bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Profiling Reveals the Transcription Factor Networks Regulating the Survival of Striatal Neurons
Authors: Yang Lin , Su Zihao , Wang Ziwu , Li Zhenmeiyu , Shang Zicong , Du Heng , Liu Guoping , Qi Dashi , Yang Zhengang , Xu Zhejun , Zhang Zhuangzhi 
Published: May 2020

AbstractThe striatum is structurally highly diverse, and its organ functionality critically depends on normal embryonic development. Although several studies have been conducted on the gene functional changes that occur during striatal development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive transcriptome profile that allowed us to explore the trajectory of striatal development and identify the correlation between the striatal development and Huntington’s disease (HD). Furthermore, we applied an integrative transcriptomic profiling approach based on machine learning to systematically map a global landscape of 277 transcription factor (TF) networks. Most of these TF networks are linked to biological processes, and some unannotated genes provide information about the corresponding mechanisms. For example, we found that the Meis2 and Six3 were crucial for the survival of striatal neurons, which was verified using conditional knockout (CKO) mice. Finally, we used RNA-Seq to speculate their downstream targets.
How to quantitatively measure, assess and correct the fluorescence crosstalk in the wide-field microscopy
Authors: Tie Hieng Chiong , Lu Lei 
Published: May 2020

AbstractDuring the multi-color fluorescence imaging, a fluorophore can be detected in the non-corresponding channel due to the broad spectra of the fluorophore and filters, resulting in the artefact called the crosstalk (crossover or bleed-through). Unfortunately, the fluorescence crosstalk is ubiquitous for the conventional fluorescence microscopy. Significant crosstalk can distort the image and lead to incorrect interpretation. Here, we introduce a simple quantitative metric, the crosstalk factor, to measure the crosstalk effect of a fluorophore on a channel in the wide-field fluorescence microscopy. We describe a cell biologist friendly protocol which should be easily implemented by cell biologists using commonly available image processing software such as ImageJ.
An anatomically accurate and personalizable head injury model: Significance of brain and white matter tract morphological variability on strain
Authors: Li Xiaogai , Zhou Zhou , Kleiven Svein 
Published: May 2020

AbstractFinite element head (FE) models are important numerical tools to study head injuries and develop protection systems. The generation of anatomically accurate and subject-specific head models with conforming hexahedral meshes remains a significant challenge. The focus of this study is to present two developmental work: First, an anatomically detailed FE head model with conforming hexahedral meshes that has smooth interfaces between the brain and the cerebrospinal fluid, embedded with white matter (WM) fiber tracts; Second, a morphing approach for subject-specific head model generation via a new hierarchical image registration pipeline integrating Demons and Dramms deformable registration algorithms. The performance of the head model is evaluated by comparing model predictions with experimental data of brain-skull relative motion, brain strain, and intracranial pressure. To demonstrate the applicability of the head model and the pipeline, six subject-specific head models of largely varying intracranial volume and shape are generated, incorporated with subject-specific WM fiber tracts. DICE similarity coefficients for cranial, brain mask, local brain regions, and lateral ventricles are calculated to evaluate personalization accuracy, demonstrating the efficiency of the pipeline in generating detailed subject-specific head models achieving satisfactory element quality without further mesh repairing. The six head models are then subjected to the same concussive loading to study sensitivity of brain strain to inter-subject variability of the brain and WM fiber morphology. The simulation results show significant differences in maximum principal strain (MPS) and axonal strain (MAS) in local brain regions (one-way ANOVA test, p<0.001), as well as their locations also vary among the subjects, demonstrating the need to further investigate the significance of subject-specific models. The techniques developed in this study may contribute to better evaluation of individual brain injury and development of individualized head protection systems in the future. This study also contains general aspects the research community may find useful: on the use of experimental brain strain close to or at injury level for head model validation; the hierarchical image registration pipeline can be used to morph other head models, such as smoothed-voxel models.
Oxytocinergic modulation of threat-specific amygdala sensitization in humans is critically mediated by serotonergic mechanisms
Authors: Liu Congcong , Lan Chunmei , Li Keshuang , Zhou Feng , Yao Shuxia , Xu Lei , Yang Ning , Zhou Xinqi , Yang Jiaxin , Yong Xue , Ma Yina , Scheele Dirk , Kendrick Keith M. , Becker Benjamin 
Published: May 2020

