Two levels of selection of rhythmicity in gene expression: energy saving for rhythmic proteins and noise optimization for rhythmic transcripts Many genes have nycthemeral rhythms of expression, i.e. a 24-hours periodic variation, at either mRNA or protein level or both, and, most rhythmic genes are tissue-specific. Here, we investigate and discuss the evolutionary origins of rhythms in gene expression. Our results suggest that thythmicity of protein expression has been favored by selection for low cost. Trends are consistent in bacteria, plants and animals, and are also supported in tissue-specific patterns in mouse. Cost cannot explain rhythm at the RNA level, and we suggest instead it allows to periodically and drastically reduce expression noise. Noise control had strongest support in mouse, with limited power in other species. Genes under stronger purifying selection are rhythmically expressed at the mRNA level, probably because they are noise sensitive genes. We also suggest that mRNA rhythmicity allows to switch between optimal precision and higher stochasticity. Higher precision allows to maximize the robustness of gene expression when the function is most needed, while higher stochasticity allows to maintain oscillations and to exhibit diverse molecular phenotypes, i.e. "blind anticipation" of cells. The ability to alternate between these two states, enabled by rhythmicity at the mRNA level, might be adaptive in fluctuating environments. Finally, the adaptive role of rhythmic expression is also supported by rhythmic genes being highly expressed yet tissue-specific genes. This provides a good evolutionary explanation for the observation that nycthemeral rhythms are often tissue-specific.
Experimental sexual selection affects the evolution of physiological and life history traits Sexual selection and sexual conflict are expected to affect all aspects of the phenotype, not only traits that are directly involved in reproduction. Here, we show coordinated evolution of multiple physiological and life history traits in response to long-term experimental manipulation of the mating system in populations of Drosophila pseudoobscura. Development time was extended under polyandry relative to monogamy in both sexes, potentially due to higher investment in traits linked to sexual selection and sexual conflict. Individuals (especially males) evolving under polyandry had higher metabolic rates and locomotor activity than those evolving under monogamy. Polyandry individuals also invested more in metabolites associated with increased endurance capacity and efficient energy metabolism and regulation, namely lipid and glycogen. Finally, polyandry males were less desiccation- and starvation-resistant than monogamy males, suggesting trade-offs between resistance and sexually selected traits. Our results provide experimental evidence that mating systems can impose selection that influences the evolution of non-sexual phenotypes such as development, activity, metabolism, and nutrient homeostasis.
Overexpression-based detection of translatable circular RNAs is vulnerable to coexistent linear RNA byproducts In RNA field, the demarcation between coding and non-coding has been negotiated by the recent discovery of occasionally translated circular RNAs (circRNAs). Although absent of 5 cap structure, circRNAs can be translated cap-independently. Complementary intron-mediated overexpression is one of the most utilized methodologies for circRNA research but not without bearing echoing skepticism for its poorly defined mechanism and latent coexistent side products. In this study, leveraging such circRNA overexpression system, we have interrogated the protein-coding potential of 30 human circRNAs containing infinite open reading frames in HEK293T cells. Surprisingly, pervasive translation signals are detected by immunoblotting. However, intensive mutagenesis reveals that numerous translation signals are generated independently of circRNA synthesis. We have developed a dual tag strategy to isolate translation noise and directly demonstrate that the fallacious translation signals originate from cryptically spliced linear transcripts. The concomitant linear RNA byproducts, presumably concatemers, can be translated to allow pseudo rolling circle translation signals, and can involve backsplicing junction (BSJ) to disqualify the BSJ-based evidence for circRNA translation. We also find non-AUG start codons may engage in the translation initiation of circRNAs. Taken together, our systematic evaluation sheds light on heterogeneous translational outputs from circRNA overexpression vector and comes with a caveat that ectopic overexpression technique necessitates extremely rigorous control setup in circRNA translation and functional investigation. Linking plankton size spectra and community composition to carbon export and its efficiency The magnitude and efficiency of particulate carbon export from the ocean surface depends not only on net primary production (NPP) but also on how carbon is consumed, respired, and repackaged by organisms. We contend that several of these processes can be captured by the size spectrum of the plankton community. However, most global models have relatively simple food-web structures that are unable to generate plankton sizespectra. Moreover, the life-cycles of multicellular zooplankton are typically not resolved, restricting the ability of models to represent time-lags that are known to impact carbon export and its efficiency (pe-ratio). Here, we use a global mechanistic size-spectrum model of the marine plankton community to investigate how particulate export and pe-ratio relate to the community size spectrum, community composition, and time-lags between predators and prey. The model generates emergent food-webs with associated size distributions for organisms and detrital particles. To resolve time-lags between phytoplankton and zooplankton, we implement the life-cycle of multicellular zooplankton (here represented by copepods). The simulation successfully captures observed patterns in biomass and energy fluxes across regions. We find that carbon export correlates best with copepod biomass and trophic level, whereas the pe-ratio correlates best with the exponent of the size spectrum and sea surface temperature (SST). Community metrics performed better than NPP or SST for both deep export and pe-ratio. Time-lags between phytoplankton and copepods did not strongly affect export or pe-ratio. We conclude by discussing how can we reconcile size-spectrum theory with field sampling.

