bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coupling between tolerance and resistance for two related Eimeria parasite species
Authors: Balard Alice , Jarquín-Díaz Víctor Hugo , Jost Jenny , Mittné Vivian , Böhning Francisca , Ďureje Ľudovít , Piálek Jaroslav , Heitlinger Emanuel 
Published: January 2020

AbstractResistance (host capacity to reduce parasite burden) and tolerance (host capacity to reduce impact on its health for a given parasite burden) manifest two different lines of defence. Tolerance can be independent from resistance, traded-off against it, or the two can be positively correlated because of redundancy in underlying (immune) processes. We here tested whether this coupling between tolerance and resistance could differ upon infection with closely related parasite species. We tested this in experimental infections with two parasite species of the genus Eimeria. We measured proxies for resistance (the (inverse of) number of parasite transmission stages (oocysts) per gram of feces at the day of maximal shedding) and tolerance (the slope of maximum relative weight loss compared to day of infection on number of oocysts per gram of feces at the day of maximal shedding for each host strain) in four inbred mouse strains and four groups of F1 hybrids belonging to two mouse subspecies, Mus musculus domesticus and M. m. musculus. We found a negative correlation between resistance and tolerance against E. falciformis, while the two are uncoupled against E. ferrisi. We conclude that resistance and tolerance against the first parasite species might be traded off, but evolve more independently in different mouse genotypes against the latter. We argue that evolution of the host immune defences can be studied largely irrespective of parasite isolates if resistance-tolerance coupling is absent or weak (E. ferrisi) but host-parasite coevolution is more likely observable and best studied in a system with negatively correlated tolerance and resistance (E. falciformis).
Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior
Authors: Biran Jakob , Gliksberg Michael , Shirat Ido , Swaminathan Amrutha , Levitas-Djerbi Talia , Appelbaum Lior , Levkowitz Gil 
Published: January 2020

AbstractThe pituitary adenylate cyclase-activating polypeptide receptor (PAC1, also known as ADCYAP1R1) is associated with post-traumatic stress disorder and modulation of stress response in general. Alternative splicing of PAC1 results in multiple gene products, which differ in their mode of signalling and tissue distribution. However, the roles of distinct splice variants in the regulation of stress behavior is poorly understood. Alternative splicing of a short exon, which is known as the “hop cassette”, occurs during brain development and in response to stressful challenges. To examine the function of this variant, we generated a splice-specific zebrafish mutant lacking the hop cassette, which we designated ‘hopless’. We show thathoplessmutant larvae display increased anxiety-like behavior, including reduced dark exploration and impaired habituation to dark exposure. Conversely, adulthoplessmutants displayed superior ability to rebound from an acute stressor, as they exhibited reduced anxiety- like responses to an ensuing novelty stress. We propose that the developmental loss of a specific PAC1 splice variant mimics prolonged mild stress exposure, which in the long term, predisposes the organism’s stress response towards a resilient phenotype. Our study presents a unique genetic model demonstrating how early-life state of anxiety paradoxically correlates with reduced stress susceptibility in adulthood.
Adaptive divergence generates distinct plastic responses in two closely relatedSeneciospecies
Authors: Walter Greg M. , Clark James , Cristaudo Antonia , Terranova Delia , Nevado Bruno , Catara Stefania , Paunov Momchil , Velikova Violeta , Filatov Dmitry , Cozzolino Salvatore , Hiscock Simon J. , Bridle Jon R. 
Published: January 2020

