeavors. We show that prose produces light curves with lower white and red noise while requiring less user interactions and offering richer functionalities for reporting.

Description: Whilst the underlying assumption of the Friedman-Lemaître-Robertson-Walker (FLRW) cosmological model is that matter is homogeneously distributed throughout the universe, gravitational influences over the life of the universe have resulted in mass clustered on a range of scales. Hence we expect that, in our inhomogeneous universe, the view of an observer will be influenced by the location and local environment. Here we analyse the one-point probability distribution functions and angular power spectra of weak-lensing (WL) convergence and magnification numerically to investigate the influence of our local environment on WL statistics in relativistic N-body simulations. To achieve this, we numerically solve the null geodesic equations which describe the propagation of light bundles backwards in time from today, and develop a ray-tracing algorithm, and from these calculate various WL properties. Our findings demonstrate how cosmological observations of large-scale structure through WL can be impacted by the locality of the observer. We also calculate the constraints on the cosmological parameters as a function of redshift from the theoretical and numerical study of the angular power spectrum of WL convergence. This study concludes the minimal redshift for the constraint on the parameter Ωm (H0) is z ∼ 0.2 (z ∼ 0.6) beyond which the local environment’s effect is negligible and the data from WL surveys are more meaningful above that redshift. The outcomes of this study will have direct consequences for future surveys, where percent-level-precision is necessary.

Description: The feedback from young stars (i.e. pre-supernova) is thought to play a crucial role in molecular cloud destruction. In this paper, we assess the feedback mechanisms acting within a sample of 5810 H ii regions identified from the PHANGS-MUSE survey of 19 nearby ( 1, and expanding, yet there is a small sample of compact H ii regions with Ptot,max/Pde 〈 1 (∼1 per cent of the sample). These mostly reside in galaxy centres (Rgal 〈 1 kpc), or, specifically, environments of high gas surface density; log(Σgas/M⊙ pc−2) ∼ 2.5 (measured on kpc-scales). Lastly, we compare to a sample of literature measurements for Ptherm and Prad to investigate how dominant pressure term transitions over around 5 dex in spatial dynamic range and 10 dex in pressure.

Description: Introduction In the era of personalized medicine with more and more patient specific targeted therapies being used, we need reliable, dynamic, faster, and sensitive biomarkers both to track the causes of disease and to develop and evolve therapies during the course of treatment. Metabolomics recently has shown substantial evidence to support its emerging role in disease diagnosis and prognosis. Aside from biomarkers and development of therapies, it is also an important goal to understand the involvement of mitochondrial DNA mtDNA in metabolic regulation, aging, and disease development. Somatic mutations of the mitochondrial genome are also heavily implicated in age-related disease and aging. The general hypothesis is that an alteration in the concentration of metabolite profiles (possibly conveyed by lifestyle and environmental factors) influences the increase of mutation rate in the mtDNA, and thereby contributes to a range of pathophysiological alterations observed in complex diseases. Methods We performed an inverted mitochondrial genome wide association analysis between mitochondrial nucleotide variants (mtSNVs) and concentration of metabolites. We used 151 metabolites and the whole sequenced mitochondrial genome from 2718 individuals to identify genetic variants associated with metabolite profiles. Because of the high coverage, next generation sequencing-based analysis of the mitochondrial genome allows for an accurate detection of mitochondrial heteroplasmy and for identification of variants associated with the metabolome. Results The strongest association was found for mt715G 〉 A located in the MT-12SrRNA with the metabolite ratio C2/C10:1 (p-value = 6.82*10−09, β = 0.909). The second most significant mtSNV was found for mt3714A 〉 G located in the MT-ND1 with the metabolite ratio PC ae C42:5/PC ae C44:5 (p-value = 1.02*10−08, β = 3.631). A large number of significant metabolite ratios were observed involving PC aa C36:6 and the variant mt10689G 〉 A, located in the MT-ND4L gene. Conclusion These results show an important interconnection between mitochondria and metabolite concentrations. Considering that some of the significant metabolites found in this study have been previously related to complex diseases such as neurological disorders and metabolic conditions, these associations found here might play a crucial role for further investigations of such complex diseases. Understanding the mechanisms that control human health and disease, in particular the role of genetic predispositions and their interaction with environmental factors is a prerequisite for the development of safe and efficient therapies for complex disorders.