AbstractBackgroundOverarching conceptualizations propose that the complex social-emotional effects of oxytocin (OXT) in humans are partly mediated by interactions with other neurotransmitter systems. Recent animal models suggest that the anxiolytic effects of OXT are critically mediated by the serotonin (5-HT) system, yet direct evidence in humans is lacking.MethodsTo determine the role of 5-HT in OXT-induced attenuation of amygdala threat reactivity and sensitization/ desensitization, we conducted a parallel-group randomized placebo-controlled double-blind experiment during which n = 121 healthy subjects underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD, TRYP-) or the corresponding placebo-control protocols before the administration of intranasal OXT or placebo intranasal spray, respectively. Mean and repetition-dependent changes in threat-specific amygdala reactivity towards threatening stimuli (angry faces) as assessed by fMRI served as the primary outcome.ResultsNo treatment main or interaction effects on amygdala threat reactivity were observed, yet OXT switched bilateral amygdala threat sensitization to desensitization and this effect was significantly attenuated during decreased central 5-HT signaling via pretreatment with TRYP-.ConclusionsThe present findings provide the first evidence for a role of OXT in threat-specific amygdala desensitization in humans and suggest that these effects are critically mediated by the 5-HT system. OXT may have a therapeutic potential to facilitate amygdala desensitization and adjunct up-regulation of 5-HT neurotransmission may facilitate OXT’s anxiolytic potential.The trial was preregistered on clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT03426176, IDNCT03426176)
Prediction of regional wildfire activity with a probabilistic Bayesian framework
Authors: Pimont F , Fargeon H , Opitz T , Ruffault J , Barbero R , Martin StPaul N , Rigolot E , Rivière M , Dupuy JL 
Published: May 2020

AbstractModelling wildfire activity is crucial for informing science-based risk management and understanding fire-prone ecosystem functioning worldwide. Models also help to disentangle the relative roles of different factors, to understand wildfire predictability or to provide insights into specific events.Here, we develop a two-component Bayesian hierarchically-structured probabilistic model of daily fire activity, which are modelled as the outcome of a marked point process in which individual fires are the points (occurrence component) and the fire sizes are the marks (size component). The space-time Poisson model for occurrence is adjusted to gridded fire counts using the integrated nested Laplace approximation (INLA) combined with the Stochastic Partial Differential Equation (SPDE) approach. The size model is based on piecewise-estimated Pareto and Generalized-Pareto distributions, also adjusted with INLA. The Fire Weather Index (FWI) and Forest Area are the main explanatory variables. Seasonal and spatial residuals as well as a post-2003 effect are included to improve the consistency of the relationship between climate and fire occurrence, in accordance with parsimonious criteria.A set of 1000 simulations of the posterior model of fire activity is evaluated at various temporal and spatial scales in Mediterranean France. The number of escaped fires (≥1ha) across the region can be coarsely reproduced at the daily scale, and is more accurately predicted on a weekly basis or longer. The regional weekly total number of larger fires (10 to 100 ha) can be predicted as well, but the accuracy decays with size, as the model uncertainty increases with event rareness. Local predictions of fire numbers or burnt areas likewise require a longer aggregation period to maintain model accuracy.Regarding the year 2003 -which was characterized by an extreme burnt area in France associated with a heat wave-, the estimation of the number of escaped fires was consistent with observations, but the model systematically underrepresents larger fires and burnt areas, which suggests that the FWI does not consistently rate the danger of large fire occurrence during heat waves.Our study sheds new light on the stochastic processes underlying fire hazard, and is promising for predicting and projecting future fire hazard in the context of climate change.
Biosynthesis and heterologous expression of cacaoidin, the first member of the lanthidin family of RiPPs
Authors: Román-Hurtado Fernando , Sánchez-Hidalgo Marina , Martín Jesús , Ortíz-López Francisco Javier , Genilloud Olga 
Published: May 2020

