bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dimethyl fumarate modulates the Duchenne muscular dystrophy disease program following short-term treatment inmdxmice
Authors: Timpani Cara A. , Kourakis Stephanie , Debruin Danielle A. , Campelj Dean G. , Pompeani Nancy , Dargahi Narges , Bautista Angelo P. , Bagaric Ryan M. , Ritenis Elya J. , Sahakian Lauren , Hafner Patricia , Arthur Peter G. , Terrill Jessica R. , Apostolopoulos Vasso , de Haan Judy B. , Guven Nuri , Fischer Dirk , Rybalka Emma 
Published: September 2022

AbstractNew medicines are urgently required to treat the fatal neuromuscular disease, Duchenne muscular dystrophy (DMD). DMD involves progressive muscle damage and weakness, which are preceded by oxidative stress, inflammation, and mitochondrial dysfunction. Dimethyl fumarate (DMF) is a potent small molecule nuclear erythroid 2-related factor 2 (Nrf2) activator with current clinical utility in the treatment of multiple sclerosis and psoriasis. Pharmaceutical targeting of Nrf2 by DMF has strong translational potential for DMD, given it: (1) promotes antioxidant defence systems; (2) has a potent immuno-modulatory profile; and (3) can be rapidly re-purposed into clinical care strategies for DMD patients. Here, we tested two weeks of daily 100mg/kg DMF versus 5mg/kg standard care prednisone (PRED) treatment during the peak muscle degeneration period in juvenilemdxmice, the gold standard murine DMD model. Both drugs modulated seed genes driving the DMD disease program and improved muscle force production in fast-twitch muscle. However, only DMF showed pro-mitochondrial effects that protected contracting muscles from fatigue, improved histopathology and augmented clinically compatible muscle function tests. In contrast, PRED treatment stunted mouse growth, worsened histopathology and modulated many normally expressed inflammatory and extracellular matrix (ECM) genes consistent with pan immunosuppression. These findings suggest DMF could be a more selective modulator of the DMD disease program with better efficacy and fewer side effects than standard care PRED therapy warranting follow-up studies to progress clinical translation.
Evolutionary conservation of sequence motifs at sites of protein modification
Authors: Li Shuang , Dohlman Henrik G. 
Published: September 2022

AbstractGene duplications are common in biology and are likely to be an important source of functional diversification and specialization. The yeast Saccharomyces cerevisiae underwent a whole genome duplication event early in evolution, and a substantial number of duplicated genes have been retained. We identified more than 3,500 instances where only one of two paralogous proteins undergoes post-translational modification despite having retained the same amino acid residue in both. We also developed a web-based search algorithm (CoSMoS.c.) that scores conservation of amino acid sequences based on 1011 wild and domesticated yeast isolates and used it to compare differentially-modified pairs of paralogous proteins. We found that the most common modifications – phosphorylation, ubiquitylation and acylation but not N-glycosylation – occur in regions of high sequence conservation. Such conservation is evident even for ubiquitylation and succinylation, where there is no established ‘consensus site’ for modification. Differences in phosphorylation were not associated with predicted secondary structure or solvent accessibility, but did mirror known differences in kinase-substrate interactions. By integrating data from large scale proteomics and genomics analysis, in a system with such substantial genetic diversity, we obtained a more comprehensive understanding of the functional basis for genetic redundancies that have persisted for 100 million years.
Feature similarity gradients detect alterations in the neonatal cortex associated with preterm birth
Authors: Galdi Paola , Cabez Manuel Blesa , Farrugia Christine , Vaher Kadi , Williams Logan ZJ , Sullivan Gemma , Stoye David Q , Quigley Alan J , Makropoulos Antonios , Thrippleton Michael J , Bastin Mark E , Richardson Hilary , Whalley Heather , Edwards A David , Bajada Claude J , Robinson Emma C , Boardman James P 
Published: September 2022