Plain Language SummaryPlankton are tiny but extremely abundant aquatic organisms. Plankton lock CO2 away from the atmosphere as they sink to the deep ocean, where carbon can be stored for hundreds of years. However, how much carbon is locked away and for how long depends on how organisms eat, defecate, and respire. We argue that these processes are reflected in the size composition of the plankton community. The size composition shows a clear relationship between the number of organisms and their body-size. The steepness of this "size-abundance relationship" describes the balance between small vs. large organisms, and has been argued to reflect how energy is transferred from small to large organisms. Since large organisms create fast-sinking particles, the size-abundance relationship could be used to estimate how much carbon is being stored in the deep ocean. Here we use a computer simulation of the global plankton community to investigate how the removal of carbon relates to the plankton community and the steepness of the sizeabundance relationship. The model successfully captures patterns observed in nature. We found that the size-abundance relationship, together with the quantity of large zooplankton better explained carbon export than other measures typically used, such as photosynthesis and temperature.

Key PointsO_LIWe use a global mechanistic size-spectrum model to investigate the relation between particulate export and plankton community metrics.
C_LIO_LIWe find a good correlation between export efficiency and the exponent of the size spectrum.
C_LIO_LITotal carbon export correlated well with copepod biomass and trophic level of active copepods in the model.
C_LI Purkinje Cell Activity in Medial and Lateral Cerebellum During Suppression of Voluntary Eye Movements in Rhesus Macaques Volitional suppression of responses to distracting external stimuli enables us to achieve our goals. This volitional inhibition of a specific behavior is supposed to be mainly mediated by the cerebral cortex. However, recent evidence supports the involvement of the cerebellum in this process. It is currently not known whether different parts of the cerebellar cortex play differential or synergistic roles in planning and execution of this behavior. Here, we measured Purkinje cell (PC) responses in the medial and lateral cerebellum in two rhesus macaques during a pro- and antisaccade task. During an antisaccade trial, non-human primates were instructed to make a saccadic eye movement away from a target, rather than towards it, as in prosaccade trials. Our data shows that the cerebellum plays an important role not only during execution of the saccades, but also during the volitional inhibition of eye movements towards the target. Simple Spike (SS) modulation during the instruction and execution period of pro- and antisaccades was prominent in PCs of both medial and lateral cerebellum. However, only the SS activity in the lateral cerebellar cortex contained information about trial identity and showed a stronger reciprocal interaction with complex spikes. Moreover, SS activity of different PC groups modulated bidirectionally in both regions, but the PCs that showed facilitating and suppressive activity were predominantly associated with instruction and execution, respectively. These findings show that different cerebellar regions and PC groups contribute to goal-directed behavior and volitional inhibition, but with different propensities, highlighting the rich repertoire of cerebellar control in executive functions.

