bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docosahexaenoic fatty acid-containing phospholipids affect plasma membrane susceptibility to disruption by bacterial toxin-induced macroapertures
Authors: Tsai Meng-Chen , Fleuriot Lucile , Janel Sébastien , Gonzalez-Rodriguez David , Morel Camille , Mettouchi Amel , Debayle Delphine , Dallongeville Stéphane , Olivo-Marin Jean-Christophe , Antonny Bruno , Lafont Frank , Lemichez Emmanuel , Barelli Hélène 
Published: December 2020

AbstractMetabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (22:6, DHA)-containing phospholipids (PLs) in physiology. Here, we study the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs) tunnels triggered by the RhoA GTPase inhibitory exotoxin C3 fromClostridium botulinum. Through lipidomic analyses, we show that primary human umbilical vein endothelial cells (HUVECs) subjected to DHA-diet undergo a 6-fold DHA-PLs enrichment in plasma membrane at the expense of monounsaturated OA-PLs. In contrast, OA-diet had almost no effect on PLs composition. Consequently, DHA treatment increases the nucleation rate of TEMs by 2-fold that we ascribe to a reduction of cell thickness. We reveal that the global transcellular area of cells remains conserved through a reduction of the width and lifetime of TEMs. Altogether, we reveal a homeostasis between plasma membrane DHA-PLs content and large-scale membrane dynamics.
Are specialised ABC transporters responsible for the circularisation of type I circular bacteriocins?
Authors: Vezina Ben , Rehm Bernd H. A. , Smith Andrew T. 
Published: December 2020

DisclaimerThe authors have withdrawn their manuscript whilst they perform further analysis to verify some interpretations and conclusions. Therefore, the authors do not wish this work to be cited as a reference. If you have any questions, please contact the corresponding author.
Short-term audiovisual spatial training enhances electrophysiological correlates of auditory selective spatial attention
Authors: Hanenberg Christina , Schlüter Michael-Christian , Getzmann Stephan , Lewald Jörg 
Published: December 2020

AbstractAudiovisual cross-modal training has been proposed as a tool to improve human spatial hearing. Here, we investigated training-induced modulations of auditory-evoked event-related potential (ERP) components that have been associated with processes of auditory selective spatial attention when a speaker of interest has to be localized in a multiple speaker (“cocktail-party”) scenario. Forty-five healthy subjects were tested, including younger (19-29 yrs;n= 21) and older (66-76 yrs;n= 24) age groups. Three conditions of short-term training (duration 15 minutes) were compared, requiring localization of non-speech targets under “cocktail-party” conditions with either (1) synchronous presentation of co-localized auditory-target and visual stimuli (audiovisual-congruency training) or (2) immediate visual feedback on correct or incorrect localization responses (visual-feedback training), or (3) presentation of spatially incongruent auditory-target and visual stimuli presented at random positions with synchronous onset (control condition). Prior to and after training, subjects were tested in an auditory spatial attention task (15 minutes), requiring localization of a predefined spoken word out of three distractor words, which were presented with synchronous stimulus onset from different positions. Peaks of ERP components were analyzed with a specific focus on the N2, which is known to be a correlate of auditory selective spatial attention. N2 amplitudes were significantly larger after audiovisual-congruency training compared with the remaining training conditions for younger, but not older, subjects. Also, at the time of the N2, electrical imaging revealed an enhancement of electrical activity induced by audiovisual-congruency training in dorsolateral prefrontal cortex (Brodmann area 9) for the younger group. These findings suggest that cross-modal processes induced by audiovisual-congruency training under “cocktail-party” conditions at a short time scale resulted in an enhancement of correlates of auditory selective spatial attention.
Isolation and characterization ofPseudomonas chlororaphisstrain ST9 and its potential as a bioinoculant for agriculture
Authors: Bertani Iris , Zampieri Elisa , Bez Cristina , Volante Andrea , Venturi Vittorio , Monaco Stefano 
Published: December 2020

