{"count":202,"next":"https://hub.stenci.la/api/projects/?limit=50&offset=50","previous":null,"results":[{"id":1316,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2020-11-16T09:03:35.825450Z","name":"article-61523","title":"An interactive meta-analysis of MRI biomarkers of myelin","description":"Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these myelin-sensitive modalities, specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable for quantifying myelin is still ongoing. In this study, we performed a systematic review of published quantitative validation studies to clarify how different these measures are when compared to the underlying histology. We analyzed the results from 43 studies applying meta-analysis tools, controlling for study sample size and using interactive visualization (https://neurolibre.github.io/myelin-meta-analysis). We report the overall estimates and the prediction intervals for the coefficient of determination and find that MT and relaxometry-based measures exhibit the highest correlations with myelin content. We also show which measures are, and which measures are not statistically different regarding their relationship with histology.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/1316.jpg","imagePath":"elife-61523.ipynb.media/fig5.jpg","imageUpdated":"2020-12-12T03:25:20.800840Z","temporary":false,"public":true,"featured":true,"key":"ddEZzoRXeThuwGg9HBidvyxtqUyh4cep","main":"era.ipynb","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":"KNVSakeFKgPLQV9MWAke76","theme":"","extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1307,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2020-11-13T09:11:08.099129Z","name":"article-60287","title":"Formicine ants swallow their highly acidic poison for gut microbial selection and control","description":"Animals continuously encounter microorganisms that are essential for health or cause disease. They are thus challenged to control harmful microbes while allowing the acquisition of beneficial microbes. This challenge is likely especially important for social insects with respect to microbes in food, as they often store food and exchange food among colony members. Here we show that formicine ants actively swallow their antimicrobial, highly acidic poison gland secretion. The ensuing acidic environment in the stomach, the crop, can limit the establishment of pathogenic and opportunistic microbes ingested with food and improve the survival of ants when faced with pathogen contaminated food. At the same time, crop acidity selectively allows acquisition and colonization by Acetobacteraceae, known bacterial gut associates of formicine ants. This suggests that swallowing of the poison in formicine ants acts as a microbial filter and that antimicrobials have a potentially widespread but so far underappreciated dual role in host-microbe interactions.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/1307.jpg","imagePath":"elife-60287.html.media/fig2.jpg","imageUpdated":"2020-12-12T03:25:49.764774Z","temporary":false,"public":true,"featured":true,"key":"4caZSy5DUBLb5R5uokoFdQDYVKPvPv2G","main":"elife-60287_v7.Rmd","containerImage":"stencila/tragust-2021","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":"4nGvxYztNHywcvyPqaBhRL","theme":"","extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1281,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2020-10-13T08:28:07.859567Z","name":"article-57067","title":"Evaluating the impact of open access policies on research institutions","description":"The proportion of research outputs published in open access journals or made available on other freely-accessible platforms has increased over the past two decades, driven largely by funder mandates, institutional policies, grass-roots advocacy, and changing attitudes in the research community. However, the relative effectiveness of these different interventions has remained largely unexplored. Here we present a robust, transparent and updateable method for analysing how these interventions affect the open access performance of individual institutes. We studied 1,207 institutions from across the world, and found that, in 2017, the top-performing universities published around 80–90% of their research open access. The analysis also showed that publisher-mediated (gold) open access was popular in Latin American and African universities, whereas the growth of open access in Europe and North America has mostly been driven by repositories.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/1281-mdueDtbjGJ4JDTAjrqqETC.jpg","imagePath":"published_version_elife.xml.media/fig3.jpg","imageUpdated":"2020-12-12T07:28:06.964902Z","temporary":false,"public":true,"featured":true,"key":"EfKC5KpocK8by9vRTHhej7pstEz8EEvA","main":"published_version_elife.ipynb","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":588,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":88,"created":"2020-07-23T08:19:58.756900Z","name":"article-43154","title":"Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria","description":"Case fatality rates in severe falciparum malaria depend on the pattern and degree of vital organ dysfunction. Recent large-scale case-control analyses of pooled severe malaria data reported that glucose-6-phosphate dehydrogenase deficiency (G6PDd) was protective against cerebral malaria but increased the risk of severe malarial anaemia. A novel formulation of the balancing selection hypothesis was proposed as an explanation for these findings, whereby the selective advantage is driven by the competing risks of death from cerebral malaria and death from severe malarial anaemia. We re-analysed these claims using causal diagrams and showed that they are subject to collider bias. A simulation based sensitivity analysis, varying the strength of the known effect of G6PDd on anaemia, showed that this bias is sufficient to explain all of the observed association. Future genetic epidemiology studies in severe malaria would benefit from the use of causal reasoning.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/588-kMdCpr4FSiaYPtjmdquN35.jpg","imagePath":"article.xml.media/fig2.jpg","imageUpdated":"2020-12-12T07:28:31.134025Z","temporary":false,"public":true,"featured":true,"key":"LyAuzSFLbS3YCCozvz6rgMfmv2nWTQYD","main":"article.rmd","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"pinned","pinned":"foogZeMyzQvSJRZeRi8cCU","theme":"","extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":583,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":1,"created":"2020-07-23T06:52:20.657037Z","name":"article-52258","title":"Inter- and intra-animal variation in the integrative properties of stellate cells in the medial entorhinal cortex","description":"Distinctions between cell types underpin organizational principles for nervous system function. Functional variation also exists between neurons of the same type. This is exemplified by correspondence between grid cell spatial scales and the synaptic integrative properties of stellate cells (SCs) in the medial entorhinal cortex. However, we know little about how functional variability is structured either within or between individuals. Using ex-vivo patch-clamp recordings from up to 55 SCs per mouse, we found that integrative properties vary between mice and, in contrast to the modularity of grid cell spatial scales, have a continuous dorsoventral organization. Our results constrain mechanisms for modular grid firing and provide evidence for inter-animal phenotypic variability among neurons of the same type. We suggest that neuron type properties are tuned to circuit-level set points that vary within and between animals.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/583.jpg","imagePath":"index.html.media/fig1.jpg","imageUpdated":"2020-12-12T03:29:52.440379Z","temporary":false,"public":true,"featured":true,"key":"LyAuzSFLbS3YCCozvz6rgMfmv2nWTQYD","main":"","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"pinned","pinned":"VMvaUEm5nPpeV3FipmR5gA","theme":"","extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":518,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":1,"created":"2020-07-22T10:20:39.447567Z","name":"article-30274","title":"Replication Study: Transcriptional amplification in tumor cells with elevated c-Myc","description":"As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Blum et al., 2015), that described how we intended to replicate selected experiments from the paper ‘Transcriptional amplification in tumor cells with elevated c-Myc’ (Lin et al., 2012). Here we report the results. We found overexpression of c-Myc increased total levels of RNA in P493-6 Burkitt’s lymphoma cells; however, while the effect was in the same direction as the original study (Figure 3E; Lin et al., 2012), statistical significance and the size of the effect varied between the original study and the two different lots of serum tested in this replication. Digital gene expression analysis for a set of genes was also performed on P493-6 cells before and after c-Myc overexpression. Transcripts from genes that were active before c-Myc induction increased in expression following c-Myc overexpression, similar to the original study (Figure 3F; Lin et al., 2012). Transcripts from genes that were silent before c-Myc induction also increased in expression following c-Myc overexpression, while the original study concluded elevated c-Myc had no effect on silent genes (Figure 3F; Lin et al., 2012). Treating the data as paired, we found a statistically significant increase in gene expression for both active and silent genes upon c-Myc induction, with the change in gene expression greater for active genes compared to silent genes. Finally, we report meta-analyses for each result.