Effects of phenotypic variation on consumer coexistence and prey community structure A popular idea in ecology is that trait variation among individuals from the same species may promote the coexistence of competing species. However, theoretical and empirical tests of this idea have yielded inconsistent findings. We manipulated intraspecific trait diversity in a ciliate competing with a nematode for bacterial prey in experimental microcosms. We found that intraspecific trait variation inverted the original competitive hierarchy to favor the consumer with variable traits, ultimately resulting in competitive exclusion. This competitive outcome was driven by foraging traits (size, speed, and directionality) that increased the ciliates fitness ratio and niche overlap with the nematode. The interplay between consumer trait variation and competition resulted in non-additive cascading effects - mediated through prey defense traits - on prey community assembly. Our results suggest that predicting consumer competitive population dynamics and the assembly of prey communities will require understanding the complexities of trait variation within consumer species.
Repeated introduction of micropollutants enhances microbial succession despite stable degradation patterns The increasing-volume release of micropollutants into natural surface waters has raised great concern due to their environmental accumulation. Persisting micropollutants can impact multiple generations of organisms, but their microbially-mediated degradation and their influence on community assembly remain understudied. Here, freshwater microbes were treated with several common micropollutants, alone or in combination, and then transferred every 5 days to fresh medium containing the same micropollutants to mimic the repeated exposure of microbes. Metabarcoding of 16S rRNA gene makers was chosen to study the succession of bacterial assemblages following micropollutant exposure. The removal rates of micropollutants were then measured to assess degradation capacity of the associated communities. The degradation of micropollutants did not accelerate over time but altered the microbial community composition. Community assembly was dominated by stochastic processes during early exposure, via random community changes and emergence of seedbanks, and deterministic processes later in the exposure, via advanced community succession. Early exposure stages were characterized by the presence of sensitive microorganisms such as Actinobacteria and Planctomycetes, which were then replaced by more tolerant bacteria such as Bacteroidetes and Gammaproteobacteria. Our findings have important implication for ecological feedback between microbe-micropollutants under anthropogenic climate change scenarios.
Sarcoplasmic reticulum calcium handling in young DBA/2J vs C57BL/10 mdx models of Duchenne muscular dystrophy The DBA/2J (D2) mdx mouse has emerged as a more severe model of Duchenne muscular dystrophy when compared to the traditional C57BL/10 (C57) mdx mouse. Here, we questioned whether sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) function would differ in muscles from young D2 and C57 mdx mice. In gastrocnemius muscles, both D2- and C57 mdx mice exhibited signs of impaired Ca2+ uptake, however, this was more severe in D2 mdx mice. Maximal SERCA activity was lowered only in D2 mdx gastrocnemius muscles and not C57 mdx muscles. Furthermore, in the left ventricle and diaphragm, Ca2+ uptake was impaired in C57 mdx muscles with lowered rates of Ca2+ uptake compared with C57 WT mice, whereas in muscles from D2 mdx mice, rates of Ca2+ uptake were unattainable due to the severe impairments in their ability to transport Ca2+. Overall, our study demonstrates that SERCA function is drastically impaired in young D2 mdx mice. A TIR-1/SARM1 phase transition underlies p38 immune pathway activation in the C. elegans intestine Intracellular signaling regulators can be concentrated into membrane-free, higher-ordered protein assemblies to initiate protective responses during stress -- a