bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COVID-19 pandemic on rare diseases- A case study on thalassaemia patients in Bangladesh
Authors: Hossain Mohammad Sorowar , Runa Farhana , Mosabbir Abdullah Al 
Published: March 2021

AbstractObjectivesThalassaemia is a life-threatening rare disease, which requires regular blood transfusion and medical care. The information on how thalassaemia patients are affected during the unprecedented COVID-19 crisis is scarce. This study aimed to assess the impact of the COVID-19 pandemic on the blood transfusion and healthcare access of thalassaemia patients at the community level in Bangladesh.MethodsA cross-sectional study was conducted among thalassaemia patients registered in a community-based ‘ thalassaemia registry’ in Jamapur, Bangladesh.ResultsAs compared to pre-COVID-19 time, the number of blood transfusions among patients under the thalassaemia registry was significantly reduced during COVID-19 pandemic (190 units versus 81 units). In addition, the median number of red cell transfusions per patient was dropped significantly from 4 units to one unit. Over 80% of patient had no access to healthcare services at all during the early phase of the pandemic.ConclusionsEmergency response with appropriate mitigative measures must be a priority for addressing an acute shortage of blood supply in situations like COVID-19 pandemic.
Relationship between constitutive and acute gene regulation, and physiological and behavioral responses, mediated by the neuropeptide PACAP
Authors: Bakalar Dana , Sweat Sean , Drossel Gunner , Jiang Sunny Z. , Samal Babru S. , Stroth Nikolas , Xu Wenqin , Zhang Limei , Zhang Haiying , Eiden Lee E. 
Published: March 2021

AbstractSince the advent of gene knockout technology in 1987, insight into the role(s) of neuropeptides in centrally- and peripherally-mediated physiological regulation has been gleaned by examining altered physiological functioning in mammals, predominantly mice, after genetic editing to produce animals deficient in neuropeptides or their cognate G-protein coupled receptors (GPCRs). These results have complemented experiments involving infusion of neuropeptide agonists or antagonists systemically or into specific brain regions. Effects of gene loss are often interpreted as indicating that the peptide and its receptor(s) are required for the physiological or behavioral responses elicited in wild-type mice at the time of experimental examination. These interpretations presume that peptide/peptide receptor gene deletion affects only the expression of the peptide/receptor itself, and therefore impacts physiological events only at the time at which the experiment is conducted. A way to support ‘real-time’ interpretations of neuropeptide gene knock-out is to demonstrate that the wild-type transcriptome, except for the deliberately deleted gene(s), in tissues of interest, is preserved in the knock-out mouse. Here, we show that there is a cohort of genes (constitutively PACAP-Regulated Genes, or cPRGs) whose basal expression is affected by constitutive knock-out of the Adcyap1 gene in C57Bl6/N mice, and additional genes whose expression in response to physiological challenge, in adults, is altered or impaired in the absence of PACAP expression (acutely PACAP-Regulated Genes, or aPRGs). Distinguishing constitutive and acute transcriptomic effects of neuropeptide deficiency on physiological function and behavior in mice reveals alternative mechanisms of action, and changing functions of neuropeptides, throughout the lifespan.
Evidence for glutamine synthetase function in mouse spinal cord oligodendrocytes
Authors: Haim Lucile Ben , Schirmer Lucas , Zulji Amel , Sabeur Khalida , Tiret Brice , Chang Sandra , Lamers Wouter H. , Chaumeil Myriam M. , Rowitch David H. 
Published: March 2021

AbstractGlutamine synthetase (GS) is a key enzyme that metabolizes glutamate into glutamine. While GS is expressed by astrocytes of the central nervous system (CNS), expression in other glial lineages has been noted. Using a combination of reporter mice and cell typespecific markers, we show that GS is expressed in myelinating oligodendrocytes (OL) but not oligodendrocyte progenitor cells (OPC) of the mouse spinal cord abutting ventral horn motor neurons. To investigate the role of GS in mature OL, we used a conditional knockout (cKO) approach to selectively delete GS-encoding gene (Glul) in OL, which caused a significant decrease in glutamine levels on spinal cord extracts. We evaluated the effect on ventral spinal cord sensorimotor circuits and observed thatGS cKOmice (CNP-cre+:Glulfl/fl) showed no differences in motor neuron numbers, size or axon density; OL differentiation and myelination in the ventral spinal cord at 1- and 6-months of age was normal. Interestingly,GS cKOmice showed an early and specific decrease in peak force while motor function remained otherwise unaffected. These findings provide evidence OL-encoded GS functions in spinal cord sensorimotor circuit.Main pointsGlutamine synthetase (GS) is highly expressed in oligodendrocytes (OL) of the mouse spinal cord.OL-specific GS loss of function causes transient decrease in peak force, but other substantial neurological dysfunction was not detected.
Occipital and parietal cortex participate in a cortical network for transsaccadic discrimination of object shape and orientation
Authors: Baltaretu B. R. , Stevens W. Dale , Freud E. , Crawford J. D. 
Published: March 2021