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/518.png","imagePath":"index.html.media/1","imageUpdated":"2020-12-12T03:31:02.132509Z","temporary":false,"public":true,"featured":true,"key":"LyAuzSFLbS3YCCozvz6rgMfmv2nWTQYD","main":"article.json","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"pinned","pinned":"W3UfJhsLALofQ5z4MpGYc3","theme":"","extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1735,"account":{"id":1807,"name":"nzhenev","displayName":"Nikita Zhenev","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/6a7/url-FTje9sMecktgJ2cVd2rUG9-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/6a7/url-FTje9sMecktgJ2cVd2rUG9-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/6a7/url-FTje9sMecktgJ2cVd2rUG9-a1a0071d4063.png"},"location":null,"website":null},"creator":1803,"created":"2023-03-13T21:16:00.587927Z","name":"test","title":"sadasdasdasd","description":"asdasdasdasd","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"GPFsv6QGBY8RDBxvKTdfqwzJhQwXZcCj","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1720,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2023-01-03T15:54:35.673624Z","name":"article-78717","title":"Robust group- but limited individual-level (longitudinal) reliability and insights into cross-phases response prediction of conditioned fear","description":"Here, we follow the call to target measurement reliability as a key prerequisite for individual-level predictions in translational neuroscience by investigating (1) longitudinal reliability at the individual and (2) group level, (3) internal consistency and (4) response predictability across experimental phases. One hundred and twenty individuals performed a fear conditioning paradigm twice 6 months apart. Analyses of skin conductance responses, fear ratings and blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) with different data transformations and included numbers of trials were conducted. While longitudinal reliability was rather limited at the individual level, it was comparatively higher for acquisition but not extinction at the group level. Internal consistency was satisfactory. Higher responding in preceding phases predicted higher responding in subsequent experimental phases at a weak to moderate level depending on data specifications. In sum, the results suggest that while individual-level predictions are meaningful for (very) short time frames, they also call for more attention to measurement properties in the field.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"ZDYkECqno6mXxadmmkfNygETTx8JmPMT","main":"elife-78717.rmd","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1709,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-11-03T13:43:12.395303Z","name":"article-77772","title":"Deep learning-based feature extraction for prediction and interpretation of sharp-wave ripples in the rodent hippocampus","description":"Local field potential (LFP) deflections and oscillations define hippocampal sharp-wave ripples (SWRs), one of the most synchronous events of the brain. SWRs reflect firing and synaptic current sequences emerging from cognitively relevant neuronal ensembles. While spectral analysis have permitted advances, the surge of ultra-dense recordings now call for new automatic detection strategies. Here, we show how one-dimensional convolutional networks operating over high-density LFP hippocampal recordings allowed for automatic identification of SWR from the rodent hippocampus. When applied without retraining to new datasets and ultra-dense hippocampus-wide recordings, we discovered physiologically relevant processes associated to the emergence of SWR, prompting for novel classification criteria. To gain interpretability, we developed a method to interrogate the operation of the artificial network. We found it relied in feature-based specialization, which permit identification of spatially segregated oscillations and deflections, as well as synchronous population firing typical of replay. Thus, using deep learning-based approaches may change the current heuristic for a better mechanistic interpretation of these relevant neurophysiological events.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"Qk7tJVVnJ2Dgor7E7oMy2axTzwgurGaV","main":"elife-77772.ipynb","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1695,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-09-02T08:04:27.831841Z","name":"article-77461","title":"BIRC6 modifies risk of invasive bacterial infection in Kenyan children","description":"Invasive bacterial disease is a major cause of morbidity and mortality in African children. Despite being caused by diverse pathogens, children with sepsis are clinically indistinguishable from one another. In spite of this, most genetic susceptibility loci for invasive infection that have been discovered to date are pathogen specific and are not therefore suggestive of a shared genetic architecture of bacterial sepsis. Here, we utilise probabilistic diagnostic models to identify children with a high probability of invasive bacterial disease among critically unwell Kenyan children with Plasmodium falciparum parasitaemia. We construct a joint dataset including 1445 bacteraemia cases and 1143 severe malaria cases, and population controls, among critically unwell Kenyan children that have previously been genotyped for human genetic variation. Using these data, we perform a cross-trait genome-wide association study of invasive bacterial infection, weighting cases according to their probability of bacterial disease. In doing so, we identify and validate a novel risk locus for invasive infection secondary to multiple bacterial pathogens, that has no apparent effect on malaria risk. The locus identified modifies splicing of BIRC6 in stimulated monocytes, implicating regulation of apoptosis and autophagy in the pathogenesis of sepsis in Kenyan children.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"TC8i4zCS75LkEhk5pUBYq457kCWmJYRF","main":"elife-77461.rmd","containerImage":"fredatherden/article-77461:latest","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1694,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-08-31T07:40:36.433146Z","name":"article-77220","title":"Flexible and efficient simulation-based inference for models of decision-making","description":"Inferring parameters of computational models that capture experimental data are a central task in cognitive neuroscience. Bayesian statistical inference methods usually require the ability to evaluate the likelihood of the model—however, for many models of interest in cognitive neuroscience, the associated likelihoods cannot be computed efficiently. Simulation-based inference (SBI) offers a solution to this problem by only requiring access to simulations produced by the model. Previously, Fengler et al. introduced likelihood approximation networks (LANs, Fengler et al., 2021) which make it possible to apply SBI to models of decision-making, but require billions of simulations for training. Here, we provide a new SBI method that is substantially more simulation efficient. Our approach, mixed neural likelihood estimation (MNLE), trains neural density estimators on model simulations to emulate the simulator, and is designed to capture both the continuous (e.g., reaction times) and discrete (choices) data of decision-making models. The likelihoods of the emulator can then be used to perform Bayesian parameter inference on experimental data using standard approximate inference methods like Markov Chain Monte Carlo sampling. We demonstrate MNLE on two variants of the drift-diffusion model and show that it is substantially more efficient than LANs: MNLE achieves similar likelihood accuracy with six orders of magnitude fewer training simulations, and is significantly more accurate than LANs when both are trained with the same budget. Our approach enables researchers to perform SBI on custom-tailored models of decision-making, leading to fast iteration of model design for scientific discovery.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"7SqnWbYQiybpXHDb3a5iRX7uk44qDKug","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1693,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-08-31T07:33:40.031407Z","name":"article-78232","title":"Nomograms of human hippocampal volume shifted by polygenic scores","description":"Nomograms are important clinical tools applied widely in both developing and aging populations. They are generally constructed as normative models identifying cases as outliers to a distribution of healthy controls. Currently used normative models do not account for genetic heterogeneity. Hippocampal volume (HV) is a key endophenotype for many brain disorders. Here, we examine the impact of genetic adjustment on HV nomograms and the translational ability to detect dementia patients. Using imaging data from 35,686 healthy subjects aged 44–82 from the UK Biobank (UKB), we built HV nomograms using Gaussian process regression (GPR), which – compared to a previous method – extended the application age by 20 years, including dementia critical age ranges. Using HV polygenic scores (HV-PGS), we built genetically adjusted nomograms from participants stratified into the top and bottom 30% of HV-PGS. This shifted the nomograms in the expected directions by ~100 mm3 (2.3% of the average HV), which equates to 3 years of normal aging for a person aged ~65. Clinical impact of genetically adjusted nomograms was investigated by comparing 818 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database diagnosed as either cognitively normal (CN), having mild cognitive impairment (MCI) or Alzheimer’s disease (AD) patients. While no significant change in the survival analysis was found for MCI-to-AD conversion, an average of 68% relative decrease was found in intra-diagnostic-group variance, highlighting the importance of genetic adjustment in untangling phenotypic heterogeneity.