process known as phase transition. Here, we show that a phase transition of the Caenorhabditis elegans Toll/interleukin-1 receptor domain protein (TIR-1), an NAD+ glycohydrolase homologous to mammalian sterile alpha and TIR motif-containing 1 (SARM1), underlies p38 PMK-1 immune pathway activation in C. elegans intestinal epithelial cells. Through visualization of fluorescently labeled TIR-1/SARM1 protein, we demonstrate for the first time that physiologic stresses, both pathogen and non-pathogen, induce multimerization of TIR-1/SARM1 into visible puncta within intestinal epithelial cells. In vitro enzyme kinetic analyses revealed that, like mammalian SARM1, the NAD+ glycohydrolase activity of C. elegans TIR-1 is dramatically potentiated by protein oligomerization and a phase transition. Accordingly, C. elegans with genetic mutations that specifically block either multimerization or the NAD+ glycohydrolase activity of TIR-1/SARM1 fail to induce p38 PMK phosphorylation, are unable to increase immune effector expression, and are dramatically susceptible to bacterial infection. Finally, we demonstrate that the TIR-1/SARM1 phase transition is modified by dietary cholesterol, revealing a new adaptive response that allows a metazoan host to anticipate pathogen threats during micronutrient deprivation, a time of relative susceptibility to infection. When cholesterol is limited, TIR-1/SARM1 oligomerizes into puncta in intestinal epithelial cells and engages its NAD+ glycohydrolase activity, which increases p38 PMK-1 phosphorylation, and primes immune effector induction in a manner that promotes pathogen clearance from the intestine during a subsequent infection. Thus, a phase transition of TIR-1/SARM1 as a prerequisite for its NAD+ glycohydrolase activity is strongly conserved across millions of years of evolution and is essential for diverse physiological processes in multiple cell types. Optical regulation of endogenous RhoA reveals selection of cellular responses by signal amplitude How protein signaling networks respond to different input strengths is an important but poorly understood problem in cell biology. For example, the small GTPase RhoA regulates both focal adhesion (FA) growth or disassembly, but whether RhoA serves as a switch selecting between cellular outcomes, or if outcomes are simply modulated by additional factors in the cell, is not clear. Here, we develop a photoswitchable RhoA guanine exchange factor, psRhoGEF, to precisely control endogenous RhoA activity. We also develop a FRET-based biosensor to allow visualization of RhoA activity together with psRhoGEF control. Using these new optical tools, we discover that low levels of RhoA activation preferentially induce FA disassembly in a Src-dependent manner, while high levels induce both FA growth and disassembly in a ROCK-dependent manner. Thus, rheostatic control of RhoA activation with photoswitchable RhoGEF reveals that cells can use signal amplitude to produce multiple responses to a single biochemical signal. "Neighbourhood watch" model: embryonic epiblast cells assess positional information in relation to their neighbours In many developing and regenerating systems, tissue pattern is established through gradients of informative morphogens, but we know little about how cells interpret these. Using experimental manipulation of early chick embryos including misexpression of an inducer (VG1 or ACTIVIN) and an inhibitor (BMP4), we test two alternative models for their ability to explain how the site of primitive streak formation is positioned relative to the rest of the embryo. In one model, cells read morphogen concentrations cell-autonomously. In the other, cells sense changes in morphogen status relative to their neighbourhood. We find that only the latter model can account for the experimental results, including some counter-intuitive predictions. This mechanism (which we name "neighbourhood watch" model) illuminates the classic "French Flag Problem" and how positional information is interpreted by a sheet of cells in a large developing system.

