bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute stress enhances associative learning via dopamine signaling in the ventral lateral striatum
Authors: Stelly Claire E. , Tritley Sean C. , Rafati Yousef , Wanat Matthew J. 
Published: December 2019

AbstractAcute stress transiently increases vigilance, whereby enhancing the detection of salient stimuli. This increased perceptual sensitivity is thought to promote associating rewarding outcomes with relevant cues. The mesolimbic dopamine system is critical for learning cue-reward associations. Dopamine levels in the ventral striatum are elevated following exposure to stress. Together, this suggests the mesolimbic dopamine system could mediate the influence of acute stress on cue-reward learning. To address this possibility, we examined how a single stressful experience influenced learning in an appetitive Pavlovian conditioning task. Male rats underwent an episode of restraint prior to the first conditioning session. This acute stress treatment augmented conditioned responding in subsequent sessions. Voltammetry recordings of mesolimbic dopamine levels demonstrated that acute stress selectively increased reward-evoked dopamine release in the ventral lateral striatum (VLS), but not in the ventral medial striatum (VMS). Antagonizing dopamine receptors in the VLS blocked the stress-induced enhancement of conditioned responding. Collectively, these findings illustrate that stress engages dopamine signaling in the VLS to facilitate appetitive learning.
Towards an evolutionarily appropriate null model: jointly inferring demography and purifying selection
Authors: Johri Parul , Charlesworth Brian , Jensen Jeffrey D. 
Published: December 2019

ABSTRACTThe question of the relative evolutionary roles of adaptive and non-adaptive processes has been a central debate in population genetics for nearly a century. While advances have been made in the theoretical development of the underlying models, and statistical methods for estimating their parameters from large-scale genomic data, a framework for an appropriate null model remains elusive. A model incorporating evolutionary processes known to be in constant operation - genetic drift (as modulated by the demographic history of the population) and purifying selection – is lacking. Without such a null model, the role of adaptive processes in shaping within- and between-population variation may not be accurately assessed. Here, we investigate how population size changes and the strength of purifying selection affect patterns of variation at neutral sites near functional genomic components. We propose a novel statistical framework for jointly inferring the contribution of the relevant selective and demographic parameters. By means of extensive performance analyses, we quantify the utility of the approach, identify the most important statistics for parameter estimation, and compare the results with existing methods. Finally, we re-analyze genome-wide population-level data from a Zambian population ofDrosophila melanogaster, and find that it has experienced a much slower rate of population growth than was inferred when the effects of purifying selection were neglected. Our approach represents an appropriate null model, against which the effects of positive selection can be assessed.
Liquid-liquid microphase separation leads to formation of membraneless organelles
Authors: Ranganathan Srivastav , Shakhnovich Eugene 
Published: December 2019

AbstractProteins and nucleic acids can spontaneously self-assemble into membraneless droplet-like compartments, both in vitro and in vivo. A key component of these droplets are multi-valent proteins that possess several adhesive domains with specific interaction partners (whose number determines total valency of the protein) separated by disordered regions. Here, using multi-scale simulations we show that such proteins self-organize into micro-phase separated droplets of various sizes as opposed to the Flory-like macro-phase separated equilibrium state of homopolymers or equilibrium physical gels. We show that the micro-phase separated state is a dynamic outcome of the interplay between two competing processes: a diffusion-limited encounter between proteins, and the dynamics within small clusters that results in exhaustion of available valencies whereby all specifically interacting domains find their interacting partners within smaller clusters, leading to arrested phase separation. We first model these multi-valent chains as bead-spring polymers with multiple adhesive domains separated by semi-flexible linkers and use Langevin Dynamics (LD) to assess how key timescales depend on the molecular properties of associating polymers. Using the time-scales from LD simulations, we develop a coarse-grained kinetic model to study this phenomenon at longer times. Consistent with LD simulations, the macro-phase separated state was only observed at high concentrations and large interaction valencies. Further, in the regime where cluster sizes approach macro-phase separation, the condensed phase becomes dynamically solid-like, suggesting that it might no longer be biologically functional. Therefore, the micro-phase separated state could be a hallmark of functional droplets formed by proteins with the sticker-spacer architecture.Significance statementMembraneless organells (MO) are ubiquitous in ‘healthy’ living cells, with an altered state in disease. Their formation is likened to liquid-liquid phase separation (LLPS) between MO-forming proteins. However most models of LLPS predict complete macrophase separation while in reality MO’s are small droplets of various sizes, which are malleable to rapid morphological changes. Here we present a microscopic multiscale theoretical study of thermodynamics and kinetics of formation of MO. We show that MO’s are long-living dynamic structures formed as a result of arrested macrophase separation. Our study provides a direct link beween the molecular properies of MO-forming proteins and the morphology and dynamics of MO paving a path to rational design and control of MO.
Water lily (Nymphaea thermarum) draft genome reveals variable genomic signatures of ancient vascular cambium losses
Authors: Povilus Rebecca A. , DaCosta Jeffery M. , Grassa Christopher , Satyaki Prasad R. V. , Moeglein Morgan , Jaenisch Johan , Xi Zhenxiang , Mathews Sarah , Gehring Mary , Davis Charles C. , Friedman William E. 
Published: December 2019