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"PY7qmRC7SfLbn6hewghceR3xR5KX2xFr","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1692,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-08-30T14:12:14.128814Z","name":"article-75055","title":"Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer’s disease transgenic mice","description":"Increased astrocytic Ca2+ signaling has been shown in Alzheimer’s disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca2+ signaling in such mice. Here, we employ an event-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca2+ response to locomotion and an uncoupling of pupil responses and astrocytic Ca2+ signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRABNE, we demonstrate a reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic underpinning of the observed reduced astrocytic Ca2+ responses. Our data points to a dysfunction in the norepinephrine–astrocyte Ca2+ activity axis, which may account for some of the cognitive deficits observed in Alzheimer’s disease.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"ancUyJDqQuM68DC9LibeYuaZdcrtJUaR","main":"elife-75055.rmd","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1682,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-07-25T14:51:21.135591Z","name":"article-77625","title":"The spatiotemporal patterns of major human admixture events during the European Holocene","description":"Recent studies have shown that admixture has been pervasive throughout human history. While several methods exist for dating admixture in contemporary populations, they are not suitable for sparse, low coverage ancient genomic data. Thus, we developed DATES (Distribution of Ancestry Tracts of Evolutionary Signals) that leverages ancestry covariance patterns across the genome of a single individual to infer the timing of admixture. DATES provides reliable estimates under various demographic scenarios and outperforms available methods for ancient DNA applications. Using DATES on~1100 ancient genomes from sixteen regions in Europe and west Asia, we reconstruct the chronology of the formation of the ancestral populations and the fine-scale details of the spread of Neolithic farming and Steppe pastoralist-related ancestry across Europe. By studying the genetic formation of Anatolian farmers, we infer that gene flow related to Iranian Neolithic farmers occurred before 9600 BCE, predating the advent of agriculture in Anatolia. Contrary to the archaeological evidence, we estimate that early Steppe pastoralist groups (Yamnaya and Afanasievo) were genetically formed more than a millennium before the start of Steppe pastoralism. Our analyses provide new insights on the origins and spread of farming and Indo-European languages, highlighting the power of genomic dating methods to elucidate the legacy of human migrations.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"YZoE29QjiJ22PB525L2EH6pMUbdnQxQd","main":"elife-77625.rmd","containerImage":"fredatherden/article-77625:test","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1680,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-07-19T13:09:38.660950Z","name":"article-75046","title":"A crowd of BashTheBug volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates","description":"Tuberculosis is a respiratory disease that is treatable with antibiotics. An increasing prevalence of resistance means that to ensure a good treatment outcome it is desirable to test the susceptibility of each infection to different antibiotics. Conventionally, this is done by culturing a clinical sample and then exposing aliquots to a panel of antibiotics, each being present at a pre-determined concentration, thereby determining if the sample isresistant or susceptible to each sample. The minimum inhibitory concentration (MIC) of a drug is the lowestconcentration that inhibits growth and is a more useful quantity but requires each sample to be tested at a range ofconcentrations for each drug. Using 96-well broth micro dilution plates with each well containing a lyophilised pre-determined amount of an antibiotic is a convenient and cost-effective way to measure the MICs of several drugs at once for a clinical sample. Although accurate, this is still an expensive and slow process that requires highly-skilled and experienced laboratory scientists. Here we show that, through the BashTheBug project hosted on the Zooniverse citizen science platform, a crowd of volunteers can reproducibly and accurately determine the MICs for 13 drugs and that simply taking the median or mode of 11–17 independent classifications is sufficient. There is therefore a potential role for crowds to support (but not supplant) the role of experts in antibiotic susceptibility testing.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"XN6UWASMVM8ntxiGvVQ3gARjQH4J3aaQ","main":"elife-75046.ipynb","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1664,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-05-30T07:58:31.279680Z","name":"article-70780","title":"The LOTUS initiative for open knowledge management in natural products research","description":"Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge management, analysis and interpretation of data in natural products research. Currently, reliance on a disparate set of non-standardized, insular, and specialized databases presents a series of challenges for data access, both within the discipline and for integration and interoperability between related fields. The fundamental elements of exchange are referenced structure-organism pairs that establish relationships between distinct molecular structures and the living organisms from which they were identified. Consolidating and sharing such information via an open platform has strong transformative potential for natural products research and beyond. This is the ultimate goal of the newly established LOTUS initiative, which has now completed the first steps toward the harmonization, curation, validation and open dissemination of 750,000+ referenced structure-organism pairs. LOTUS data is hosted on Wikidata and regularly mirrored on https://lotus.naturalproducts.net. Data sharing within the Wikidata framework broadens data access and interoperability, opening new possibilities for community curation and evolving publication models. Furthermore, embedding LOTUS data into the vast Wikidata knowledge graph will facilitate new biological and chemical insights. The LOTUS initiative represents an important advancement in the design and deployment of a comprehensive and collaborative natural products knowledge base.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/1664-ianUMkfhL7hvbPhjxMRLgJ.png","imagePath":"thumbnail.png","imageUpdated":"2022-06-21T09:29:32.349512Z","temporary":false,"public":true,"featured":false,"key":"QDa7ev2NnAVdHq8Gf7RJhkJuUfJ7A82G","main":"elife-70780.rmd","containerImage":"adafede/lotus-stencila:latest","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"live","pinned":null,"theme":"elife","extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1661,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-05-11T16:17:30.075735Z","name":"article-76887","title":"Genetic variation of putative myokine signaling is dominated by biological sex and sex hormones","description":"Skeletal muscle plays an integral role in coordinating physiological homeostasis, where signaling to other tissues via myokines allows for coordination of complex processes. Here, we aimed to leverage natural genetic correlation structure of gene expression both within and across tissues to understand how muscle interacts with metabolic tissues. Specifically, we performed a survey of genetic correlations focused on myokine gene regulation, muscle cell composition, cross-tissue signaling, and interactions with genetic sex in humans. While expression levels of a majority of myokines and cell proportions within skeletal muscle showed little relative differences between males and females, nearly all significant cross-tissue enrichments operated in a sex-specific or hormone-dependent fashion; in particular, with estradiol. These sex- and hormone-specific effects were consistent across key metabolic tissues: liver, pancreas, hypothalamus, intestine, heart, visceral, and subcutaneous adipose tissue. To characterize the role of estradiol receptor signaling on myokine expression, we generated male and female mice which lack estrogen receptor α specifically in skeletal muscle (MERKO) and integrated with human data. These analyses highlighted potential mechanisms of sex-dependent myokine signaling conserved between species, such as myostatin enriched for divergent substrate utilization pathways between sexes. Several other putative sex-dependent mechanisms of myokine signaling were uncovered, such as muscle-derived tumor necrosis factor alpha (TNFA) enriched for stronger inflammatory signaling in females compared to males and GPX3 as a male-specific link between glycolytic fiber abundance and hepatic inflammation. Collectively, we provide a population genetics framework for inferring muscle signaling to metabolic tissues in humans. We further highlight sex and estradiol receptor signaling as critical variables when assaying myokine functions and how changes in cell composition are predicted to impact other metabolic organs.