Summary statementIn a large developing system, the chick embryo before gastrulation, cells interpret gradients of positional signals relative to their neighbours to position the primitive streak, establishing bilateral symmetry. Embryonic exposure to cannabidiol disrupts active neural circuits, an effect increased by Δ-9-tetrahydrocannabinol and involving CB1R and CB2R in zebrafish In the light of legislative changes and the widespread use of cannabis as a recreational and medicinal drug, delayed effects of cannabis upon brief exposure during embryonic development are of high interest as early pregnancies often go undetected. Here, zebrafish embryos were exposed to cannabidiol (CBD) and {Delta}-9-tetrahydrocannabinol l (THC) until the end of gastrulation (1-10 hours post-fertilization) and analyzed later in development (4-5 days post-fertilization). In order to measure neural activity, we implemented CaMPARI (Calcium-Modulated Photoactivatable Ratiometric Integrator) and optimized the protocol for a 96-well format complemented by locomotor analysis. Our results revealed that neural activity was decreased by CBD more than THC. At higher doses, both cannabinoids could dramatically reduce neural activity and locomotor activity. Interestingly, the decrease was more pronounced when CBD and THC were combined. At the receptor level, CBD-mediated reduction of locomotor activity was partially prevented using cannabinoid type 1 and 2 receptor inhibitors. Overall, we report that CBD toxicity occurs via two cannabinoid receptors and is synergistically enhanced by THC exposure to negatively impact neural activity late in larval development. Future studies are warranted to reveal other cannabinoids and receptors involved in this pathway to understand the subsequent health implications of cannabis consumption on fetal development. Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome Shwachman-Diamond syndrome (SDS; OMIM: #260400) is caused by variants in SBDS (Shwachman-Bodian-Diamond syndrome gene), which encodes a protein that plays an important role in ribosome assembly. Recent reports suggest that recessive variants in EFL1 are also responsible for SDS. However, the precise genetic mechanism that leads to EFL1-induced SDS remains incompletely understood. Here we present three unrelated Korean SDS patients that carry biallelic pathogenic variants in EFL1 with biased allele frequencies, resulting from a bone marrow-specific somatic uniparental disomy (UPD) in chromosome 15. The recombination events generated cells that were homozygous for the relatively milder variant, allowing for the evasion of catastrophic physiological consequences. Still, the milder EFL1 variant was solely able to impair 80S ribosome assembly and induce SDS features in cell line, zebrafish, and mouse models. The loss of EFL1 resulted in a pronounced inhibition of terminal oligo-pyrimidine element-containing ribosomal protein transcript 80S assembly. Therefore, we propose a more accurate pathogenesis mechanism of EFL1 dysfunction that eventually leads to aberrant translational control and ribosomopathy. Earliest photic zone niches probed by ancestral microbial rhodopsins For billions of years, life has continuously adapted to dynamic physical conditions near the Earths surface. Fossils and other preserved biosignatures in the paleontological record are the most direct evidence for reconstructing the broad historical contours of this adaptive interplay. However, biosignatures dating to Earths earliest history are exceedingly rare. Here, we combine phylogenetic inference of primordial rhodopsin proteins with modeled spectral features of the Precambrian Earth environment to reconstruct the paleobiological history of this essential family of photoactive transmembrane proteins. Our results suggest that ancestral microbial rhodopsins likely acted as light-driven proton pumps and were spectrally tuned toward the absorption of green light, which would have enabled their hosts to occupy depths in a water column or biofilm where UV wavelengths were attenuated. Subsequent diversification of rhodopsin functions and peak absorption frequencies was enabled by the expansion of surface ecological niches induced by the accumulation of atmospheric oxygen. Inferred ancestors retain distinct associations between extant functions and peak absorption frequencies. Our findings suggest that novel information encoded by biomolecules can be used as "paleosensors" for conditions of ancient, inhabited niches of host organisms not represented elsewhere in the paleontological record. The coupling of functional diversification and spectral tuning of this taxonomically diverse protein family underscores the utility of rhodopsins as universal testbeds for inferring remotely detectable biosignatures on inhabited planetary bodies. Distinct cellular origins and differentiation process account for distinct oncogenic and clinical behaviors of leiomyosarcomas Differentiated phenotypes in solid tumors mostly lead to a better outcome than in their more immature counterparts. In leiomyosarcoma (LMS), a very aggressive tumor for