bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plexin-B2 is a key regulator of cell mechanics during multicellular organization
Authors: Junqueira Alves Chrystian , Dariolli Rafael , Hannah Theodore , Wiener Robert J. , Daviaud Nicolas , Tejero Rut , Gusella G. Luca , Tsankova Nadejda M. , Dias Rodrigo Alves , Furtado de Mendonça José Paulo R. , Azeloglu Evren U. , Friedel Roland H. , Zou Hongyan 
Published: October 2019

SUMMARYDuring multicellular organization, individual cells need to constantly respond to environmental cues and adjust contractile and adhesive forces in order to maintain tissue integrity. The signaling pathways linking biochemical cues and tissue mechanics are unclear. Here, we show that Plexin-B2 regulates mechanochemical integration during multicellular organization. In human embryonic stem cells (hESCs), Plexin-B2 controls cell shape and tissue geometry in both 2D epithelial colony and 3D spheroid aggregates by regulating actomyosin contractility and junctional/cell-matrix adhesive properties. Atomic force microscopy (AFM) directly demonstrates that Plexin-B2 modulates cell stiffness in hESC colonies, which in turn impacts cell proliferation and cell fate specification through β-catenin signaling and YAP mechanosensing. YAP also functions as a mechanoregulator downstream of Plexin-B2, thus forming a mechanochemical integrative loop. In human neuroprogenitor cells (hNPCs), Plexin-B2 similarly controls cell stiffness and tensile forces, as revealed by AFM and FRET tension sensor studies. Strikingly, Plexin-B2-deficient hNPCs display accelerated neuronal differentiation. From an organogenesis perspective, Plexin-B2 maintains cytoarchitectural integrity of neuroepithelium, as modeled in cerebral organoids. On a signaling level, Plexin-B2 engages extracellular as well as intracellular Ras-GAP and RBD domains for mechanoregulation through Rap and Rac GTPases. Our data unveil a fundamental function of Plexin-B2 for mechanochemical integration during multicellular organization, and shed light on the principle of force-mediated regulation of stem cell biology and tissue morphogenesis.
Alanine, arginine, and proline but not glutamine are the feed-back regulators in the liver-alpha cell axis in mice
Authors: Galsgaard Katrine D. , Jepsen Sara Lind , Kjeldsen Sasha A.S. , Pedersen Jens , Wewer Albrechtsen Nicolai J. , Holst Jens J. 
Published: October 2019

AbstractAimTo identify the amino acids that stimulate glucagon secretion in mice and whether the metabolism of these relies on glucagon receptor signaling.MethodsPancreata of female C57BL/6JRj mice were perfused with 19 individual amino acids (1 mM) and secretion of glucagon was assessed using a specific glucagon radioimmunoassay. Separately, a glucagon receptor antagonist (GRA; 25-2648, 100 mg/kg) or vehicle was administered to female C57BL/6JRj mice three hours prior to an intraperitoneal injection of four different isomolar (in total 7 µmol/g body weight) amino acid mixtures; mixture 1: alanine, arginine, cysteine, and proline; mixture 2: asparatate, glutamate, histidine, and lysine; mixture 3: citrulline, methionine, serine, and threonine; and mixture 4: glutamine, leucine, isoleucine, and valine. Blood glucose, plasma glucagon, amino acid, and insulin concentrations were measured using well characterized methodologies.ResultsAlanine (P=0.03), arginine (P<0.001), and proline (P=0.03) but not glutamine (P=0.2) stimulated glucagon secretion from the perfused mouse pancreas. Cysteine had the numerically largest effect on glucagon secretion but did not reach statistical significance (P=0.08). However, when the four isomolar amino acid mixtures were administered there were no significant difference (P>0.5) in plasma concentrations of glucagon across mixture 1-4. Plasma concentrations of total amino acids were higher after administration of GRA when mixture 1 (P=0.004) or mixture 3 (P=0.04) were injected.ConclusionOur data suggest that alanine, arginine, and proline but not glutamine are involved in the liver-alpha cell axis in mice as they all increased glucagon secretion and their disappearance rate was altered by GRA.Graphical abstract
Abrogation of pathogenic attributes in drug resistantCandida aurisstrains by farnesol
Authors: Srivastava Vartika , Ahmad Aijaz 
Published: October 2019