Description: Motivation Reverse engineering of gene regulatory networks (GRNs) has long been an attractive research topic in system biology. Computational prediction of gene regulatory interactions has remained a challenging problem due to the complexity of gene expression and scarce information resources. The high-throughput spatial gene expression data, like in situ hybridization images that exhibit temporal and spatial expression patterns, has provided abundant and reliable information for the inference of GRNs. However, computational tools for analyzing the spatial gene expression data are highly underdeveloped. Results In this study, we develop a new method for identifying gene regulatory interactions from gene expression images, called ConGRI. The method is featured by a contrastive learning scheme and deep Siamese convolutional neural network architecture, which automatically learns high-level feature embeddings for the expression images and then feeds the embeddings to an artificial neural network to determine whether or not the interaction exists. We apply the method to a Drosophila embryogenesis dataset and identify GRNs of eye development and mesoderm development. Experimental results show that ConGRI outperforms previous traditional and deep learning methods by a large margin, which achieves accuracies of 76.7% and 68.7% for the GRNs of early eye development and mesoderm development, respectively. It also reveals some master regulators for Drosophila eye development. Availabilityand implementation https://github.com/lugimzheng/ConGRI. Supplementary information Supplementary data are available at Bioinformatics online.

Description: Cellulose is the most abundant biological compound on Earth and while it is the predominant building constituent of plants, it is also a key extracellular matrix component in many diverse bacterial species. While bacterial cellulose was first described in the 19th century, it was not until this last decade that a string of structural works provided insights into how the cellulose synthase BcsA, assisted by its inner-membrane partner BcsB, senses c-di-GMP to simultaneously polymerize its substrate and extrude the nascent polysaccharide across the inner bacterial membrane. It is now established that bacterial cellulose can be produced by several distinct types of cellulose secretion systems and that in addition to BcsAB, they can feature multiple accessory subunits, often indispensable for polysaccharide production. Importantly, the last years mark significant progress in our understanding not only of cellulose polymerization per se but also of the bigger picture of bacterial signaling, secretion system assembly, biofilm formation and host tissue colonization, as well as of structural and functional parallels of this dominant biosynthetic process between the bacterial and eukaryotic domains of life. Here, we review current mechanistic knowledge on bacterial cellulose secretion with focus on the structure, assembly and cooperativity of Bcs secretion system components.

Description: We study differential rotation in late-stage shell convection in a 3D hydrodynamic simulation of a rapidly rotating 16 M⊙ helium star with a particular focus on the convective oxygen shell. We find that the oxygen shell develops a quasi-stationary pattern of differential rotation that is neither described by uniform angular velocity as assumed in current stellar evolution models of supernova progenitors, nor by uniform specific angular momentum. Instead, the oxygen shell develops a positive angular velocity gradient with faster rotation at the equator than at the pole by tens of percent. We show that the angular momentum transport inside the convection zone is not adequately captured by a diffusive mixing-length flux proportional to the angular velocity or angular momentum gradient. Zonal flow averages reveal stable large-scale meridional flow and an entropy deficit near the equator that mirrors the patterns in the angular velocity. The structure of the flow is reminiscent of simulations of stellar surface convection zones and the differential rotation of the Sun, suggesting that similar effects are involved; future simulations will need to address in more detail how the interplay of buoyancy, inertial forces, and turbulent stresses shapes differential rotation during late-stage convection in massive stars. If convective regions develop positive angular velocity gradients, angular momentum could be shuffled out of the core region more efficiently, potentially making the formation of millisecond magnetars more difficult. Our findings have implications for neutron star birth spin periods and supernova explosion scenarios that involve rapid core rotation.