AbstractThe evolution of plastic responses to external cues allows species to track the environmental variation they regularly experience. However, it remains unclear how plasticity evolves during adaptation. To test whether distinct patterns of plasticity is associated with recent adaptive divergence, we quantified plasticity for two closely related but ecologically divergent Sicilian daisy species (Senecio, Asteraceae). We sampled c.40 genotypes of each species from natural populations on and around Mt Etna and then reciprocally transplanted multiple clones of each genotype into four field sites along an elevational gradient representing each species’ native range, the edge of their range, and conditions outside their native range. At each elevation we quantified survival and measured leaf traits that included investment (specific leaf area), morphology, chlorophyll fluorescence, pigment content and gene expression. As evidence of adaptive divergence, both species performed better at their native site and better than the species from the other habitat. Traits and differentially expressed genes that changed with elevation in one species often showed little change in the other species, or changed in the opposite direction. Adaptive divergence is therefore associated with the evolution of distinct plastic responses to environmental variation, despite these two species sharing a recent common ancestor.
Exploring the impact of lesser-known social dynamics on wolf populations through an individual-based approach
Authors: Bauduin Sarah , Grente Oksana , Santostasi Nina Luisa , Ciucci Paolo , Duchamp Christophe , Gimenez Olivier 
Published: January 2020

AbstractThe occurrence of wolf populations in human-dominated landscapes is challenging worldwide because of conflicts with human activities. Modeling is an important tool to predict wolf dynamics and expansion, and help in decision making concerning management and conservation. However, some individual behaviors and pack dynamics of the wolf life cycle are still unclear to ecologists. Here we present an individual-based model (IBM) to project wolf populations while exploring the lesser-known processes of the wolf life cycle. IBMs are bottom-up models that simulate the fate of individuals interacting with each other, with population-level properties emerging from the individual-level simulations. IBMs are particularly adapted to represent social species such as the wolf that exhibits complex individual interactions. Our IBM predicts wolf demography including fine-scale individual behavior and pack dynamics based on up-to-date scientific literature. We explore four processes of the wolf life cycle whose consequences on population dynamics are still poorly understood: the pack dissolution following the loss of a breeder, the adoption of young dispersers by packs, the establishment of new packs through budding, and the different types of breeder replacement. While running different versions of the IBM to explore these processes, we also illustrate the modularity and flexibility of our model, an asset to model wolf populations experiencing different ecological and demographic conditions. The different parameterization of pack dissolution, territory establishment by budding, and breeder replacement processes influence the most the projections of wolf populations. As such, these processes require further field investigation to be better understood. The adoption process has a lesser impact on model predictions. Being coded in R to facilitate its understanding, we expect that our model will be used and further adapted by ecologists for their own specific applications.
Novel function acquired by theCulex quinquefasciatusmosquito D7 salivary protein enhances blood feeding on mammals
Authors: Martin-Martin Ines , Paige Andrew , Valenzuela Leon Paola Carolina , Gittis Apostolos G. , Kern Olivia , Bonilla Brian , Chagas Andrezza Campos , Ganesan Sundar , Garboczi David N. , Calvo Eric 
Published: January 2020

AbstractAdult female mosquitoes require a vertebrate blood meal to develop eggs and continue their life cycle. During blood feeding, mosquito saliva is injected at the bite site to facilitate blood meal acquisition through anti-hemostatic compounds that counteract blood clotting, platelet aggregation, vasoconstriction and host immune responses. D7 proteins are among the most abundant components of the salivary glands of several blood feeding insects. They are members of a family of proteins that have evolved through gene duplication events to encode D7 proteins of several lengths. Here, we examine the ligand binding specificity and physiological relevance of two D7 long proteins, CxD7L1 and CxD7L2, fromCulex quinquefasciatusmosquitoes, the vector of medical and veterinary diseases such as filariasis, avian malaria, and West Nile virus infections. CxD7L1 and CxD7L2 were assayed by microcalorimetry for binding of potential host ligands involved in hemostasis, including bioactive lipids, biogenic amines, and nucleotides/nucleosides. CxD7L2 binds serotonin, histamine, and epinephrine with high affinity as well as the thromboxane A2 analog U-46619 and several cysteinyl leukotrienes, as previously described for other D7 proteins. CxD7L1 does not bind any of the ligands that are bound by CxD7L2. Unexpectedly, CxD7L1 exhibited high affinity for adenine nucleotides and nucleosides, a binding capacity not reported in any D7 family member. We solved the crystal structure of CxD7L1 in complex with bound ADP to 1.97 Å resolution. The binding pocket for ADP is located between the two domains of CxD7L1, whereas all known D7s bind ligands either within the N-terminal or the C-terminal domains. We demonstrated that these two CxD7 long proteins inhibit human platelet aggregation inex vivoexperiments. CxD7L1 and CxD7L2 help blood feeding in mosquitoes by scavenging host molecules that promote vasoconstriction, platelet aggregation, itch, and pain at the bite site. The novel ADP-binding function acquired by CxD7L1 evolved to enhance blood feeding in mammals where ADP plays a key role in platelet aggregation.
Characterizing expression of candidate genes of a glutamate receptor pathway inArabidopsis thalianausing real-time RT-PCR
Authors: Wurdeman Julie , Brooks Tessa Durham 
Published: January 2020