Significance StatementThe antisaccade task is commonly used in research and clinical evaluation as a test of volitional and flexible control of behavior. It requires volitional suppression of prosaccades, a function that has been attributed to the neocortex. However, recent findings indicate that cerebellum also contributes to this behavior. We recorded from neurons in the medial and lateral cerebellum to evaluate their responses in this task. We found that both regions significantly modulated their activity during this task, but only cells in the lateral cerebellum encoded the stimulus identity in each trial. These results indicate that the cerebellum actively contributes to the control of flexible behavior and that lateral and medial cerebellum play different roles during volitional eye movements. Morphology of immatures of the thelytokous ant, Monomorium triviale Wheeler (Formicidae: Myrmicinae: Solenopsidini) with descriptions of the extraordinary last-instar queen larvae The ant genus Monomorium is one of the most species-rich but taxonomically problematic groups in the hyperdiverse subfamily Myrmicinae. An East Asian species, M. triviale Wheeler, produces both reproductive queens and sterile workers via obligate thelytokous parthenogenesis. Here, we describe the immature forms of M. triviale based on light and scanning electron microscopy observations, with a note on the striking caste dimorphism in the last larval instar. The last-instar queen larvae were easily recognized by their large size, "aphaenogastroid" body shape, and rows of doorknob-like tubercles on the lateral and dorsal body surface. This type of queen-specific structure has not been found in ants in general, let alone congeneric species found in Japan. In stark contrast to the queen larvae, worker larvae showed a "pheidoloid" body shape and a body surface similar to other ants. The worker larvae were estimated to have three instars, consistent with previously described congeners. The pupae of both castes had no cocoon, a characteristic commonly described in other Myrmicinae species. In total, the developmental period from egg to adult worker averaged 59 days under 25{degrees}C. We discuss possible functions of the tubercles of queen larvae based on previous studies. Bulk-assembly of monodisperse coacervates and giant unilamellar vesicles with programmable hierarchical complexity Compartmentalization is an essential step for the emergence of protocellular life on the early earth and the endeavor to bottom-up construct synthetic cells in the lab. Among manifold natural strategies for compartmentalization, assembly of lipid vesicles or coacervate droplets with resemblance to cell envelope or cytoplasm have emerged as two dominant paradigms. However, the spontaneous assembly of lipid vesicles or coacervates generally results in polydisperse microcompartments and lacks the ability to efficiently integrate functional building blocks towards defined complexity, which give rise to the difficulty to achieve the order and complexity towards the scope of that of life via spontaneous assembly. Herein, we show that the interplay of coacervates and colloidal particles provides a bulk-assembly approach to form monodisperse coacervates and giant unilamellar vesicles (GUVs) with programmable hierarchical complexity. The hierarchical complexity of the synthetic cell microcompartments can be delicately engineered from the control of the spatial or temporal organization of components in entity unit to manifold forms of interconnected synthetic cell consortia, achieving a compartment hierarchy analogous to the organelle-cell-tissue structure. The increase in complexity gives rise to emergent properties, for instance, collective morphology evolution of coacervate assemblages, gated permeability of GUVs without sophisticated protein machinery, and remarkable structural and functional stability of GUVs at extreme conditions. This work paves an unprecedented step to form monodisperse, hierarchical coacervates and GUVs via bulk-assembly, which provides a prebiotically plausible approach for the proper integration of inanimate matter towards the order and complexity of life and monodisperse, hierarchical microdroplets for follow-up scientific and technological applications. The relative speed of the glucorticoid stress response varies independently of scope and is predicted by environmental variability and longevity across birds. The acute glucocorticoid response is a key mediator of the coordinated vertebrate response to unpredictable challenges. Rapid glucocorticoid increases initiate changes that allow animals to cope with stressors. The scope of the glucocorticoid response -- defined here as the absolute increase in glucocorticoids -- is associated with individual differences in performance and varies across species with environment and life history. In addition to varying in scope, responses can differ enormously in speed; however, relatively little is known about whether speed and absolute glucocorticoid levels covary, how selection shapes speed, or what aspects of speed are important. We used corticosterone samples collected at 5 time points from 1,750 individuals of 60 species of birds to ask i) how the speed and scope of