1.AbstractCacaoidin is the first member of the new lanthidin RiPP family, a lanthipeptide produced by the strainStreptomyces cacaoiCA-170360 with unprecedented features such as an unusually high number of D-amino acids, a double methylation in the N-terminal alanine and a tyrosine residue glycosylated with a disaccharide. In this work, we describe the complete identification, cloning and heterologous expression of the cacaoidin biosynthetic gene cluster, which shows unique RiPP genes.
Allelic expression analysis of Imprinted and X-linked genes from bulk and single-cell transcriptomes
Authors: Martini Paolo , Sales Gabriele , Diamante Linda , Perrera Valentina , Colantuono Chiara , Riccardo Sara , Cacchiarelli Davide , Romualdi Chiara , Martello Graziano 
Published: May 2020

AbstractGenomic imprinting and X chromosome inactivation (XCI) are two prototypical epigenetic mechanisms whereby a set of genes is expressed mono-allelically in order to fine-tune their expression levels. Defects in genomic imprinting have been observed in several neurodevelopmental disorders, in a wide range of tumours and in induced pluripotent stem cells (iPSCs). Single Nucleotide Variants (SNVs) are readily detectable by RNA-sequencing allowing determination of whether imprinted or X-linked genes are aberrantly expressed from both alleles, although standardised analysis methods are still missing. We have developed a tool, named BrewerIX, that provides comprehensive information about the allelic expression of a large, manually-curated set of imprinted and X-linked genes. BrewerIX does not require programming skills, runs on a standard personal computer, and can analyze both bulk and single-cell transcriptomes of human and mouse cells directly from raw sequencing data. BrewerIX confirmed previous observations regarding the bi-allelic expression of some imprinted genes in naive pluripotent cells and extended them to preimplantation embryos. BrewerIX identified also misregulated imprinted genes in breast cancer cells and in human organoids and identified new genes escaping XCI in human somatic cells. We believe BrewerIX will be useful for the study of genomic imprinting and XCI during development and reprogramming, and for detecting aberrations in cancer, iPSCs and organoids. Due to its ease of use to non-computational biologists, its implementation could become standard practice during sample assessment, thus raising robustness and reproducibility of future studies.
Body size and tree species composition determine variation in prey consumption in a forest-inhabiting generalist predator
Authors: van Schrojenstein Lantman Irene M. , Vesterinen Eero J. , Hertzog Lionel R. , Martel An , Verheyen Kris , Lens Luc , Bonte Dries 
Published: May 2020

AbstractTrophic interactions may strongly depend on body size and environmental variation, but this prediction has been seldom tested in nature. Many spiders are generalist predators that use webs to intercept flying prey. The size and mesh of orb webs increases with spider size, allowing a more efficient predation on larger prey. We studied to this extent the orb-weaving spider Araneus diadematus inhabiting forest fragments differing in edge distance, tree diversity and tree species. These environmental variables are known to correlate to insect composition, richness and abundance. We anticipated these forest characteristics to be a principle driver of prey consumption. We additionally hypothesised them to impact spider size at maturity and expect shifts towards larger prey-size distributions in larger individuals independently from the environmental context.We quantified spider diet by means of metabarcoding of nearly 1000 A. diadematus from a total of 53 forest plots. This approach allowed a massive screening of consumption dynamics in nature, though at the cost of identifying the exact prey identity, as well as their abundance and putative intraspecific variation. Our study confirmed A. diadematus as a generalist predator, with more than 300 prey ZOTUs detected in total. At the individual level, we found large spiders to consume fewer different species, but adding larger species to their diet. Tree species composition affected both prey species richness and size in the spider’s diet, although tree diversity per se had no influence on the consumed prey. Edges had an indirect effect on the spider diet as spiders closer to the forest edge were larger and therefore consumed larger prey. We conclude that both intraspecific size variation and tree species composition shape the consumed prey of this generalist predator.
Acetyl-Leucine slows disease progression in lysosomal storage disorders
Authors: Kaya Ecem , Smith David A , Smith Claire , Morris Lauren , Bremova-Ertl Tatiana , Cortina-Borja Mario , Fineran Paul , Morten Karl J , Poulton Joanna , Boland Barry , Spencer John , Strupp Michael , Platt Frances M 
Published: May 2020