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"MR7f48ZXzvdSx7sfhJD8vAoCapo42m66","main":"elife-76887.rmd","containerImage":"fredatherden/article-76887:latest","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1660,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-05-10T13:12:12.152457Z","name":"article-75308","title":"Conformist social learning leads to self-organised prevention against adverse bias in risky decision making","description":"Given the ubiquity of potentially adverse behavioural bias owing to myopic trial-and-error learning, it seems paradoxical that improvements in decision-making performance through conformist social learning, a process widely considered to be bias amplification, still prevail in animal collective behaviour. Here we show, through model analyses and large-scale interactive behavioural experiments with 585 human subjects, that conformist influence can indeed promote favourable risk taking in repeated experience-based decision making, even though many individuals are systematically biased towards adverse risk aversion. Although strong positive feedback conferred by copying the majority’s behaviour could result in unfavourable informational cascades, our differential equation model of collective behavioural dynamics identified a key role for increasing exploration by negative feedback arising when a weak minority influence undermines the inherent behavioural bias. This ‘collective behavioural rescue’, emerging through coordination of positive and negative feedback, highlights a benefit of collective learning in a broader range of environmental conditions than previously assumed and resolves the ostensible paradox of adaptive collective behavioural flexibility under conformist influences.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"H8natvq8wRnyGz5nczJ3YYrbrHj32XSF","main":"elife-75308.rmd","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1656,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-05-06T08:54:48.429430Z","name":"article-72865","title":"Condensation of Ede1 promotes the initiation of endocytosis","description":"Clathrin-mediated endocytosis is initiated by a network of weakly interacting proteins through a poorly understood mechanism. Ede1, the yeast homolog of mammalian Eps15, is an early-arriving endocytic protein and a key initiation factor. In the absence of Ede1, most other early endocytic proteins lose their punctate localization and endocytic uptake is decreased. We show that in yeast cells, cytosolic concentration of Ede1 is buffered at a critical level. Excess amounts of Ede1 form large condensates which recruit other endocytic proteins and exhibit properties of phase-separated liquid droplets. We demonstrate that the central region of Ede1, containing a coiled-coil and a prion-like region, is essential for both the condensate formation and the function of Ede1 in endocytosis. The functionality of Ede1 mutants lacking the central region can be partially rescued by an insertion of heterologous prion-like domains. Conversely, fusion of a heterologous lipid-binding domain with the central region of Ede1 can promote clustering into stable plasma membrane domains. We propose that the ability of Ede1 to form condensed networks supports the clustering of early endocytic proteins and promotes the initiation of endocytosis.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"K8kgG8hKHz5rzgnMamuyKGZUX36ZFpnh","main":"elife-72865.rmd","containerImage":"fredatherden/article-72865","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1654,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-04-25T14:52:11.047625Z","name":"article-72626","title":"Patient-specific Boolean models of signalling networks guide personalised treatments","description":"Prostate cancer is the second most occurring cancer in men worldwide. To better understand the mechanisms of tumorigenesis and possible treatment responses, we developed a mathematical model of prostate cancer which considers the major signalling pathways known to be deregulated. We personalised this Boolean model to molecular data to reflect the heterogeneity and specific response to perturbations of cancer patients. A total of 488 prostate samples were used to build patient-specific models and compared to available clinical data. Additionally, eight prostate cell line-specific models were built to validate our approach with dose-response data of several drugs. The effects of single and combined drugs were tested in these models under different growth conditions. We identified 15 actionable points of interventions in one cell line-specific model whose inactivation hinders tumorigenesis. To validate these results, we tested nine small molecule inhibitors of five of those putative targets and found a dose-dependent effect on four of them, notably those targeting HSP90 and PI3K. These results highlight the predictive power of our personalised Boolean models and illustrate how they can be used for precision oncology.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"dbV4vpDzd44UZYTz5BwUwFv7rVxxP2N9","main":"elife-72626_v1.rmd","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1649,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-03-25T12:37:07.261854Z","name":"article-72666","title":"Ecdysone coordinates plastic growth with robust pattern in the developing wing","description":"Animals develop in unpredictable, variable environments. In response to environmental change, some aspects of development adjust to generate plastic phenotypes. Other aspects of development, however, are buffered against environmental change to produce robust phenotypes. How organ development is coordinated to accommodate both plastic and robust developmental responses is poorly understood. Here, we demonstrate that the steroid hormone ecdysone coordinates both plasticity of organ size and robustness of organ pattern in the developing wings of the fruit fly Drosophila melanogaster. Using fed and starved larvae that lack prothoracic glands, which synthesize ecdysone, we show that nutrition regulates growth both via ecdysone and via an ecdysone-independent mechanism, while nutrition regulates patterning only via ecdysone. We then demonstrate that growth shows a graded response to ecdysone concentration, while patterning shows a threshold response. Collectively, these data support a model where nutritionally regulated ecdysone fluctuations confer plasticity by regulating disc growth in response to basal ecdysone levels and confer robustness by initiating patterning only once ecdysone peaks exceed a threshold concentration. This could represent a generalizable mechanism through which hormones coordinate plastic growth with robust patterning in the face of environmental change.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"UmXtfSxbbLZz9iPdmJTy3pyY8rXXgcUD","main":"elife-72666.rmd","containerImage":"fredatherden/article-72666:latest","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1648,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-03-24T17:59:09.958899Z","name":"article-63853","title":"Automated annotation of birdsong with a neural network that segments spectrograms","description":"Songbirds provide a powerful model system for studying sensory-motor learning. However, many analyses of birdsong require time-consuming, manual annotation of its elements, called syllables. Automated methods for annotation have been proposed, but these methods assume that audio can be cleanly segmented into syllables, or they require carefully tuning multiple statistical models. Here, we present TweetyNet: a single neural network model that learns how to segment spectrograms of birdsong into annotated syllables. We show that TweetyNet mitigates limitations of methods that rely on segmented audio. We also show that TweetyNet performs well across multiple individuals from two species of songbirds, Bengalese finches and canaries. Lastly, we demonstrate that using TweetyNet we can accurately annotate very large datasets containing multiple days of song, and that these predicted annotations replicate key findings from behavioral studies. In addition, we provide open-source software to assist other researchers, and a large dataset of annotated canary song that can serve as a benchmark. We conclude that TweetyNet makes it possible to address a wide range of new questions about birdsong.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"csSy9867djKmccuQPziduFfxyVZKGz6m","main":"elife-63853.ipynb","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1647,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-03-23T17:14:06.035471Z","name":"article-76559","title":"Meta-Research: Author-level data confirm the widening gender gap in publishing rates during COVID-19","description":"Publications are essential for a successful academic career, and there is evidence that the COVID-19 pandemic has amplified existing gender disparities in the publishing process. We used longitudinal publication data on 431,207 authors in four disciplines - basic medicine, biology, chemistry and clinical medicine - to quantify the differential impact of COVID-19 on the annual publishing rates of men and women. In a difference-in-differences analysis, we estimated that the average gender difference in publication productivity increased from –0.26 in 2019 to –0.35 in 2020; this corresponds to the output of women being 17% lower than the output of men in 2109, and 24% lower in 2020. An age-group comparison showed a widening gender gap for both early-career and mid-career scientists. The increasing gender gap was most pronounced among highly productive authors and in biology and clinical medicine. Our study demonstrates the importance of reinforcing institutional commitments to diversity through policies that support the inclusion and retention of women in research.