AbstractSaccades change eye position and interrupt vision several times per second, necessitating neural mechanisms for continuous perception of object identity, orientation, and location. Neuroimaging studies suggest that occipital and parietal cortex play complementary roles for transsaccadic perception of intrinsic versus extrinsic spatial properties, e.g., dorsomedial occipital cortex (cuneus) is sensitive to changes in spatial frequency, whereas the supramarginal gyrus (SMG) is modulated by changes in object orientation. Based on this, we hypothesized that both structures would be recruited to simultaneously monitor identityandorientation across saccades. To test this, we merged two previous neuroimaging protocols: 21 participants viewed a 2D object and then, after sustained fixation or a saccade, judged whether the shapeororientation of the represented object changed. We, then, performed a bilateral region-of-interest analysis on identified cuneus and SMG sites. As hypothesized, cuneus showed both saccade and feature (i.e., orientation vs. shape change) modulations, and right SMG showed saccade-feature interactions. Further, the cuneus activity time course correlated with several other cortical saccade / visual areas, suggesting a ‘functional network’ for feature discrimination. These results confirm the involvement of occipital / parietal cortex in transsaccadic vision and support complementary roles in spatial versus identity updating.
H3K9 methyltransferase EHMT2/G9a controls ERVK-driven non-canonical imprinted genes
Authors: Zeng Tie-Bo , Pierce Nicholas , Szabó Piroska E. 
Published: March 2021

AbstractUnlike regular imprinted genes, non-canonical imprinted genes are known to not depend on gamete-specific DNA methylation difference. Instead, the paternal allele-specific expression of these genes in the extra-embryonic lineages depends on an H3K27me3-based imprint in the oocyte, but this marking is not maintained beyond pre-implantation development. The maintenance of non-canonical imprinting corresponds to maternal allele-specific DNA methylation and paternal allele-specific H3K4me3 at their somatic DMRs, which occur at ERVK repeats. We hypothesized that EHMT2, the main euchromatic H3K9 methyltransferase, also has a role in this process. Using reciprocal mouse crosses and allele-specific RNA-seq analysis, we found that the maternal allele of each known non-canonical imprinted gene was derepressed from its ERVK promoter in theEhmt2−/−ectoplacental cone of somite-matched 8.5 dpc embryos. In theEhmt2−/−embryos, loss of DNA methylation accompanied the derepression of both parental alleles of those ERVK promoters. Our study identifies EHMT2 as an essential player that maintains the repressed chromosomal state in non-canonical imprinting.
Multisystem inflammatory syndrome in European White children – study of 274 cases
Authors: Ludwikowska Kamila Maria , Okarska-Napierała Magdalena , Dudek Natalia , Tracewski Paweł , Kusa Jacek , Piwoński Krzysztof , Afelt Aneta , Cysewski Dominik , Biela Mateusz , Werner Bożena , Jackowska Teresa , Suski Catherine , Kursa Miron Bartosz , Kuchar Ernest , Szenborn Leszek 
Published: March 2021

