bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-dimensional mapping identifies distinct vascular niches for myelopoiesis
Authors: Zhang Jizhou , Wu Qingqing , Johnson Courtney B. , Olsson Andre , Slaughter Anastasiya , May Margot , Weinhaus Benjamin , D’Alessandro Angelo , Engel James Douglas , Jiang Jean X. , Koffron J. Matthew , Huang L. Frank , Salomonis Nathan , Grimes H. Leighton , Lucas Daniel 
Published: April 2020

SummaryIn contrast to virtually all other tissues in the body the anatomy of differentiation in the bone marrow remains unknown. This is due to the lack of strategies to examine blood cell production in situ, which are required to better understand differentiation, lineage commitment decisions, and to define how spatial organizing cues inform tissue function. Here we developed imaging approaches to map all myeloid cells in whole bones and generated 3D atlases of granulocyte and monocyte/dendritic cell differentiation during homeostasis. We found that myeloid progenitors leave the hematopoietic stem cell niche during differentiation. Granulocyte and monocyte dendritic cell progenitors (MDP) do not interact, instead they localize to different sinusoids where they give rise to clusters of immature cells. MDP cluster with Ly6Clomonocytes and conventional dendritic cells; these localize to a unique subset of colony stimulating factor 1 (CSF1, the major regulator of monopoiesis1) -expressing sinusoids. Csf1 deletion in the vasculature disrupted the MDP clusters and their interaction with sinusoids, leading to reduced MDP numbers and differentiation ability, with subsequent loss of peripheral Ly6Clomonocytes and dendritic cells. These data indicate that there is a specific spatial organization of definitive hematopoiesis and that local cues produced by distinct blood vessels are responsible for this organization. These maps provide a blueprint for in situ analyses of hematopoiesis in blood disorders.
Invasion of epithelial cells are correlated with secretion of Biosurfactant via the type 3 secretion system (SST3) ofShigella flexneri
Authors: Kinavouidi Duchel Jeanedvi Kinouani , Kayath Christian Aimé , NGuimbi Etienne 
Published: April 2020

AbstractBiosurfactants are amphipathic molecules produced by many microorganisms, usually bacteria, fungi and yeasts. They possess the property of reducing the tension of the membrane interfaces. No studies have been conducted onShigellaspecies showing their involvement of biosurfactant like molecules (BLM) in pathogenicity. This study aims to show that environmental and clinical strains ofShigellaare able to produce BLM by emulsifying gasoline and diesel fuels. Our study has shown that BLM are secreted in the extracellular medium with EI24 ranging from 80 to 100%. The secretion is depending on the type III secretion system (T3SS). We did show thatS. flexneri,S. boydiiandS. sonneiare able to interact with hydrophobic areas with respectively 17.64%, 21.42% and 22.22% of hydrophobicity. 100 mM Benzoic and 1.5mg/mL Salycilic acids have been inhibited T3SS and this totally stops the BLM secretion.Pseudomonas aeruginosawhich has T3SS is able to produce 100% of BLM in the presence or in the absence of both T3SS inhibitors. The secreted BLM is extractable with an organic solvent such as chloroform and could entirely be considered like lipopeptide or polypeptidic compound. By secreting BLM,Shigellais able to perform multicellular phenomena like “swarming” allowing to invade and disseminate inside epithelial cells.
Geometric differences between nuclear envelopes of Wild-type and Chlamydia trachomatis-infected HeLa cells
Authors: Karabağ Cefa , Jones Martin L. , Peddie Christopher J. , Weston Anne E. , Collinson Lucy M. , Reyes-Aldasoro Constantino Carlos 
Published: April 2020