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"bqxC2TWLBjvj2btxBKHYtcrF4hpah4Hk","main":"elife-76559.rmd","containerImage":"fredatherden/article-76559:latest","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1636,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-03-01T14:52:56.101692Z","name":"article-72837","title":"STAT3-mediated allelic imbalance of novel genetic variant Rs1047643 and B-cell-specific super-enhancer in association with systemic lupus erythematosus","description":"Mapping of allelic imbalance (AI) at heterozygous loci has the potential to establish links between genetic risk for disease and biological function. Leveraging multi-omics data for AI analysis and functional annotation, we discovered a novel functional risk variant rs1047643 at 8p23 in association with systemic lupus erythematosus (SLE). This variant displays dynamic AI of chromatin accessibility and allelic expression on FDFT1 gene in B cells with SLE. We further found a B-cell restricted super-enhancer (SE) that physically contacts with this SNP-residing locus, an interaction that also appears specifically in B cells. Quantitative analysis of chromatin accessibility and DNA methylation profiles further demonstrated that the SE exhibits aberrant activity in B cell development with SLE. Functional studies identified that STAT3, a master factor associated with autoimmune diseases, directly regulates both the AI of risk variant and the activity of SE in cultured B cells. Our study reveals that STAT3-mediated SE activity and cis-regulatory effects of SNP rs1047643 at 8p23 locus are associated with B cell deregulation in SLE.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"WPtAQTshyufAP9tn3hx7METWnJKZLtJj","main":"elife-72837.rmd","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1627,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-02-15T12:14:18.242383Z","name":"article-72904","title":"Charting brain growth and aging at high spatial precision","description":"Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2–100) and used normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision-making.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/1627-7YQ9GQJoAV5jrYa7a2GMEo.jpg","imagePath":"elife-72904.xml.media/fig1.jpg","imageUpdated":"2022-02-28T14:22:36.963053Z","temporary":false,"public":true,"featured":false,"key":"ePk3spnmbk8zRF25dErUuZ6DEoRRNQWH","main":"elife-72904_article_code.ipynb","containerImage":"fredatherden/article-72904:latest","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1621,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-02-03T15:23:12.205567Z","name":"article-74153","title":"Absolute quantitation of individual SARS-CoV-2 RNA molecules provides a new paradigm for infection dynamics and variant differences","description":"Despite an unprecedented global research effort on SARS-CoV-2, early replication events remain poorly understood. Given the clinical importance of emergent viral variants with increased transmission, there is an urgent need to understand the early stages of viral replication and transcription. We used single-molecule fluorescence in situ hybridisation (smFISH) to quantify positive sense RNA genomes with 95% detection efficiency, while simultaneously visualising negative sense genomes, subgenomic RNAs, and viral proteins. Our absolute quantification of viral RNAs and replication factories revealed that SARS-CoV-2 genomic RNA is long-lived after entry, suggesting that it avoids degradation by cellular nucleases. Moreover, we observed that SARS-CoV-2 replication is highly variable between cells, with only a small cell population displaying high burden of viral RNA. Unexpectedly, the B.1.1.7 variant, first identified in the UK, exhibits significantly slower replication kinetics than the Victoria strain, suggesting a novel mechanism contributing to its higher transmissibility with important clinical implications.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"ayLZzokkAXVufCPHanWhrNBoKLHqAZYD","main":"elife-74153.rmd","containerImage":"fredatherden/article-74153:latest","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1620,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-02-03T14:40:11.616862Z","name":"article-75795","title":"Unique structure and positive selection promote the rapid divergence of Drosophila Y chromosomes","description":"Y chromosomes across diverse species convergently evolve a gene-poor, heterochromatic organization enriched for duplicated genes, LTR retrotransposons, and satellite DNA. Sexual antagonism and a loss of recombination play major roles in the degeneration of young Y chromosomes. However, the processes shaping the evolution of mature, already degenerated Y chromosomes are less well-understood. Because Y chromosomes evolve rapidly, comparisons between closely related species are particularly useful. We generated de novo long-read assemblies complemented with cytological validation to reveal Y chromosome organization in three closely related species of the Drosophila simulans complex, which diverged only 250,000 years ago and share >98% sequence identity. We find these Y chromosomes are divergent in their organization and repetitive DNA composition and discover new Y-linked gene families whose evolution is driven by both positive selection and gene conversion. These Y chromosomes are also enriched for large deletions, suggesting that the repair of double-strand breaks on Y chromosomes may be biased toward microhomology-mediated end joining over canonical non-homologous end-joining. We propose that this repair mechanism contributes to the convergent evolution of Y chromosome organization across organisms.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"BsFyvDAD6PwZbBjsN2ohyWn9Q2ARwxnX","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1616,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-02-01T09:14:22.140827Z","name":"article-72357","title":"Risk factors relate to the variability of health outcomes as well as the mean: A GAMLSS tutorial","description":"Background: Risk factors or interventions may affect the variability as well as the mean of health outcomes. Understanding this can aid aetiological understanding and public health translation, in that interventions which shift the outcome mean and reduce variability are typically preferable to those which affect only the mean. However, most commonly used statistical tools do not test for differences in variability. Tools that do have few epidemiological applications to date, and fewer applications still have attempted to explain their resulting findings. We thus provide a tutorial for investigating this using GAMLSS (Generalised Additive Models for Location, Scale and Shape).\nMethods: The 1970 British birth cohort study was used, with body mass index (BMI; N = 6007) and mental wellbeing (Warwick-Edinburgh Mental Wellbeing Scale; N = 7104) measured in midlife (42–46 years) as outcomes. We used GAMLSS to investigate how multiple risk factors (sex, childhood social class, and midlife physical inactivity) related to differences in health outcome mean and variability.\nResults: Risk factors were related to sizable differences in outcome variability—for example males had marginally higher mean BMI yet 28% lower variability; lower social class and physical inactivity were each associated with higher mean and higher variability (6.1% and 13.5% higher variability, respectively). For mental wellbeing, gender was not associated with the mean while males had lower variability (–3.9%); lower social class and physical inactivity were each associated with lower mean yet higher variability (7.2% and 10.9% higher variability, respectively).\nConclusions: The results highlight how GAMLSS can be used to investigate how risk factors or interventions may influence the variability in health outcomes. This underutilised approach to the analysis of continuously distributed outcomes may have broader utility in epidemiologic, medical, and psychological sciences. A tutorial and replication syntax is provided online to facilitate this (https://osf.io/5tvz6/).