the glucocorticoid response covary and ii) whether variation in absolute or relative speed is predicted by environmental context or life history. As predicted by a recent model, faster absolute glucocorticoid responses were strongly associated with a larger scope. Despite this covariation, the relative speed of the glucocorticoid response (standardized within species) varied independently of absolute scope, suggesting that selection could operate on both features independently. Species with faster relative glucocorticoid responses lived in locations with more variable temperature and had shorter lifespans. Our results suggest that rapid changes associated with the speed of the glucocorticoid response, such as those occurring through non-genomic receptors, might be an important determinant of coping ability and we emphasize the need for studies designed to measure speed independently of absolute glucocorticoid levels. Myoparr-associated and -independent multiple roles of heterogeneous nuclear ribonucleoprotein K during skeletal muscle cell differentiation RNA-binding proteins (RBPs) regulate cell physiology via the formation of ribonucleic-protein complexes with coding and non-coding RNAs. RBPs have multiple functions in the same cells; however, the precise mechanism through which their pleiotropic functions are determined remains unknown. In this study, we revealed the multiple inhibitory functions of heterogeneous nuclear ribonucleoprotein K (hnRNPK) for myogenic differentiation. We first identified hnRNPK as a lncRNA Myoparr binding protein. Gain- and loss-of-function experiments showed that hnRNPK repressed the expression of myogenin at the transcriptional level. The hnRNPK-binding region of Myoparr was required to repress myogenin expression. Moreover, hnRNPK repressed the expression of a set of genes coding for aminoacyl-tRNA synthetases in a Myoparr-independent manner. Mechanistically, hnRNPK regulated the eIF2/Atf4 pathway, one branch of the intrinsic pathways of the endoplasmic reticulum sensors, in differentiating myoblasts. Thus, our findings demonstrate that hnRNPK plays lncRNA-associated and - independent multiple roles during myogenic differentiation, indicating that the analysis of lncRNA-binding proteins will be useful for elucidating both the physiological functions of lncRNAs and the multiple functions of RBPs. Define protein variant functions with high-complexity mutagenesis libraries and enhanced mutation detection software ASMv1.0 Open reading frame (ORF) variant libraries have advanced our ability to query the functions of a large number of variants of a protein simultaneously in a single experiment. Variant libraries targeting full-length ORFs typically consists of all possible single-amino-acid substitutions and a stop codon at each amino-acid position. Because a variant differs from the template ORF by a single codon variation, variant quantification presents the most profound challenge to this technology. Efforts such as dividing a library into sub-libraries for direct sequencing, or tag-directed subassembly are practical only for small ORFs. Our approach, however, features an enhanced variant-calling tool that processes massive shotgun sequencing data, allowing one to screen a single variant library for ORFs sized up to [~]3600 bases. The variant-calling tool detects variants reliably, and also presents variant annotations in datafiles enabling analyses that have reshaped our strategies governing library design, screen deconvolution, sequencing and sequencing data analysis. Protein-protein interactions on membrane surfaces analysed using pull-downs with supported bilayers on silica beads Discovery-based proteomics workflows that identify novel interactors rely on immunoprecipitations or pull-downs with genetically-tagged bait proteins immobilized on appropriate matrices. But strategies to analyse protein interactions on a diffusible membrane surface combined with the practical ease of pull-downs remain unavailable. Such strategies are important to analyse protein complexes that mature in composition and stability because of diffusion-based encounter between participant proteins. Here, we describe a generic pull-down strategy to analyse such complexes using chelating lipid-containing supported bilayers formed on silica beads. These templates can display desired His-tagged bait proteins on a diffusible membrane surface. Using clathrin-mediated endocytosis as a paradigm, we find that the clathrin-binding adaptor protein epsin1 displayed as bait on these templates pulls down significantly higher amounts of clathrin from brain lysates than when immobilized on conventional matrices. Together, our results establish the potential of such templates as superior matrices for analysing protein-protein interactions and resultant complexes formed on membrane surfaces. TeamTree analysis: a new approach to evaluate scientific production Advances in science and technology depend on the work of research teams and the publication of results through peer-reviewed articles representing a growing socio-economic resource. Current methods to mine the scientific literature regarding a field of interest focus on content, but the workforce credited by authorship remains largely