bluuebunny/crossref_metadata_2025_split huggingface dataset:
Women exposure to Di(2-ethylhexyl)phthalate (DEHP) and bisphenol A (BPA) from different residing areas in Italy: data from the LIFE PERSUADED project
Authors: Carli Fabrizia , Tait Sabrina , Busani Luca , Ciociaro Demetrio , Latta Veronica Della , Pala Anna Paola , Deodati Annalisa , Raffaelli Andrea , Pratesi Filippo , Conte Raffaele , Maranghi Francesca , Tassinari Roberta , Fabbrizi Enrica , Toffol Giacomo , Cianfarani Stefano , Rocca Cinzia La , Gastaldelli Amalia ,   LIFE PERSUADED Project Group
Published: June 2022

AbstractPhthalates and bisphenol A (BPA) are plasticizers used in many industrial products that can act as endocrine disruptors. In the frame of the LIFE PERSUADED project, we measured the urinary concentrations of BPA and Di (2-ethylhexyl) phthalate (DEHP) metabolites in 900 Italian women enrolled between 2015 and 2017 and living in North, Centre and South of Italy in both rural and urban areas.The whole cohort, representative of the Italian female adult population, was exposed to DEHP and BPA with measurable levels above the limit of detection (LOD) in more than 99% and 95% of the samples, respectively. The exposure patterns differed for the two chemicals in the three macro-areas with the highest urinary levels for DEHP in South compared to Central and Northern Italy and for BPA in Northern compared to Central and Southern Italy. BPA levels were higher in women living in urban areas, whereas no difference between areas was observed for DEHP. The estimated daily intake of BPA was 0.11 μg/kg per day, about 36-fold below the current temporary Tolerable Daily Intake of 4 μg/kg per day established by the European Food Safety Authority in 2015. The analysis of cumulative exposure showed a positive correlation between DEHP and BPA.These results suggest to further limit the exposure to DEHP and BPA through specific legislative measures.
Computational Identification of Ligand-Receptor Pairs that Drive Human Astrocyte Development
Authors: Voss AJ , Lanjewar SN , Sampson MM , King A , Hill E , Sing A , Sojka C , Sloan SA 
Published: June 2022

SUMMARYExtrinsic signaling between diverse cell types is crucial to nervous system development. Ligand binding is a key driver of developmental processes, but it remains a significant challenge to disentangle how collections of these signals act cooperatively to affect changes in recipient cells. In the developing human brain, cortical progenitors transition from neurogenesis to gliogenesis in a stereotyped progression that is influenced by extrinsic ligands. Therefore, we sought to use the wealth of published genomic data in the developing human brain to identify and then test novel ligand combinations that act synergistically to drive gliogenesis. Using computational tools, we identified ligand-receptor pairs that are expressed at appropriate developmental stages, in relevant cell types, and whose activation is predicted to cooperatively stimulate complimentary astrocyte gene signatures. We then tested a group of five neuronally-secreted ligands and validated their synergistic contributions to astrocyte development within both human cortical organoids and primary fetal tissue. We confirm cooperative capabilities of these ligands far greater than their individual capacities and discovered that their combinatorial effects converge on AKT/mTOR signaling to drive transcriptomic and morphological features of astrocyte development. This platform provides a powerful agnostic framework to identify and test how extrinsic signals work in concert to drive developmental processes.HIGHLIGHTSComputational prediction of active ligand-receptor pairs in the developing brainSynergistic contributions of predicted ligands drive astrocyte developmentLigands induce transcriptomic and morphological features of mature astrocytesCooperative ligand activity converges on AKT/mTOR signaling
Highly-Automated, High-Throughput Replication of Yeast-based Logic Circuit Design Assessments
Authors: Goldman Robert P. , Moseley Robert , Roehner Nicholas , Cummins Bree , Vrana Justin D. , Clowers Katie J. , Bryce Daniel , Beal Jacob , DeHaven Matthew , Nowak Joshua , Higa Trissha , Biggers Vanessa , Lee Peter , Hunt Jeremy P. , Mosqueda Lorraine , Haase Steven B. , Weston Mark , Zheng George , Deckard Anastasia , Gopaulakrishnan Shweta , Stubbs Joseph F. , Gaffney Niall I. , Vaughn Matthew W. , Maheshri Narendra , Mikhalev Ekaterina , Bartley Bryan , Markeloff Richard , Mitchell Tom , Nguyen Tramy , Sumorok Daniel , Walczak Nicholas , Myers Chris , Zundel Zach , Hatch Benjamin , Scholz James , Colonna-Romano John , Mosqueda Lorraine 
Published: June 2022