Description: Motivation Alignment-free (AF) distance/similarity functions are a key tool for sequence analysis. Experimental studies on real datasets abound and, to some extent, there are also studies regarding their control of false positive rate (Type I error). However, assessment of their power, i.e., their ability to identify true similarity, has been limited to some members of the D2 family. The corresponding experimental studies have concentrated on short sequences, a scenario no longer adequate for current applications, where sequence lengths may vary considerably. Such a State of the Art is methodologically problematic, since information regarding a key feature such as power is either missing or limited. Results By concentrating on a representative set of word-frequency based AF functions, we perform the first coherent and uniform evaluation of the power, involving also Type I error for completeness. Two Alternative models of important genomic features (CIS Regulatory Modules and Horizontal Gene Transfer), a wide range of sequence lengths from a few thousand to millions, and different values of k have been used. As a result, we provide a characterization of those AF functions that is novel and informative. Indeed, we identify weak and strong points of each function considered, which may be used as a guide to choose one for analysis tasks. Remarkably, of the fifteen functions that we have considered, only four stand out, with small differences between small and short sequence length scenarios. Finally, in order to encourage the use of our methodology for validation of future AF functions, the Big Data platform supporting it is public. Availability The software is available at: https://github.com/pipp8/power_statistics Supplementary information Supplementary data are available at Bioinformatics online.

Description: Galactic black hole X-ray binaries (BHXBs) provide excellent laboratories to study accretion, as their relatively quick evolution allows us to monitor large changes in the in-flowing and/or out-flowing material over human timescales. However, the details of how the inflow-outflow coupling evolves during a BHXB outburst remain an area of active debate. In this work we attempt to probe the physical changes underlying the system evolution, by performing a systematic analysis of the multi-wavelength data of three BHXB sources: XTE J1752-223, MAXI J1659-152, and XTE J1650-500, during hard and hard-intermediate states. Using the power spectral hue which characterises the X-ray variability properties, we identify several clusters of BHXB epochs and perform the joint multi-wavelength spectral modelling to test their commonality with a physical jet model. Under the assumption that the corona is related to the base of the jet, we find that the power spectral hue traces the variation of the coronal radius (from ∼10Rg − ∼ 40Rg) in multiple BHXBs at hard and hard-intermediate states, and that the data are consistent with moderately truncated accretion discs (

Description: We describe the Dark Energy Survey (DES) Deep Fields, a set of images and associated multi-wavelength catalogue (ugrizJHKs) built from Dark Energy Camera (DECam) and Visible and Infrared Survey Telescope for Astronomy (VISTA) data. The DES Deep Fields comprise 11 fields (10 DES supernova fields plus COSMOS), with a total area of ∼30 square degrees in ugriz bands and reaching a maximum i-band depth of 26.75 (AB, 10σ, 2″). We present a catalogue for the DES 3-year cosmology analysis of those four fields with full 8-band coverage, totalling 5.88 sq. deg. after masking. Numbering 2.8million objects (1.6million post masking), our catalogue is drawn from images coadded to consistent depths of r = 25.7, i = 25, z = 24.3 mag. We use a new model-fitting code, built upon established methods, to deblend sources and ensure consistent colours across the u-band to Ks-band wavelength range. We further detail the tight control we maintain over the point-spread function modelling required for the model fitting, astrometry and consistency of photometry between the four fields. The catalogue allows us to perform a careful star-galaxy separation and produces excellent photometric redshift performance (NMAD = 0.023 at i 〈 23). The Deep-Fields catalogue will be made available as part of the cosmology data products release, following the completion of the DES 3-year weak lensing and galaxy clustering cosmology work.