which neither chemotherapy nor targeted or immune therapies have demonstrated efficacy, a relatively transcriptionally uniform subgroup of well differentiated tumors has been described and is associated with poor survival. In this disease, differentiation does not systematically hinder tumor progression, so it is a good model for studying the relation between these two mechanisms. By applying ad hoc bioinformatic methods, we conducted a comprehensive analysis in order to detect subgroups of leiomyosarcoma and finely investigate their transcriptomic and genomic profiles. We first used unsupervised hierarchical clustering to identify the most transcriptionally homogeneous LMS subgroup, which we named  hLMS. We derived a transcriptional signature that could consistently stratify patients with similar clinical and genomic characteristics in TCGA and ICGC cohorts. Functional analysis of the signature showed over-expression of SRF and E2Fs targets harboring histone modifications that were specifically identified in smooth muscles in hLMS. By integrating multi-omics data, we identified punctual and structural variations as well as the potential cellular origins of each group of LMS using GTEX normal tissue gene expression. Altogether, our results suggest that hLMS, but not oLMS (other LMS), may originate from vascular smooth muscle cells in which oncogenesis is driven by the MYOCD/SRF axis, which is essential for hLMS survival. We propose that the phenotypic plasticity of vascular smooth muscle cells coupled with MYOCD/SRF pathway overactivation could explain how hLMS balance this uncommon interplay between differentiation and aggressiveness. The genome of the cereal pest Sitophilus oryzae: a transposable element haven BackgroundThe rice weevil Sitophilus oryzae is one of the most important agricultural pests, causing extensive damage to cereal in fields and to stored grains. S. oryzae has an intracellular symbiotic relationship (endosymbiosis) with the Gram-negative bacterium Sodalis pierantonius and is a valuable model to decipher host-symbiont molecular interactions.

ResultsWe sequenced the Sitophilus oryzae genome using a combination of short and long reads to produce the best assembly for a Curculionidae species to date. We show that S. oryzae has undergone successive bursts of transposable element (TE) amplification, representing 72% of the genome. In addition, we show that many TE families are transcriptionally active, and changes in their expression are associated with insect endosymbiotic state. S. oryzae has undergone a high gene expansion rate, when compared to other beetles. Reconstruction of host-symbiont metabolic networks revealed that, despite its recent association with cereal weevils (30 Kyear), S. pierantonius relies on the host for several amino acids and nucleotides to survive and to produce vitamins and essential amino-acids required for insect development and cuticle biosynthesis.

ConclusionsHere we present the genome of an agricultural pest beetle, which may act as a foundation for pest control. In addition, S. oryzae may be a useful model for endosymbiosis, and studying TE evolution and regulation, along with the impact of TEs on eukaryotic genomes. Loss of Acta2 in cardiac fibroblasts does not prevent myofibroblast differentiation or affect cardiac repair after myocardial infarction In response to myocardial infarction (MI), quiescent cardiac fibroblasts differentiate into myofibroblasts mediating tissue repair in the infarcted area. One of the most widely accepted markers of myofibroblast differentiation is the expression of Acta2 which encodes smooth muscle alpha-actin (SMA) that is assembled into stress fibers. However, the requirement of Acta2 in the myofibroblast differentiation of cardiac fibroblasts and its role in post-MI cardiac repair were still not known. To answer these questions, we generated a tamoxifen-inducible cardiac fibroblast-specific Acta2 knockout mouse line. Surprisingly, mice that lacked Acta2 in cardiac fibroblasts had a normal survival rate after MI. Moreover, Acta2 deletion did not affect the function or overall histology of infarcted hearts. No difference was detected in the proliferation, migration, or contractility between WT cardiac fibroblasts and Acta2-null cardiac myofibroblasts. Additional analysis identified that Acta2-null cardiac myofibroblasts had a normal total filamentous actin level and total actin level. Acta2 deletion caused a unique compensatory increase in the transcription level of Actg2 and a possible increase in the protein abundance of cytoplasmic actin isoforms. In conclusion, the deletion of Acta2 does not prevent the myofibroblast differentiation of cardiac fibroblasts or affect the post-MI cardiac repair, and the increase in the expression of non-SMA actin isoforms and the functional redundancy between actin isoforms are likely able to compensate for the loss of Acta2 in cardiac myofibroblasts. A small molecule antagonizes jasmonic acid perception and auxin responses in vascular and nonvascular plants The phytohormone JA-Ile regulates many stress responses and developmental