AbstractIn this work, the geometrical characteristics of two different types of cells observed with Electron Microscopy were analysed. The nuclear envelope of Wild-type HeLa cells and Chlamydia trachomatis-infected HeLa cells were automatically segmented and then modelled against a spheroid and converted to a two-dimensional surface. Geometric measurements from this surface and the volumetric nuclear envelope were extracted to compare the two types of cells. The measurements included the nuclear volume, the sphericity of the nucleus, its flatness or spikiness. In total 13 different cells were segmented: 7 Wild-type and 6 Chlamydia trachomatis-infected. The cells were statistically different in the following measurements. Wild-type HeLa cells have greater volumes than that of Chlamydia trachomatis-infected HeLa cells and they are more spherical as Jaccard index suggests. Standard deviation (σ), and range of values for the nuclear envelope, which shows the distance of the highest peaks and deepest valleys from the spheroid, were also extracted from the modelling against a spheroid and these metrics were used to compare two different data sets in order to draw conclusions.
Linking Activity in Human Superior Temporal Cortex to Perception of Noisy Audiovisual Speech
Authors: Rennig Johannes , Beauchamp Michael S 
Published: April 2020

AbstractRegions of the human posterior superior temporal gyrus and sulcus (pSTG/S) respond to the visual mouth movements that constitute visual speech and the auditory vocalizations that constitute auditory speech. We hypothesized that these multisensory responses in pSTG/S underlie the observation that comprehension of noisy auditory speech is improved when it is accompanied by visual speech. To test this idea, we presented audiovisual sentences that contained either a clear auditory component or a noisy auditory component while measuring brain activity using BOLD fMRI. Participants reported the intelligibility of the speech on each trial with a button press. Perceptually, adding visual speech to noisy auditory sentences rendered them much more intelligible. Post-hoc trial sorting was used to examine brain activations during noisy sentences that were more or less intelligible, focusing on multisensory speech regions in the pSTG/S identified with an independent visual speech localizer. Univariate analysis showed that less intelligible noisy audiovisual sentences evoked a weaker BOLD response, while more intelligible sentences evoked a stronger BOLD response that was indistinguishable from clear sentences. To better understand these differences, we conducted a multivariate representational similarity analysis. The pattern of response for intelligible noisy audiovisual sentences was more similar to the pattern for clear sentences, while the response pattern for unintelligible noisy sentences was less similar. These results show that for both univariate and multivariate analyses, successful integration of visual and noisy auditory speech normalizes responses in pSTG/S, providing evidence that multisensory subregions of pSTG/S are responsible for the perceptual benefit of visual speech.Significance StatementEnabling social interactions, including the production and perception of speech, is a key function of the human brain. Speech perception is a complex computational problem that the brain solves using both visual information from the talker’s facial movements and auditory information from the talker’s voice. Visual speech information is particularly important under noisy listening conditions when auditory speech is difficult or impossible to understand alone Regions of the human cortex in posterior superior temporal lobe respond to the visual mouth movements that constitute visual speech and the auditory vocalizations that constitute auditory speech. We show that the pattern of activity in cortex reflects the successful multisensory integration of auditory and visual speech information in the service of perception.
Messenger RNA levels of enzymes involved in glycerolipid synthesis in the brain of the mouse and its alterations inAgpat2-/-and db/db mice
Authors: González-Hódar Lila , Agarwal Anil K. , Cortés Víctor 
Published: April 2020

AbstractAimsExpression of genes encoding enzymes involved in glycerolipid and monoacylglycerol pathways in specific brain regions is poorly known and its impact in insulin resistance (IR) and type 2 diabetes (T2D) in the brain remains unreported. We determined mRNA levels of enzymes involved in glycerolipid synthesis in different regions of the mouse brain and evaluated their changes in two models of IR and T2D, theAgpat2-/-andLeprdb/dbmice.MethodsCerebral cortex, hypothalamus, hippocampus and cerebellum were dissected from adultAgpat2-/-mice,Leprdb/dbmice and their respective wild type littermates. Total RNA was isolated and mRNA abundance was measured by RT-qPCR.Key findingsGPAT1, AGPAT1-4, LIPIN1/2, DGAT1/2 and MOGAT1 mRNAs were detected in all studied brain regions, whereas GPAT2, LIPIN3 and MOGAT2 were undetectable. Abundance of AGPATs, LIPIN1 and DGAT1, was higher in cerebellum and hypothalamus. LIPIN2 and MOGAT1 levels were higher in hypothalamus, and DGAT2 was higher in cortex and hypothalamus. InAgpat2-/-mice, LIPIN1 levels were increased in all the brain regions. By contrast, GPAT1 in cortex and hypothalamus, AGPAT3 in hippocampus and hypothalamus, AGPAT4 in hypothalamus, and MOGAT1 in cortex, hypothalamus and cerebellum were lower inAgpat2-/-mice.Leprdb/dbmice showed fewer and milder changes, with increased levels of GPAT1 and LIPIN1 in cerebellum, and AGPAT3 in hypothalamus.Conclusions and SignificanceEnzymes of glycerolipids synthesis are differentially expressed across regions of the mouse brain. Two mouse models of IR and T2D have altered gene expression of glycerolipid enzymes in the brain.
DNA replication and chromosome positioning throughout the interphase in three dimensional space of plant nuclei
Authors: Alžběta Němečková , Koláčková Veronika , Jan Vrána , Jaroslav Doležel , Eva Hřibová 
Published: April 2020