Description: We present a multi-wavelength investigation of the H ii region G347.600+00.211, located at a distance of 7.9 kpc. We analyse the gas and dust properties aiming to disentangle the origin of the region as well as its role in the formation of new stars. G347.600+00.211 is very conspicuous at 1420 MHz and infrared wavelengths, showing an incomplete shell-like structure with two distinct zones of very intense emission. The infrared bubble S8 is part of the shell structure. The spatial distribution of the molecular gas shows the presence of six clouds located around the ionized region and showing a good morphological correlation with the 8 μm emission. Cold dust is coincident with the dense gas shown in the CO measurements. As for the origin of the region, we found that the massive cluster [DBS2003]179 and two Wolf–Rayet (WR) stars are located at the same distance than the ionized gas. Based on a stellar density analysis, we inferred that one of the WR stars, 1181-81L, is also a probable member of the cluster. Both the cluster and the WR stars are not only within the ring–like structure, but are also located near the two spots of very heightened emission, suggesting they may be responsible for this bright emission. Finally, as expanding H ii regions are hypothesised to trigger star formation, we used different infrared point source catalogues to search for young stellar object candidates (cYSOs). A total of 33 cYSOs and 4 CH ii regions were identified projected on to the photo–dissociation regions and molecular clouds.

Description: We have previously described two flow cytometry-based in vitro genotoxicity tests: micronucleus (MN) scoring (MicroFlow ®) and a multiplexed DNA damage response biomarker assay (MultiFlow ®). Here, we describe a strategy for combining the assays in order to efficiently supplement MN analyses with a panel of biomarkers that comment on cytotoxicity (i.e., relative nuclei count, relative increased nuclei count, cleaved PARP-positive chromatin, and ethidium monoazide-positive chromatin) and genotoxic mode of action (i.e., γH2AX, phospho-histone H3, p53 activation, and polyploidy). For these experiments, human TK6 cells were exposed to each of 32 well-studied reference chemicals in 96-well plates for 24 continuous hr. The test chemicals were evaluated over a range of concentrations in the presence and absence of a rat liver S9-based metabolic activation system. MultiFlow assay data were acquired at 4 and 24 hr, and MN were scored at 24 hr. Testing 32 chemicals in two metabolic activation arms translated into 64 a priori calls: 42 genotoxicants and 22 non-genotoxicants. The MN assay showed high sensitivity and moderate specificity (90% and 68%, respectively). When a genotoxic call required significant MN and MultiFlow responses, specificity increased to 95% without adversely affecting sensitivity. The dose response data were analyzed with PROAST Benchmark Dose (BMD) software in order to calculate potency metrics for each endpoint, and ToxPi software was used to synthesize the resulting lower and upper bound 90% confidence intervals into visual profiles. The BMD/ToxPi combination was found to represent a powerful strategy for synthesizing multiple BMD confidence intervals, as the software output provided MoA information as well as insights into genotoxic potency.

Description: In this paper we present and validate the galaxy sample used for the analysis of the Baryon Acoustic Oscillation signal (BAO) in the Dark Energy Survey (DES) Y3 data. The definition is based on a colour and redshift-dependent magnitude cut optimized to select galaxies at redshifts higher than 0.5, while ensuring a high quality determination. The sample covers ∼ 4100 square degrees to a depth of i = 22.3 (AB) at 10σ. It contains 7,031,993 galaxies in the redshift range from z= 0.6 to 1.1, with a mean effective redshift of 0.835. Redshifts are estimated with the machine learning algorithm DNF, and are validated using the VIPERS PDR2 sample. We find a mean redshift bias of zbias ∼  0.01 and a mean uncertainty, in units of 1 + z, of σ68 ∼  0.03. We evaluate the galaxy population of the sample, showing it is mostly built upon Elliptical to Sbc types. Furthermore, we find a low level of stellar contamination of $lesssim 4{{ m per cent}}$. We present the method used to mitigate the effect of spurious clustering coming from observing conditions and other large-scale systematics. We apply it to the BAO sampleand calculate weights that are used to get a robust estimate of the galaxy clustering signal. This paper is one of a series dedicated to the analysis of the BAO signal in DES Y3. In the companion papers we present the galaxy mock catalogues used to calibrate the analysis and the angular diameter distance constraints obtained through the fitting to the BAO scale.

