bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modern Japanese ancestry-derived variants revealed the formation process of the current Japanese regional gradations
Authors: Watanabe Yusuke , Ohashi Jun 
Published: December 2020

SummaryModern Japanese have two major ancestral populations: the indigenous Jomon hunter gatherers and continental East Asian farmers. To figure out the formation process of current Japanese population, we developed a reference-free detection method of variants derived from ancestral populations using a summary statistic, the ancestry-marker index (AMI). We confirmed by computer simulations thatAMIcan detect ancestry-derived variants even in an admixed population of recently diverged source populations with high accuracy, which cannot be achieved by the most widely used statistics, S*, for identifying archaic ancestry. We applied theAMIto modern Japanese samples and identified 208,648 single nucleotide polymorphisms (SNPs) that were likely derived from the Jomon people (Jomon-derived variants). The analysis of Jomon-derived variants in 10,842 modern Japanese individuals recruited from all over Japan revealed that the admixture proportions of the Jomon people varied between prefectures, probably due to the differences of population sizes of immigrants in the final Jomon to the Yayoi period. The estimated allele frequencies of genome-wide SNPs in the ancestral populations of modern Japanese suggested their phenotypic characteristics possibly for adaptation to their respective livelihoods; higher triglycerides and blood sugar for the Jomon ancestry and higher C-reactive protein and eosinophil counts for continental ancestry. According to our findings, we propose a formation model of modern Japanese population; regional variations in admixture proportions of the Jomon people and continental East Asians formed genotypic and phenotypic gradations of current Japanese archipelago populations.
Spatial organization of the transcriptome in individual neurons
Authors: Wang Guiping , Ang Cheen-Euong , Fan Jean , Wang Andrew , Moffitt Jeffrey R. , Zhuang Xiaowei 
Published: December 2020

AbstractNeurons are highly polarized cells with complex neurite morphology. Spatial organization and local translation of RNAs in dendrites and axons play an important role in many neuronal functions. Here we performed super-resolution spatial profiling of RNAs inside individual neurons at the genome scale using multiplexed error-robust fluorescencein situhybridization (MERFISH), and mapped the spatial organization of up to ∼4,200 RNA species (genes) across multiple length scales, ranging from sub-micrometer to millimeters. Our data generated a quantitative intra-neuronal atlas of RNAs with distinct transcriptome compositions in somata, dendrites, and axons, and revealed diverse sub-dendritic distribution patterns of RNAs. Moreover, our spatial analysis identified distinct groups of genes exhibiting specific spatial clustering of transcripts at the sub-micrometer scale that were dependent on protein synthesis and differentially dependent on synaptic activity. Overall, these data provide a rich resource for characterizing the subcellular organization of the transcriptome in neurons with high spatial resolution.
Mutated clones driving leukemic transformation are already detectable at the single cell level in CD34-positive cells in the chronic phase of primary myelofibrosis
Authors: Parenti Sandra , Rontauroli Sebastiano , Carretta Chiara , Mallia Selene , Genovese Elena , Chiereghin Chiara , Peano Clelia , Tavernari Lara , Bianchi Elisa , Fantini Sebastian , Sartini Stefano , Romano Oriana , Bicciato Silvio , Tagliafico Enrico , Della Porta Matteo , Manfredini Rossella 
Published: December 2020

ABSTRACTDisease progression of myeloproliferative neoplasms is the result of increased genomic complexity. Since the ability to predict disease evolution is crucial for clinical decision, we studied single cell genomics and transcriptomics of CD34-positive cells from a primary myelofibrosis (PMF) patient who progressed to acute myeloid Leukemia (AML) while receiving Ruxolitinib.Single cell genomics allowed the reconstruction of clonal hierarchy and demonstrated thatTET2was the first mutated gene whileFLT3was the last one. Disease evolution was accompanied by increased clonal heterogeneity and mutational rate, but clones carryingTP53andFLT3mutations were already present in chronic phase.Single cell transcriptomics unraveled repression of interferon signaling suggesting an immunosuppressive effect exerted by Ruxolitinib. Moreover, AML transformation was associated with a differentiative block and immune escape.These results suggest that single cell analysis can unmask tumor heterogeneity and provide meaningful insights about PMF progression that might guide personalized therapy.
Central metabolism as a potential origin of sex differences in morphine analgesia but not in the induction of analgesic tolerance in mice
Authors: Gabel Florian , Hovhannisyan Volodya , Andry Virginie , Goumon Yannick 
Published: December 2020