AbstractWe describe an experimental campaign that replicated the performance assessment of logic gates engineered into cells of S. cerevisiae by Gander, et al. Our experimental campaign used a novel high throughput experimentation framework developed under DARPA’s Synergistic Discovery and Design (SD2) program: a remote robotic lab at Strateos executed a parameterized experimental protocol. Using this protocol and robotic execution, we generated two orders of magnitude more flow cytometry data than the original experiments. We discuss our results, which largely, but not completely, agree with the original report, and make some remarks about lessons learned.
Decreasing Wapl dosage partially corrects transcriptome phenotypes in Nipbl-/+ embryonic mouse brain
Authors: Kean Connor M. , Tracy Christopher J. , Mitra Apratim , Van Winkle Matthew T , Gebert Claudia M , Noeker Jacob , Calof Anne L. , Lander Arthur D. , Kassis Judith A. , Pfeifer Karl 
Published: June 2022

AbstractCohesin rings interact with DNA and modulate expression of thousands of genes. NIPBL loads cohesin onto chromosomes and WAPL takes it off. Heterozygous mutations in NIPBL lead to a developmental disorder called Cornelia de Lange syndrome. Nipbl heterozygous mice are a good model for this disease but mutations in WAPL were not known to cause disease or gene expression changes in mammals. Here we show dysregulation of >1000 genes in WaplΔ/+ embryonic mouse brains. The patterns of dysregulation are highly similar to Nipbl heterozygotes, suggesting that Wapl mutations may also cause disease in humans. Since WAPL and NIPBL have opposite effects on cohesin’s association with DNA, we asked whether a heterozygous Wapl mutation could correct phenotypes seen in Nipbl heterozygous mice. In fact, both gene expression and embryonic growth are partially corrected. Our data are consistent with the view that cohesin dynamics play a key role in regulating gene expression.
Comprehensive characterization of the transcriptional response to COVID-19 in multiple organs reveals shared signatures across tissues
Authors:   The COVID Tissue Atlas Consortium, Granados Alejandro A , Bucher Simon , Agrawal Aditi , Song Hanbing , Chen Ann T , Peng Tien , Neff Norma , Pisco Angela Oliveira , Huang Franklin , Wang Bruce 
Published: June 2022

AbstractInfection by Coronavirus SARS-CoV2 is a severe and often deadly disease that has implications for the respiratory system and multiple organs across the human body. While the effects in the lung have been extensively studied, less is known about COVID-19’s cellular impact across other organs. Here we contribute a single-nuclei RNA sequencing atlas comprising six human organs across 20 autopsies where we analyzed the transcriptional changes due to COVID-19 in multiple cell types. Computational cross-organ analysis for endothelial cells and macrophages identified systemic transcriptional changes in these cell types in COVID-19 samples. In addition, analysis of signaling pathways from multiple datasets showed several systemic dysregulations of signaling interaction in different cell types. Altogether, the COVID Tissue Atlas enables the investigation of both cell type-specific and cross-organ transcriptional responses to COVID-19, providing insights into the molecular networks affected by the disease and highlighting novel potential targets for therapies and drug development.
Demes: a standard format for demographic models
Authors: Gower Graham , Ragsdale Aaron P. , Bisschop Gertjan , Gutenkunst Ryan N. , Hartfield Matthew , Noskova Ekaterina , Schiffels Stephan , Struck Travis J. , Kelleher Jerome , Thornton Kevin R. 
Published: June 2022