processes in plants. A co-receptor complex formed by the F-box protein COI1 (Coronatine Insensitive 1) and a JAZ (Jasmonate ZIM-domain) repressor perceives the hormone. JA-Ile antagonists are invaluable tools for exploring the role of JA-Ile in specific tissues and developmental stages, and for identifying regulatory processes of the signalling pathway. Using two complementary chemical screens, we identified three compounds that exhibit a robust inhibitory effect on both the hormone-mediated COI-JAZ interaction and degradation of JAZ1 and JAZ9 in vivo. One molecule, J4, also restrains specific JA-induced physiological responses in different angiosperm plants, including JA-mediated gene expression, growth inhibition, chlorophyll degradation and anthocyanin accumulation. Interaction experiments with purified proteins indicate that J4 directly interferes with the formation of the Arabidopsis (Arabidopsis thaliana) COI1-JAZ complex otherwise induced by JA. The antagonistic effect of J4 on COI1- JAZ also occurs in the liverwort Marchantia polymorpha, suggesting the mode of action is conserved in land plants. Besides JA signalling, J4 works as an antagonist of the closely-related auxin signalling pathway, preventing TIR1/Aux-IAA interaction and auxin responses in planta, including hormone-mediated degradation of an auxin repressor, gene expression and gravitropic response. However, J4 does not affect other hormonal pathways. Altogether, our results show that this dual antagonist competes with JA-Ile and auxin, preventing the formation of phylogenetically related receptor complexes. J4 may be a useful tool to dissect both the JA-Ile and auxin pathways in particular tissues and developmental stages since it reversibly inhibits these pathways.

One sentence summaryA chemical screen identified a molecule that antagonizes jasmonate perception by directly interfering with receptor complex formation in phylogenetically distant vascular and non-vascular plants. Reconstitution of minimal motility system based on Spiroplasma swimming by expressing two bacterial actins in synthetic minimal bacterium Motility is one of the most important features of life, but its evolutionary origin remains unknown. In this study, we focused on Spiroplasma, commensal, or parasitic bacteria. They swim by switching the helicity of a ribbon-like cytoskeleton that comprises six proteins, each of which evolved from a nucleosidase and bacterial actin called MreB. We expressed these proteins in a synthetic, non-motile minimal bacterium, JCVI-syn3.0B, whose reduced genome was computer-designed and chemically synthesized. The synthetic bacterium exhibited swimming motility with features characteristic of Spiroplasma swimming. Moreover, some combinations of the two proteins produced a helical cell shape and swimming, suggesting that the swimming originated from the differentiation and coupling of bacterial actins, and we also obtained a minimal system for motility of the synthetic bacterium.

One-Sentence SummaryThe minimal system comprised two bacterial actins that provided cell helicity and swimming to the synthetic minimal bacterium. 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. A novel two-generation approach to the population dynamics of gregarious parasitoids Parasitoids, as important natural enemies, help maintain balance in natural ecosystems. Their population dynamics is generally predicted from the number of individuals. Here, using gregarious parasitoids as models, we show that this traditional approach omits one important parameter: the mothers manipulation of offspring fertility due to the clutch size-body size- fertility correlation. As a result of this correlation, when females deliberately adjust the number of offspring laid in a host, they determine not only the number but also the body sizes and reproductive potentials of those offspring. For the first time in the model species Anaphes flavipes, we determined the parasitoids offspring fertility from clutch size. Using this, we experimentally clarified the advantage of specific clutch size combinations and we show that identical fertility in the F1 generation can lead to distinctly different fertility values in the F2 generation. Even with the same number of hosts, lower fertility in the F1 generation can cause higher fertility in the F2 generation. Based on these results, we propose a novel two-generation approach which includes the clutch size-body size-fertility correlation. Our novel approach provides a new perspective for determining the individual fitness levels of gregarious parasitoids with new options for the modelling of parasitoid population dynamics. Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children The evolution of influenza viruses is fundamentally shaped by within-host processes. However, the within-host evolutionary dynamics of influenza viruses remain incompletely understood, in part because most studies have focused on within-host virus diversity of infections in otherwise healthy adults based on single timepoint data. Here, we analysed the within-host evolution of 82 longitudinally-sampled individuals, mostly young children, infected with A/H3N2 or A/H1N1pdm09 viruses between 2007 and 2009. For A/H1N1pdm09 infections during the 2009 pandemic, nonsynonymous changes were common early in infection but decreased or remained constant throughout infection. For A/H3N2 viruses, early infection was dominated by purifying selection. However, as infections progressed, nonsynonymous variants increased in frequencies even though within-host virus titres decreased, leading to the maintenance of virus diversity via mutation-selection balance. Our findings suggest that this maintenance of genetic diversity in these children combined with their longer duration of infection may provide important opportunities for within-host virus evolution. Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia Cystic Fibrosis (CF) is caused by genetic defects that impair the cystic fibrosis transmembrane conductance regulator (CFTR) channel in airway epithelial cells. These defects may be overcome by specific CFTR modulating drugs, for which the efficacy can be predicted in a personalized manner using 3D nasal-brushing-derived airway organoids in a forskolin-induced swelling assay. Despite of this, previously described application of 3D airway organoids in CFTR function assays have not been fully optimal. In this report we therefore describe an alternative method of culturing nasal brushing-derived airway organoids, which are created from an equally differentiated airway epithelial monolayer of a 2D air-liquid interface culture. In addition, we have defined organoid culture conditions, with the growth factor/cytokine combination neuregulin-1{beta} and interleukine-1{beta}, which enabled consistent detection of CFTR modulator responses in nasal airway organoids cultures from subjects with CF. Outsourced hearing in an orb-weaving spider that uses its web as an auditory sensor Hearing is a fundamental sense of many animals, including all mammals, birds, some reptiles, amphibians, fish, and arthropods. The auditory organs of these animals are extremely diverse in anatomy after hundreds of millions of years of evolution, yet all are made up of cellular tissues and are morphologically part of bodies of animals. Here we show hearing in the orb-weaving spider, Larinioides sclopetarius is not constrained by the organisms body but is extended through outsourcing hearing to its extended phenotype, the proteinaceous, self-manufactured orb-web. We find the wispy, wheel-shaped orb-web acts as a hyperacute acoustic "antenna" to capture the sound-induced air particle movements that approach the maximum physical efficiency, better than the acoustic responsivity of all previously known eardrums. By sensing the motion of web threads, the spider remotely detects and localizes the source of an incoming airborne acoustic wave such as those emitted by approaching prey or predators. By outsourcing its acoustic sensors to its web, the spider is released from body size constraints and permits the araneid spider to increase its sound-sensitive surface area enormously, up to 10,000 times greater than the spider itself. The spider also enables the flexibility to functionally adjust and regularly regenerate its "external eardrum" according to its needs. The "outsourcing" and "supersizing" of auditory function in spiders provides unique features for studying extended and regenerative sensing, and designing novel acoustic flow detectors for precise fluid dynamic measurement and manipulation. Probing Patterning in Microbial Consortia with picCASO: a Cellular Automaton for Spatial Organisation Microbial consortia exhibit spatial patterning across diverse environments. Since probing the self-organization of natural microbial communities is limited by their inherent complexity, synthetic models have emerged as attractive alternatives. In this study, we develop novel frameworks of bacterial communication and explore the emergent spatiotemporal organization of microbes. Specifically, we build quorum sensing-mediated models of microbial growth that are utilized to characterize the dynamics of communities from arbitrary initial configurations and establish the effectiveness of our communication strategies in coupling the growth rates of microbes. Our simulations indicate that the behavior of quorum sensing-coupled consortia can be most effectively modulated by the rates of secretion of AHLs. Such a mechanism of control enables the construction of desired relative populations of constituent species in spatially organized populations. Our models accurately recapitulate previous experiments that have investigated pattern formation in synthetic multi-cellular systems. Additionally, our software tool enables the easy implementation and analysis of our frameworks for a variety of initial configurations and simplifies the development of sophisticated gene circuits facilitating distributed computing. Overall, we demonstrate the potential of spatial organization as a tunable parameter in synthetic biology by introducing a communication paradigm based on the location and strength of coupling of microbial strains.