AbstractCandida auris, a decade oldCandidaspecies, has been identified globally as a significant nosocomial multidrug resistant (MDR) pathogen responsible for causing invasive outbreaks. Biofilms and overexpression of efflux pumps such as Major Facilitator Superfamily and ATP Binding Cassette are known to cause multidrug resistance inCandidaspecies, includingC. auris. Therefore, targeting these factors may prove an effective approach to combat MDR inC. auris. In this study, 25 clinical isolates ofC. aurisfrom different hospitals of South Africa were used. All the isolates were found capable enough to form biofilms on 96-well microtiter plate that was further confirmed by MTT reduction assay. In addition, these strains have active drug efflux mechanism which was supported by rhodamine-6-G extracellular efflux and intracellular accumulation assays. Antifungal susceptibility profile of all the isolates against commonly used drugs was determined following CLSI recommended guidelines. We further studied the role of farnesol, an endogenous quorum sensing molecule, in modulating development of biofilms and drug efflux inC. auris. The MIC for planktonic cells ranged from 62.5-125 mM and for sessile cells was 125 mM (0 h and 4 h biofilm) and 500 mM (12 h and 24 h biofilm). Farnesol inhibited biofilm formation, blocked efflux pumps and downregulated biofilm- and efflux pump-associated genes. Modulation ofC. aurisbiofilm formation and efflux pump activity by farnesol represent a promising approach for controlling life threatening infections caused by this pathogen.
Single-cell transcriptome profiling reveals neutrophil heterogeneity and orchestrated maturation during homeostasis and bacterial infection
Authors: Xie Xuemei , Shi Qiang , Wu Peng , Zhang Xiaoyu , Kambara Hiroto , Su Jiayu , Yu Hongbo , Park Shin-Young , Guo Rongxia , Ren Qian , Zhang Sudong , Xu Yuanfu , Silberstein Leslie E. , Cheng Tao , Ma Fengxia , Li Cheng , Luo Hongbo R. 
Published: October 2019

SummaryThe full neutrophil heterogeneity and differentiation landscape remains incompletely characterized. Here we profiled >25,000 differentiating and mature mouse neutrophils using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of neutrophil maturation, function, and fate decision in their steady state and during bacterial infection. Eight neutrophil populations were defined by distinct molecular signatures. The three mature peripheral blood neutrophil subsets arise from distinct maturing bone marrow neutrophil subsets. Driven by both known and uncharacterized transcription factors, neutrophils gradually acquire microbicidal capability as they traverse the transcriptional landscape, representing an evolved mechanism for fine-tuned regulation of an effective but balanced neutrophil response. Bacterial infection reprograms the genetic architecture of neutrophil populations, alters dynamic transition between each subpopulation, and primes neutrophils for augmented functionality without affecting overall heterogeneity. In summary, these data establish a reference model and general framework for studying neutrophil-related disease mechanisms, biomarkers, and therapeutic targets at single-cell resolution.Graphical AbstractHighlightsA comprehensive single-cell resolution transcriptional landscape of mouse neutrophil maturation and fate decision under steady-state and bacterial infection conditions.The pathogen clearance machinery in neutrophils is continuously and gradually built during neutrophil differentiation, maturation, and aging, driven by both known and uncharacterized transcription factors.The three mature neutrophil subsets in peripheral blood, including a novel ISG-expressing subset, are derived from distinct bone marrow neutrophil precursors.Bacterial infection reprograms the genetic architecture of neutrophil populations, alters dynamic transition between each subpopulation, and primes neutrophils for augmented functionality without affecting overall neutrophil heterogeneity.Bacterial infection-induced emergency granulopoiesis is mediated by augmented proliferation of early stage neutrophil progenitors and accelerated post-mitotic maturation.
Bulked segregant RNA-Seq reveals differential genes and non-synonymous genetic variants linked to sucrose accumulation in sugarcane
Authors: Banerjee Nandita , Kumar Sanjeev , Annadurai A. , Singh P. K , Singh J. , Singh R.K. , Kumar Sanjeev 
Published: October 2019