unexplored, and appropriate measures of scientific production are debated. Here, a new bibliometric approach named TeamTree analysis is introduced that visualizes the development and composition of the workforce driving a field. A new citation-independent measure that scales with the H index estimates impact based on publication record, genealogical ties and collaborative connections. This author-centered approach complements existing tools to mine the scientific literature and to evaluate research across disciplines. Barcode aware adaptive sampling for GridION and PromethION Oxford Nanopore sequencers. Adaptive sampling enables selection of individual DNA molecules from sequencing libraries, a unique property of nanopore sequencing. Here we develop our adaptive sampling tool readfish to become "barcode-aware" enabling selection of different targets within barcoded samples or filtering out individual barcodes. We show that multiple human genomes can be assessed for copy number and structural variation on a single sequencing flow cell using sample specific customised target panels on both GridION and PromethION devices. Material-mediated histogenesis using mechano-chemically microstructured cell niches Stem-cell derived tissue models are commonly cultured under globally-delivered stimuli that trigger histogenesis via self-organizing activity. However, the culture of such tissue models is prone to stochastic behavior, limiting the reproducibility of cellular composition and resulting in non-physiological architectures. To overcome these shortcomings, we developed a method for printing cell niche microenvironments with microstructured cues that mediate local histogenic processes, including mechanosensing and differentiation of selected cell types. Microstructured cues include independently tunable mechano-chemical properties, with conjugated peptides, proteins, and morphogens across a range of Youngs moduli. By rationally designing niches, we mediate the structure of tissues derived from stem-cell-progenitor sources, including a bone-fat assembly from stromal mesenchyme, and embryonic tissues derived from hiPSC. We show that microstructured cues can recapitulate mechano-chemical signals resembling early embryonic histogenesis. This outcome includes a role for niche mechanics in human embryonic organization, where soft niche mechanics bias markers of mesendodermal differentiation and epithelial-to-mesenchymal-transition (EMT), as well as a demonstration of a material-mediated morphogen signaling centers able to induce foci of mesenchymal and EMT differentiation. Thus, microstructured materials can mediate local histogenic processes to enhance the structure and composition of tissue models. Coupled myovascular expansion directs cardiac growth and regeneration BackgroundHeart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that they are spatiotemporally coupled.

Methods and ResultsWe show that coupled myovascular expansion during cardiac growth or regeneration is dependent upon VEGF-VEGFR2 signaling, as genetic deletion of Vegfr2 from CECs or inhibition of VEGFA abrogates both CEC and CM proliferation. Repair of cryoinjury displays poor spatial coupling of CEC and CM proliferation. Boosting CEC density after cryoinjury with virus encoding Vegfa enhances regeneration. Using Mendelian randomization, we demonstrate that circulating VEGFA levels are positively linked with human myocardial mass, suggesting that Vegfa can stimulate human cardiac growth.

ConclusionsOur work demonstrates the importance of coupled CEC and CM expansion and reveals a myovascular niche that may be therapeutically targeted for heart regeneration. Visual Clustering of Transcriptomic Data from Primary and Metastatic Tumors - Dependencies and Novel Pitfalls Personalized Oncology is a rapidly evolving area and offers cancer patients therapy options more specific than ever. Yet, there is still a lack of understanding regarding transcriptomic similarities or differences of metastases and corresponding primary sites. Applying two unsupervised dimension reduction methods (t-Distributed Stochastic Neighbor Embedding (t-SNE) and Uniform Manifold Approximation Projection (UMAP)) on three datasets of metastases (n=682 samples) with three different data transformations (unprocessed, log10 as well as log10+1 transformed values), we visualized potential underlying clusters. Additionally, we analyzed two datasets (n=616 samples) containing metastases and primary tumors of one entity, to point out potential familiarities. Using these methods, no tight link between site of resection and cluster formation outcome could be demonstrated, neither for datasets consisting of solely metastasis nor mixed datasets. Instead, dimension reduction methods and data transformation significantly impacted visual clustering results. Our findings strongly suggest data transformation to be considered as another key element in interpretation of visual clustering approaches along with initialization and different parameters. Furthermore, the results indicate only minor transcriptional differences for metastases and corresponding primary tumors. Diverse stem-chondrichthyan oral structures and evidence for an independently acquired acanthodid dentition