Description: SIRT3 is an NAD+-dependent protein deacetylase localized in mitochondria. Several studies reported localization of SIRT3 in the cytoplasm or nucleus, but data of these studies were not consistent. We detected expression of mitochondrial (SIRT3mt) and cytoplasmic (SIRT3ct) Sirt3 mRNAs in the mouse brain, and we also found SIRT3 immunostaining of mitochondria and cytoplasm in the brain and cultured neural cells. However, expression levels of SIRT3ct in COS cells transfected with SIRT3ct cDNA were much lower than those of SIRT3mt. We found that SIRT3ct but not SIRT3mt was promptly degraded by ubiquitin-dependent degradation, in which SIRT3ct degradation was mediated mainly by ubiquitination of NH2-terminal methionine and partly by that of lysine residues of SIRT3ct. SIRT3ct expression level was significantly enhanced by treatment of cells with staurosporine or H2O2. H2O2 treatment promoted nuclear translocation of SIRT3ct and induced histone H3 deacetylation and superoxide dismutase 2 expression. Overexpression of SIRT3ct decreased cell death caused by H2O2 at levels similar to those achieved by overexpression of SIRT3mt. Knockdown of Sirt3 mRNA increased cell death caused by amyloid-β (Aβ), and overexpression of SIRT3ct suppressed the toxic function of Aβ in PC12 cells. These results indicate that SIRT3ct promotes cell survival under physiological and pathological conditions.

Description: Summary Finite-difference (FD) modeling of seismic waves in the vicinity of dipping interfaces gives rise to artifacts. Examples are phase and amplitude errors, as well as staircase diffractions. Such errors can be reduced in two general ways. In the first approach, the interface can be anti-aliased (i.e., with an anti-aliased step-function, or a lowpass filter). Alternatively, the interface may be replaced with an equivalent medium (i.e., using Schoenberg & Muir (SM) calculus or orthorhombic averaging). We test these strategies in acoustic, elastic isotropic, and elastic anisotropic settings. Computed FD solutions are compared to analytical solutions. We find that in acoustic media, anti-aliasing methods lead to the smallest errors. Conversely, in elastic media, the SM calculus provides the best accuracy. The downside of the SM calculus is that it requires an anisotropic FD solver even to model an interface between two isotropic materials. As a result, the computational cost increases compared to when using isotropic FD solvers. However, since coarser grid spacings can be used to represent the dipping interfaces, the two effects (an expensive FD solver on a coarser FD grid) equal out. Hence, the SM calculus can provide an efficient means to reduce errors, also in elastic isotropic media.

Description: We explore, using numerical simulations, the influence of mass and distance on the evolution of triple black hole systems. Following in the direction of Burrau’s famous 3,4,5 problem, black holes are initially placed at the vertices of Pythagorean triangles. Numerical integration of orbits was conducted using relativistic corrections (post-Newtonian) up to the 2.5th order with ARCcode. As a descriptor of the evolution of the systems, the lifetimes, the number of two-body encounters and the number of mergers were all analysed. We found that as the mass unit of the black holes increased there was strong positive correlation with the fraction of mergers (0.9868), strong negative correlation with the average number of two-body encounters (-0.9016) and the average lifetimes of the triple systems decayed exponentially (determination coefficient of 0.9986). Around the mass unit range of 105.5M⊙-105.6M⊙, there was a transition from escape dominated dynamics to merger dominated dynamics. However, in the mass unit range of 106 M⊙ − 109M⊙ with 1 pc distance unit, we find that 25 per cent of cases resulted in the escape of a supermassive black hole (SMBH) which may be a cause for wandering SMBH’s found in some galaxies/galactic merger remnants.