AbstractUnderstanding the demographic history of populations is a key goal in population genetics, and with improving methods and data, ever more complex models are being proposed and tested. Demographic models of current interest typically consist of a set of discrete populations, their sizes and growth rates, and continuous and pulse migrations between those populations over a number of epochs, which can require dozens of parameters to fully describe. There is currently no standard format to define such models, significantly hampering progress in the field. In particular, the important task of translating the model descriptions in published work into input suitable for population genetic simulators is labor intensive and error prone. We propose the Demes data model and file format, built on widely used technologies, to alleviate these issues. Demes provides a well-defined and unambiguous model of populations and their properties that is straightforward to implement in software, and a text file format that is designed for simplicity and clarity. We provide thoroughly tested implementations of Demes parsers in multiple languages including Python and C, and showcase initial support in several simulators and inference methods. An introduction to the file format and a detailed specification are available at:https://popsim-consortium.github.io/demes-spec-docs/.
Marine particle microbiomes during a spring diatom bloom contain active sulfate-reducing bacteria
Authors: Siebers R. , Schultz D. , Farza M. S. , Brauer A. , Zühlke D. , Mücke P. A , Wang F. , Bernhardt J. , Teeling H. , Becher D. , Riedel K. , Kirstein I. V. , Wiltshire K. H. , Hoff K.J. , Schweder T. , Urich T. , Bengtsson M. M. 
Published: June 2022

AbstractPhytoplankton blooms fuel marine food webs with labile dissolved carbon, but also lead to the formation of particulate organic matter composed of living and dead algal cells. These particles contribute to carbon sequestration, yet are also sites of intense algal-bacterial interactions and provide diverse niches for microbes to thrive. We analyzed 16S and 18S ribosomal RNA gene amplicon sequences obtained from 51 time points and metaproteomes from 3 time points during a spring phytoplankton bloom in the North Sea. Particulate fractions larger than 10 µm diameter were collected at near daily intervals between early March and late May in 2018. Network analysis identified two major modules representing bacteria co-occurring with diatoms and with dinoflagellates, respectively. The diatom network module included known sulfate-reducingDesulfobacterotaas well as potentially sulfur-oxidizingEctothiorhodospiraceae. Metaproteome analyses confirmed presence of key enzymes involved in dissimilatory sulfate reduction, a process known to occur in sinking particles at greater depths. Our results indicate the presence of sufficiently anoxic niches in the particle fraction of an active phytoplankton bloom to sustain sulfate reduction, which may have implications for algal-bacterial interactions and carbon export during blooms.
Diffusion MR imaging in the cortical spinal tract of idiopathic scoliosis
Authors: Frankó Edit , Joly Olivier , Coubard Olivier A. , Baudrillard Jean-Claude , Morin Christian , Rousié Dominique 
Published: June 2022

AbstractMany studies have shown that idiopathic scoliosis is not only a deformity of the spine. It is often associated with neurological impairment without any macroscopic abnormality in the brain. In our previous diffusion MRI study, we demonstrated that children with right-thoracic idiopathic scoliosis had abnormal white matter microstructure of the crossing premotor fibres in the corpus callosum. Based on this, we hypothesized that similar microstructural changes could affect the main descending white matter tracts, the corticospinal tract.We compared the fractional anisotropy values along the corticospinal tracts in ten patients with right-thoracic and ten patients with left-thoracic idiopathic scoliosis to 49 healthy controls.We found abnormal left-right asymmetry of the fractional anisotropy values in scoliosis patients at the level of the pons. Whereas at upper levels the values were similar across all groups.Our results suggest that abnormal sensorimotor integration at the level of the pons is associated with the development of idiopathic scoliosis.
Single nuclei transcriptomics of muscle reveals intra-muscular cell dynamics linked to dystrophin loss and rescue
Authors: Scripture-Adams Deirdre D. , Chesmore Kevin N. , Barthélémy Florian , Wang Richard T. , Nieves-Rodriguez Shirley , Wang Derek W. , Mokhonova Ekaterina I. , Douine Emilie D. , Wan Jijun , Little Isaiah , Rabichow Laura N. , Nelson Stanley F. , Miceli M. Carrie 
Published: June 2022