AbstractFor more than 225 million years, all seed plants were woody trees, shrubs, or vines (1–4). Shortly after the origin of angiosperms ~135 million years ago (MYA) (5), the Nymphaeales (water lilies) became one of the first lineages to deviate from their ancestral, woody habit by losing the vascular cambium (6), the meristematic population of cells that produces secondary xylem (wood) and phloem. Many of the genes and gene families that regulate differentiation of secondary tissues also regulate the differentiation of primary xylem and phloem (7–9), which are produced by apical meristems and retained in nearly all seed plants. Here we sequence and assemble a draft genome of the water lily Nymphaea thermarum, an emerging system for the study of early flowering plant evolution, and compare it to genomes from other cambium-bearing and cambium-less lineages (like monocots and Nelumbo). This reveals lineage-specific patterns of gene loss and divergence. Nymphaea is characterized by a significant contraction of the HD-ZIP III transcription factors, specifically loss of REVOLUTA, which influences cambial activity in other angiosperms. We also find the Nymphaea and monocot copies of cambium-associated CLE signaling peptides display unique substitutions at otherwise highly conserved amino acids. Nelumbo displays no obvious divergence in cambium-associated genes. The divergent genomic signatures of convergent vascular cambium loss reveals that even pleiotropic genes can exhibit unique divergence patterns in association with independent trait loss events. Our results shed light on the evolution of herbaceousness – one of the key biological innovations associated with the earliest phases of angiosperm evolution.Significance StatementFor ~225 million years, all seed plants were woody trees, shrubs, or vines. Shortly after the origin of flowering plants ~135 million years ago, Nymphaeales (water lilies) became one of the first seed plant lineages to become herbaceous through loss of the meristematic cell population known as the vascular cambium. We sequence and assemble the draft genome of the water lily Nymphaea thermarum, and compare it to genomes of other plants that have retained or lost the vascular cambium. By using both genome-wide and candidate-gene analysis, we find lineage-specific patterns of gene loss and divergence associated with cambium loss. Our reveal divergent genomic signatures of convergent trait loss in a system characterized by complex gene-trait relationships.
The human telomeric nucleosome displays distinct structural and dynamic properties
Authors: Soman Aghil , Liew Chong Wai , Teo Hsiang Ling , Berezhnoy Nikolay V. , Olieric Vincent , Korolev Nikolay , Rhodes Daniela , Nordenskiöld Lars 
Published: December 2019