Description: Epigenetic therapy has significant potential for cancer treatment. However, few small potent molecules have been identified against DNA or RNA modification regulatory proteins. Current approaches for activity detection of DNA/RNA methyltransferases and demethylases are time-consuming and labor-intensive, making it difficult to subject them to high-throughput screening. Here, we developed a fluorescence polarization-based ‘High-Throughput Methyl Reading’ (HTMR) assay to implement large-scale compound screening for DNA/RNA methyltransferases and demethylases-DNMTs, TETs, ALKBH5 and METTL3/METTL14. This assay is simple to perform in a mix-and-read manner by adding the methyl-binding proteins MBD1 or YTHDF1. The proteins can be used to distinguish FAM-labelled substrates or product oligonucleotides with different methylation statuses catalyzed by enzymes. Therefore, the extent of the enzymatic reactions can be coupled with the variation of FP binding signals. Furthermore, this assay can be effectively used to conduct a cofactor competition study. Based on the assay, we identified two natural products as candidate compounds for DNMT1 and ALKBH5. In summary, this study outlines a powerful homogeneous approach for high-throughput screening and evaluating enzymatic activity for DNA/RNA methyltransferases and demethylases that is cheap, easy, quick, and highly sensitive.

Description: Summary Distributed Acoustic Sensing (DAS) networks promise to revolutionize observational seismology by providing cost-effective, highly dense spatial sampling of the seismic wavefield, especially by utilizing pre-deployed telecomm fiber in urban settings for which dense seismic network deployments are difficult to construct. However, each DAS channel is sensitive only to one projection of the horizontal strain tensor and therefore gives an incomplete picture of the horizontal seismic wavefield, limiting our ability to make a holistic analysis of instrument response. This analysis has therefore been largely restricted to pointwise comparisons where a fortuitious coincidence of reference three-component seismometers and co-located DAS cable allows. We evaluate DAS instrument response by comparing DAS measurements from the PoroTomo experiment with strain-rate wavefield reconstructed from the nodal seismic array deployed in the same experiment, allowing us to treat the entire DAS array in a systematic fashion irrespective of cable geometry relative to the location of nodes. We found that, while the phase differences are in general small, the amplitude differences between predicted and observed DAS strain-rates average a factor of 2 across the array and correlate with near-surface geology, suggesting that careful assessment of DAS deployments is essential for applications that require reliable assessments of amplitude. We further discuss strategies for empirical gain corrections and optimal placement of point sensor deployments to generate the best combined sensitivity with an already deployed DAS cable, from a wavefield reconstruction perspective.

Description: The Mediterranean Basin has experienced extensive change in geology and climate over the past six million years. Yet, the relative importance of key geological events for the distribution and genetic structure of the Mediterranean fauna remains poorly understood. Here, we use population genomic and phylogenomic analyses to establish the evolutionary history and genetic structure of common wall lizards (Podarcis muralis). This species is particularly informative because, in contrast to other Mediterranean lizards, it is widespread across the Iberian, Italian, and Balkan peninsulas, and in extra-Mediterranean regions. We found strong support for six major lineages within P. muralis, which were largely discordant with the phylogenetic relationship of mitochondrial DNA. The most recent common ancestor of extant P. muralis was likely distributed in the Italian Peninsula, and experienced an “Out-of-Italy” expansion following the Messinian salinity crisis (∼5 Mya), resulting in the differentiation into the extant lineages on the Iberian, Italian and Balkan peninsulas. Introgression analysis revealed that both inter- and intraspecific gene flows have been pervasive throughout the evolutionary history of P. muralis. For example, the Southern Italy lineage has a hybrid origin, formed through admixture between the Central Italy lineage and an ancient lineage that was the sister to all other P. muralis. More recent genetic differentiation is associated with the onset of the Quaternary glaciations, which influenced population dynamics and genetic diversity of contemporary lineages. These results demonstrate the pervasive role of Mediterranean geology and climate for the evolutionary history and population genetic structure of extant species.