AbstractTheArabidopsis thalianagenome contains twenty genes that are analogous to mammalian ionotropic glutamate receptors. There are sixteen mammalian glutamate receptors, which are best known for their roles in neuroplasticity, learning, and memory. The large number of glutamate receptors inA. thalianasuggests they play important roles in the plant’s growth and development, possibly serving to regulate function like they do in non-excitable mammalian tissues. A specific glutamate receptor,GLR3.3, is highly expressed in root tissue of plants, and has been found to promote stronger, more coordinated curvature development during the process of gravitropism. Gravitropism is the ability of a plant to change its orientation to that of the gravity vector when displaced from its gravitational set point angle (GSPA). A previous association study identified six candidate genes which were correlated with the same phenotypic characteristics of gravitropism asGLR3.3. Utilizing real time RT-PCR (qRT-PCR) expression profiles were created for each candidate gene, includingGLR3.3.A qRT-PCR method was developed to provide a more quantitative and sensitive way for measuring gene expression than traditional PCR methods. Furthermore, MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines were followed to ensure data robustness. Expression profiles that were similar toGLR3.3were hypothesized to be good candidates as cell signaling components of this novel pathway. This is the beginning of a process that will identify aGLR-dependent pathway, the role of this novel pathway in the gravitropic response, and the influence ofGLRsin plant physiology.
Patterns of selection against centrosome amplification in human cell lines
Authors: Dias Louro Marco António , Bettencourt-Dias Mónica , Bank Claudia 
Published: January 2020

The presence of extra centrioles, or centrosome amplification, is a hallmark of cancer cells. Centriole numbers in cancer cell populations appear to be at an equilibrium maintained by centriole overproduction and selection, reminiscent of mutation-selection balance. It is not known if the interaction between centriole overproduction and selection can quantitatively explain the intra- and inter-population heterogeneity in centriole numbers.Here, we define mutation-selection-like models and employ a model selection approach to infer patterns of centriole overproduction and selection in a diverse panel of cell lines. Surprisingly, we infer strong and uniform selection against any number of extra centrioles, in most cell lines. However, we do not detect significant differences in parameter estimates between different cell lines. Finally we assess the accuracy and precision of our inference method and find that it increases non-linearly as a function of the number of sampled cells. We discuss the biological implications of our results and how our methodology can inform future experiments.
The Wg and Dpp morphogens regulate gene expression by modulating the frequency of transcriptional bursts
Authors: Bakker Rachael , Mani Madhav , Carthew Richard W. 
Published: January 2020

ABSTRACTMorphogen signaling contributes to the proper spatiotemporal expression of genes during development. One method of regulation of signaling-responsive genes is at the level of transcription. Single-cell quantitative studies of transcription have revealed that transcription occurs intermittently, in bursts. Although the effects of many gene regulatory mechanisms on transcriptional bursting have been studied, it remains unclear how morphogen gradients affect this dynamic property of downstream genes. Here we have adapted smFISH for use in theDrosophilawing imaginal disc in order to measure nascent and mature mRNA of genes downstream of the Wg and Dpp morphogen gradients. We compared our experimental results with predictions from stochastic models of transcription. Our results indicate that the transcription levels of these genes appear to share a common method of control via burst frequency modulation. Our data helps further elucidate the link between developmental gene regulatory mechanisms and transcriptional bursting.
Evidence for a growing population of eastern migratory monarch butterflies is currently insufficient
Authors: Thogmartin Wayne E. , Szymanski Jennifer A. , Weiser Emily L. 
Published: January 2020