AbstractIn Duchenne muscular dystrophy, dystrophin loss leads to chronic muscle damage, dysregulation of repair, fibro-fatty replacement, and weakness. We develop methodology to efficiently isolate individual nuclei from frozen skeletal muscle, allowing single nuclei sequencing of irreplaceable archival samples from small samples. We apply this method to identify cell and gene expression dynamics within human DMD and mdx mouse muscle, characterizing treatment effects of dystrophin rescue by exon skipping therapy at single nuclei resolution. DMD exon 23 skipping events are directly observed and increased in myonuclei from treated mice. We describe partial rescue of type IIa and IIx myofibers, expansion of a novel MDSC-like myeloid population, recovery of repair/remodeling M2-macrophage, and repression of inflammatory POSTN1+ fibroblasts in response to exon skipping and partial dystrophin restoration. Use of this method enables exploration of cellular and transcriptomic mechanisms of dystrophin loss and repair.
SARS-CoV-2 Variant Spike and accessory gene mutations alter pathogenesis
Authors: McGrath M.E. , Xue Y. , Dillen C. , Oldfield L. , Assad-Garcia N. , Zaveri J. , Singh N. , Baracco L. , Taylor L. , Vashee S. , Frieman M. 
Published: June 2022

AbstractThe ongoing COVID-19 pandemic is a major public health crisis. Despite the development and deployment of vaccines against SARS-CoV-2, the pandemic persists. The continued spread of the virus is largely driven by the emergence of viral variants, which can evade the current vaccines through mutations in the Spike protein. Although these differences in Spike are important in terms of transmission and vaccine responses, these variants possess mutations in the other parts of their genome which may affect pathogenesis. Of particular interest to us are the mutations present in the accessory genes, which have been shown to contribute to pathogenesis in the host through innate immune signaling, among other effects on host machinery. To examine the effects of accessory protein mutations and other non-spike mutations on SARS-CoV-2 pathogenesis, we synthesized viruses where the WA1 Spike is replaced by each variant spike genes in a SARS-CoV-2/WA-1 infectious clone. We then characterized the in vitro and in vivo replication of these viruses and compared them to the full variant viruses. Our work has revealed that non-spike mutations in variants can contribute to replication of SARS-CoV-2 and pathogenesis in the host and can lead to attenuating phenotypes in circulating variants of concern. This work suggests that while Spike mutations may enhance receptor binding and entry into cells, mutations in accessory proteins may lead to less clinical disease, extended time toward knowing an infection exists in a person and thus increased time for transmission to occur.SignificanceA hallmark of the COVID19 pandemic has been the emergence of SARS-CoV-2 variants that have increased transmission and immune evasion. Each variant has a set of mutations that can be tracked by sequencing but little is known about their affect on pathogenesis. In this work we first identify accessory genes that are responsible for pathogenesis in vivo as well as identify the role of variant spike genes on replication and disease in mice. Isolating the role of Spike mutations in variants identifies the non-Spike mutations as key drivers of disease for each variant leading to the hypothesis that viral fitness depends on balancing increased Spike binding and immuno-evasion with attenuating phenotypes in other genes in the SARS-CoV-2 genome.
Estimating somatic mutation rates by Duplex Sequencing in non-model organisms: Daphnia magna as a case study
Authors: Sobel Eli , Coate Jeremy E. , Schaack Sarah 
Published: June 2022

AbstractSomatic mutations are evolutionarily important as determinants of individual organismal fitness, as well as being a focus of clinical research on age-related disease, such as cancer. Identifying somatic mutations and quantifying mutation rates, however, is extremely challenging and genome-wide somatic mutation rates have only been reported for a few model organisms. Here, we describe the application of Duplex Sequencing on bottlenecked WGS libraries to quantify genome-wide somatic base substitution rates in Daphnia magna. Daphnia, historically an ecological model system, has more recently been the focus of mutation studies, in part because of its high germline mutation rates. Using our protocol and pipeline, we estimate a somatic mutation rate of 2.14 × 10−7 substitutions per site (in a genotype where the germline rate is 3.60 × 10−9 substitutions per site per generation). To obtain this estimate, we tested multiple dilution levels to maximize sequencing efficiency, and developed bioinformatic filters needed to minimize false positives when a high quality reference genome is not available. In addition to laying the groundwork for estimating genotypic variation in rates of somatic mutations within D. magna, we provide a framework for quantifying somatic mutations in other non-model systems, and also highlight recent innovations to single molecule sequencing that will help to further refine such estimates.
Deep Learning Based Registration of Serial Whole-slide Histopathology Images in Different Stains
Authors: Roy Mousumi , Wang Fusheng , Teodoro George , Bhattarai Shristi , Bhargava Mahak , Rekha T Subbanna , Aneja Ritu , Kong Jun 
Published: June 2022