ABSTRACTIn rodents, morphine analgesia is influenced by sex. However, conflicting results exist regarding the interaction between sex and morphine analgesic tolerance. Morphine is metabolized in the liver and brain into morphine-3-glucuronide (M3G). Sex differences in morphine metabolism and differential metabolic adaptations during tolerance development might explain the behavioral discrepancies. The present article investigates the differences in peripheral and central morphine metabolism after acute and chronic morphine treatment in male and female mice.The first experiment aimed to determine whether morphine analgesia and tolerance differ between male and female mice using the tail-immersion test. The second experiment evaluated morphine and M3G metabolic kinetics in the blood using LC-MS/MS. Morphine and M3G were also quantified in several central nervous system (CNS) regions after acute and chronic morphine treatment. Finally, the blood-brain barrier permeability of M3G was assessed in male and female mice.This study demonstrated that female mice showed weaker morphine analgesia. In addition, tolerance appeared earlier in females but the sex discrepancies observed seemed to be due to the initial differences in morphine analgesia rather than to sex-specific mechanisms involving metabolism. Additionally, compared to male mice, female mice showed higher levels of M3G in the blood and in several CNS regions, whereas lower levels of morphine were observed in these brain regions. These differences are attributable mainly to morphine central metabolism, which differed between males and females in pain-related brain regions, consistent with the weaker analgesic effect in females. However, the role of morphine metabolism in analgesic tolerance seems rather limited.
Non-autophagy role of Atg5 and NBR1 in unconventional secretion of IL-12 prevents gut dysbiosis and inflammation
Authors: Merkley Seth D. , Goodfellow Samuel M. , Guo Yan , Wilton Zoe E.R. , Byrum Janie R. , Schwalm Kurt C. , Dinwiddie Darrell L. , Gullapalli Rama R. , Deretic Vojo , Hernandez Anthony Jimenez , Bradfute Steven B. , In Julie G. , Castillo Eliseo F. 
Published: December 2020

ABSTRACTIntestinal myeloid cells play a critical role in balancing intestinal homeostasis and inflammation. Here, we report that expression of the autophagy related 5 (Atg5) protein in myeloid cells prevents dysbiosis and excessive intestinal inflammation by limiting IL-12 production. Mice with a selective genetic deletion ofAtg5in myeloid cells (Atg5ΔMye) showed signs of dysbiosis prior to colitis and exhibited severe intestinal inflammation upon colitis induction that was characterized by increased IFNγ production. This increase in IFNγ was due to excess IL-12 secretion fromAtg5-deficient myeloid cells. Atg5 functions to limit IL-12 secretion through modulation of late endosome (LE) acidity. Additionally, the autophagy cargo receptor NBR1, which accumulates in Atg5-deficient cells, played a role by delivering IL-12 to LE. Restoration of the intestinal microbiota and alleviation of intestinal inflammation was achieved by genetic deletion of IL-12 in Atg5ΔMye mice. In summary, Atg5 expression in intestinal myeloid cells acts as an anti-inflammatory brake to regulate IL-12 thus preventing dysbiosis and uncontrolled IFNγ-driven intestinal inflammation.
Corpus callosum morphology across the lifespan in baboons (Papio anubis): a cross-sectional study of relative mid-sagittal surface area and thickness
Authors: Westerhausen René , Meguerditchian Adrien 
Published: December 2020