Author SummaryInteracting microorganisms that coexist in a given environment tend to have well-defined spatial arrangements. While the emergence of such organization is seen across different microbiomes in nature, it is hitherto not well understood. Decoding the inherent spatial patterning of microbes is constrained by the complexity of their natural habitats. Here, we take advantage of synthetic models of microbial communities to study the dynamics of emergent spatial organization. Our framework of bacterial communication utilizes modular synthetic devices to couple growth rates. In addition to uncovering potential principles of spatial organization, this work enables the construction of complex genetic circuits distributed across communicating strains. Additionally, we have developed a software tool, picCASO, that streamlines the investigation of microbial systems communicating through such frameworks. Identifying complex motifs in massive omics data with a variable-convolutional layer in deep neural network Motif identification is among the most common and essential computational tasks for bioinformatics and genomics. Here we proposed a novel convolutional layer for deep neural network, named Variable Convolutional (vConv) layer, for effective motif identification in high-throughput omics data by learning kernel length from data adaptively. Empirical evaluations on DNA-protein binding and DNase footprinting cases well demonstrated that vConv-based networks have superior performance to their convolutional counterparts regardless of model complexity. Meanwhile, vConv could be readily integrated into multi-layer neural networks as an "in-place replacement" of canonical convolutional layer. All source codes are freely available on GitHub for academic usage. A tool for assessing alignment of biomedical data repositories with open, FAIR, citation and trustworthy principles Increasing attention is being paid to the operation of biomedical data repositories in light of efforts to improve how scientific data is handled and made available for the long term. Multiple groups have produced recommendations for functions that biomedical repositories should support, with many using requirements of the FAIR data principles as guidelines. However, FAIR is but one set of principles that has arisen out of the open science community. They are joined by principles governing open science, data citation and trustworthiness, all of which are important aspects for biomedical data repositories to support. Together, these define a framework for data repositories that we call OFCT: Open, FAIR, Citable and Trustworthy. Here we developed an instrument using the open source PolicyModels toolkit that attempts to operationalize key aspects of OFCT principles and piloted the instrument by evaluating eight biomedical community repositories listed by the NIDDK Information Network (dkNET.org). Repositories included both specialist repositories that focused on a particular data type or domain, in this case diabetes and metabolomics, and generalist repositories that accept all data types and domains. The goal of this work was both to obtain a sense of how much the design of current biomedical data repositories align with these principles and to augment the dkNET listing with additional information that may be important to investigators trying to choose a repository, e.g., does the repository fully support data citation? The evaluation was performed from March to November 2020 through inspection of documentation and interaction with the sites by the authors. Overall, although there was little explicit acknowledgement of any of the OFCT principles in our sample, the majority of repositories provided at least some support for their tenets. Topographic projection of retinal ganglion cell axons at single-cell precision underlies retinotopy in the mouse superior colliculus Retinotopy, like all long-range projections, can arise from the axons themselves or their targets, but details of the connectivity remain unknown. Using two-photon axonal imaging, we functionally mapped the mouse retinocollicular projection at single-cell resolution. We found a near-perfect match between the spatial patterns of retinal ganglion cell axon terminals in the superior colliculus and their corresponding receptive fields, indicating that retinotopy arises from topographic axonal organizations at single-cell precision. Characterization of methylation profiles in spontaneous preterm birth placental villous tissue Preterm birth is a global public health crisis which results in significant neonatal and maternal mortality. Yet little is known regarding the molecular mechanisms of idiopathic spontaneous preterm birth, and we have few diagnostic markers for adequate assessment of placental development and function. Previous