AbstractThe development of biotechnologies based on beneficial microorganisms for improving soil fertility and crop yields could help addressing many current agriculture challenges, such as food security, climate change, pests control, soil depletion while decreasing the use of chemical fertilizers and pesticides. Plant Growth Promoting (PGP) microbes can be used as probiotics in order to increase plant tolerance/resistance to abiotic/biotic stresses and in this context strains belonging to thePseudomonas chlororaphisgroup have shown to have potential as PGP candidates. In this work a newP. chlororaphisisolate is reported and tested for (i)in vitroPGP features, (ii) whole genome sequence analysis, and (iii) its effects on root microbiome, plant growth and on the expression of different plant genes in greenhouse experiments. The potential use of thisP. chlororaphisstrain as a plant probiotic is discussed.
4sUDRB-sequencing for genome-wide transcription bursting quantification in breast cancer cells
Authors: Beckman William F. , Lermo Jiménez Miguel Ángel , Moerland Perry D. , Westerhoff Hans V. , Verschure Pernette J. 
Published: December 2020

AbstractEpigenetics maintains cell-identity specific gene-expression patterns. However, within a population of isogenic cells of the same identity, a substantial variability in gene expression and responsiveness is still observed. Transcription bursting is a substantial source of this gene-expression variability or ‘noise’, contributing to phenotypic heterogeneity and potentially driving both physiological and pathological processes such as differentiation or tumorigenesis and drug resistance. Identification of transcription-bursting dynamics at a genome-wide scale has been restricted to inferring bursts in mRNA production computationally from the heterogeneity of mRNA levels in single cell transcriptomic data. Systematic characterisation of the genomic and epigenetic chromatin context of genes with defined transcription bursting behaviour has been incomplete. Here, we measured the bursting of transcription itself by genome-wide nascent RNA sequencing of breast cancer MCF-7 cells upon synchronisation of transcription with a transcription elongation inhibitor and by calibration using live cell imaging of nascent PP7-taggedGREB1transcription. Comparing across the entire genome, we find transcription bursting to be ubiquitous, with burst sizes of up to 160 transcripts. Transcription bursting is strongly correlated with steady state gene expression between genes, whereas both burst frequency and nascent transcript degradation only correlate weakly. Individual genes deviate strongly from this trend and engage both in anomalous burst size and frequency. We find that the presence of the TATA box or Inr sequence within gene promoters are significantly associated with a larger burst size, as are promoter-associated YY1 and E2F1 transcription-factor binding motifs. Enrichment of the transcription start site with epigenetic marks such as H3K79me2 and H3K27ac is also strongly associated with the transcription burst size. Finally, we show that in these MCF-7 breast-cancer cells, genes with a larger transcription burst size exhibit a larger immediate transcriptional response following endocrine drug treatment. Our genome-wide transcription-bursting analysis method paves the way to elucidate the dynamic role of epigenetic regulation on dynamic transcription in pathophysiology.
Lineage-specific dynamics of erasure of X-upregulation during inactive-X reactivation
Authors: Naik HC , Chandel D , Majumdar S , Arava M , Baro R , Bv H , Hari K , Parichitran  , Avinchal  , Jolly MK , Gayen S 
Published: December 2020

AbstractIn mammals, sex chromosome dosage is compensated through X-chromosome inactivation and active-X upregulation. It is believed that during early development, X-chromosome inactivation and active X upregulation happen in a highly coordinated fashion. However, such coordination between two X-chromosomes in other developmental contexts remains unexplored. Here, we have profiled the coordination between two X-chromosomes in female cells in different developmental contexts and cell types: pre-implantation embryos, embryonic epiblast cells, iPSC reprogramming, germ cell reprogramming, B-cell, and extra-embryonic endoderm stem (XEN) cells. Interestingly, we found that two X-chromosomes in female cells are not always coordinated; instead, it happens in a lineage-specific manner. Specially, while embryonic mouse epiblast cells, iPSC undergo erasure of X-upregulation upon reactivation of the inactive X, germ cells do not. Importantly, we show that the erasure of X-upregulation in epiblast or iPSC is potentially mediated via undifferentiated embryonic transcription Factor 1 (UTF1), which is absent or lowly expressed in late germ cells and therefore, germ cells are unable to erase upregulation. Moreover, we found that partial reactivation of the inactive X is insufficient to drive the erasure of upregulation globally, nor from their counterparts on the active X in XEN and B-cells. Finally, through a phenomenological mathematical model, we show that cross-inhibition between two X-chromosomes can reproduce the dynamics of reactivation and erasure of upregulation. Altogether, our study provides insight into the coordination between two X-chromosomes in female cells in different developmental contexts and related mechanistic aspects.Abstract Figure
Variation and process of life history evolution in insular dwarfism as revealed by a natural experiment
Authors: Hayashi Shoji , Kubo Mugino O. , Sánchez-Villagra Marcelo R. , Taruno Hiroyuki , Izawa Masako , Shiroma Tsunehiro , Nakano Takayoshi , Fujita Masaki 
Published: December 2020