AbstractThe eastern migratory population of monarch butterflies has experienced a multi-decadal decline, but a recent increase in abundance (to 6.05 ha in winter 2018) has led some observers to question whether the population has reversed its long-standing decline and embarked on a trajectory of increasing abundance. We examined this possibility through changepoint analyses, first assessing whether a change in trajectory existed and whether that change was sufficient to alter our estimated risk for the population. We found evidence of a change in trajectory in 2014, but insufficient statistical support for a significantly increasing population since that time (β = 0.285, 95% CI = −0.127, 0.697). If the population estimate for winter 2019 is ≥4.0 ha, we will then be able to credibly assert the population has been increasing since 2014. However, given estimated levels of time series variability, presumed habitat capacity and no recent change in status or trend, there was a 13.5% probability of observing a population estimate as large or larger than was reported for winter 2018. Despite insufficient evidence for an increasing population, near-term risk of quasi-extinction by 2023 has declined (mean risk declining from 43% to 20%) because of higher abundance estimates since 2014. Our analyses highlight the incredible difficulty in drawing robust conclusions from annual changes in abundance over a short time series, especially for an insect that commonly exhibits considerable year-to-year variation. Thus, we urge caution when drawing conclusions regarding species status and trends for any species for which limited data are available.
BAcTrace a new tool for retrograde tracing of neuronal circuits
Authors: Cachero Sebastian , Gkantia Marina , Bates Alexander S. , Frechter Shahar , Blackie Laura , McCarthy Amy , Sutcliffe Ben , Strano Alessio , Aso Yoshinori , Jefferis Gregory S.X.E. 
Published: January 2020

AbstractNew tools and techniques have enabled many key advances in our understanding of the brain. To elucidate circuit function, it is necessary to identify, record from and manipulate networks of connected neurons. Here we present BAcTrace (BotulinumActivatedTracer), the first fully genetically encoded, retrograde, transsynaptic labelling system. BAcTrace is based onC. botulinumneurotoxin A, Botox, which we have engineered to act as a Trojan horse that jumps retrogradely between neurons to activate an otherwise silent transcription factor. We validate BAcTrace at three connections in theDrosophilaolfactory system and show that it enables electrophysiological recordings of connected neurons. Finally, in a challenging circuit with highly divergent connections, we used Electron Microscopy connectomics to show that BAcTrace correctly identifies 12 out of 16 connections.
Drag-induced directionality switching of kinesin-5 Cin8 revealed by cluster-motility analysis
Authors: Pandey Himanshu , Reithmann Emanuel , Goldstein-Levitin Alina , Al-Bassam Jawdat , Frey Erwin , Gheber Larisa 
Published: January 2020

AbstractDirected active motion of motor proteins is a vital process in virtually all eukaryotic cells. Nearly a decade ago, the discovery of directionality switching of mitotic kinesin-5 motors challenged the long-standing paradigm that individual kinesin motors are characterized by an intrinsic directionality. While several kinesin motors have now been shown to exhibit context-dependent directionality that can be altered under diverse experimental conditions, the underlying mechanism remains unknown. Here, we studied clustering-induced directionality switching of the mitotic kinesin-5 Cin8, using a fluorescence-based single-molecule motility assay combined with biophysical theory. Based on the detailed characterization of the motility of single motors and clusters of Cin8, we developed a predictive molecular model, that quantitatively agrees with experimental data. This combined approach allowed us to quantify the response of Cin8 motors to external forces as well as the interactions between Cin8 motors, and thereby develop a detailed understanding of the molecular mechanism underlying directionality switching. The main insight is that directionality switching is caused by a single feature of Cin8: an asymmetric response of active motion to forces that oppose motion, here referred to as drag. This general mechanism explains why bidirectional motor proteins are capable of reversing direction in response to seemingly unrelated experimental factors including clustering, changes in the ionic strength of the buffer, increased motor density and molecular crowding, and in motility assays.Significance StatementKinesin-5 motor proteins perform essential functions in chromosome segregation during mitotic cell division. Surprisingly, several kinesin-5 motors have the ability to reverse directionality under different experimental conditions, which contradicts the long-standing paradigm that individual kinesin motors are characterized by an intrinsic directionality. The mechanism underlying this ability to switch directionality has remained elusive. Here, we combine fluorescence-based motility assays and theoretical modeling to analyze cluster-size-dependent motility of the bidirectional kinesin-5 Cin8. Our results show that bidirectional motors can switch directionality because they exhibit an asymmetric response of active motion to drag. This mechanism explains multiple seemingly unrelated experimental factors that have been shown to cause directionality switching of kinesin motors.
New candidates for regulated gene integrity revealed through precise mapping of integrative genetic elements
Authors: Mageeney Catherine M. , Lau Britney Y. , Wagner Julian M. , Hudson Corey M. , Schoeniger Joseph S. , Krishnakumar Raga , Williams Kelly P. 
Published: January 2020