\nFunding: DB is supported by the Economic and Social Research Council (grant number ES/M001660/1), The Academy of Medical Sciences / Wellcome Trust (“Springboard Health of the Public in 2040” award: HOP001/1025); DB and LW are supported by the Medical Research Council (MR/V002147/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"UnLTUzwCydFWwjwqXD2Mi9AmE5JCATWQ","main":"elife-72357.rmd","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1612,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-01-25T14:03:53.868330Z","name":"article-71858","title":"Synaptic targets of photoreceptors specialized to detect color and skylight polarization in Drosophila","description":"Color and polarization provide complementary information about the world and are detected by specialized photoreceptors. However, the downstream neural circuits that process these distinct modalities are incompletely understood in any animal. Using electron microscopy, we have systematically reconstructed the synaptic targets of the photoreceptors specialized to detect color and skylight polarization in Drosophila, and we have used light microscopy to confirm many of our findings. We identified known and novel downstream targets that are selective for different wavelengths or polarized light, and followed their projections to other areas in the optic lobes and the central brain. Our results revealed many synapses along the photoreceptor axons between brain regions, new pathways in the optic lobes, and spatially segregated projections to central brain regions. Strikingly, photoreceptors in the polarization-sensitive dorsal rim area target fewer cell types, and lack strong connections to the lobula, a neuropil involved in color processing. Our reconstruction identifies shared wiring and modality-specific specializations for color and polarization vision, and provides a comprehensive view of the first steps of the pathways processing color and polarized light inputs.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"LBnf3D5UAhkVuckYTh8WskefXnYp5jGV","main":"elife-71858.rmd","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1611,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2022-01-25T14:03:22.994453Z","name":"article-64620","title":"Valence biases in reinforcement learning shift across adolescence and modulate subsequent memory","description":"As individuals learn through trial and error, some are more influenced by good outcomes, while others weight bad outcomes more heavily. Such valence biases may also influence memory for past experiences. Here, we examined whether valence asymmetries in reinforcement learning change across adolescence, and whether individual learning asymmetries bias the content of subsequent memory. Participants ages 8–27 learned the values of ‘point machines,’ after which their memory for trial-unique images presented with choice outcomes was assessed. Relative to children and adults, adolescents overweighted worse-than-expected outcomes during learning. Individuals’ valence biases modulated incidental memory, such that those who prioritized worse- (or better-) than-expected outcomes during learning were also more likely to remember images paired with these outcomes, an effect reproduced in an independent dataset. Collectively, these results highlight age-related changes in the computation of subjective value and demonstrate that a valence-asymmetric valuation process influences how information is prioritized in episodic memory.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"EjkdrUZfTcAUfPv5t5w4RMN2PTGmWFi5","main":"elife-64620.rmd","containerImage":"fredatherden/article-64620","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1601,"account":{"id":582,"name":"reubano","displayName":"Reuben Cummings","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/5b6/url-72QaQCtuM8ANGWjEkXph9Z-10c070f1761f.jpeg","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/5b6/url-72QaQCtuM8ANGWjEkXph9Z-5b678ba0c304.jpeg","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/5b6/url-72QaQCtuM8ANGWjEkXph9Z-a1a0071d4063.jpeg"},"location":null,"website":null},"creator":578,"created":"2022-01-17T01:45:42.104975Z","name":"test","title":"Test Title","description":"Test description","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"DhjPVoJm5hL83upaLXfq3rnTsKa9kKLA","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":"bootstrap","extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1593,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-12-16T13:31:27.228177Z","name":"article-73348","title":"MCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interface","description":"Dramatic change in chromosomal DNA morphology between interphase and mitosis is a defining features of the eukaryotic cell cycle. Two types of enzymes, namely cohesin and condensin confer the topology of chromosomal DNA by extruding DNA loops. While condensin normally configures chromosomes exclusively during mitosis, cohesin does so during interphase. The processivity of cohesin’s loop extrusion during interphase is limited by a regulatory factor called WAPL, which induces cohesin to dissociate from chromosomes via a mechanism that requires dissociation of its kleisin from the neck of SMC3. We show here that a related mechanism may be responsible for blocking condensin II from acting during interphase. Cells derived from patients affected by microcephaly caused by mutations in the MCPH1 gene undergo premature chromosome condensation. We show that deletion of Mcph1 in mouse embryonic stem cells unleashes an activity of condensin II that triggers formation of compact chromosomes in G1 and G2 phases, accompanied by enhanced mixing of A and B chromatin compartments, and this occurs even in the absence of CDK1 activity. Crucially, inhibition of condensin II by MCPH1 depends on the binding of a short linear motif within MCPH1 to condensin II’s NCAPG2 subunit. MCPH1’s ability to block condensin II’s association with chromatin is abrogated by the fusion of SMC2 with NCAPH2, hence may work by a mechanism similar to cohesin. Remarkably, in the absence of both WAPL and MCPH1, cohesin and condensin II transform chromosomal DNAs of G2 cells into chromosomes with a solenoidal axis.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"4UDuvrq5fFmVNx9YGSFPXnYY4EDfo62p","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1588,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-12-10T14:23:59.365646Z","name":"article-69577","title":"Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1","description":"A gene signature was previously found to be correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus and simian-human immunodeficiency virus challenge models in non-human primates. In this report, we investigated the presence of this signature as a correlate of reduced risk in human clinical trials and potential mechanisms of protection. The absence of this gene signature in the DNA/rAd5 human vaccine trial, which did not show efficacy, strengthens our hypothesis that this signature is only enriched in studies that demonstrated protection. This gene signature was enriched in the partially effective RV144 human trial that administered the ALVAC/protein vaccine, and we find that the signature associates with both decreased risk of HIV-1 acquisition and increased vaccine efficacy (VE). Total RNA-seq in a clinical trial that used the same vaccine regimen as the RV144 HIV vaccine implicated antibody-dependent cellular phagocytosis (ADCP) as a potential mechanism of vaccine protection. CITE-seq profiling of 53 surface markers and transcriptomes of 53,777 single cells from the same trial showed that genes in this signature were primarily expressed in cells belonging to the myeloid lineage, including monocytes, which are major effector cells for ADCP. The consistent association of this transcriptome signature with VE represents a tool both to identify potential mechanisms, as with ADCP here, and to screen novel approaches to accelerate the development of new vaccine candidates.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"EHt2n2bob7b84vTL66vZBbYMwg3TsR3U","main":"elife-69577-enriched.rmd","containerImage":"fredatherden/article-69577","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1587,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-12-10T11:16:13.184474Z","name":"article-71601","title":"Investigating the replicability of preclinical cancer biology","description":"Replicability is an important feature of scientific research, but aspects of contemporary research culture, such as an emphasis on novelty, can make replicability seem less important than it should be. The Reproducibility Project: Cancer Biology was set up to provide evidence about the replicability of preclinical research in cancer biology by repeating selected experiments from high-impact papers. A total of 50 experiments from 23 papers were repeated, generating data about the replicability of a total of 158 effects. Most of the original effects were positive effects (136), with the rest being null effects (22). A majority of the original effect sizes were reported as numerical values (117), with the rest being reported as representative images (41). We employed seven methods to assess replicability, and some of these methods were not suitable for all the effects in our sample. One method compared effect sizes: for positive effects, the median effect size in the replications was 85% smaller than the median effect size in the original experiments, and 92% of replication effect sizes were smaller than the original. The other methods were binary – the replication was either a success or a failure – and five of these methods could be used to assess both positive and null effects when effect sizes were reported as numerical values. For positive effects, 40% of replications (39/97) succeeded according to three or more of these five methods, and for null effects 80% of replications (12/15) were successful on this basis; combining positive and null effects, the success rate was 46% (51/112). A successful replication does not definitively confirm an original finding or its theoretical interpretation. Equally, a failure to replicate does not disconfirm a finding, but it does suggest that additional investigation is needed to establish its reliability.