AbstractThe early life environment programmes cortical architecture and cognition across the life course. A measure of cortical organisation that integrates information from multi-modal MRI and is unbound by arbitrary parcellations has proven elusive, which hampers efforts to uncover the perinatal origins of cortical health. Here, we use the Vogt-Bailey index to provide a fine-grained description of regional homogeneities and sharp variations in cortical microstructure based on feature gradients, and we investigate the impact of being born preterm on cortical development. Preterm infants have a homogeneous microstructure in temporal and occipital lobes, and the medial parietal, cingulate, and frontal cortices, compared with term infants. These observations replicated across two independent datasets and were robust to differences that remain in the data after matching samples and alignment of processing and quality control strategies. We conclude that cortical microstructural architecture is altered in preterm infants in a spatially distributed rather than localised fashion.
An experimental and theoretical approach to understand the interaction between particles and mucosal tissues
Authors: Arzi Roni Sverdlov , Davidovich-Pinhas Maya , Cohen Noy , Sosnik Alejandro 
Published: September 2022

AbstractNanonization of poorly water-soluble drugs has shown great potential in improving their oral bioavailability by enhancing the dissolution rate and saturation solubility. Moreover, due to particle size reduction and larger surface area, the number of contact points with the gastrointestinal mucus favors adhesion. Similar phenomena could be anticipated when nano-pollutants come into direct contact with mucosal tissues. However, the fundamental features that govern the interaction of particles with mucus have not been investigated in a systematic and rational way before. In this work, we synthesize mucin hydrogels of different pore sizes with rheological properties that closely mimic the properties of freshly extracted porcine mucin. By using fluorescent pure curcumin particles, we characterize the effect of particle size (hydrodynamic diameter of 200 nm, and 1.2 and 1.3 μm), concentration (18, 35, and 71 μg mL−1), and hydrogel crosslinking density (which is directly related to the stiffness and governs the average pore size) on the diffusion-driven particle penetrationin vitro. Next, we derive a phenomenological model that describes the physics behind the diffusion-derived penetration of particles into the mucin network and considers the contributions of the particle size, the particle concentration, and the crosslinking density of the mucin hydrogel. Finally, we challenge our experimental-theoretical approach by preliminarily assessing the oral pharmacokinetics of an anti-cancer model drug, namely dasatinib, in pristine and nanonized forms and two clinically relevant doses in rats. For of a dose of 10 mg kg−1, drug nanonization leads to a significant ~8- and ~21-fold increase of the drug oral bioavailability and half-life, respectively, with respect to the unprocessed micron-sized drug. When the drug dose of pure drug nanoparticles (which is directly related to the local concentration of the drug in the gastrointestinal tract) was increased to 15 mg mL−1, the oral bioavailability increased though not significantly, suggesting the saturation of the penetration sites in the mucus, as demonstrated by thein vitromodel. Our overall results reveal the potential of this experimental-theoretical approach, shed light on the interaction of particulate matter and mucosal tissues, and pave the way for the development of tools that enable a more rational design of nano-drug delivery systems for mucosal administration and the assessment of risk factors related to the exposure of mucosal tissues to nano-pollutants.
Demographic History Inference and the Polyploid Continuum
Authors: Blischak Paul D. , Sajan Mathews , Barker Michael S. , Gutenkunst Ryan N. 
Published: September 2022

AbstractPolyploidy is an important generator of evolutionary novelty across diverse groups in the Tree of Life, including many crops. However, the impact of whole-genome duplication (WGD) depends on the mode of formation: doubling within a single lineage (autopolyploidy) versus doubling after hybridization between two different lineages (allopolyploidy). Researchers have historically treated these two scenarios as completely separate cases based on patterns of chromosome pairing, but these cases represent ideals on a continuum of chromosomal interactions among duplicated genomes. Understanding the history of polyploid species thus demands quantitative inferences of demographic history and rates of exchange between subgenomes. To meet this need, we developed diffusion models for genetic variation in polyploids with subgenomes that cannot be bioinformatically separated and with potentially variable inheritance patterns, implementing them in the dadi software. We validated our models using forward SLiM simulations and found that our inference approach is able to accurately infer evolutionary parameters (timing, bottleneck size) involved with the formation of auto- and allotetraploids, as well as exchange rates in segmental allotetraploids. We then applied our models to empirical data for allotetraploid shepherd’s purse (Capsella bursa-pastoris), finding evidence for allelic exchange between the subgenomes. Taken together, our model provides a foundation for demographic modeling in polyploids using diffusion equations, which will help increase our understanding of the impact of demography and selection in polyploid lineages.
WikiGOA: Gene set enrichment analysis based on Wikipedia and the Gene Ontology
Authors: Lubiana Tiago , Dias Thomaz Lüscher , Peixe Débora Guerra , Nakaya Helder Takashi Imoto 
Published: September 2022