ABSTRACTTelomeres protect the ends of our chromosomes and are key to maintaining genomic integrity during cell division and differentiation. However, our knowledge of telomeric chromatin and nucleosome structure at the molecular level is limited. Here, we aimed to define the structure, dynamics as well as properties in solution of the human telomeric nucleosome. We first determined the 2.2 Å crystal structure of a human telomeric nucleosome core particle (NCP) containing 145 bp DNA, which revealed the same helical path for the DNA as well as symmetric stretching in both halves of the NCP as that of the 145 bp ‘601’ NCP. In solution, the telomeric nucleosome exhibited a less stable and a markedly more dynamic structure compared to NCPs containing DNA positioning sequences. These observations provide molecular insights into how telomeric DNA forms nucleosomes and chromatin and advance our understanding of the unique biological role of telomeres.
Predicting genotypic values associated with gene interactions using neural networks: A simulation study for investigating factors affecting prediction accuracy
Authors: Onogi Akio 
Published: December 2019

AbstractGenomic prediction has been applied to various species of plants and livestock to enhance breeding efficacy. Neural networks including deep neural networks are attractive candidates to predict phenotypic values. However, the properties of neural networks in predicting non-additive effects have not been clarified. In this simulation study, factors affecting the prediction of genetic values associated with gene interactions (i.e., epistasis) were investigated using multilayer perceptron. The results suggested that (1) redundant markers should be pruned, although markers in LD with QTLs are less harmful, (2) predicting epistatic genetic values with neural networks in real populations would be infeasible using training populations of 1000 samples, (3) neural networks with two or fewer hidden layers and a sufficient number of units per hidden layer would be useful, particularly when a certain number of interactions is involved, and (4) neural networks have greater capability to predict epistatic genetic values than random forests, although neural networks are more sensitive to training population size and the level of epistatic genetic variance. These lessons also would be applicable to other regression problems in which interactions between explanatory variables are expected,e.g., gene-by-environment interactions.
Two tandem mechanisms control bimodal expression of the flagellar genes inSalmonella enterica
Authors: Wang Xiaoyi , Koirala Santosh , Aldridge Phillip D. , Rao Christopher V. 
Published: December 2019

ABSTRACTFlagellar gene expression is bimodal inSalmonella enterica. Under certain growth conditions, some cells express the flagellar genes whereas others do not. This results in mixed populations of motile and non-motile cells. In the present study, we found that two independent mechanisms control bimodal expression of the flagellar genes. One was previously found to result from a double negative-feedback loop involving the flagellar regulators YdiV and FliZ. This feedback loop governs bimodal expression of class 2 genes. In this work, a second mechanism was found to govern bimodal expression of class 3 genes. In particular, class 3 gene expression is still bimodal even when class 2 gene expression is not. Using a combination of experimental and modeling approaches, we found that class 3 bimodalilty results from the σ28-FlgM developmental checkpoint.IMPORTANCEMany bacterial use flagella to swim in liquids and swarm over surface. InSalmonella enterica, over fifty genes are required to assemble flagella. The expression of these genes is tightly regulated. Previous studies have found that flagella gene expression is bimodal inS. enterica, which means that only a fraction of cells express flagellar genes and are motile. In the present study, we found that two separate mechanisms induce this bimodal response. One mechanism, which was previously identified, tunes the fraction of motile cells in response to nutrients. The other results from a developmental checkpoint that couples flagellar gene expression to flagellar assembly. Collectively, these results further our understanding of how flagellar gene expression is regulated inS. enterica.
Making the best of a bad job? Chick mortality and flexible female brood care in Snowy Plovers
Authors: Kupán Krisztina , Székely Tamás , Cruz-López Medardo , Seymour Keeley , Küpper Clemens 
Published: December 2019