ABSTRACTIntegrative genetic elements (IGEs) are mobile multigene DNA units that integrate into and excise from host bacterial chromosomes. Each IGE usually targets a specific site within a conserved host gene, integrating in a manner that preserves target gene function. However, a small number of bacterial genes are known to be inactivated upon IGE integration and reactivated upon excision, regulating phenotypes of virulence, mutation rate, and terminal differentiation in multicellular bacteria. The list ofregulatedgene integrity (RGI) cases has been slow-growing because IGEs have been challenging to precisely and comprehensively locate in genomes. We present software (TIGER) that maps IGEs with unprecedented precision and withoutattBsite bias. TIGER uses a comparative genomic, ping-pong BLAST approach, based on the principle that the IGE integration module (i.e., itsint-attPregion) is cohesive. The resultant IGEs, along with integrase phylogenetic analysis and gene inactivation tests, revealed 19 new cases of genes whose integrity is regulated by IGEs (includingdut, eccCa1, gntT, hrpB, merA, ompN, prkA, tqsA, traG, yifB, yfaTandynfE), as well as recovering previously known cases (insigK, spsM, comK, mlrA, andhlbgenes). It also recovered known clades of site-promiscuous integrases and identified possible new ones.
Early life stress reduces voluntary exercise and its prevention of diet-induced obesity and metabolic dysfunction in mice
Authors: Eller-Smith Olivia C. , Morris E. Matthew , Thyfault John P. , Christianson Julie A. 
Published: January 2020

AbstractThe development of obesity-related metabolic syndrome (MetS) involves a complex interaction of genetic and environmental factors. One environmental factor found to be significantly associated with MetS is early life stress (ELS). We have previously reported on our mouse model of ELS, induced by neonatal maternal separation (NMS), that displays altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis and increased sensitivity in the urogenital organs, which was attenuated by voluntary wheel running. Here, we are using our NMS model to determine if ELS-induced changes in the HPA axis also influence weight gain and MetS. Naïve (non-stressed) and NMS male mice were given free access to a running wheel and a low-fat control diet at 4-weeks of age. At 16-weeks of age, half of the mice were transitioned to a high fat/sucrose (HFS) diet to investigate if NMS influences the effectiveness of voluntary exercise to prevent diet-induced obesity and MetS. Overall, we observed a greater impact of voluntary exercise on prevention of HFS diet-induced outcomes in naïve mice, compared to NMS mice. Although body weight and fat mass were still significantly higher, exercise attenuated fasting insulin levels and mRNA levels of inflammatory markers in epididymal adipose tissue in HFS diet-fed naïve mice. Only moderate changes were observed in exercised NMS mice on a HFS diet, although this could partially be explained by reduced running distance within this group. Interestingly, sedentary NMS mice on a control diet displayed impaired glucose homeostasis and moderately increased pro-inflammatory mRNA levels in epididymal adipose, suggesting that early life stress alone impairs metabolic function and negatively impacts the therapeutic effect of voluntary exercise.