AbstractGene sets curated to Gene Ontology terms are widely used by the transcriptomics communityPresence in Wikipedia is a common proxy for the relevance of a concept.In this work, we describe the use of Wikidata to generate a dataset comprising only gene sets with a corresponding Wikipedia page.We refer to the dataset as “WikiGOA”, standing for “Wikipedia Gene Ontology Annotations”We use the dataset to analyze gene expression data and show that it provides readily understandable results.We envision WikiGOA to be useful for exploring complex biological datasets both in academic research and educational contexts.NoteThis report was written in a non-standard, experimental format, where assertions are expressed in bullet points. This was done to clarify statements and assumptions, simplify reading and pave the way for conversion to structured formats (e.g., nanopublications). [1]
Inflammation-mediated Upregulation of VCAM-1 but not KIM-1 during Acute Kidney Injury to Chronic Kidney Disease Transition
Authors: Melchinger Isabel , Guo Kailin , Guo Jiankan , Xu Leyuan 
Published: September 2022

ABSTRACTBackgroundPatients with acute kidney injury (AKI) have higher risks of developing chronic kidney disease (CKD). The basis for the AKI-to-CKD transition remains poorly understood, but studies in animal models suggest a linkage between the inflammatory response to injury and subsequent nephron loss and interstitial fibrosis. The proximal tubule is the primary venue of injury and progression of disease during this process.MethodsMouse unilateral ischemia/reperfusion injury (U-IRI) model was used to study the kinetics of proximal injury marker expression during AKI-to-CKD transition. Immortalized MPT cells and primary cultured renal cells were used to study factor(s) that induce vascular cell adhesion protein-1 (VCAM-1) expression in proximal tubule cells.ResultsKidney injury molecule-1 (KIM-1) was rapidly upregulated on day 1 after injury and gradually reduced close to the baseline; whereas VCAM-1 was not upregulated on day 1 but markedly increased afterwards during AKI-to-CKD transition. The proximal tubular VCAM-1 expression is induced by proinflammatory cytokines including TNFα and IL-1β. Blockade of these signaling pathways by using NF-κB inhibitor or by using double null mutant Myd88 and Trif derived PCRC in vitro or decrease of immune cell recruitment using Ccr2 null mouse in vivo significantly suppressed VCAM-1 expression. Human single cell transcriptome analysis identified a distinct cluster of injured proximal tubules that highly expressed VCAM1 but not HAVCR1 (KIM1), and the population of these VCAM1-positive proximal tubule cells was associated with CKD progression and VCAM-1 levels were significantly higher in the patients with Stage 3 CKD as compared to the healthy references.ConclusionsProximal tubule cells upregulated KIM-1 and VCAM-1 in an orchestrated fashion after injury. Upregulation of VCAM-1 associated with chronic tubular injury and interstitial fibrosis and may mark the earliest molecular event during AKI-to-CKD transition.
Cardiomyocyte ploidy is dynamic during postnatal development and varies across genetic backgrounds
Authors: Swift Samantha K. , Purdy Alexandra L. , Kolell Mary E. , Flinn Michael A. , Lahue Caitlin , Buddell Tyler , Akins Kaelin A. , Foster Parker , O’Meara Caitlin C. , Rau Christoph D. , Patterson Michaela 
Published: September 2022

SUMMARYSomatic polyploidization, an adaptation by which cells increase their DNA content to support cell and organ growth, is observed in many mammalian cell types, including cardiomyocytes. Although polyploidization is beneficial in many contexts, progression to a polyploid state is often accompanied by a loss of proliferative capacity. Recent work suggests that heterogeneity in cardiomyocyte ploidy is highly influenced by genetic diversity. However, the developmental course by which cardiomyocytes reach their final ploidy state has only been investigated in select genetic backgrounds. Here, we assessed cardiomyocyte number, cell cycle activity, and ploidy dynamics across two divergent inbred mouse strains; C57Bl/6J and A/J. Both strains are born and reach adulthood with a comparable number of cardiomyocytes, however the end composition of ploidy classes and developmental progression to reach the final state and number differ substantially. In addition to corroborating previous findings that identified Tnni3k as a mediator of cardiomyocyte ploidy, we also uncover a novel role for Runx1 and Tnni3k in ploidy dynamics and cardiomyocyte cytokinesis. These data provide novel insight into the developmental path to cardiomyocyte ploidy states and challenge the paradigm that polyploidization and hypertrophy are the only mechanisms for growth in the mouse heart after the first week of life.
The functional organization of retinal ganglion cell receptive fields across light levels
Authors: Ruda Kiersten , Rudzite Andra M. , Field Greg D. 
Published: September 2022