AbstractIslands are a classic focus for evolutionary studies. One subject of much interest has been the evolution of “dwarfs”, significantly smaller island mammals relative to their continental counterparts. Although a consensus has been achieved that multivariate ecological causes are behind body size changes, the processes involved remain largely unexplored. Life history variables, including the age of first reproduction, growth rate, and longevity, are probably key to understanding the process of insular dwarfism. The Japanese Archipelago with numerous islands offers a unique natural experiment of evolution into different sizes within the same group of organisms, deer. Thus, we investigated eight deer populations with a total number of 52 individuals exhibiting body size variation, both extant and fossil, to clarify the effect of insularity on life history traits. We applied several methods to both extant and extinct populations to resolve life history changes among deer populations. Skeletochronology, using lines of arrested growth formed in long bones (femur and tibia), successfully reconstructed body growth curves and revealed a gradual change in growth trajectories reflecting the degree of insularity. Slower growth rates with prolonged growth periods in more isolated deer populations were revealed. An extensive examination of bone microstructure further corroborated this fact, with much slower growth and later somatic maturity evident in fossil insular deer isolated for more than 1.5 Myr. Finally, mortality patterns assessed by demographic analysis showed variation among deer populations, with a life history of insular populations shifting toward the “slow life”.
Processive Dynamics of the Usher Assembly Platform During UropathogenicEscherichia coliP Pilus Biogenesis
Authors: Du Minge , Yuan Zuanning , Werneburg Glenn T. , Henderson Nadine S. , Chauhan Hemil , Kovach Amanda , Zhao Gongpu , Johl Jessica , Li Huilin , Thanassi David G. 
Published: December 2020

ABSTRACTUropathogenicEscherichia coli(UPEC) assemble hair-like surface structures termed pili or fimbriae to initiate infection of the urinary tract. P pili mediate the adherence of UPEC to the kidney epithelium, facilitating bacterial colonization and pyelonephritis1. P pili are assembled through the conserved chaperone-usher (CU) pathway2-4. In this pathway, a dedicated chaperone facilitates the folding of nascent pilus subunits in the periplasm and an integral outer membrane (OM) protein termed the usher provides the assembly platform and secretion channel for the pilus fiber. Much of the structural and functional understanding of the CU pathway has been gained through investigations of type 1 pili, which promote UPEC binding to the bladder epithelium and the development of cystitis5. In contrast, the structural basis for P pilus biogenesis at the usher has remained elusive. This is in part due to the flexible and variable-length P pilus tip fiber, creating structural heterogeneity, as well as difficulties in isolating stable P pilus assembly intermediates from bacteria. Here, we have devised a method to circumvent these hindrances and determined cryo-EM structures of the activated PapC usher in the process of secreting two- and three-subunit P pilus assembly intermediates. These structures show processive steps in P pilus biogenesis, reveal differences between P and type 1 pili, and capture new conformational dynamics of the usher assembly machine.
Evidence that pain sensitivity is rhythmic in humans, mainly driven by the endogenous circadian system and little by sleep
Authors: Daguet I , Raverot V , Bouhassira D , Gronfier C 
Published: December 2020