Description: Birds in the clade Palaeognathae, excluding Tinamiformes, have morphologically conserved karyotypes and less differentiated ZW sex chromosomes compared with those of other birds. In particular, the sex chromosomes of the ostrich and emu have exceptionally large recombining pseudoautosomal regions (PARs), while non-PARs are classified into two strata according to the date of their origins: stratum 0 (S0) and stratum 1 (S1). However, the construction and analysis of the genome sequences in these regions in the clade Palaeognathae can be challenging because assembling the S1 region is difficult owing to low sequence diversity between gametologs (Z-linked and W-linked sequences). We addressed this issue by applying the Platanus-allee assembler and successfully constructed the haplotype-resolved (phased) assembly for female emu, cassowary, and ostrich using only sequence read data derived from the Illumina platform. Comparative genomic and phylogenetic analyses based on assembled Z-linked and W-linked sequences confirmed that the S1 region of emu and cassowary formed in their common ancestor. Moreover, the interspersed repetitive sequence landscapes in the S1 regions of female emu showed an expansion of younger repetitive elements in the W-linked S1 region, suggesting an interruption in homologous recombination in the S1 region. These results provide novel insights into the trajectory of sex chromosome evolution in the clade Palaeognathae and suggest that the Illumina-based phased assembly method is an effective approach for elucidating the evolutionary process underlying the transition from homomorphic to differentiated sex chromosomes.

Description: The metallicity of a star affects its evolution in a variety of ways, changing stellar radii, luminosities, lifetimes, and remnant properties. In this work, we use the population synthesis code binary_c to study how metallicity affects novae in the context of binary stellar evolution. We compute a 16-point grid of metallicities ranging from Z = 10−4 to 0.03, presenting distributions of nova white dwarf masses, accretion rates, delay-times, and initial system properties at the two extremes of our 16-point metallicity grid. We find a clear anti-correlation between metallicity and the number of novae produced, with the number of novae at Z = 0.03 roughly half that at Z = 10−4. The white dwarf mass distribution has a strong systematic variation with metallicity, while the shape of the accretion rate distribution is relatively insensitive. We compute a current nova rate of approximately 33 novae per year for the Milky Way, a result consistent with observational estimates relying on extra-Galactic novae but an under-prediction relative to observational estimates relying on Galactic novae. However, the shape of our predicted Galactic white dwarf mass distribution differs significantly to existing observationally derived distributions, likely due to our underlying physical assumptions. In M31, we compute a current nova rate of approximately 36 novae per year, under-predicting the most recent observational estimate of $65^{+15}_{-16}$. Finally, we conclude that when making predictions about currently observable nova rates in spiral galaxies, or stellar environments where star formation has ceased in the distant past, metallicity can likely be considered of secondary importance compared to uncertainties in binary stellar evolution.

Description: We present methods for emulating the matter power spectrum by combining information from cosmological N-body simulations at different resolutions. An emulator allows estimation of simulation output by interpolating across the parameter space of a limited number of simulations. We present the first implementation in cosmology of multi-fidelity emulation, where many low-resolution simulations are combined with a few high-resolution simulations to achieve an increased emulation accuracy. The power spectrum’s dependence on cosmology is learned from the low-resolution simulations, which are in turn calibrated using high-resolution simulations. We show that our multi-fidelity emulator predicts high-fidelity counterparts to percent-level relative accuracy when using only 3 high-fidelity simulations and outperforms a single-fidelity emulator that uses 11 simulations, although we do not attempt to produce a converged emulator with high absolute accuracy. With a fixed number of high-fidelity training simulations, we show that our multi-fidelity emulator is ≃ 100 times better than a single-fidelity emulator at k ≤ 2 hMpc−1, and ≃ 20 times better at 3 ≤ k 〈 6.4 hMpc−1. Multi-fidelity emulation is fast to train, using only a simple modification to standard Gaussian processes. Our proposed emulator shows a new way to predict non-linear scales by fusing simulations from different fidelities.