AbstractDespite the recent progress, our understanding of the principles of plant genome organization and its dynamics in three-dimensional space of interphase nuclei remains limited. In this study, DNA replication timing and interphase chromosome positioning was analyzed in sevenPoaceaespecies differing in genome size. A multidisciplinary approach combining newly replicated DNA labelling by EdU, nuclei sorting by flow cytometry, three-dimensional immuno-FISH, and confocal microscopy revealed similar replication timing order for telomeres and centromeres as well as for euchromatin and heterochromatin in all seven species. The Rabl configuration of chromosomes that lay parallel to each other and their centromeres and telomeres are localized at opposite nuclear poles, was observed in wheat, oat, rye and barley with large genomes, as well as inBrachypodiumwith a small genome. On the other hand, chromosomes of rice with a small genome and maize with relatively large genome did not assume proper Rabl configuration. In all species, the interphase chromosome positioning inferred from the location of centromeres and telomeres was stable throughout the interphase. These observations extend earlier studies indicating a more complex relation between genome size and interphase chromosome positioning, which is controlled by factors currently not known.HighlightTelomere and centromere replication timing and interphase chromosome positioning in seven grass species differing in genome size indicates a more complex relation between genome size and the chromosome positioning.
Testing and Correcting for Weak and Pleiotropic Instruments in Two-Sample Multivariable Mendelian Randomisation
Authors: Sanderson Eleanor , Spiller Wes , Bowden Jack 
Published: April 2020

AbstractMultivariable Mendelian Randomisation (MVMR) is a form of instrumental variable analysis which estimates the direct effect of multiple exposures on an outcome using genetic variants as instruments. Mendelian Randomisation and MVMR are frequently conducted using two-sample summary data where the association of the genetic variants with the exposures and outcome are obtained from separate samples. If the genetic variants are only weakly associated with the exposures either individually or conditionally, given the other exposures in the model, then standard inverse variance weighting will yield biased estimates for the effect of each exposure. Here we develop a two-sample conditional F-statistic to test whether the genetic variants strongly predict each exposure conditional on the other exposures included in a MVMR model. We show formally that this test is equivalent to the individual level data conditional F-statistic, indicating that conventional rule-of-thumb critical values of F > 10, can be used to test for weak instruments. We then demonstrate how reliable estimates of the causal effect of each exposure on the outcome can be obtained in the presence of weak instruments and pleiotropy, by re-purpousing a commonly used heterogeneity Q-statistic as an estimating equation. Furthermore, the minimised value of this Q-statistic yields an exact test for heterogeneity due to pleiotropy. We illustrate our methods with an application to estimate the causal effect of blood lipid fractions on age related macular degeneration.
TheArabidopsisNOT4A E3 ligase coordinates PGR3 expression to regulate chloroplast protein translation
Authors: Bailey Mark , Ivanauskaite Aiste , Grimmer Julia , Akintewe Oluwatunmise , Payne Adrienne C. , Etherington Ross , Labandera Anne-Marie , Osborne Rory , Rantala Marjaana , Baginsky Sacha , Mulo Paula , Gibbs Daniel J. 
Published: April 2020