AbstractPain intensity has been reported to fluctuate during the day in some experimental and clinical conditions, but the mechanisms underlying these fluctuations are unknown. Although the circadian timing system is known to regulate a wide range of physiological functions, its implication in pain regulation is unknown. We show here, using highly controlled laboratory constant routine conditions, that pain sensitivity is rhythmic over the 24-hours and strongly controlled by the endogenous circadian timing system. We find that pain sensitivity follows a sinusoidal circadian rhythmicity, with a maximum in the middle of the night and a minimum in the afternoon. We also find a weak homeostatic control of pain sensitivity, with a linear increase over the 34 hours of prolonged wakefulness, which parallels that of sleep pressure. Using mathematical modelling, we describe that the circadian system accounts for 80% of the full magnitude of pain sensitivity over the 24 hours, and that sleep-related processes account for only 20%. This result reveals that nocturnal analgesia is predominantly induced by the circadian system and has been wrongly attributed only to sleep. Our findings highlight the need to consider the time of day in pain assessment, and suggest that personalized circadian medicine may be a promising approach to pain management.Significance statementWe discovered that sensitivity to pain is rhythmic in healthy humans, that sensitivity is maximal at night and minimal in the afternoon. Contrarily to the current thinking that sleep is the best painkiller, we find that the 24-h rhythmicity of sensitivity to pain is mainly controlled by a biological circadian clock in our body, and very little by our sleep. Our article reveals the neurobiological mechanisms involved in driving the rhythmicity of pain perception in humans, with the main time-piece located in the brain (the suprachiasmatic nuclei in the hypothalamus). Our findings challenge the current vision of pain physiology, and reveal the need to consider time-of-day and internal biological time for pain evaluation and pain management.
The position of single-base deletions in the VNTR sequence of the carboxyl ester lipase (CEL) gene determines pathogenicity
Authors: Gravdal Anny , Xiao Xunjun , Cnop Miriam , Jellas Khadija El , Njølstad Pål R. , Lowe Mark E. , Johansson Bente B. , Molven Anders , Fjeld Karianne 
Published: December 2020

ABSTRACTVariable number of tandem repeat (VNTR) sequences present in the genome can have functional consequences that contribute to human disease. This is the case for theCELgene, which encodes the digestive enzyme carboxyl ester lipase.CELhas a VNTR located in exon 11, and rare single-base deletions (DELs) within this region cause MODY8, an inherited disorder characterized by exocrine pancreatic dysfunction and diabetes. Here, we have studied how the position of single-base deletions within theCELVNTR affects the protein’s pathogenic properties. We investigated four naturally occurringCELvariants with single-base deletions in different VNTR segments (DEL1, DEL4, DEL9, DEL13), of which only DEL1 and DEL4 have been observed in MODY8 patients. When expressed in a cellular model system, only DEL1 and DEL4 exhibited significantly reduced secretion and increased intracellular aggregation compared to normal CEL. We found that all DEL variants had slightly decreased enzymatic activity and that their level of O-glycosylation was affected. Moreover, only DEL1 and DEL4 significantly increased endoplasmic reticulum (ER) stress. In conclusion,CELsingle-base deletion variants have the highest pathogenic potential when the mutational event has taken place in the proximal VNTR part, resulting in the longest aberrant protein tails. Thus, DEL1 and DEL4 are pathogenicCELvariants, whereas we consider DEL13 as benign and DEL9 as likely benign. These findings have implications for our understanding of howCELmutations cause pancreatic disease through protein misfolding and proteotoxicity, leading to ER stress and activation of the unfolded protein response.
Amino Acids Promote Mitochondrial-Derived Compartment Formation in Mammalian Cells
Authors: Schuler Max-Hinderk , English Alyssa M. , VanderMeer Leah , Shaw Janet M. , Hughes Adam L. 
Published: December 2020

SUMMARYWe recently identified a new cellular structure in yeast, called the Mitochondrial-Derived Compartment (MDC), that forms on mitochondria in response to amino acid excess. While emerging evidence supports an important function for MDCs in protecting cells from metabolic stress, whether this system exists beyond yeast remains unclear. Here, we show that MDCs are conserved in mammals, and like their yeast counterparts, are responsive to the intracellular amino acid content. Specifically, we find that inhibition of protein translation stimulates formation of dynamic, micron-sized compartments that associate with the mitochondrial network. These compartments are enriched for the carrier receptor Tomm70A and other select mitochondrial outer and inner membrane cargo, associate with the ER membrane, and require the conserved GTPase Miro1 for formation. Mammalian MDCs are responsive to changes in amino acid levels during translation inhibition, and are not activated by other common cellular stressors. Thus, MDCs represent an evolutionarily conserved nutrient-responsive mitochondrial remodeling system.
Species-specific sensitivity to TGFβ signaling and changes to the Mmp13 promoter underlie avian jaw development and evolution
Authors: Smith Spenser S. , Chu Daniel , Qu Tiange , Schneider Richard A. 
Published: December 2020