AbstractBackgroundDespite the growing literature on multisystem inflammatory syndrome in children (MIS-C), the data in European White population is limited. Our aim was to capture MIS-C emergence in Poland (central Europe) and to describe its characteristics with a focus on severity determinants.MethodsPatients who met the MIS-C definition (fever, multiorgan failure, inflammation, and proven SARS-CoV-2 infection or contact) were reported retrospectively and prospectively in an online survey. Study definitions fulfilment was automatically evaluated by a dedicated software. For the assessment of univariate relationships, either directed or divided by sex, age, or disease severity, we used the test for two categorical variables and the Kruskal-Wallis test for categorical-continuous variable pairs.FindingsThe analysis involved 274 children, 62.8% boys, median age 8.8 years. Besides one Asian, all were European White. Merely 23 (8.4%) required paediatric intensive care treatment (PICU). They were older (11.2 vs. 8.4 years), and at hospital admission had higher respiratory rate (30 v. 20/minute), lower systolic blood pressure (89 vs. 100 mmHg), prolonged capillary refill time (40% vs. 11%), and decreased consciousness (22% vs. 5%).Teenage boys had more common cardiac involvement (fraction 25.9% vs. 14.7%) and macrophage activation syndrome (31.0% vs. 15.2%) than others. Boys were also more often hospitalised in PICU with age (from median 11.2 years to 9.1).InterpretationThe severity of MIS-C is not as uniform as it seemed, ethnicity and sex may affect MIS-C phenotype. Management might not be universally applicable and should rather be adjusted to the specific population.FundingPSP: 501-D402-20-0006100
Genomic analysis of patient-derived xenograft models reveals intra-tumor heterogeneity in endometrial cancer and can predict tumor growth inhibition with talazoparib
Authors: Bonazzi Vanessa F. , Kondrashova Olga , Smith Deborah , Nones Katia , Sengal Asmerom T. , Ju Robert , Packer Leisl M. , Koufariotis Lambros T. , Kazakoff Stephen H. , Davidson Aimee L. , Ramarao-Milne Priya , Lakis Vanessa , Newell Felicity , Rogers Rebecca , Davies Claire , Nicklin James , Garrett Andrea , Chetty Naven , Perrin Lewis , Pearson John V. , Patch Ann-Marie , Waddell Nicola , Pollock Pamela 
Published: March 2021

AbstractBackgroundEndometrial cancer (EC) is a major gynecological cancer with increasing incidence. It comprised of four molecular subtypes with differing etiology, prognoses, and response to chemotherapy. In the future, clinical trials testing new single agents or combination therapies will be targeted to the molecular subtype most likely to respond. Pre-clinical models that faithfully represent the molecular subtypes of EC are urgently needed, we sought to develop and characterize a panel of novel EC patient-derived xenograft (PDX) models.MethodsHere, we report whole exome or whole genome sequencing of 11 PDX models and the matched primary tumor. Analysis of multiple PDX lineages and passages was performed to study tumor heterogeneity across lineages and/or passages. Based on recent reports of frequent defects in the homologous recombination (HR) pathway in EC, we assessed mutational signatures and HR deficiency scores and correlated these within vivoresponses to the PARP inhibitor (PARPi) talazoparib in six PDXs representing the different molecular subtypes of EC.ResultsPDX models were successfully generated from all four molecular subtypes of EC and uterine carcinosarcomas, and they recapitulated morphology and the molecular landscape of primary tumors without major genomic drift. We also observed a wide range of inter-tumor and intra-tumor heterogeneity, well captured by different PDX lineages, which could lead to different treatment responses. Anin vivoresponse to talazoparib was detected in two p53mut models consistent with stable disease, however both lacked the HR deficiency genomic signature.ConclusionsEC PDX models represent the four molecular subtypes of disease and can capture intra-tumoral heterogeneity of the original primary tumor. PDXs of the p53mut molecular subtype showed sensitivity to PARPi, however, deeper and more durable responses will likely require combination of PARPi with other agents.
DataJoint Elements: Data Workflows for Neurophysiology
Authors: Yatsenko Dimitri , Nguyen Thinh , Shen Shan , Gunalan Kabilar , Turner Christopher A. , Guzman Raphael , Sasaki Maho , Sitonic Daniel , Reimer Jacob , Walker Edgar Y. , Tolias Andreas S. 
Published: March 2021

AbstractA new resource—DataJoint Elements—provides modular designs for assembling complete workflow solutions to organize data and computations for common neurophysiology experiments. The designs are derived from working solutions developed in leading research groups using the open-source DataJoint framework to integrate data collection and analysis in collaborative workflows.
Robust phylogenetic position of the enigmatic hydrozoanMargelopsis haeckeliirevealed within the family Corymorphidae
Authors: Kupaeva Daria , Lebedeva Tatiana , Kobrinsky Zachariah , Vanwalleghem Daniel , Prudkovsky Andrey , Kremnyov Stanislav 
Published: March 2021