AbstractChloroplast function requires the coordinated action of nuclear- and chloroplast-derived proteins, including several hundred nuclear-encoded pentatricopeptide repeat (PPR) proteins that regulate plastid mRNA metabolism. Despite their large number and importance, regulatory mechanisms controlling PPR expression are poorly understood. Here we show that the Arabidopsis NOT4A ubiquitin-ligase positively regulates PROTON GRADIENT 3 (PGR3), a PPR protein required for translating 30S ribosome subunits and several thylakoid-localised photosynthetic components within chloroplasts. Loss of NOT4A function leads to a strong depletion of plastid ribosomes, which reduces mRNA translation and negatively impacts photosynthetic capacity, causing pale-yellow and slow-growth phenotypes. Quantitative transcriptome and proteome analyses reveal that these defects are due to a lack of PGR3 expression innot4a, and we show that normal plastid function is restored through transgenic PGR3 expression. Our work identifies NOT4A as crucial for ensuring robust photosynthetic function during development and stress-response, through modulating PGR3 levels to coordinate chloroplast protein synthesis.
Activation of silent secondary metabolite gene clusters by nucleosome map-guided positioning of the synthetic transcription factor VPR-dCas9
Authors: Schüller Andreas , Wolansky Lisa , Berger Harald , Studt Lena , Gacek-Matthews Agnieszka , Sulyok Michael , Strauss Joseph 
Published: April 2020

AbstractCurrent methods for forced expression of selected target genes are based on promoter exchange or on overexpressing native or hybrid transcriptional activators in which gene-specific DNA binding domains are coupled to strong activation domains. While these approaches are very useful for promoters with known or synthetically introduced transcription factor binding sites, they are not suitable to turn on genes in biosynthetic gene clusters which often lack pathway-specific activators. To expand the discovery toolbox, we designed a Cas9-based RNA guided synthetic transcription activation system forAspergillus nidulansbased on enzymatically disabled dCas9 fused to three consecutive activation domains (VPR-dCas9). Targeting two biosynthetic gene clusters involved in the production of secondary metabolites, we demonstrate the utility of the system. Especially in silent regions facultative heterochromatin and strictly positioned nucleosomes can constitute a relevant obstacle to the transcriptional machinery. To avoid this negative impact and to facilitate optimal positioning of RNA-guided VPR-dCas9 to our targeted promoters we have created a genome-wide nucleosome map to identify the cognate nucleosome-free-regions (NFRs). Based on these maps, different single-guide RNAs (sgRNA) were designed and tested for their targeting and activation potential. Our results demonstrate that the system can be used to activate silent BGCs inA. nidulans, partially to very high expression levels and also open the opportunity to stepwise turn on individual genes within a BGC that allows to decipher the correlated biosynthetic pathway.
Immunity to infections in arboviral vectors by integrated viral sequences: an evolutionary perspective
Authors: Crava Cristina , Varghese Finny S. , Pischedda Elisa , Halbach Rebecca , Palatini Umberto , Marconcini Michele , Mattia Annamaria , Redmond Seth , Afrane Yaw , Ayala Diego , Paupy Christophe , Carballar-Lejarazu Rebeca , Miesen Pascal , van Rij Ronald P. , Bonizzoni Mariangela 
Published: April 2020

ABSTRACTIn the model organismDrosophila melanogaster, the PIWI-interacing RNA pathway contributes in silencing transposable elements (TEs) through smallRNAs (piRNAs), which arise from genomic loci (piRNA clusters) that contain sequences of previously-acquired TEs. As such, they are a functionally-immune archive of previous TE invasions that is passed to the offspring. In the arboviral vectorAedes aegypti, piRNA clusters contain TEs and endogenous viral elements from nonretroviral RNA viruses (nrEVEs) which produce piRNAs, supporting the hypothesis that nrEVEs are heritable immunity effectors. However, direct evidence that nrEVEs mediate adaptive immunity is lacking. Here, by using an analytic approach intersecting population genomics with molecular biology we demonstrate that the composition of piRNA clusters is modular through acquisition and absence of nrEVEs. We show that the genomes of wild-caught mosquitoes have a different set of nrEVEs than those annotated in the reference genome, including population-specific integrations. nrEVEs are not distributed in mosquito genomes only by genetic drift, but some show signs of positive selection. Moreover, by comparing natural mosquito populations expressing or lacking two newly characterised nrEVEs with high sequence complementarity to cell fusing agent virus, we show that nrEVEs confer antiviral immunity in ovaries against the cognate virus. Our results confirm that some nrEVEs have been co-opted for adaptive immunity to viral infections.
Pangaea: A modular and extensible collection of tools for mining context dependent gene relationships from the biomedical literature
Authors: Pirvan Liviu , Samarajiwa Shamith A. 
Published: April 2020

