bluuebunny/crossref_metadata_2025_split huggingface dataset:
DecipheringLegionellaeffector delivery by Icm/Dot secretion system reveals a new role for c-diGMP signaling
Authors: Allombert J. , Jaboulay C. , Michard C. , Andréa C. , Charpentier X. , Vianney A. , Doublet P. 
Published: September 2019

AbstractSecretion of bacterial effector proteins into host cells plays a key role in bacterial virulence. Yet, the dynamics of the secretion systems activity remains poorly understood, especially when machineries deal with the export of numerous effectors. We address the question of multi-effector secretion by focusing on theLegionella pneumophilaIcm/Dot T4SS that translocates a record number of 300 effectors. We set up a kinetic translocation assay, based on theβ-lactamase translocation reporter system combined with the effect of the protonophore CCCP. When used for translocation analysis of Icm/Dot substrates constitutively produced byL. pneumophila,this assay allows a fine monitoring of the secretion activity of the T4SS, independently of the expression control of the effectors. We observed that effectors are translocated with a specific timing, suggesting a control of their docking/translocation by the T4SS. Their delivery is accurately organized to allow effective manipulation of the host cell, as exemplified by the sequential translocation of effectors targeting Rab1, namely SidM/DrrA, LidA, LepB. Remarkably, the timed delivery of effectors does not depend only on their interaction with chaperone proteins but implies cyclic-di-GMP signaling, as the diguanylate cyclase Lpl0780/Lpp0809, contributes to the timing of translocation.Graphical abstractHighlightsThe dynamics of multi-effector secretion is addressed in the paradigmLegionellaIcm/Dot T4SSA kinetic translocation assay allowing a fine monitoring of the T4SS activity is set upSpecific secretion patterns consistent with sequential functions in the host are reportedT4SS-dependent translocation is promoted by a diguanylate cyclaseUnreported control of Type 4 secretion by the second messenger c-di-GMP signaling is revealed
Full-annual demography and seasonal cycles in a resident vertebrate
Authors: Guimarães Murilo , Correa Décio , Gaiarsa Marília Palumbo , Kéry Marc 
Published: September 2019

AbstractDemography is usually studied at a single point in time within a year when species, mostly long-distance migrants, are more active and easier to find. However, this provides only a low-resolution glimpse into demographic temporal patterns, compromising a complete understanding of species’ population dynamics over full annual cycles. The full annual cycle is often influenced by environmental seasonality, which induces a cyclic behavior in many species. However, cycles have rarely been explicitly included in models for demographic parameters, and most information on full annual cycle demography is restricted to migratory species. Here we used a high-resolution capture-recapture study of a resident tropical lizard to assess the full intra-annual demography and within-year periodicity in survival, temporary emigration and recapture probabilities. We found important variation over the annual cycle and up to 92% of the total monthly variation explained by cycles. Fine-scale demographic studies and assessments on the importance of cycles within parameters are fundamental to understand population persistence over time.
Humanin vitromodel of material-driven vascular regeneration reveals how cyclic stretch and shear stress differentially modulate inflammation and tissue formation
Authors: van Haaften Eline E. , Wissing Tamar B. , Kurniawan Nicholas A. , Smits Anthal I.P.M. , Bouten Carlijn V.C. 
Published: September 2019

1AbstractResorbable synthetic scaffolds designed to regenerate living tissues and organs inside the body emerge as a clinically attractive technology to replace diseased blood vessels. However, mismatches between scaffold design andin vivohemodynamic loading (i.e., cyclic stretch and shear stress) can result in aberrant inflammation and adverse tissue remodeling, leading to premature graft failure. Yet, the underlying mechanisms remain elusive. Here, a humanin vitromodel is presented that mimics the transient local inflammatory and biomechanical environments that drive scaffold-guided tissue regeneration. The model is based on the co-culture of human (myo)fibroblasts and macrophages in a bioreactor platform that decouples cyclic stretch and shear stress. Using a resorbable supramolecular elastomer as the scaffold material, it is revealed that cyclic stretch initially reduces pro-inflammatory cytokine secretion and, especially when combined with shear stress, stimulates IL-10 secretion. Moreover, cyclic stretch stimulates downstream (myo)fibroblast proliferation and neotissue formation. In turn, shear stress attenuates cyclic-stretch-induced tissue growth by enhancing MMP-1/TIMP-1-mediated collagen remodeling, and synergistically alters (myo)fibroblast phenotype when combined with cyclic stretch. The findings suggest that shear stress acts as a stabilizing factor in cyclic stretch-induced tissue formation and highlight the distinct roles of hemodynamic loads in the design of resorbable vascular grafts.
Engineering recombination between diverged yeast species reveals genetic incompatibilities
Authors: Bozdag G. Ozan , Ono Jasmine , Denton Jai A. , Karakoc Emre , Hunter Neil , Leu Jun-Yi , Greig Duncan 
Published: September 2019