Description: Extrachromosomal circular DNA (eccDNA) are present within all eukaryotic organisms and actively contribute to gene expression changes. MicroDNA (200-1000bp) are the most abundant type of eccDNA and can amplify tRNA, microRNA, and novel si-like RNA sequences. Due to the heterogeneity of microDNA and the limited technology to directly quantify circular DNA molecules, the specific DNA repair pathways that contribute to microDNA formation have not been fully elucidated. Using a sensitive and quantitative assay that quantifies eight known abundant microDNA, we report that microDNA levels are dependent on resection after double-strand DNA break (DSB) and repair by Microhomology Mediated End Joining (MMEJ). Further, repair of DSB without resection by canonical Non-Homologous End Joining (c-NHEJ) diminishes microDNA formation. MicroDNA levels are induced locally even by a single site-directed DSB, suggesting that excision of genomic DNA by two closely spaced DSB is not necessary for microDNA formation. Consistent with all this, microDNA levels accumulate as cells undergo replication in S-phase, when DNA breaks and repair are elevated, and microDNA levels are decreased if DNA synthesis is prevented. Thus, formation of microDNA occurs during the repair of endogenous or induced DNA breaks by resection-based DNA repair pathways.

Description: Structural variants have a considerable impact on human genomic diversity. However, their evolutionary history remains mostly unexplored. Here, we developed a new method to identify potentially adaptive structural variants based on a similarity-based analysis that incorporates genotype frequency data from 26 populations simultaneously. Using this method, we analyzed 57,629 structural variants and identified 576 structural variants that show unusual population differentiation. Of these putatively adaptive structural variants, we further showed that 24 variants are multiallelic and overlap with coding sequences, and 20 variants are significantly associated with GWAS traits. Closer inspection of the haplotypic variation associated with these putatively adaptive and functional structural variants reveals deviations from neutral expectations due to (i) population differentiation of rapidly evolving multi-allelic variants, (ii) incomplete sweeps, and (iii) recent population-specific negative selection. Overall, our study provides new methodological insights, documents hundreds of putatively adaptive variants, and introduces evolutionary models that may better explain the complex evolution of structural variants.

Description: The regeneration-associated gene (RAG) expression program is activated in injured peripheral neurons after axotomy and enables long-distance axon re-growth. Over 1000 genes are regulated, and many transcription factors are upregulated or activated as part of this response. However, a detailed picture of how RAG expression is regulated is lacking. In particular the transcriptional targets and specific functions of the various transcription factors are unclear. Jun was the first regeneration-associated transcription factor identified and the first shown to be functionally important. Here we fully define the role of Jun in the RAG expression program in regenerating facial motor neurons. At 1, 4, and 14 days after axotomy, Jun upregulates 11%, 23% and 44% of the RAG program, respectively. Jun functions relevant to regeneration include cytoskeleton production, metabolic functions and cell activation, and the down-regulation of neurotransmission machinery. In silico analysis of promoter regions of Jun targets identifies stronger over-representation of AP1-like sites than CRE-like sites, although CRE sites were also over-represented in regions flanking AP1 sites. Strikingly, in motor neurons lacking Jun, an alternative SRF-dependent gene expression program is initiated after axotomy. The promoters of these newly expressed genes exhibit over-representation of CRE sites in regions near to SRF target sites. This alternative gene expression program includes plasticity-associated transcription factors, and leads to an aberrant early increase in synapse density on motor neurons. Jun thus has the important function in the early phase after axotomy of pushing the injured neuron away from a plasticity response and towards a regenerative phenotype.

Description: Luminous Blue Variables (LBVs) are massive stars that are likely to be a transitionary phase between O stars and hydrogen-free classical Wolf-Rayet stars. The variability of these stars has been an area of study for both professional and amateur astronomers for more than a century. In this paper, we present five years of precision photometry of the classical LBV P Cygni taken with the BRITE-Constellation nanosatellites. We have analyzed these data with Fourier analysis to search for periodicities that could elucidate the drivers of variability for these stars. These data show some long-timescale variability over the course of all six calendar years of observations, but the frequencies needed to reproduce the individual light curves are not consistent from one year to the next. These results likely show that there is no periodic phenomenon present for P Cygni, meaning that the variability is largely stochastic. We interpret the data as being caused by internal gravity waves similar to those seen in other massive stars, with P Cygni exhibiting a larger amplitude and lower characteristic frequency than the main-sequence or blue supergiant stars previously studied. These results show evidence that LBVs may be an extrapolation of the blue supergiants, which have previously been shown to be an extension of main-sequence stars in the context of the stochastic low-frequency photometric variability.