AbstractAcetyl-DL-leucine (ADLL) is a derivative of the branched chain amino acid leucine. In observational clinical studies ADLL improved symptoms of ataxia, in particular in patients with the lysosomal storage disorder (LSD), Niemann-Pick disease type C 1 (NPC1). Here, we investigated ADLL and its enantiomers acetyl-L-leucine (ALL) and acetyl-D-leucine (ADL) in symptomaticNpc1-/-mice and observed an improvement in ataxia with both enantiomers and ADLL. When ADLL and ALL were administered pre-symptomatically toNpc1-/-mice, both treatments delayed disease progression and extended life span, whereas ADL did not. These data are consistent with ALL being the neuroprotective enantiomer. Altered glucose and antioxidant metabolism were found to be implicated as one of the potential mechanisms of action of the L enantiomer inNpc1-/-mice. When miglustat and ADLL were used in combination significant synergy resulted. In agreement with these pre-clinical data, when NPC1 patients were evaluated after 12 months of ADLL treatment, rates of disease progression were slowed, with stabilisation or improvement in multiple neurological domains. A beneficial effect of ADLL on gait was also observed in this study in a mouse model of GM2 gangliosidosis (Sandhoff disease) and in Tay-Sachs and Sandhoff disease patients in individual-cases of off-label-use. Taken together, we have identified an unanticipated neuroprotective effect of acetyl-L-leucine and underlying mechanisms of action in LSDs, supporting its further evaluation in clinical trials in lysosomal disorders.
Identification a novel subset of alveolar type 2 cells expanding following pneumonectomy and enriched in PD-L1
Authors: Ahmadvand Negah , Khosravi Farhad , Lingampally Arun , Wasnick Roxana , Vazquez-Armendariz Ivonne , Heiner Monika , Rivetti Stefano , Lv Yuqing , Wilhelm Jochen , Gunther Andreas , Herold Susanne , Alam Denise Al , Chen Chengshui , Minoo Parviz , Zhang Jin-San , Bellusci Saverio 
Published: May 2020

ABSTRACTAlveolar type 2 (AT2) cells are heterogeneous cells; where specialized AT2 subpopulations within this lineage exhibit stem cell properties. However, the existence of quiescent, immature cells within the AT2 lineage, which get activated during lung regeneration, is unknown.SftpcCreERT2/+; tdTomatoflox/floxmice were used for the labelling of AT2 cells and labeled subpopulations were analyzed by flow cytometry, qPCR, ATAC-seq, gene arrays, pneumonectomy, and culture of precision-cut lung slides. Human lungs from donor and IPF were also analyzed.In mice, we detected two distinct AT2 subpopulations with low tdTomato level (TomLow) and high tdTomato level (TomHigh). TomLowexpress lower level of AT2 differentiation markers,Fgfr2bandEtv5, while TomHigh, asbona fidemature AT2 cells, show higher level ofSftpc,Sftpb,Sftpa1,Fgfr2b, andEtv5. ATAC-seq analysis indicates that TomLowand TomHighconstitute two distinct cell populations with specific silencing ofSftpc,Rosa26and cell cycle gene loci in TomLow. Upon pneumonectomy, TomLowbut not TomHighcells proliferate and upregulate the expression ofFgfr2b,Etv5,Sftpc,Ccnd1andCcnd2compared to sham. TomLowcells overexpress PD-L1, an immune inhibitory membrane receptor ligand, which is used by flow cytometry to differentially isolate these two sub-populations. In the human lung, PD-L1 and HTII-280 antibodies are used by flow cytometry to differentially sort mature AT2 (HTII-280-high, PD-L1-low) as well as an additional subpopulation of epithelial cells characterized by HTII-280-Low and PD-L1-high.We have identified a novel population of AT2 quiescent immature progenitor cells in mouse that proliferate upon pneumonectomy and provided evidence for the existence of such cells in human.Significance of the workThe characterization and mechanism of the proliferation of a novel and relevant pool of AT2 progenitor cells for the repair/regeneration process after injury are critical to improving respiratory function in patients with lung disease.
Type I PRMT inhibition protects against C9ORF72 arginine-rich dipeptide repeat toxicity
Authors: Premasiri Alan S. , Gill Anna L. , Vieira Fernando G. 
Published: May 2020