AbstractTwo major functions performed by the retina are to establish the parallel processing of visual information and to adapt visual encoding to the trillion-fold range of light intensities encountered in the environment. Previous work has highlighted many specialized cell types and circuits that instantiate parallel processing and light adaptation. However, fully understanding either process requires identifying how light adaptation and parallel processing interact. One possibility is that light adaptation causes uniform or proportional scaling to the receptive fields (RFs) of different retinal ganglion cell (RGC) types, the output neurons of the retina. Alternatively, light adaptation could cause a reorganization of RF structures across RGC types. A third possibility is that RFs across different RGC types are more similar under some conditions (e.g., low light levels) and more divergent under other conditions. To resolve these possibilities, we examined how the spatiotemporal RF structure of six simultaneously measured RGC types in the rat retina change from rod-to cone-mediated light levels. While light adaptation altered the RF properties of all six RGC types, we found that the relative structure across different RGC types was largely preserved across light levels. However, in both the spatial and temporal domains, one of the six RGC types exhibited adaptation distinct from the other types, resulting in a partial reorganization of RF properties across RGC types. These measurements identify how parallel visual processing interacts with light adaptation and highlights the challenges to stably encode visual scenes across light levels.
Improved estimates of abortion rates in tsetse (Glossinaspp)
Authors: Hargrove J. W. 
Published: September 2022

AbstractAbortion rates were assessed for 170, 846 tsetse (154,228G. pallidipesand 19,618G. m. morsitans) sampled in Zimbabwe in 1988 - 1999. Abortions were diagnosed for flies where the uterus was empty and the largest oocyte awaiting ovulation was <82% of the expected mature length. Of tsetse caught in odour-baited traps, 0.64% (95% ci: 0.59 - 0.69) ofG. pallidipesand 1.00% (0.76-1.29) ofG. m. morsitanswere diagnosed as having suffered a recent abortion. For flies from artificial refuges, abortion rates were higher, 2.03% (1.77 - 2.31) and 2.28% (1.85 - 2.79) for the two species, respectively. Abortion rates decreased with increasing wing fray and contrary to laboratory findings, did not increase in the oldest flies; they were highest in the hottest months and years, and increased with decreasing adult wing length. Percentages of tsetse with empty uteri, regardless of abortion status, were significantly higher than the estimated abortion percentages. For tsetse from traps, 4.01% (95% ci: 3.90 – 4.13) ofG. pallidipesand 2.52% (2.14-2.95) ofG. m. morsitanshad empty uteri; for flies from artificial refuges the percentage were 12.69% (12.07 – 13.34) and 14.90% (13.82 -16.02), respectively.
RECOMBINATION HOTSPOTS IN SOYBEAN [GLYCINE MAX (L.) MERR.]
Authors: McConaughy Samantha , Amundsen Keenan , Song Qijian , Pantalone Vince , Hyten David 
Published: September 2022

ABSTRACTRecombination allows for the exchange of genetic material between two parents which plant breeders exploit to make new and improved cultivars. This recombination is not distributed evenly across the chromosome. In crops, recombination mostly occurs in euchromatic regions of the genome and even then, recombination is focused into clusters of crossovers termed recombination hotspots. Understanding the distribution of these hotspots along with the sequence motifs associated with them may lead to methods that enable breeders to better exploit recombination in breeding. To map recombination hotspots and identify sequence motifs associated with hotspots in soybean [Glycine max (L.) Merr.], two bi-parental recombinant inbred lines (RILs) populations were genotyped with 50,000 SNP markers using the SoySNP50k Illumina Infinium assay. A total of 451 recombination hotspots were identified in the two populations. Despite being half-sib populations, only 18 hotspots were in common between the two populations. While pericentromeric regions did exhibit extreme suppression of recombination, twenty-seven percent of the detected hotspots were located in the pericentromic regions of the chromosomes. Two genomic motifs associated with hotspots are similar to human, dog, rice, wheat, drosophila, and arabidopsis. These motifs were a CCN repeat motif and a poly-A motif. Genomic regions spanning other hotspots were significantly enriched with the tourist family of mini-inverted-repeat transposable elements (MITEs) that resides in less than 0.34% of the soybean genome. The characterization of recombination hotspots in these two large soybean bi-parental populations demonstrates that hotspots do occur throughout the soybean genome and are enriched for specific motifs but their locations may not be conserved between different populations.
Fragile X Mental Retardation Protein (FMRP) expression in human nociceptor axons of the spinal dorsal horn— Implications for RNA targeting and localized translation
Authors: Mitchell Molly E. , Cook Lauren C. , Shiers Stephanie I. , Tavares-Ferreira Diana , Akopian Armen N , Dussor Gregory , Price Theodore J 
Published: September 2022