AbstractThe major cause of the sterility of F1 hybrids formed betweenSaccharomyces cerevisiaeandSaccharomyces paradoxusis anti-recombination. The failure of homologous chromosomes from the different species to recombine causes them to mis-segregate, resulting in aneuploid gametes, most of which are inviable. These effects of anti-recombination have previously impeded the search for other forms of incompatibility, such as negative genetic interactions (Bateson-Dobzhoansky-Muller incompatibilities). By suppressing the meiotic expression ofMSH2andSGS1, we could increase recombination and improve hybrid fertility seventy-fold. This allowed us to recover meiotic tetrads in which all four gametes were viable, ensuring that segregation had occurred properly to produce perfectly haploid, not aneuploid, recombinant hybrid gametes. We sequenced the genomes of 84 such tetrads, and discovered that some combinations of alleles from different species were significantly under-represented, indicating that there are incompatible genes contributing to reproductive isolation.
Dispersal ability predicts evolutionary success among mammalian carnivores
Authors: Faurby S. , Werdelin L. , Antonelli A. 
Published: September 2019

AbstractUnderstanding why some clades contain more species than others is a major challenge in evolutionary biology, and variation in dispersal ability and its connection to diversification rate may be part of the explanation. Several studies have suggested a negative relationship between dispersal capacity and diversification rate among living mammals. However, this pattern may differ when also considering extinct species, given known extinction biases. The colonization of new areas by various lineages may be associated with both diversity increases in those colonising lineages and declines in the lineages already present. Past diversity declines are, however, effectively impossible to infer based on phylogenies of extant taxa, and the underlying process may, therefore, be difficult to determine. Here we produce a novel species-level phylogeny of all known extant and extinct species of the order Carnivora and related extinct groups (1,723 species in total) to show that there is instead a positive relationship between dispersal rate and diversification rate when all extinct species are included. Species that disperse between continents leave more descendant species than non-dispersers, and dispersing species belong to lineages that at the time of dispersal were diversifying faster than the average non-disperser. Our study showcases the importance of combining fossils and phylogenies to better understand evolutionary and biogeographic patterns.
Rapid Reconstruction of Time-varying Gene Regulatory Networks with Limited Main Memory
Authors: Pyne Saptarshi , Anand Ashish 
Published: September 2019

AbstractReconstruction of time-varying gene regulatory networks underlying a time-series gene expression data is a fundamental challenge in the computational systems biology. The challenge increases multi-fold if the target networks need to be constructed for hundreds to thousands of genes. There have been constant efforts to design an algorithm that can perform the reconstruction task correctly as well as can scale efficiently (with respect to both time and memory) to such a large number of genes. However, the existing algorithms either do not offer time-efficiency, or they offer it at other costs – memory-inefficiency or imposition of a constraint, known as the ‘smoothly time-varying assumption’. In this paper, two novel algorithms – ‘an algorithm for reconstructing Time-varying Gene regulatory networks with Shortlisted candidate regulators - which is Light on memory’ (TGS-Lite) and ‘TGS-Lite Plus’ (TGS-Lite+) – are proposed that are time-efficient, memory-efficient and do not impose the smoothly time-varying assumption. Additionally, they offer state-of-the-art reconstruction correctness as demonstrated with three benchmark datasets.Source Codehttps://github.com/sap01/TGS-Lite-supplem/tree/master/sourcecode
Task-generic and task-specific connectivity modulations in the ADHD brain: An integrated analysis across multiple tasks
Authors: Chauvin Roselyne J. , Buitelaar Jan K. , Sprooten Emma , Oldehinkel Marianne , Franke Barbara , Hartman Catharina , Heslenfeld Dirk J. , Hoekstra Pieter J. , Oosterlaan Jaap , Beckmann Christian F. , Mennes Maarten 
Published: September 2019