AbstractThe axons forming the corpus callosum enable integration and coordination of cognitive processing between the cerebral hemispheres. In the aging human brain, these functions are affected by progressive axon and myelin deteriorations, which results in a substantial atrophy of the midsagittal corpus callosum in old age. In non-human primates, these degenerative processes are less pronounced as previous morphometric studies on capuchin monkey, rhesus monkeys, and chimpanzees do not find old-age callosal atrophy. The objective of the present study was to extend these previous findings by studying the aging trajectory of the corpus callosum of the olive baboon (Papio anubis) across the lifespan. For this purpose, total relative (to forebrain volume) midsagittal area, subsectional area, and regional thickness of the corpus callosum was assessed in 91 male and female animals using non-invasive MRI-based morphometry. The studied age range was 2.5 to 26.6 years, and the sample included 11 old-age animals (above the age of 20 years). Fitting lifespan trajectories using general additive modelling (GAM) we found that the relative area of the total corpus callosum and the anterior subsection follow a positive linear trajectory. That is, both measures increased slowly but continuously from childhood into old age, and no stagnation of growth or decline was observed in old age. Thus, comparable with all other non-human primates studied to-date, baboons do not show callosal atrophy in old age. This observation lends supports to the notion that atrophy of the corpus callosum is a unique characteristic of human brain aging.
Easyreporting simplifies the implementation of Reproducible Research Layers in R software
Authors: Righelli Dario , Angelini Claudia 
Published: December 2020

AbstractDuring last years “irreproducibility” became a general problem in omics data analysis due to the use of sophisticated and poorly described computational procedures. For avoiding misleading results, it is necessary to inspect and reproduce the entire data analysis as a unified product. Reproducible Research (RR) provides general guidelines for public access to the analytic data and related analysis code combined with natural language documentation, allowing third-parties to reproduce the findings. We developedeasyreporting, a novel R/Bioconductor package, to facilitate the implementation of an RR layer inside reports/tools without requiring any knowledge of the R Markdown language. We describe the main functionalities and illustrate how to create an analysis report using a typical case study concerning the analysis of RNA-seq data. Then, we also show how to trace R functions automatically. Thanks to this latter feature,easyreportingresults beneficial for developers to implement procedures that automatically keep track of the analysis steps within Graphical User Interfaces (GUIs).Easyreportingcan be useful in supporting the reproducibility of any data analysis project and the implementation of GUIs. It turns out to be very helpful in bioinformatics, where the complexity of the analyses makes it extremely difficult to trace all the steps and parameters used in the study.
Concatemeric Broccoli reduces mRNA stability, aggregates and induces p-body formation
Authors: Rink Marco R. , Baptista Marisa A.P. , Hennig Thomas , Whisnant Adam W. , Wolf Natalia , Seibel Jürgen , Dölken Lars , Bosse Jens B. 
Published: December 2020

AbstractFluorogenic aptamers are an alternative to established methodology for real-time imaging of RNA transport and dynamics. We developed Broccoli-aptamer concatemers ranging from 4 to 128 substrate-binding site repeats and characterized their behavior fused to an mCherry-coding mRNA in transient transfection, stable expression, and in recombinant cytomegalovirus infection. Concatemerization of substrate-binding sites increased Broccoli fluorescence up to a concatemer length of 16 copies, upon which fluorescence did not increase and mCherry signals declined. This was due to the combined effects of RNA aptamer aggregation, a nuclear export defect and reduced RNA stability. Unfortunately, both cellular and cytomegalovirus genomes were unable to maintain and express high Broccoli concatemer copy numbers, possibly due to recombination events. Overexpression of Broccoli-tagged mRNA led to the formation of p-bodies. However, Broccoli RNAs did not localize to these sites. Interestingly, negative effects of Broccoli concatemers could be partially rescued by introducing linker sequences in between Broccoli repeats warranting further studies. Finally, we show that even though substrate-bound Broccoli is easily photobleached, it can still be utilized in live-cell imaging by adapting a time-lapse imaging protocol.
Scanning the rice Global MAGIC population for dynamic genetic control of seed traits under vegetative drought
Authors: Marrano Annarita , Moyers Brook T. 
Published: December 2020