AbstractMotivationPangaea is a scalable and extensible command line interface (CLI) software that integrates gene-relationship detection features to extract context-dependent structured gene-gene and gene-term relationships from the biomedical literature. It provides computational methods to identify biological relationships between a collection of genes and can be used to search and extract different types of contextual relationships amongst genes.ResultsWe implemented a CLI-based software for downloading PubMed articles and extracting gene relationships from abstracts using natural language processing methods. In terms of scalability, the software was designed to support the retrieval and processing of millions of articles whilst minimising memory requirements and optimising for parallel processing on multiple CPU cores. To allow extensibility, the tool permits the use of contextual custom-made models for the text processing parts, and the output is serialised as JSON objects to allow flexible post-processing workflows.AvailabilityThe software is available online at:https://github.com/ss-lab-cancerunit/pangaea
Multivoxel Neural Reinforcement Changes Resting-State Functional Connectivity Within the Threat Regulation Network
Authors: Taschereau-Dumouchel Vincent , Chiba Toshinori , Koizumi Ai , Kawato Mitsuo , Lau Hakwan 
Published: April 2020

AbstractUsing neural reinforcement, participants can be trained to pair a reward with the activation of specific multivoxel patterns in their brains. In a double-blind placebo-controlled experiment, we previously showed that this intervention can decrease the physiological reactivity associated with naturally feared animals. However, the mechanisms behind the effect remain incompletely understood and its usefulness for treatment remains unclear. If the intervention fundamentally changed the brain responses, we might expect to observe relatively stable changes in the functional connectivity within the threat regulation network. To evaluate this possibility, we conducted functional magnetic resonance imaging (fMRI) sessions while subjects were at rest, before and after neural reinforcement, and quantified the changes in resting-state functional connectivity accordingly. Our results indicate that neural reinforcement increased the connectivity of prefrontal regulatory regions with the amygdala and the ventral temporal cortex (where the visual representations of phobic targets are). Surprisingly, we found no evidence of Hebbian-like learning during neural reinforcement, contrary to what one may expect based on previous neurofeedback studies. These results suggest that multivoxel neural reinforcement, also known as decoded neurofeedback (DecNef), may operate via unique mechanisms, distinct from those involved in conventional neurofeedback.
Ethical leadership and organizational cynicism: the mediating role of leader-member exchange and organizational identification
Authors: Qian Yuxia , Jian Guowei 
Published: April 2020

PurposeThis study aims to construct and empirically test a theoretical model of a mediated relationship between ethical leadership and organizational cynicism.Design/methodology/approachFrom a communication perspective, this study examines the underlying mechanism of the association between ethical leadership and organizational cynicism. A cross-sectional survey was sent to participants in different occupations. Path analysis was used to test the overall model fit.FindingsThe results indicate that ethical leadership has both a direct and indirect effect on organizational cynicism through the mediating role of leader-member exchange (LMX) and organizational identification. However, a surprising finding is that the mediating mechanisms of LMX and organizational identification are not in a parallel structure, but in a serial pattern. That is, the mediating role of LMX is further mediated by organizational identification.Originality/valueThis study contributes to the literature in several aspects. First, the study sheds light on leadership as an important source of organizational cynicism. In particular, the theoretical model presents pathways that show how the predictive effects of ethical leadership on organizational cynicism are mediated through leader-member relationships and organizational identification. Second, the theoretical analysis on the mediating process highlights the role of communication in facilitating the influence of leadership and constructing organizational identification. Third, the mediating model offers concrete guidance for organizations in their attempt to mitigate organizational cynicism.