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"8QJbu2Fr2fAgrdzj2qAD9Y4Npi2ptY6G","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1585,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-12-08T15:23:16.555151Z","name":"article-69298","title":"Exposure to landscape fire smoke reduced birthweight in low- and middle-income countries: findings from a siblings-matched case-control study","description":"Background: Landscape fire smoke (LFS) has been associated with reduced birthweight, but evidence from low- and middle-income countries (LMICs) is rare.\nMethods: \nHere, we present a sibling-matched case–control study of 227,948 newborns to identify an association between fire-sourced fine particulate matter (PM2.5) and birthweight in 54 LMICs from 2000 to 2014. We selected mothers from the geocoded Demographic and Health Survey with at least two children and valid birthweight records. Newborns affiliated with the same mother were defined as a family group. Gestational exposure to LFS was assessed in each newborn using the concentration of fire-sourced PM2.5. We determined the associations of the within-group variations in LFS exposure with birthweight differences between matched siblings using a fixed-effects regression model. Additionally, we analyzed the binary outcomes of low birthweight (LBW) or very low birthweight (VLBW).\nResults: According to fully adjusted models, a 1 µg/m3 increase in the concentration of fire-sourced PM2.5 was significantly associated with a 2.17 g (95% confidence interval [CI] 0.56–3.77) reduction in birthweight, a 2.80% (95% CI 0.97–4.66) increase in LBW risk, and an 11.68% (95% CI 3.59–20.40) increase in VLBW risk.\nConclusions: Our findings indicate that gestational exposure to LFS harms fetal health.\nFunding: PKU-Baidu Fund, National Natural Science Foundation of China, Peking University Health Science Centre, and CAMS Innovation Fund for Medical Sciences.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/1585-NaAzchuhW5qCuMH8tUGcqk.jpg","imagePath":"elife-69298.xml.media/fig1.jpg","imageUpdated":"2021-12-08T16:04:08.417743Z","temporary":false,"public":true,"featured":false,"key":"Y7BQzrY6avA3Bs73S9VekEM2RK4Dnwwc","main":"elife-69298-enriched.rmd","containerImage":"fredatherden/article-69298","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1583,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-12-03T18:34:45.088187Z","name":"article-68015","title":"Topological network analysis of patient similarity for precision management of acute blood pressure in spinal cord injury","description":"Background: Predicting neurological recovery after spinal cord injury (SCI) is challenging. Using topological data analysis, we have previously shown that mean arterial pressure (MAP) during SCI surgery predicts long-term functional recovery in rodent models, motivating the present multicenter study in patients. Methods: Intra-operative monitoring records and neurological outcome data were extracted (n = 118 patients). We built a similarity network of patients from a low-dimensional space embedded using a non-linear algorithm, Isomap, and ensured topological extraction using persistent homology metrics. Confirmatory analysis was conducted through regression methods. Results: Network analysis suggested that time outside of an optimum MAP range (hypotension or hypertension) during surgery was associated with lower likelihood of neurological recovery at hospital discharge. Logistic and LASSO (least absolute shrinkage and selection operator) regression confirmed these findings, revealing an optimal MAP range of 76–[104-117] mmHg associated with neurological recovery. Conclusions: We show that deviation from this optimal MAP range during SCI surgery predicts lower probability of neurological recovery and suggest new targets for therapeutic intervention. Funding: NIH/NINDS: R01NS088475 (ARF); R01NS122888 (ARF); UH3NS106899 (ARF); Department of Veterans Affairs: 1I01RX002245 (ARF), I01RX002787 (ARF); Wings for Life Foundation (ATE, ARF); Craig H. Neilsen Foundation (ARF); and DOD: SC150198 (MSB); SC190233 (MSB); DOE: DE-AC02-05CH11231 (DM).","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"BkZoUPwQL6c4XEaF5UjJeTDRmmVujcdT","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1568,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-11-11T16:04:31.168999Z","name":"article-67403","title":"Information content differentiates enhancers from silencers in mouse photoreceptors","description":"Enhancers and silencers often depend on the same transcription factors (TFs) and are conflated in genomic assays of TF binding or chromatin state. To identify sequence features that distinguish enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF cone-rod homeobox (CRX) in mouse retinas. Both enhancers and silencers contain more TF motifs than inactive sequences, but relative to silencers, enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. The ability of information content to distinguish enhancers and silencers targeted by the same TF illustrates how motif context determines the activity of cis-regulatory sequences.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"WU6dGN6tTo6j5aHrvd7JebVBVPETzNLC","main":"era.ipynb","containerImage":"stencila/elife-67403","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1552,"account":{"id":473,"name":"danetheory","displayName":"Branden Dane","email":"Dane@TheoryLabs.dev","image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/946/1939718_10151888583812411_1863867708_o-10c070f1761f.jpeg","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/946/1939718_10151888583812411_1863867708_o-5b678ba0c304.jpeg","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/946/1939718_10151888583812411_1863867708_o-a1a0071d4063.jpeg"},"location":"New York City, NY","website":"https://TheoryLabs.dev"},"creator":469,"created":"2021-09-27T19:20:23.067146Z","name":"in-the-beginning","title":"And so it begins","description":"Welcome to the desert of the real.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/and_another_duck_RESIZED.jpeg","imagePath":"__uploaded__","imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"SK9iBhTqjgusGRLn9EuC5MfBHJqSqg3p","main":"README","containerImage":"","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1550,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-09-22T15:50:35.951710Z","name":"article-67490","title":"Non-linear dimensionality reduction on extracellular waveforms reveals cell type diversity in premotor cortex","description":"Cortical circuits are thought to contain a large number of cell types that coordinate to produce behavior. Current in vivo methods rely on clustering of specified features of extracellular waveforms to identify putative cell types, but these capture only a small amount of variation. Here, we develop a new method (WaveMAP) that combines non-linear dimensionality reduction with graph clustering to identify putative cell types. We apply WaveMAP to extracellular waveforms recorded from dorsal premotor cortex of macaque monkeys performing a decision-making task. Using WaveMAP, we robustly establish eight waveform clusters and show that these clusters recapitulate previously identified narrow- and broad-spiking types while revealing previously unknown diversity within these subtypes. The eight clusters exhibited distinct laminar distributions, characteristic firing rate patterns, and decision-related dynamics. Such insights were weaker when using feature-based approaches. WaveMAP therefore provides a more nuanced understanding of the dynamics of cell types in cortical circuits.","imageFile":"https://storage.googleapis.com/stencila-hub-media/projects/images/1550-QYiYjYzyqSPr82JqZnAR5c.jpg","imagePath":"elife-67490.xml.media/fig2.jpg","imageUpdated":"2021-09-22T19:55:28.454792Z","temporary":false,"public":true,"featured":false,"key":"6RgZSZQ4zQdunQnMoWhgpop6ERoJ2ifE","main":"main.ipynb","containerImage":"","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1530,"account":{"id":450,"name":"john3","displayName":"John Blischak","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/176/url-4gGksWEizQqSuQo7gNw7Mq-10c070f1761f.jpeg","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/176/url-4gGksWEizQqSuQo7gNw7Mq-5b678ba0c304.jpeg","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/176/url-4gGksWEizQqSuQo7gNw7Mq-a1a0071d4063.jpeg"},"location":null,"website":null},"creator":446,"created":"2021-08-26T14:47:44.689185Z","name":"my-test-project","title":"My test project","description":"Going through the Google Docs tutorial at https://help.stenci.la/guides/gsuita/google-docs-tutorial","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"L9kD8czb6fZUA2nGfHb7V94cLMjPNcbQ","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1523,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-08-18T11:16:25.583064Z","name":"article-64846","title":"NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1","description":"The molecular basis underlying glioblastoma (GBM) heterogeneity and plasticity is not fully understood. Using transcriptomic data of human patient-derived brain tumor stem cell lines (BTSCs), classified based on GBM-intrinsic signatures, we identify the AP-1 transcription factor FOSL1 as a key regulator of the mesenchymal (MES) subtype. We provide a mechanistic basis to the role of the neurofibromatosis type 1 gene (NF1), a negative regulator of the RAS/MAPK pathway, in GBM mesenchymal transformation through the modulation of FOSL1 expression. Depletion of FOSL1 in NF1-mutant human BTSCs and Kras-mutant mouse neural stem cells results in loss of the mesenchymal gene signature and reduction in stem cell properties and in vivo tumorigenic potential. Our data demonstrate that FOSL1 controls GBM plasticity and aggressiveness in response to NF1 alterations.