ABSTRACTDevelopmental control of jaw length is critical for survival. The jaw skeleton arises from neural crest mesenchyme and previously we demonstrated that these progenitors upregulate bone-resorbing enzymes includingMatrix metalloproteinase 13(Mmp13)when generating short quail beaks versus long duck bills. Inhibiting bone resorption orMmp13increases jaw length. Here, we uncover mechanisms establishing species-specific levels ofMmp13and bone resorption. Quail show greater activation of, and sensitivity toTransforming Growth Factor-Beta(TGFβ) signaling than duck; where mediators like SMADs and targets likeRunx2,which bindMmp13, become elevated. Inhibiting TGFβ signaling decreases bone resorption. We discover a SMAD binding element in the quailMmp13promoter not found in duck and single nucleotide polymorphisms (SNPs) near a RUNX2 binding element that affect expression. Switching the SNPs and SMAD site abolishes TGFβ-sensitivity in the quailMmp13promoter but makes duck responsive. Thus, differential regulation of TGFβ signaling andMmp13promoter structure underlie avian jaw development and evolution.
Postural effects on arm movement variability are idiosyncratic and feedback-dependent
Authors: Phataraphruk Preyaporn , Rahman Qasim , Lakshminarayanan Kishor , Fruchtman Mitchell , Buneo Christopher A. 
Published: December 2020

AbstractReaching movements are subject to noise arising during the sensing, planning and execution phases of movement production, which contributes to movement variability. When vision of the moving hand is available, reaching variability appears to be strongly influenced by noise occurring during the specification and/or online updating of movement plans in visual coordinates. In contrast, when vision of the hand is unavailable, variability appears more dependent upon hand movement direction, suggesting a greater influence of execution noise. Given that execution noise acts in part at the muscular level, we hypothesized that reaching variability should depend not only on movement direction but initial arm posture as well. Moreover, given that the effects of execution noise are more apparent when movements are performed without vision of the hand, we reasoned that postural effects would be more evident when visual feedback was withheld. To test these hypotheses, subjects planned memory-guided reaching movements to three frontal plane targets, using either an “adducted” or “abducted” initial arm posture. Movements were then executed with and without hand vision. We found that the effects of initial arm posture on movement variability were idiosyncratic in both visual feedback conditions. In addition, without visual feedback, posture-dependent differences in variability varied with movement extent, growing abruptly larger in magnitude during the terminal phases of movement, and were moderately correlated with differences in mean endpoint positions. The results emphasize the role of factors other than noise (i.e. biomechanics and suboptimal sensorimotor integration) in constraining patterns of movement variability in 3D space.
Prefrontal solution to the bias-variance tradeoff during reinforcement learning
Authors: Kim Dongjae , Jeong Jaeseung , Lee Sang Wan 
Published: December 2020

AbstractThe goal of learning is to maximize future rewards by minimizing prediction errors. Evidence have shown that the brain achieves this by combining model-based and model-free learning. However, the prediction error minimization is challenged by a bias-variance tradeoff, which imposes constraints on each strategy’s performance. We provide new theoretical insight into how this tradeoff can be resolved through the adaptive control of model-based and model-free learning. The theory predicts the baseline correction for prediction error reduces the lower bound of the bias–variance error by factoring out irreducible noise. Using a Markov decision task with context changes, we showed behavioral evidence of adaptive control. Model-based behavioral analyses show that the prediction error baseline signals context changes to improve adaptability. Critically, the neural results support this view, demonstrating multiplexed representations of prediction error baseline within the ventrolateral and ventromedial prefrontal cortex, key brain regions known to guide model-based and model-free learning.One sentence summaryA theoretical, behavioral, computational, and neural account of how the brain resolves the bias-variance tradeoff during reinforcement learning is described.