AbstractGrain size and weight are important yield components in rice (Oryza sativaL.). There is still uncertainty about the genetic control of these traits under drought stress, the most pressing emerging issue in many rice cultivation areas. To address this lack of knowledge, we investigated the genetic architecture of seed size, shape, and weight using the rice Global Multi-parent Advanced Generation Intercross (MAGIC) population, grown under well-watered and vegetative drought conditions. We measured variation in seed size and shape with a new high-throughput phenotyping method based on a desktop scanner and the open-source package Plant Computer Vision (PlantCV). Besides being affordable, rapid, and accurate, our method captured the phenotypic divergence between drought and well-watered samples, expressed as 12 different traits that include traditional size metrics and new grain shape measures. Overall, under water deficit, the MAGIC lines produced smaller and shorter seeds. We identified ten MAGIC lines with traits that make them good candidates for the release of rice cultivars with high yield potential under vegetative drought stress. We ran a marker-trait association analysis for the measured seed-related traits. Most of the identified marker-trait associations showed strong genotype-by-environment interactions (GxE), with most allele effects being conditionally neutral. These results suggest dynamic genetic control of seed size, shape, and weight under vegetative drought stress in rice, highlighting the importance of understanding the contribution of GxE interactions on trait variation to develop resilient and high-yielding rice varieties. Our study confirms that combining low-cost and high-throughput phenotyping strategies with a diverse genetic material suited for multi-environmental trial provides solutions for adapting rice cultivation to current and future environmental adversities.
Cortical microtubule remodelling during strigolactone- and light-mediated growth inhibition of Arabidopsis hypocotyls
Authors: Krasylenko Yuliya A. , Komis George , Hlynska Sonya , Vavrdová Tereza , Ovečka Miroslav , Pospíšil Tomáš , Šamaj Jozef 
Published: December 2020

AbstractStrigolactones are phytohormones involved in shoot branching and hypocotyl elongation. The latter phenomenon was addressed herein by the exogenous application of a synthetic strigolactone GR24 and an inhibitor of strigolactone biosynthesis TIS108 on hypocotyls of wild type Arabidopsis and a strigolactone signalling mutantmax2-1 (more axillary growth 2-1). Owing to the interdependence between light and strigolactone signalling, the present work was extended to seedling cultivation under a standard light/dark regime, or under continuous darkness. Given the essential role of the cortical microtubules in cell elongation, their organization and dynamics were characterized under the conditions of altered strigolactone signalling using fluorescence microscopy methods with different spatiotemporal capacities such as confocal laser scanning microscopy and structured illumination microscopy. It was found that the strigolactone-dependent inhibition of hypocotyl elongation correlated with changes in cortical microtubule organization and dynamics, visualized in living wild type andmax2-1seedlings stably expressing genetically-encoded fluorescent molecular markers for microtubules. Quantitative analysis of microscopic datasets revealed that chemical and/or genetic manipulation of strigolactone signalling affected microtubule remodelling, especially under light conditions. The application of GR24 and TIS108 in dark conditions partially alleviated cytoskeletal rearrangement, suggesting a new mechanistic connection between the cytoskeletal behaviour and the light-dependence of strigolactone signalling.HighlightStrigolactones regulate organization and dynamics of cortical microtubules in hypocotyl cells, which contributes to the light-mediated inhibition of hypocotyl growth in Arabidopsis seedlings.
Electrophysiological characterization of human atria: the understated role of temperature
Authors: Majumder Rupamanjari , Mohamed Nazer Afnan Nabizath , Panfilov Alexander V. , Bodenschatz Eberhard , Wang Yong 
Published: December 2020