AbstractSucrose is the key economic trait in sugarcane which is a highly polyploid multi-species hybrid and shows a complex pattern of trait inheritance. The excessively large genome of sugarcane is comparatively less explored through Next Generation Sequencing tools for creating superior varieties. In this study, RNAseq libraries of two extreme bulks from a segregating full-sib population and its parents were used to identify 9905 condition-specific non-synonymous genetic variants (NSVs), out of which 43 had a very high degree of differential enrichment (Δf >0.5) for contrasting sucrose accumulating conditions. The statistical model used in this study which was able to quantify the relative effect of NSVs on the trait detected highly significant positive and negative effect NSVs located in the coding regions of genes involved in sucrose metabolism, photosynthesis, mitochondrial electron transport, glycolysis and transcription. In addition, a few differential pre-mature stop codons that could result in production of truncated proteins were also detected in genes coding for aquaporin, GAPDH, aldolase, cytochrome C-oxidase, chlorophyll synthase and plant plasma membrane intrinsic proteins. Additionally, a total of 2140 differentially expressed genes (DEGs) linked to high sucrose accumulation were identified. Among the DEGs, sucrose phosphate synthase III, genes involved in transport, auxin signal transduction, etc., were upregulated, while those involved in electron transfer, cytochrome P450, etc., were downregulated in high sucrose accumulation conditions. This study was able to give finer insights in to the role of allelic heterozygosity on sucrose accumulation and the identified NSVs and DEGs could be useful as candidate markers in marker-assisted breeding for developing high sugar varieties.
Chromosome-wide distribution and characterization of intersubspecific meiotic noncrossovers in mice
Authors: Gergelits Vaclav , Parvanov Emil , Simecek Petr , Forejt Jiri 
Published: October 2019

AbstractDuring meiosis, the recombination-initiating DNA double-strand breaks (DSBs) are repaired by crossovers or noncrossovers (gene conversions). While crossovers are easily detectable, the noncrossover identification is hampered by the small size of their converted tracts and the necessity of sequence polymorphism to detect them. We report identification and characterization of a mouse chromosome-wide set of noncrossovers by NGS sequencing of 10 mouse chromosome substitution strains. Based on 94 identified noncrossovers we determined the mean length of a conversion tract to be 32 basepairs. The spatial chromosome-wide distribution of noncrossovers and crossovers significantly differed, though both sets overlapped the known hotspots of PRDM9-directed histone methylation and DNA DSBs, thus proving their origin in the standard DSB repair pathway. A significant deficit of noncrossovers descending from asymmetric DSBs pointed to sister chromatids as an alternative template for their repair. The finding has implications for the molecular mechanism of hybrid sterility in mice.
Reducing shade avoidance can improve Arabidopsis canopy performance against competitors
Authors: Pantazopoulou Chrysoula K. , Bongers Franca J. , Pierik Ronald 
Published: October 2019