ABSTRACTThe most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a repeat expansion mutation in the C9orf72 gene. Repeat-associated non-AUG (RAN) translation of this expansion produces five species of dipeptide repeat proteins (DRPs). The arginine containing DRPs, polyGR and polyPR, are consistently reported to be the most toxic. Here, we uncover Type I protein arginine methyltransferase (PRMT) inhibitors as possible therapeutics for polyGR- and polyPR- related toxicity. Furthermore, we reveal data that suggest that asymmetric dimethylation (ADMe) of polyGR is a determining factor in its pathogenesis.
Fold recognition by scoring protein map similarities using the congruence coefficient
Authors: Di Lena Pietro , Baldi Pierre 
Published: May 2020

AbstractMotivationProtein fold recognition is a key step for template-based modeling approaches to protein structure prediction. Although closely related folds can be easily identified by sequence homology search in sequence databases, fold recognition is notoriously more difficult when it involves the identification of distantly related homologues. Recent progress in residue-residue contact and distance prediction opens up the possibility of improving fold recognition by using structural information contained in predicted distance and contact maps.ResultsHere we propose to use thecongruence coefficientas a metric of similarity between maps. We prove that this metric has several interesting mathematical properties which allow one to compute in polynomial time its exact mean and variance over all possible (exponentially many) alignments between two symmetric matrices, and assess the statistical significance of similarity between aligned maps. We perform fold recognition tests by recovering predicted target contact/distance maps from the two most recent CASP editions and over 27,000 non-homologous structural templates from the ECOD database. On this large benchmark, we compare fold recognition performances of different alignment tools with their own similarity scores against those obtained using the congruence coefficient. We show that the congruence coefficient overall improves fold recognition over other methods, proving its effectiveness as a general similarity metric for protein map comparison.AvailabilityThe software CCpro is available as part of the Scratch suitehttp://scratch.proteomics.ics.uci.edu/
A large accessory protein interactome is rewired across environments
Authors: Liu Zhimin , Miller Darach , Li Fangfei , Liu Xianan , Levy Sasha 
Published: May 2020

SummaryTo characterize how protein-protein interaction (PPI) networks change, we quantified the relative PPI abundance of 1.6 million protein pairs in yeast across 9 growth conditions, with replication, for a total of 44 million measurements. Our multi-condition screen identified 13,764 pairwise PPIs, a 3-fold increase over PPIs identified in one condition. A few “immutable” PPIs are present across all conditions, while most “mutable” PPIs are rarely observed. Immutable PPIs aggregate into highly connected “core” network modules, with most network remodeling occurring within a loosely connected “accessory” module. Mutable PPIs are less likely to co-express, co-localize, and be explained by simple mass action kinetics, and more likely to contain proteins with intrinsically disordered regions, implying that environment-dependent association and binding is critical to cellular adaptation. Our results show that protein interactomes are larger than previously thought and contain highly dynamic regions that reorganize to drive or respond to cellular changes.
Maturation of Purkinje cell firing properties relies on granule cell neurogenesis
Authors: van der Heijden Meike E. , Lackey Elizabeth P. , Işleyen Fatma S. , Brown Amanda M. , Perez Ross , Lin Tao , Zoghbi Huda Y. , Sillitoe Roy V. 
Published: May 2020

SUMMARYPreterm infants that suffer cerebellar insults often develop motor disorders and cognitive difficulty. Granule cells are especially vulnerable, and they likely instigate disease by impairing the function of Purkinje cells. Here, we use regional genetic manipulations andin vivoelectrophysiology to test whether granule cells help establish the firing properties of Purkinje cells during postnatal mouse development. We generated mice that lack granule cell neurogenesis and tracked the structural and functional consequences on Purkinje cells in these agranular pups. We reveal that Purkinje cells fail to acquire their typical connectivity and morphology, and the formation of characteristic Purkinje cell firing patterns is delayed by one week. We also show that the agranular pups have impaired motor behaviors and vocal skills. These data argue that granule cell neurogenesis sets the maturation time window for Purkinje cell function and refines cerebellar-dependent behaviors.