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"MY9ySvvURovttQQH6SywHJMj2wyUg7bY","main":"elife-64846-edited.rmd","containerImage":"fredatherden/article-64846","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1517,"account":{"id":443,"name":"kaloo","displayName":"kaloo baloo","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/88c/url-D9Vpi83iwUKLBVJE9BDKGm-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/88c/url-D9Vpi83iwUKLBVJE9BDKGm-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/88c/url-D9Vpi83iwUKLBVJE9BDKGm-a1a0071d4063.png"},"location":null,"website":null},"creator":439,"created":"2021-08-11T02:16:21.938856Z","name":"kaloohub","title":"hub1","description":"ss","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"QDhs2bPLkdnb7CF9ZKjVpNUsQK4fbmQw","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1511,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-08-02T16:04:20.922687Z","name":"article-67460","title":"Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes","description":"Background: Early identification of severe dengue patients is important regarding patient\nmanagement and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).\nMethods: We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.\nResults: On days 1–3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.\nConclusions: Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.\nFunding: This study was supported by the EU’s Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"YNvsEXUDWMkH3svQvo62RvMuZTFb9sHm","main":"elife-67460-enriched-final.rmd","containerImage":"stencila/elife-67460","sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1485,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-06-16T08:31:33.884942Z","name":"article-55665","title":"Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration","description":"Axolotls are uniquely able to resolve spinal cord injuries, but little is known about the mechanisms underlying spinal cord regeneration. We previously found that tail amputation leads to reactivation of a developmental-like program in spinal cord ependymal cells (Rodrigo Albors et al., 2015), characterized by a high-proliferation zone emerging 4 days post-amputation (Rost et al., 2016). What underlies this spatiotemporal pattern of cell proliferation, however, remained unknown. Here, we use modeling, tightly linked to experimental data, to demonstrate that this regenerative response is consistent with a signal that recruits ependymal cells during ~85 hours after amputation within ~830 μm of the injury. We adapted Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) technology to axolotls (AxFUCCI) to visualize cell cycles in vivo. AxFUCCI axolotls confirmed the predicted appearance time and size of the injury-induced recruitment zone and revealed cell cycle synchrony between ependymal cells. Our modeling and imaging move us closer to understanding bona fide spinal cord regeneration.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"7EWiDYgqwF83RRxnQtkpk3W3chpLaV94","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1484,"account":{"id":32,"name":"arinbasu","displayName":null,"email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-10c070f1761f.jpeg","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-5b678ba0c304.jpeg","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-a1a0071d4063.jpeg"},"location":null,"website":null},"creator":8,"created":"2021-06-15T20:06:44.377721Z","name":"analysis-pandas-16-june","title":"Testing","description":"Test project","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"KbSTPDgkfpFkAQe2UHBCjeRsTXLGH52P","main":"main.ipynb","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":"stencila","extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1483,"account":{"id":32,"name":"arinbasu","displayName":null,"email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-10c070f1761f.jpeg","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-5b678ba0c304.jpeg","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-a1a0071d4063.jpeg"},"location":null,"website":null},"creator":8,"created":"2021-06-15T19:35:51.964190Z","name":"analysis-16-june","title":"How to write a research paper in Stencila","description":"How to write a research paper in Stencila","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"cvU4TRcCd4XxhJua5YJubHmngoEtUHGf","main":"main.ipynb","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":"","extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1479,"account":{"id":32,"name":"arinbasu","displayName":null,"email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-10c070f1761f.jpeg","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-5b678ba0c304.jpeg","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-a1a0071d4063.jpeg"},"location":null,"website":null},"creator":8,"created":"2021-06-15T06:54:07.244585Z","name":"write-paper-2021","title":"Write a paper in stencila","description":"Data driven paper in stencila","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"Hd7XbLtzxUKGJEFC7hAztNn9688t7PnG","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1477,"account":{"id":32,"name":"arinbasu","displayName":null,"email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-10c070f1761f.jpeg","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-5b678ba0c304.jpeg","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/2ce/url-TJeMik9gSdLoTQFn2A5Fca-a1a0071d4063.jpeg"},"location":null,"website":null},"creator":8,"created":"2021-06-15T02:06:00.868633Z","name":"test-with-stencila","title":"Testing out new stencila","description":"Testing out stencila over again.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"T5P7sFPZMjAUqKec56U2SNNpY4rqLxgB","main":"2021_06_14.ipynb","containerImage":"","sessionTimeout":600,"sessionTimelimit":3600,"sessionMemory":500,"liveness":"latest","pinned":null,"theme":"stencila","extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1470,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-05-25T11:35:07.023666Z","name":"article-68068","title":"Simple biochemical features underlie transcriptional activation domain diversity and dynamic, fuzzy binding to Mediator","description":"Gene activator proteins comprise distinct DNA-binding and transcriptional activation domains (ADs). Because few ADs have been described, we tested domains tiling all yeast transcription factors for activation in vivo and identified 150 ADs. By mRNA display, we showed that 73% of ADs bound the Med15 subunit of Mediator, and that binding strength was correlated with activation. AD-Mediator interaction in vitro was unaffected by a large excess of free activator protein, pointing to a dynamic mechanism of interaction. Structural modeling showed that ADs interact with Med15 without shape complementarity (‘fuzzy’ binding). ADs shared no sequence motifs, but mutagenesis revealed biochemical and structural constraints. Finally, a neural network trained on AD sequences accurately predicted ADs in human proteins and in other yeast proteins, including chromosomal proteins and chromatin remodeling complexes. These findings solve the longstanding enigma of AD structure and function and provide a rationale for their role in biology.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"dM7ouW9dF5B7sCjCwm9rJ8ZWogr7ESDz","main":null,"containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null},{"id":1469,"account":{"id":110,"name":"elife","displayName":"eLife","email":null,"image":{"small":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-10c070f1761f.png","medium":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-5b678ba0c304.png","large":"https://storage.googleapis.com/stencila-hub-media/__processed__/948/elife-logo-a1a0071d4063.png"},"location":"Cambridge, UK","website":"https://elifesciences.org/"},"creator":99,"created":"2021-05-24T08:18:52.504384Z","name":"article-65658","title":"An agnostic study of associations between ABO and RhD blood group and phenome-wide disease risk","description":"Background:\nThere are multiple known associations between the ABO and RhD blood groups and disease. No systematic population-based studies elucidating associations between a large number of disease categories and blood group have been conducted.\n\nMethods:\nUsing SCANDAT3-S, a comprehensive nationwide blood donation-transfusion database, we modeled outcomes for 1217 disease categories including 70 million person-years of follow-up, accruing from 5.1 million individuals.\n\nResults:\nWe discovered 49 and 1 associations between a disease and ABO and RhD blood groups, respectively, after adjustment for multiple testing. We identified new associations such as a decreased risk of kidney stones and blood group B as compared to blood group O. We also expanded previous knowledge on other associations such as pregnancy-induced hypertension and blood groups A and AB as compared to blood group O and RhD positive as compared to negative.\n\nConclusions:\nOur findings generate strong further support for previously known associations, but also indicate new interesting relations.\n\nFunding:\nSwedish Research Council.","imageFile":null,"imagePath":null,"imageUpdated":null,"temporary":false,"public":true,"featured":false,"key":"4ptVxj8q8FTotF6hs5VHmsFWk8QLiTqM","main":"elife-65658_interactive.ipynb","containerImage":null,"sessionTimeout":null,"sessionTimelimit":null,"sessionMemory":null,"liveness":"latest","pinned":null,"theme":null,"extraHead":null,"extraTop":null,"extraBottom":null,"role":null}]}