studies of placental pathology and our transcriptomics studies suggest a role for placental maturity in idiopathic spontaneous preterm birth. It is known that placental DNA methylation changes over gestation. We hypothesized that if placental hypermaturity is present in our samples, we would observe a unique idiopathic spontaneous preterm birth DNA methylation profile potentially driving the gene expression differences we previously identified in our placental samples. Our results indicate the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern suggesting hypermaturity. Only seven significant differentially methylated regions fitting the idiopathic spontaneous preterm birth specific (relative to the controls) profile were identified, indicating unusually high similarity in DNA methylation between idiopathic spontaneous preterm birth and term birth samples. We identified an additional 1,718 significantly methylated regions in our gestational age matched controls were the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern, again indicating a striking level of similarity between the idiopathic spontaneous preterm birth and term birth samples. Pathway analysis of these regions revealed differences in genes within the WNT and Cadherin signaling pathways, both of which are essential in placental development and maturation. Taken together, these data demonstrate that the idiopathic spontaneous preterm birth samples are molecularly more mature than expected given their respective gestational age which likely impacts birth timing. Flexibility of Short-chain dehydrogenase is interconnected to its promiscuity for the reduction of multiple ketone intermediates Short-chain dehydrogenases/reductases (SDRs) are a convenient class of enzymes used to synthesize enantiopure alcohols. Several studies describe native or engineered SDRs for converting substrates of interest using cost and time-intensive high-throughput approaches. The classification of SDRs is based on chain length and cofactor binding site. Of these, the shorter  Classical and the longer  Extended enzymes participate in ketoreduction. However, comparative analysis of various modelled SDRs reveals a length independent conserved N-terminal Rossmann fold and a variable C-terminus region for both types. The general hypothesis is that the latter domain influences the enzymes flexibility that may affect the observed promiscuity of the enzyme. We have used a machine learning algorithm on this flexible domain to build a rationale to screen promiscuous candidates. We have built a data set consisting of physicochemical properties derived from the amino-acid composition of enzymes to select closely associated promiscuous mesophilic enzymes. The resulting in vitro studies on pro-pharmaceutical substrates illustrate a direct correlation between the C-terminal lid-loop structure, enzyme melting temperature and the turnover number. We present a walkthrough for exploring promiscuous SDRs for catalyzing enantiopure alcohols of industrial importance. Interplay between receptor binding, immune escape and protein stability determines the natural selection of SARS-CoV-2 variants Emergence of new SARS-CoV-2 variants has raised concerns at the effectiveness of vaccines and antibody therapeutics developed against the unmutated wild-type virus. We examined the effect of 12 most commonly occurring mutations in the receptor binding domain on its expression, stability, activity, and antibody escape potential-some of the factors that may influence the natural selection of mutants. Recombinant proteins were expressed in human cells. Stability was measured using thermal denaturation melts. Activity and antibody escape potential were measured using isothermal titration calorimetry in terms of binding to ACE2 and to a neutralizing human antibody CC12.1, respectively. Our results show that variants differ in their expression levels with the two least stable variants showing lesser expression. Out of the 8 well-expressed mutants, only 2 (N501Y and K417T/E484K/N501Y) showed stronger affinity to ACE2, 4 (Y453F, S477N, T478I and S494P) have similar affinity, whereas the other 2 (K417N and E484K) have weaker affinity when compared to the wild-type. In terms of CC12.1 binding, when compared to the wild-type, 4 variants (K417N, Y453F, N501Y and K417T/E484K/N501Y) have weaker affinity, 2 (S477N and S494P) have similar affinity, and 2 (T478I and E484K) have stronger affinity. Taken together, these results indicate that multiple factors contribute towards the natural selection of variants, and all these factors need be considered to understand the evolution of the virus. In addition, since not all variants can escape a given neutralizing antibody, antibodies to treat new variants can be chosen based on the specific mutations in that variant.