ABSTRACTFor routine pathology diagnosis and imaging based biomedical research, Whole-Slide Image (WSI) analyses have been largely limited to a 2D tissue image space. For a more definitive tissue representation to support fine-resolution spatial and integrative analyses, it is critical to extend such tissue based investigations to a 3D tissue space with spatially aligned serial tissue WSIs in different stains, such as Hematoxylin and Eosin (H&E) and Immunohistochemistry (IHC) biomarkers. However, such WSI registration is technically challenged by the overwhelming image scale, the complex histology structure change, and the significant difference in tissue appearances in different stains. We propose a novel translation based deep learning registration network CycGANRegNet that spatially aligns serial WSIs stained in H&E and by IHC biomarkers without prior deformation information for the model training. First, synthetic IHC images are produced from H&E slides through a robust image synthesis algorithm. Next, the synthetic and the real IHC images are registered through a Fully Convolutional Network with multi-scaled deformable vector fields and a joint loss optimization. We perform the registration at the full image resolution, retaining the tissue details in the results. Evaluated with a dataset of 76 breast cancer patients with one H&E and two IHC serial WSIs for each patient, CycGANRegNet outperforms multiple state-of-the-art deep learning based and conventional pathology image registration methods. Our results suggest that CycGAN-RegNet can produce promising registration results with serial WSIs in different stains, enabling integrative 3D tissue-based biomedical investigations.
U1 snRNP suppresses microRNA biogenesis by alternative intronic polyadenylation in melanoma
Authors: Vorlova Sandra , Blahetek Gina , Barbieri Ruggero , Kerstan Yvonne , Rosa Annabelle , Bundalo Maja , Egg Manuel , Butt Elke , Henke Erik , Dölken Lars , Houben Roland , Schilling Bastian , Fischer Utz , Erhard Florian , Zernecke Alma 
Published: June 2022

AbstractActivation of intronic polyadenylation signals results in premature cleavage and polyadenylation (PCPA). The majority of mammalian miRNAs are also located within intronic regions of protein-coding genes and are transcriptionally co-expressed with their host genes. Here we show that U1-dependent PCPA by telescripting dysregulates miRNA biogenesis. When U1 is reduced, miR-211 levels are decreased as a direct consequence of activation of a newly identified alternative intronic polyadenylation signal located upstream of miR-211 within its host gene TRPM1. Various melanoma cell lines revealed decreased U1 levels and a shift from full-length to truncated TRPM1 isoforms with concomitant decreased miR-211 expression. Modulation of TRPM1 alternative polyadenylation (APA) by morpholino oligonucleotides inhibits and potentially restores miR-211 expression to endogenous levels. This mechanism of intronic PCPA and its effects on miRNA biogenesis represents a previously unrecognized layer of gene expression regulation suitable for therapeutic modulation.Graphical Abstract
Effects of Reduced Achilles Subtendons Relative Displacement on Healthy Elderly Walking: A Simulation Study
Authors: Khosrotabar Morteza , Aftabi Hamidreza , Karimpour Morad , Ahmadabadi Majid Nili 
Published: June 2022

AbstractWalking in healthy elderly people is characterized by lower performance. Since conventional training programs have had limited success in improving gait performance, it is essential to identify underlying causes of walking deficits in healthy elderly adults. Recent studies have qualitatively shown that the decreased relative displacement of Achilles subtendons is likely the primary contributor to lower propulsion in the elderly’s walking by creating a higher dependency on their triceps-surae muscle functions. Due to the invasive nature of experimental investigations, in this study, we developed a computational model and analyzed the effects of reduced Achilles subtendons relative displacement on the total metabolic rate and muscles’ force profiles during normal walking. Our musculoskeletal simulations revealed a 17% increase in the total metabolic rate in elderly adults whose Achilles subtendons were restricted to have no relative displacement. Changing the restriction level resulted in significant changes in the force distribution of the plantar flexor muscles, notably, a 40% reduction in the Medial Gastrocnemius and a 124% increase in the Soleus forces during the propulsion phase of walking. Also, we quantitatively presented the higher dependency of triceps-surae muscle functions regarding the limitation on their corresponding Achilles subtendons’ relative displacement. The results of this study confirm the experimental observations and can be used as initial insight into devising novel rehabilitation training programs with the focus on improving Achilles subtendons relative displacement.