AbstractThe loss of crop yield due to weeds is an urgent agricultural problem. Although herbicides are an effective way to control weeds, more sustainable solutions for weed management are desirable. It has been proposed that crop plants can communally suppress weeds by shading them out. Shade avoidance responses, such as upward leaf movement (hyponasty) and stem or petiole elongation, enhance light capture of individual plants, increasing their individual fitness. The shading capacity of the entire crop community might, however, be more effective if aspects of shade avoidance are suppressed. Testing this hypothesis in crops is hampered by the lack of well-characterized mutants. We therefore investigated if Arabidopsis competitive performance at the community level against invading competitors is affected by the ability to display shade avoidance. We tested two mutants: pif4pif5 that has mildly reduced petiole elongation and hyponasty and pif7 with normal elongation but absent hyponasty in response to shade. Although pif4pif5 performed similar to wildtype, we found that pif7 showed significantly increased canopy biomass and suppression of invading competitors as compared to its wildtype. Our data thus show that modifying specific shade avoidance aspects has potential for plant community performance. This may help to suppress weeds in crop stands.HighlightHyponastic response in canopies facilitates light penetration and weed growth. Inhibition of this response to neighbors increased canopy biomass, canopy closure and suppression of competitors.
Elevated CO2and warming change the nutrient status and use efficiency ofPanicum maximumJacq
Authors: Carvalho Juliana Mariano , de Mello Prado Renato , Barreto Rafael Ferreira , Habermann Eduardo , Branco Roberto Botelho Ferraz , Martinez Carlos Alberto 
Published: October 2019

AbstractPanicum maximumJacq. ‘Mombaça’ (guinea grass) is a C4forage grass widely used in tropical pastures for cattle feeding. In this study, we evaluated the isolated and combined effects of warming and elevated CO2concentration [CO2] during summer on the nutrient content, nutrient accumulation, nutrient use efficiency and growth ofP. maximumunder field conditions with adequate water supply. The temperature and [CO2] in the field were controlled by temperature free-air controlled enhancement and free-air CO2enrichment systems, respectively. We tested two levels of canopy temperature: ambient temperature and 2°C above ambient temperature, as well as two levels of atmospheric [CO2]: ambient [CO2] (aCO2) and 200 ppm above ambient CO2(eCO2). The experiment was established in a completely randomised design with four replications, in a 2×2 factorial scheme. After the pasture establishment, plants were exposed to the treatments for 30 days, with evaluations at 9, 16, 23 and 30 days after the treatments started. Results were dependent on the time of the evaluation, but in the last evaluation (beginning of the grazing), contents of N, K, Mg and S did not change as a function of treatments, P decreased as a function of warming, in [aCO2] and [eCO2], and Ca increased under [eCO2] combined with warming. There was an increase in root dry mass under warming treatment. Combined treatment increased N, Ca and S accumulation without a corresponding increase in the use efficiency of these same nutrients, indicating that the fertiliser dose should increase in the next decades due to human-induced climate change. Our short-term results suggest that the combination of high [CO2] and temperature will increaseP. maximumproductivity and that the nutritional requirement for N, Ca and S will increase.
Aberrant connectivity in auditory precision encoding in schizophrenia spectrum disorder and across the continuum of psychotic-like experiences
Authors: Larsen Kit Melissa , Dzafic Ilvana , Darke Hayley , Pertile Holly , Carter Olivia , Sundram Suresh , Garrido Marta I. 
Published: October 2019

AbstractBackgroundThe ability to generate a precise internal model of statistical regularities is impaired in schizophrenia. Predictive coding accounts of schizophrenia suggest that psychotic symptoms may be explained by a failure to build precise beliefs or a model of the world. The precision of this model may vary with context. For example, in a noisy environment the model will be more imprecise compared to a model built in an environment with lower noise. However compelling, this idea has not yet been empirically studied in schizophrenia. Methods: In this study, 62 participants engaged in a stochastic mismatch negativity paradigm with high and low precision. We included inpatients with a schizophrenia spectrum disorder (N=20), inpatients with a psychiatric disorder but without psychosis (N=20), and healthy controls (N=22), with comparable sex ratio and age distribution. Bayesian mapping and dynamic causal modelling were employed to investigate the underlying microcircuitry of precision encoding of auditory stimuli. Results: We found strong evidence (exceedance p > 0.99) for differences in the underlying connectivity associated with precision encoding between the three groups as well as on the continuum of psychotic-like experiences assessed across all participants. Critically, we show changes in interhemispheric connectivity between the two inpatient groups, with some connections further aligning on the continuum of psychotic-like experiences. Conclusions: While our results suggest continuity in backward connectivity alterations with psychotic-like experiences regardless of diagnosis, they also point to specificity for the schizophrenia spectrum disorder group in interhemispheric connectivity alterations.
B cells extract antigens using Arp2/3-generated actin foci interspersed with linear filaments
Authors: Roper Sophie I. , Wasim Laabiah , Malinova Dessislava , Way Michael , Cox Susan , Tolar Pavel 
Published: October 2019