ABSTRACTAmbient temperature has a profound influence on cellular electrophysiology through direct control over the gating mechanisms of different ion channels. In the heart, low temperature is known to favour prolongation of the action potential. However, not much is known about the influence of temperature on other important characterisation parameters such as the resting membrane potential (RMP), excitability, morphology and characteristics of the action potential (AP), restitution properties, conduction velocity (CV) of signal propagation, etc. Here we present the first, detailed, systematicin silicostudy of the electrophysiological characterization of cardiomyocytes from different regions of the normal human atria, based on the effects of ambient temperature (5 −50°C). We observe that RMP decreases with increasing temperature. At ∼ 48°C, the cells lose their excitability. Our studies show that different parts of the atria react differently to the same changes in temperature. In tissue simulations a drop in temperature correlated positively with a decrease in CV, but the decrease was region-dependent, as expected. In this article we show how this heterogeneous response can provide an explanation for the development of a proarrhythmic substrate during mild hypothermia. We use the above concept to propose a treatment strategy for atrial fibrillation that involves severe hypothermia in specific regions of the heart for a duration of only ∼ 200ms.
Association of CD44−/CD24−Breast Cancer Cells with Late Stage Tumor Recurrence
Authors: Qiao Xinbo , Zhang Yixiao , Sun Lisha , Ma Qingtian , Yang Jie , Ai Liping , Xue Jinqi , Chen Guanglei , Zhang Hao , Ji Ce , Gu Xi , Lei Haixin , Yang Yongliang , Liu Caigang 
Published: December 2020

AbstractTumor metastasis remains the main cause of breast cancer-related deaths, especially the later breast cancer distant metastasis. This study assessed CD44−/CD24−tumor cells in 576 tissue specimens for associations with clinicopathological features and metastasis and then investigated the underlying molecular events. The data showed that level of CD44−/CD24−cells was associated with later postoperative distant tumor metastasis. Furthermore, CD44−/CD24−triple negative cells could spontaneously convert into CD44+/CD24−cancer stem cells (CSCs) with properties similar to CD44+/CD24−CSCs from parental MDA-MB-231 cells in terms of gene expression, tumor cell xenograft formation, and lung metastasisin vitroandin vivo. Single-cell RNA sequencing identified RHBDL2 as a regulator that enhanced spontaneous CD44+/CD24−CSC conversion, whereas knockdown of RHBDL2 expression inhibited YAP/NF-κB signaling and blocked spontaneous CD44−/CD24−cell conversion to CSCs. These data suggested that the level of CD44−/CD24−tumor cells could predict breast cancer prognosis, metastasis, and response to adjuvant therapy.
From letters to composed concepts: A magnetoencephalography study of reading
Authors: Flick Graham , Abdullah Osama , Pylkkänen Liina 
Published: December 2020

ABSTRACTLanguage comprehension requires the recognition of individual words and the combination of their meanings to yield complex concepts or interpretations. Rather than simple concatenation, this combinatory process often requires the insertion of unstated semantic material between words, based on thematic or feature knowledge of the concepts. For example, the phrasehorse barnis not interpreted as a blend of a horse and a barn, but specifically a barn in which horses are kept. Mounting evidence suggests two cortical semantic hubs, in left temporoparietal and anterior temporal cortex, underpin thematic and feature concept knowledge, but much remains unclear about how these putative hubs contribute to combinatory language processing. Using magnetoencephalography, we contrasted source-localized responses to modifier-noun phrases involving thematic relations vs. feature modifications, while also examining how lower-level orthographic processing fed into responses supporting word combination. Twenty-eight participants completed three procedures examining responses to letter-strings, adjective-noun phrases, and noun-noun combinations that varied the semantic relations between words. We found that while color + noun phrases engaged the left anterior temporal lobe (150-300 ms after phrasal head), posterior temporal lobe (150-300 ms), and angular gyrus (300-450 ms), only left posterior temporal lobe responses were sensitive to implicit thematic relations between composing nouns (150-300 ms). We additionally identified a left temporo-occipital progression from orthographic to lexical processing, feeding into ventral anterior areas engaged in the combination of word meanings. Finally, by examining source signal leakage, we characterized the degree to which these responses could be distinguished from one another, using linear source estimation.