The teeth of sharks famously form a series of transversely-organised files with conveyor-belt replacement that are borne directly on the jaw cartilages, in contrast to the dermal plate-borne dentition of bony fishes that undergoes site-specific replacement. A major obstacle in understanding how this system evolved is the poorly understood relationships of the earliest chondrichthyans and the profusion of morphologically and terminologically diverse bones, cartilages, splints and whorls that they possess. Here we use tomographic methods to investigate mandibular structures in several early branching  acanthodian-grade stem-chondrichthyans. We show that the dentigerous jaw bones of disparate genera of ischnacanthids are united by a common construction, being growing bones with non-shedding dentition. Mandibular splints, which support the ventro-lateral edge of the Meckels cartilage in some taxa, are formed from dermal bone and may be an acanthodid synapomorphy. We demonstrate that the teeth of Acanthodopsis are borne directly on the mandibular cartilage and that this taxon is deeply nested within an edentulous radiation, representing an unexpected independent origin of teeth. Many or even all of the range of unusual oral structures may be apomorphic, but they should nonetheless be considered when building hypotheses of tooth and jaw evolution, both in chondrichthyans and more broadly. Fatal COVID-19 and non-COVID-19 Acute Respiratory Distress Syndrome is Associated with Incomplete Alveolar Type 1 Epithelial Cell Differentiation from the Transitional State Without Fibrosis ARDS due to COVID-19 and other etiologies results from injury to the alveolar epithelial cell (AEC) barrier resulting in noncardiogenic pulmonary edema, which causes acute respiratory failure; clinical recovery requires epithelial regeneration. During physiologic regeneration in mice, AEC2s proliferate, exit the cell cycle, and transiently assume a transitional state before differentiating into AEC1s; persistence of the transitional state is associated with pulmonary fibrosis in humans. It is unknown whether transitional cells emerge and differentiate into AEC1s without fibrosis in human ARDS and why transitional cells differentiate into AEC1s during physiologic regeneration but persist in fibrosis. We hypothesized that incomplete but ongoing AEC1 differentiation from transitional cells without fibrosis may underlie persistent barrier permeability and fatal acute respiratory failure in ARDS. Immunostaining of postmortem ARDS lungs revealed abundant transitional cells in organized monolayers on alveolar septa without fibrosis. They were typically cuboidal or partially spread, sometimes flat, and occasionally expressed AEC1 markers. Immunostaining and/or interrogation of scRNAseq datasets revealed that transitional cells in mouse models of physiologic regeneration, ARDS, and fibrosis express markers of cell cycle exit but only in fibrosis express a specific senescence marker. Thus, in severe, fatal early ARDS, AEC1 differentiation from transitional cells is incomplete, underlying persistent barrier permeability and respiratory failure, but ongoing without fibrosis; senescence of transitional cells may be associated with pulmonary fibrosis. Active feature selection discovers minimal gene sets for classifying cell types and disease states with single-cell mRNA-seq data Sequencing costs currently prohibit the application of single-cell mRNA-seq to many biological and clinical analyses. Targeted single-cell mRNA-sequencing reduces sequencing costs by profiling reduced gene sets that capture biological information with a minimal number of genes. Here, we introduce an active learning method (ActiveSVM) that identifies minimal but highly-informative gene sets that enable the identification of cell-types, physiological states, and genetic perturbations in single-cell data using a small number of genes. Our active feature selection procedure generates minimal gene sets from single-cell data through an iterative cell-type classification task where misclassified cells are examined at each round of analysis to identify maximally informative genes through an  active support vector machine (ActiveSVM) classifier. By focusing computational resources on misclassified cells, ActiveSVM scales to analyze data sets with over a million single cells. We demonstrate that ActiveSVM feature selection identifies gene sets that enable 90% cell-type classification accuracy across a variety of data sets including cell atlas and disease characterization data sets. The method generalizes to reveal genes that respond to genetic perturbations and to identify region specific gene expression patterns in spatial transcriptomics data. The discovery of small but highly informative gene sets should enable substantial reductions in the number of measurements necessary for application of single-cell mRNA-seq to clinical tests, therapeutic discovery, and genetic screens. Effects of the social environment on movement-integrated habitat selection O_LIMovement links the distribution of habitats with the social environment of animals using those habitats; yet integrating movement, habitat selection, and socioecology remains an opportunity for further study.