AbstractAttention-Deficit/Hyperactivity Disorder (ADHD) is associated with altered functioning in multiple cognitive domains and neural networks. This paper offers an overarching biological perspective across these. We applied a novel strategy that extracts functional connectivity modulations in the brain across one (Psingle), two (Pmix) or three (Pall) cognitive tasks and compared the pattern of modulations between participants with ADHD (n-89), unaffected siblings (n=93) and controls (n=84; total N=266; age range=8-27 years).Participants with ADHD had significantly fewer Pallconnections (modulated regardless of task), but significantly more task-specific (Psingle) connectivity modulations than the other groups. The amplitude of these Psinglemodulations was significantly higher in ADHD. Unaffected siblings showed a similar degree of Pallconnectivity modulation as controls but a similar degree of Psingleconnectivity modulation as ADHD probands. Pallconnections were strongly reproducible at the individual level in controls, but showed marked heterogeneity in both participants with ADHD and unaffected siblings.The pattern of reduced task-generic and increased task-specific connectivity modulations in ADHD may be interpreted as reflecting a less efficient functional brain architecture due to a reduction in the ability to generalise processing pathways across multiple cognitive domains. The higher amplitude of unique task-specific connectivity modulations in ADHD may index a more “effortful” coping strategy. Unaffected siblings displayed a task connectivity profile in between that of controls and ADHD probands, supporting an endophenotype view. Our approach provides a new perspective on the core neural underpinnings of ADHD.
A framework for quantifying deviations from dynamic equilibrium theory
Authors: Kalyuzhny Michael , Flather Curtis H. , Shnerb Nadav M. , Kadmon Ronen 
Published: September 2019

AbstractCommunity assembly is governed by colonization and extinction processes, and the simplest model describing it is Dynamic Equilibrium (DE) theory, which assumes that communities are shaped solely by stochastic colonization and extinction events. Despite its potential to serve as a null model for community dynamics, there is currently no accepted methodology for measuring deviations from the theory and testing it. Here we propose a novel and easily applicable methodology for quantifying deviations from the predictions and assumptions of DE by comparing observed community time-series to a randomization-based null model. We show that this methodology has good statistical properties on simulated data, and it can detect deviations from both the assumptions and predictions of DE in the classical Florida Keys experiment. We discuss alternative methods and present guidelines for practical use of the methodology, hoping it will enhance the applicability of DE as a reference for studying changes in ecological communities.
Sex-specific molecular specialization and activity rhythm dependent gene expression changes in honey bee antennae
Authors: Jain Rikesh , Brockmann Axel 
Published: September 2019

ABSTRACTEusocial insects, like honey bees, which show an elaborate division of labor involving morphologically and physiologically specialized phenotypes provide a unique toolkit to study molecular underpinnings of behavior as well as neural processing. In this study, we performed an extensive RNA-seq based comparison of gene expression levels in the antennae of honey bee drones and foragers collected at different time of days and activity states to identify molecules involved in peripheral olfactory processing and provide insights into distinct strategies in sensory processing. First, honey bee drone and worker antennae differ in the number of olfactory receptor genes (ORs) showing a biased expression pattern. Only 19 Ors were higher expressed in drone antennae, whereas 54 Ors were higher expressed in workers. Second, drone antennae showed predominant higher expression of genes involved in energy metabolism, and worker antennae showed a higher expression of genes involved in neuronal communication. Third, drones and afternoon-trained foragers showed similar daily changes in the expression of major clock genes, per and cry2. Most of the other genes showing changes with the onset of daily activity were specific to drones and foragers suggesting sex-specific circadian changes in antennae. Drone antennae are specialized to detect small amounts of queen’s pheromone and quickly respond to changes in pheromone concentration involving energetically costly action potentials, whereas forager antennae are predominantly involved in behavioral context dependent detection and discrimination of complex odor mixtures which requires mechanisms of sensory filtering and neural plasticity.
The basolateral nucleus of the amygdala regulates both the predictive and incentive motivational properties of reward cues
Authors: Servonnet Alice , Hernandez Giovanni , Hage Cynthia El , Rompré Pierre-Paul , Samaha Anne-Noël 
Published: September 2019