AbstractFragile X Mental Retardation Protein (FMRP) regulates activity-dependent RNA localization and local translation to modulate synaptic plasticity throughout the CNS. Mutations in theFMR1gene that hinder or ablate FMRP function cause Fragile X Syndrome (FXS), a disorder associated with sensory processing dysfunction. FXS pre-mutations are associated with increased FMRP expression and neurological impairments including sex dimorphic presentations of chronic pain. In mice, FMRP ablation causes dysregulated DRG neuron excitability and synaptic vesicle exocytosis, spinal circuit activity, and decreased translation-dependent nociceptive sensitization. Activity-dependent, local translation is a key mechanism for enhancing primary nociceptor excitability which promotes pain in animals and humans. These works indicate that FMRP likely regulates nociception and pain at the level of the primary nociceptor or spinal cord. Therefore, we sought to better understand FMRP expression in the human dorsal root ganglion (DRG) and spinal cord using immunostaining in organ donor tissues. We find that FMRP is highly expressed in DRG and spinal neuron subsets with substantia gelatinosa exhibiting the most abundant immunoreactivity in spinal synaptic fields. Here, it is expressed in nociceptor axons. FMRP puncta colocalized with Nav1.7 and TRPV1 receptor signals suggesting a pool of axoplasmic FMRP localizes to plasma membrane-associated loci in these branches. Interestingly, FMRP puncta exhibited notable colocalization with calcitonin gene-related peptide (CGRP) immunoreactivity selectively in female spinal cord. Our results support a regulatory role for FMRP in human nociceptor axons of the dorsal horn and implicate it in the sex dimorphic actions of CGRP signaling in nociceptive sensitization and chronic pain.
A large nuclear and mitochondrial sequence dataset for phylogenetic analysis of the hyperdiverse Asterophryinae frogs of the New Guinea region with data on lifestyle, GPS coordinates, elevation, and multispecies communities with accompanying code
Authors: Hill Ethan C. , Jarman Mary J. , Fraser Claire J. , Gao Diana F. , Henry Elizabeth R. , Fisher Allison R. , Iova Bulisa , Allison Allen , Butler Marguerite A. 
Published: September 2022

AbstractThe data provided here is related to the article “Resolving the Deep Phylogeny: Implications for Early Adaptive Radiation, Cryptic, and Present-day Ecological Diversity of Papuan Microhylid Frogs” [1]. The dataset is based on 233 tissue samples of the subfamily Asteroprhyinae, with representatives from all recognized genera, in addition to three outgroup taxa. The sequence dataset contains over 2400 characters per sample for five genes (three nuclear loci: BDNF, NXC-1, and SIA; and two mitochondrial loci: ND4 and CYTB) and is 99% complete. New primers were designed for all loci and accession numbers for the raw sequence data are provided. The sequences are used with geological time calibrations to produce time-calibrated Bayesian inference and Maximum Likelihood phylogenetic reconstructions using BEAST2 and IQTREE. Lifestyle data (arboreal, scansorial, terrestrial, fossorial, semi-aquatic) were collected from the literature and field notes and used to infer ancestral character states for each lineage. Collection location data (GPS and elevation data) were used to verify sites where multiple species or candidate species co-occur. All sequence data, alignments, and associated metadata (voucher specimen number, species identification, type locality status, GPS, elevation, site with species list, and lifestyle) as well as the code to produce all analyses and figures are provided.