C_LIO_LIHere, our objective was to disentangle the roles of habitat selection and social association as drivers of collective movement in a gregarious ungulate. To accomplish this objective, we (1) assessed whether socially familiar individuals form discrete social communities and whether social communities have high spatial, but not necessarily temporal, overlap; and (2) we modelled the relationship between collective movement and selection of foraging habitats using socially informed integrated step selection analysis.
C_LIO_LIWe used social network analysis to assign individuals to social communities and determine short and long-term social preference among individuals. Using integrated step selection functions (iSSF), we then modelled the effect of social processes, i.e., nearest neighbour distance and social preference, and movement behaviour on patterns of habitat selection.
C_LIO_LIBased on assignment of individuals to social communities and home range overlap analyses, individuals assorted into discrete social communities, and these communities had high spatial overlap. By unifying social network analysis with iSSF, we identified movement-dependent social association, where individuals foraged with more familiar individuals, but moved collectively with any between foraging patches.
C_LIO_LIOur study demonstrates that social behaviour and space use are inter-related based on spatial overlap of social communities and movement-dependent habitat selection. Movement, habitat selection, and social behaviour are linked in theory. Here, we put these concepts into practice to demonstrate that movement is the glue connecting individual habitat selection to the social environment.
C_LI Multiple brace root phenotypes promote anchorage and limit root lodging in maize Plant mechanical failure (lodging) causes global yield losses of 7-66% in cereal crops. We have previously shown that the above-ground nodal roots (brace roots) in maize are critical for anchorage. However, it is unknown how brace root phenotypes vary across genotypes and the functional consequence of this variation. This study quantifies the contribution of brace roots to anchorage, brace root traits, plant height, and root lodging susceptibility in 52 maize inbred lines. We show that the contribution of brace roots to anchorage and root lodging susceptibility varies among genotypes and this contribution can be explained by plant architectural variation. Additionally, supervised machine learning models were developed and show that multiple plant architectural phenotypes can predict the contribution of brace roots to anchorage and root lodging susceptibility. Together these data define the plant architectures that are important in lodging resistance and show that the contribution of brace roots to anchorage is a good proxy for root lodging susceptibility. Bias correction for inverse variance weighting Mendelian randomization BackgroundInverse-variance weighted two-sample Mendelian randomization (IVW-MR) is the most widely used approach that utilizes genome-wide association studies (GWAS) summary statistics to infer the existence and the strength of the causal effect between an exposure and an outcome. Estimates from this approach can be subject to different biases due to the use of weak instruments and winners curse, which can change as a function of the overlap between the exposure and outcome samples.

MethodsWe developed a method (MRlap) that simultaneously considers weak instrument bias and winners curse, while accounting for potential sample overlap. Assuming spike-and-slab genomic architecture and leveraging LD-score regression and other techniques, we could analytically derive, reliably estimate, and hence correct for the bias of IVW-MR using association summary statistics only.

ResultsWe tested our approach using simulated data for a wide range of realistic settings. In all the explored scenarios, our correction reduced the bias, in some situations by as much as 30 folds. When applied to real data on obesity-related exposures, we observed significant differences between IVW-based and corrected effects, both for non-overlapping and fully overlapping samples. Additionally, our results are consistent with the fact that the strength of the biases will decrease as the sample size increases. Finally, we also showed that the overall bias is also dependent on the genetic architecture of the exposure, and traits with low heritability and/or high polygenicity are more strongly affected.