ABSTRACTReward-associated stimuli can acquire both predictive and incentive motivational properties. These conditioned stimuli (CS) can then guide reward-seeking behaviour in adaptive (e.g., locating food) and maladaptive (e.g., binge eating) ways. The basolateral amygdala (BLA) contributes to learning of the predictive value of CS, but less is known about BLA contributions to the incentive motivational properties of appetitive CS. Here we studied the influence of BLA neuron activity on both the predictive and incentive motivational effects of CS. Water-restricted male rats learned to associate a light-tone cue (CS) with water delivery into a port. We assessed the predictive value to the CS by measuring CS-evoked port entries during Pavlovian conditioning. We assessed CS-evoked incentive motivation by measuring lever-pressing for the CS during instrumental responding sessions. During Pavlovian conditioning, we paired CS presentations with photo-stimulation of channelrhodopsin-2 (ChR2)-expressing BLA neurons. This potentiated CS-evoked port entries during conditioning, but suppressed subsequent lever-pressing for the CS. This indicates increased conditioned responding to the CS, but an apparent decrease in incentive motivation for that CS. However, in rats previously naïve to photo-stimulation, pairing BLA-ChR2 stimulations during lever-pressing for the CS intensified responding, indicating enhanced motivation for the CS. Rats did not self-administer BLA-ChR2 stimulations, suggesting that BLA activation does not carry a primary reward signal. Lastly, intra-BLA infusions of d-amphetamine also intensified lever-pressing for the CS. These converging findings suggest that BLA mediated-activity enhances both the predictive and incentive motivational properties of CS, allowing BLA-dependent circuits to guide behaviour in the presence of reward-associated cues.SIGNIFICANCE STATEMENTCues paired with rewards can guide animals to valuable resources such as food. Cues can also promote dysfunctional reward-seeking behaviour, as in over-eating. Reward-paired cues influence reward seeking through two major mechanisms. First, reward-paired cues are predictive and thus evoke anticipation of future rewards. Second, reward-paired cues are powerful motivators and they can evoke pursuit in their own right. Here we show that increasing neural activity in the basolateral amygdala enhances both the predictive and motivational effects of reward-paired cues. The basolateral amygdala therefore facilitates cue-induced control over behaviour by both increasing anticipation for impending rewards and making reward cues more attractive.
Estrogen-related receptor agonism reverses mitochondrial dysfunction and inflammation in the aging kidney
Authors: Wang Xiaoxin X. , Myakala Komuraiah , Libby Andrew E. , Panov Julia , Ranjit Suman , Takahashi Shogo , Jones Bryce A. , Bhasin Kanchan , Qi Yue , Krausz Kristopher W. , Zerfas Patricia M. , Velenosi Thomas J. , Patel Daxesh P. , Daneshpajouhnejad Parnaz , Titievsky Avi , Sharov Vadim , Ostretsov Boris , Billon Cyrielle , Chatterjee Arindam , Walker John K. , Kopp Jeffrey B. , Rosenberg Avi Z. , Gonzalez Frank J. , Guha Udayan , Brodsky Leonid , Burris Thomas P. , Levi Moshe 
Published: September 2019