AbstractThe life-cycle and polyp morphology of representatives of Margelopsidae are very different from all other species in the hydrozoan clade Aplanulata. Their evolutionary origin and phylogenetic position has been the subject of significant speculation. A recent molecular study based only on COI data placed Margelopsidae as a sister group to all Aplanulata, an unexpected result because margelopsid morphology suggests affiliation with Tubulariidae or Corymorphidae. Here we used multigene analyses, including nuclear (18S rRNA and 28S rRNA) and mitochondrial (16S rRNA and COI) markers of the hydroid stage of the margelopsid speciesMargelopsis haeckeliiHartlaub, 1897 and the medusa stage ofMargelopsis hartlaubiiBrowne, 1903 to resolve their phylogenetic position with respect to other hydrozoans. Our data provide strong evidence thatM. haeckelii, the type species ofMargelopsis, is a member of the family Corymorphydae. In contrast,M. hartlaubiiBrowne, 1903 is sister toPlotocnide borealisWagner, 1885, a member of Boreohydridae. These results invalidate the family Margelopsidae. The phylogenetic signal of polyp and medusa stages is discussed in light of concept of inconsistent evolution and molecular phylogenetic analysis.
Micrococcal nuclease sequencing of porcine sperm suggests a nucleosomal involvement on semen quality and early embryo development
Authors: Gòdia Marta , Hammoud Saher Sue , Naval-Sanchez Marina , Ponte Inma , Rodríguez-Gil Joan Enric , Sánchez Armand , Clop Alex 
Published: March 2021

AbstractBackgroundThe mammalian mature spermatozoon has a unique chromatin structure in which the vast majority of histones are replaced by protamines during spermatogenesis and a small fraction of nucleosomes are retained at specific locations of the genome. The chromatin structure of sperm remains unresolved in most livestock species, including the pig. However, its resolution could provide further light into the identification of the genomic regions related to sperm biology and embryo development and it could also help identifying molecular markers for sperm quality and fertility traits. Here, for the first time in swine, we performed Micrococcal Nuclease coupled with high throughput sequencing on pig sperm and characterized the mono-nucleosomal (MN) and sub-nucleosomal (SN) chromatin fractions.ResultsWe identified 25,293 and 4,239 peaks in the mono-nucleosomal and sub-nucleosomal fractions, covering 0.3% and 0.02% of the porcine genome, respectively. A cross-species comparison of nucleosome-associated DNAs in sperm revealed positional conservation of the nucleosome retention between human and pig. Gene ontology analysis of the genes mapping nearby the mono-nucleosomal peaks and identification of putative transcription factor binding motifs within the mono-nucleosomal peaks showed enrichment for sperm function and embryo development related processes. We found motif enrichment for the transcription factor Znf263, which in humans was suggested to be a key regulator of the genes with paternal preferential expression during early embryo development. Moreover, we found enriched co-occupancy between the RNAs present in pig sperm and the RNA related to sperm quality, and the mono-nucleosomal peaks. We also found preferential co-location between GWAS hits for semen quality in swine and the mono-nucleosomal sites identified in this study.ConclusionsThese results suggest a clear relationship between nucleosome positioning in sperm and sperm and embryo development.
Interpreting Null Models of Resting-State Functional MRI
Authors: Liégeois Raphaël , Yeo B. T. Thomas , Van De Ville Dimitri 
Published: March 2021

AbstractNull models are necessary for assessing whether a dataset exhibits non-trivial statistical properties. These models have recently gained interest in the neuroimaging community as means to explore dynamic properties of functional Magnetic Resonance Imaging (fMRI) time series. Interpretation of null-model testing in this context may not be straightforward because (i) null hypotheses associated to different null models are sometimes unclear and (ii) fMRI metrics might be ‘trivial’, i.e. preserved under the null hypothesis, and still be useful in neuroimaging applications. In this commentary, we review several commonly used null models of fMRI time series and discuss the interpretation of the corresponding tests. We argue that, while null-model testing allows for a better characterization of the statistical properties of fMRI time series and associated metrics, it should not be considered as a mandatory validation step to assess their relevance in neuroimaging applications.
A novel theoretical framework for simultaneous measurement of excitatory and inhibitory conductances
Authors: Müller-Komorowska Daniel , Parabucki Ana , Elyasaf Gal , Katz Yonatan , Beck Heinz , Lampl Ilan 
Published: March 2021