AbstractAntibody production depends on B cell internalization and presentation of antigens to helper T cells. To acquire antigens displayed by antigen-presenting cells, B cells form immune synapses and extract antigens by the mechanical activity of the acto-myosin cytoskeleton. While cytoskeleton organization driving the initial formation of the B cell synapse has been studied, how the cytoskeleton supports antigen extraction remains poorly understood. Here we show that after initial cell spreading, F-actin in B cell synapses forms a highly dynamic pattern composed of actin foci interspersed with linear filaments and myosin IIa. The foci are generated by Arp2/3-mediated branched-actin polymerization and stochastically associate with antigen clusters to mediate internalization. However, antigen extraction also requires the activity of formins, which reside near the foci and produce the interspersed filaments. Thus, a cooperation of branched-actin foci supported by linear filaments underlies B cell mechanics during antigen extraction.
Gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure
Authors: Zrimec Jan , Buric Filip , Muhammad Azam Sheikh , Chen Rhongzen , Verendel Vilhelm , Töpel Mats , Zelezniak Aleksej 
Published: October 2019

AbstractUnderstanding the genetic regulatory code that governs gene expression is a primary, yet challenging aspiration in molecular biology that opens up possibilities to cure human diseases and solve biotechnology problems. However, the fundamental question of how each of the individual coding and non-coding regions of the gene regulatory structure interact and contribute to the mRNA expression levels remains unanswered. Considering that all the information for gene expression regulation is already present in living cells, here we applied deep learning on over 20,000 mRNA datasets in 7 model organisms ranging from bacteria to Human. We show that in all organisms, mRNA abundance can be predicted directly from the DNA sequence with high accuracy, demonstrating that up to 82% of the variation of gene expression levels is encoded in the gene regulatory structure. Coding and non-coding regions carry both overlapping and orthogonal information and additively contribute to gene expression levels. By searching for DNA regulatory motifs present across the whole gene regulatory structure, we discover that motif interactions can regulate gene expression levels in a range of over three orders of magnitude. The uncovered co-evolution of coding and non-coding regions challenges the current paradigm that single motifs or regions are solely responsible for gene expression levels. Instead, we show that the correct combination of all regulatory regions must be established in order to accurately control gene expression levels. Therefore, the holistic system that spans the entire gene regulatory structure is required to analyse, understand, and design any future gene expression systems.
No evidence for motion dazzle in an evolutionary citizen science game
Authors: Hughes Anna E. , Griffiths David , Troscianko Jolyon , Kelley Laura A. 
Published: October 2019

AbstractThe motion dazzle hypothesis posits that high contrast geometric patterns can cause difficulties in tracking a moving target, and has been argued to explain the patterning of animals such as zebras. Research to date has only tested a small number of patterns, offering equivocal support for the hypothesis. Here, we take a genetic programming approach to allow patterns to evolve based on their fitness (time taken to capture) and thus find the optimal strategy for providing protection when moving. Our ‘Dazzle Bug’ citizen science game tested over 1.5 million targets in a touch screen game at a popular visitor attraction. Surprisingly, we found that targets lost pattern elements during evolution and became closely background matching. Modelling results suggested that targets with lower motion energy were harder to catch. Our results indicate that low contrast, featureless targets offer the greatest protection against capture when in motion, challenging the motion dazzle hypothesis.