ABSTRACTBackgroundA gradual decline in renal function occurs even in healthy aging individuals. In addition to aging per se, concurrent metabolic syndrome and hypertension, which are common in the aging population, can induce mitochondrial dysfunction and inflammation, which collectively contribute to age-related kidney dysfunction and disease. Here we studied the role of the nuclear hormone receptors, the estrogen-related receptors (ERRs) in regulation of age-related mitochondrial dysfunction and inflammation. ERRs were decreased in aging human and mouse kidneys and were preserved in aging mice with lifelong caloric restriction (CR).MethodsA pan-ERR agonist was used to treat 21-month-old mice for 8-weeks. In addition, 21-month-old mice were treated with a STING inhibitor for 3 weeks.ResultsRemarkably, only an 8-week treatment with a pan-ERR agonist reversed the age-related increases in albuminuria, podocyte loss, mitochondrial dysfunction and inflammatory cytokines, including the cGAS-STING and STAT3 signaling pathways. A 3-week treatment of 21-month-old mice with a STING inhibitor reversed the increases in inflammatory cytokines and the senescence marker p21 but also unexpectedly reversed the age-related decreases in PGC-1α, ERRα, mitochondrial complexes and MCAD expression.ConclusionsOur studies identified ERRs as important modulators of age-related mitochondrial dysfunction and inflammation. These findings highlight novel druggable pathways that can be further evaluated to prevent progression of age-related kidney disease.Significance StatementThere is an increasing need for prevention and treatment strategies for age-related kidney disease. The hallmarks of aging kidneys are decreased mitochondrial function and increased inflammation. The expression of the nuclear hormone receptors estrogen-related receptors (ERRs) are decreased in aging human and mouse kidneys. This paper investigates the role of ERRs in the aging kidney. Treatment of aging mice with a pan-ERR agonist reversed the age-related increases in albuminuria and podocyte loss, mitochondrial dysfunction and inflammatory cytokines, including the cGAS-STING signaling pathways. Treatment of aging mice with a STING inhibitor decreased inflammation and increased mitochondrial gene expression. These findings identify ERRs as important modulators of age-related mitochondrial dysfunction and inflammation.
Epitope containing short peptides capture distinct IgG serodynamics that enable DIVA for live-attenuated vaccines
Authors: Xue Qinghong , Xu Hongke , Liu Huaidong , Pan Jiaojiao , Yang Jiao , Sun Miao , Chen Yanfei , Xu Wenwen , Cai Xuepeng , Ma Hongwei 
Published: September 2019

AbstractDifferentiating infected from vaccinated animals (DIVA) strategies have been central enabling techniques in several successful viral disease elimination programs. However, owing to their long and uncertain development process, no DIVA-compatible vaccines are available for many important diseases. We report herein a new DIVA strategy based on hybrid protein-peptide microarrays which can theoretically work with any vaccine. Leading from our findings from Peste des petits ruminants (PPR), we found 4 epitope containing short peptides (ECSPs) which have distinct IgG serodynamics: anti-ECSP IgGs only exist for 10-60 days post vaccination (dpv), while anti-protein IgGs remained at high levels for >1000 dpv. These data enabled design of a DIVA diagnostic microarray containing 4 ECSPs and 3 proteins, which unlike cELISA and VNT, enables ongoing monitoring of serological differences between vaccinated individuals and individuals exposed to the pathogen. For 50 samples after 60 dpv, 20 animals were detected with positive anti-ECSP IgGs, indicating recent infections in vaccinated goat/sheep herds. These DIVA diagnostic microarrays will almost certainly facilitate eradication programs for (re-)emerging pathogens and zoonoses.
Interleukin 11 expression causes murine inflammatory bowel disease
Authors: Lim Wei-Wen , Ng Benjamin , Widjaja Anissa , Xie Chen , Su Liping , Ko Nicole , Lim Sze-Yun , Kwek Xiu-Yi , Lim Stella , Cook Stuart A , Schafer Sebastian 
Published: September 2019

AbstractInterleukin 11 (IL11) is a profibrotic cytokine, secreted by myofibroblasts and damaged epithelial cells. Smooth muscle cells (SMCs) also secrete IL11 under pathological conditions and express the IL11 receptor. Here we examined the effects of SMC-specific, conditional expression of murine IL11 in a transgenic mouse (Il11SMC). Within days of transgene activation, Il11SMC mice developed loose stools and progressive bleeding and rectal prolapse, which was associated with a 65% mortality by two weeks. The bowel of Il11SMC mice was inflamed, fibrotic and had a thickened wall, which was accompanied by activation of ERK and STAT3. In other organs, including heart, lung, liver, kidney and skin there was a phenotypic spectrum of fibro-inflammation, together with consistent ERK activation. To investigate further the importance of stromal-derived IL11 in the inflammatory bowel phenotype we used a second model with fibroblast-specific expression of IL11, the Il11Fib mouse. This additional model largely phenocopied the Il11SMC bowel phenotype. These data show that IL11 secretion from the stromal niche is sufficient to drive inflammatory bowel disease in mice. Given that IL11 expression in colonic stromal cells predicts anti-TNF therapy failure in patients with ulcerative colitis or Crohn’s disease, we suggest IL11 as a therapeutic target for inflammatory bowel disease.