ConclusionsOur method not only reduces bias in causal effect estimation but also enables the use of much larger GWAS sample sizes, by allowing for potentially overlapping samples. Persistent Immune and Clotting Dysfunction Detected in Saliva and Blood Plasma after COVID-19 A growing number of studies indicate that coronavirus disease 2019 (COVID-19) is associated with inflammatory sequelae, but molecular signatures governing the normal vs. pathologic convalescence process have not been well-delineated. We characterized global immune and proteome responses in matched plasma and saliva samples obtained from COVID-19 patients collected between 4-6 weeks after initial clinical symptoms resolved. Convalescent subjects showed robust IgA and IgG responses and positive antibody correlations between matched saliva and plasma samples. However, global shotgun proteomics revealed persistent inflammatory patterns in convalescent samples including dysfunction of salivary innate immune cells and clotting factors in plasma (e.g., fibrinogen and antithrombin), with positive correlations to acute COVID-19 disease severity. Saliva samples were characterized by higher concentrations of IgA, and proteomics showed altered pathways that correlated positively with IgA levels. Our study positions saliva as a viable fluid to monitor immunity beyond plasma to document COVID-19 immune, inflammatory, and coagulation-related sequelae. Structure of Infective Getah Virus at 2.8 A-resolution Determined by Cryo-EM Getah virus (GETV), a member of genus alphavirus, is a mosquito-borne pathogen that can cause pyrexia and reproductive losses in animals. Although antibodies to GETV have been found in over 10% of healthy people, there are no reports of clinical symptom associated with GETV. The biological and pathological properties of GETV are largely unknown. Here, we present the structure of infective GETV at a resolution of 2.8 [A] with the capsid protein and the envelope glycoproteins E1 and E2. We have identified numerous glycosylation and S-acylation sites in E1 and E2. The surface-exposed glycans revealed their impact on the viral immune evasion and host cell invasion. The S-acylation sites involve in stabilizing the transmembrane assembly. In addition, a cholesterol and a phospholipid molecule are observed in a transmembrane hydrophobic pocket, together with two more cholesterols surrounding the pocket. The structural information will assist structure-based antiviral and vaccine design. Phylogenomic evidence for the Origin of Obligately Anaerobic Anammox Bacteria around the Great Oxidation Event The anaerobic ammonium oxidation (anammox) bacteria could transform ammonium and nitrite to dinitrogen gas, and this obligate anaerobic process accounts for up to half of the global nitrogen loss in surface environments. Yet its origin and evolution, which may give important insights into the biogeochemistry of early Earth, remains enigmatic. Here, we performed comprehensive phylogenomic analysis and showed a single origin of anammox bacteria within the phylum Planctomycetes. After accommodating the uncertainties and factors influencing time estimates, which includes implementing both a traditional cyanobacteria-based and a recently developed mitochondria-based approach, we estimated that anammox bacteria originated at early Proterozoic and most likely around the so-called Great Oxidation Event (GOE; 2.32 to 2.5 billion years ago [Ga]) which fundamentally changed global biogeochemical cycles. We further showed that during the origin of anammox bacteria, genes involved in oxidative stress, bioenergetics and anammox granules formation were recruited, which might have contributed to their survival on an increasingly oxic Earth. Our findings suggest the rising levels of atmospheric oxygen, which made nitrite increasingly available, was a potential driving force for the emergence of anammox bacteria. This is one of the first studies that link the GOE to the evolution of obligate anaerobic bacteria. Neurological mechanism of sensory deficits after developmental exposure to non-dioxin-like polychlorinated biphenyls (PCBs) in zebrafish larvae The most abundant polychlorinated biphenyl (PCB) congeners found in the environment and in humans are neurotoxic. This is of particular concern for early life stages because the exposure of the more vulnerable developing nervous system to chemicals can result in neurobehavioral disorders. To uncover currently unknown links between PCB target mechanisms and neurobehavioral deficits, we investigated the effects of the non-dioxin-like (NDL) congener PCB153 on neuronal morphology and synaptic transmission linked to the proper execution of a sensorimotor response using zebrafish as a vertebrate model. Zebrafish that were exposed during development to concentrations similar to those found in human cord blood and PCB contaminated sites showed a delay in startle response. A similar delay was observed for other NDL congeners but not for the potent dioxin-like congener PCB126. Morphological and biochemical data demonstrate that while exposure to PCB153 induced swelling of afferent sensory neurons, the disruption of dopaminergic and GABAergic signaling is the dominant mechanism associated with motor movement. The effects on important and broadly conserved signaling mechanisms in vertebrates suggest that NDL PCBs may contribute to neurodevelopmental abnormalities in humans and, with the startle response being critical for the survival of fish, to evolutionary adaptation in wildlife.