AbstractFiring of neurons throughout the brain is determined by the precise relations between excitatory and inhibitory inputs and disruption of their balance underlies many psychiatric diseases. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs simultaneously. We developed a new analytical framework for instantaneous and simultaneous measurements of both the excitatory and inhibitory neuronal inputs during a single trial under current clamp recording. This can be achieved by injecting a current composed of two high frequency sinusoidal components followed by analytical extraction of the conductances. We demonstrate the ability of this method to measure both inputs in a single trial under realistic recording constraints and from morphologically realistic CA1 pyramidal model cells. Experimental implementation of our new method will facilitate the understanding of fundamental questions about the health and disease of the nervous system.ClassificationSystem Neuroscience, Cellular and Molecular Neuroscience
Impact of blood storage conditions on the transcript profile of plasma cell-free RNA
Authors: Sun Jinghua , Yang Xi , Wang Taifu , Xing Yanru , Chen Haixiao , Zhu Sujun , Zeng Juan , Zhou Qing , Chen Fang , Zhang Xiuqing , Wang Wen-Jing 
Published: March 2021

AbstractBACKGROUNDPlasma cell-free RNA (cfRNA) are potential biomarkers for disease prediction and diagnosis. However, pre-analysis factors, such as the delay in blood processing and storage may lead to unreliable results, though no study has systematically evaluated the effect of blood storage conditions on the whole transcriptome of plasma cfRNA yet.METHODSWe collected peripheral blood samples from four healthy subjects and allowed them to stand at room temperature or 4◻ for different time periods (0h, 2h, 6h and 24h) prior to plasma separation. Then, plasma cfRNA stability was evaluated by measuring expression changes of cell-free mRNA, lncRNA and miRNA using high throughput sequencing-based profiling. Finally, their paired leukocyte RNA data were integrated to depict the effect of leukocytes on plasma cfRNA during storage.RESULTSPlasma mRNA and lncRNA presented high correlations (Pearson R2≥ 0.8) and fewer variations when blood was stored at 4◻ for 6 hours or stored at RT for 2 hours. miRNA was more stable, with minimal R2of 0.86 at 4◻ for at least 24 hours or at RT for 6 hours. Correlations of plasma RNA and leukocyte RNA increased with the incubation time, and the relative proportion of neutrophils in plasma grown from 14.3% to 61.2% at RT (P= 0.004), indicating leukocyte RNA contamination. Besides, the tissue enriched genes in plasma were down-regulated with the extension of storage time.CONCLUSIONSOur results characterized the effects of short-term storage of blood samples on plasma cfRNA, which will facilitate further researches or clinical applications to avoid bias resulting from sample processing.
Facilitating population genomics of non-model organisms through optimized experimental design for reduced representation sequencing
Authors: Christiansen Henrik , Heindler Franz M. , Hellemans Bart , Jossart Quentin , Pasotti Francesca , Robert Henri , Verheye Marie , Danis Bruno , Kochzius Marc , Leliaert Frederik , Moreau Camille , Patel Tasnim , Van de Putte Anton P. , Vanreusel Ann , Volckaert Filip A. M. , Schön Isa 
Published: March 2021

AbstractGenome-wide data are invaluable to characterize differentiation and adaptation of natural populations. Reduced representation sequencing (RRS) subsamples a genome repeatedly across many individuals. However, RRS requires careful optimization and fine-tuning to deliver high marker density while being cost-efficient. The number of genomic fragments created through restriction enzyme digestion and the sequencing library setup must match to achieve sufficient sequencing coverage per locus. Here, we present a workflow based on published information and computational and experimental procedures to investigate and streamline the applicability of RRS. In an iterative process genome size estimates, restriction enzymes and size selection windows were tested and scaled in six classes of Antarctic animals (Ostracoda, Malacostraca, Bivalvia, Asteroidea, Actinopterygii, Aves). Achieving high marker density would be expensive in amphipods, the malacostracan target taxon, due to the large genome size. We propose alternative approaches such as mitogenome or target capture sequencing for this group. Pilot libraries were sequenced for all other target taxa. Ostracods, bivalves, sea stars, and fish showed overall good coverage and marker numbers for downstream population genomic analyses. In contrast, the bird test library produced low coverage and few polymorphic loci, likely due to degraded DNA. Prior testing and optimization are important to identify which groups are amenable for RRS and where alternative methods may currently offer better cost-benefit ratios. The steps outlined here are easy to follow for other non-model taxa with little genomic resources, thus stimulating efficient resource use for the many pressing research questions in molecular ecology.