AbstractOffspring desertion represents a trade-off between current and future reproductive success. Its timing is crucial as the termination of parental care has profound consequences for the fitness of the parents and their offspring. However, the decision process involved with termination of care is still poorly understood. Snowy PloversCharadrius nivosusshow highly flexible brood care with females either deserting the brood early or providing care for an extended period. Deserting females often quickly remate and start a new breeding attempt. Using a dynamic modelling framework, we investigated the decision-making process for continuation or termination of care by females over a seven-year period. The length of female care increased over the season likely reflecting lower re-mating opportunities for deserting females late in the season. Present brood size, assessed daily during the brood care period, was strongly related to the length of female care: females were more likely to stay and care for larger than for smaller broods. Chick death and desertion frequently coincided, suggesting that poor offspring condition served as a trigger for female desertion. Overall, deserting females had a similar number of fledglings to caring females. This suggests that for many females, desertion was not a strategy to escape the shackles of monogamy and secure higher reproductive success through sequential polygamy. Rather, most deserting females made the best of a bad job when conditions were poor and their continued presence did not make a difference for the survival of their young. We conclude that when making the decision to continue or terminate care, Snowy Plover females monitor the condition of their offspring closely and adjust their care flexibly to the value and needs of their young.
HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4+ T cell death
Authors: Daussy Coralie F , Galais Mathilde , Pradel Baptiste , Robert-Hebmann Véronique , Sagnier Sophie , Pattingre Sophie , Biard-Piechaczyk Martine , Espert Lucile 
Published: December 2019

AbstractThe immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4+ T lymphocytes death. The viral envelope glycoproteins (Env), expressed at the surface of infected cells, play a key role in this process. Env triggers autophagy, process necessary to subsequent apoptosis, and to production of Reactive Oxygen Species (ROS) in bystander CD4+ T cells. Here, we demonstrate that Env-induced oxidative stress is responsible for their death by apoptosis. Moreover, we report that peroxisomes, organelles involved in the control of oxidative stress, are targeted by Env-mediated autophagy. Indeed, we observe a selective autophagy-dependent decrease in the expression of peroxisomal proteins, catalase and PEX14, upon Env exposure, since the down-regulation of either BECLIN 1 or p62/SQSTM1 restores their expression levels. Fluorescence studies allowed us to conclude that Env-mediated autophagy degrades these entire organelles and specifically the mature ones. Together, our results on Env-induced pexophagy provide new clues on HIV-1-induced immunodeficiency.
Enhanced sensory coding in mouse vibrissal and visual cortex through TRPA1
Authors: Kheradpezhouh Ehsan , Tang Matthew F. , Mattingley Jason B. , Arabzadeh Ehsan 
Published: December 2019

AbstractTransient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel, which is broadly expressed throughout the body. Despite its expression in the mammalian cortex, little is known about the contribution of TRPA1 to cortical function. Here we investigate the role of TRPA1 in sensory information processing by performing electrophysiological recording and 2-photon calcium imaging from two sensory areas in mice: the primary vibrissal somatosensory cortex (vS1) and the primary visual cortex (V1). In vS1, local activation of TRPA1 by its agonist AITC significantly increased the spontaneous activity of cortical neurons, their evoked response to vibrissal stimulation, and their response range, consistent with a positive gain modulation. TRPA1 inhibition with HC-030031 reversed these modulations to below initial control gains. The gain modulations were absent in TRPA1 Knockout mice. In V1, TRPA1 activation increased the gain of direction and orientation selectivity similarly to the gain modulations observed in vS1 cortex. Linear decoding analysis of V1 population activity confirmed faster and more reliable encoding of visual signals in the presence of TRPA1 activation. Overall, our findings reveal a physiological role for TRPA1 in enhancing sensory signals in the mammalian cortex.
Cell cycle dynamics of lamina associated DNA
Authors: van Schaik Tom , Vos Mabel , Peric-Hupkes Daan , van Steensel Bas 
Published: December 2019

AbstractIn mammalian interphase nuclei more than one thousand large genomic regions are positioned at the nuclear lamina (NL). These lamina associated domains (LADs) are involved in gene regulation and may provide a backbone for the overall folding of interphase chromosomes. While LADs have been characterized in great detail, little is known about their dynamics during interphase, in particular at the onset of G1 phase and during DNA replication. To study these dynamics, we developed an antibody-based variant of the DamID technology (named pA-DamID) that allows us to map and visualize genome – NL interactions with high temporal resolution. Application of pA-DamID combined with synchronization and cell sorting experiments reveals that LAD – NL contacts are generally rapidly established early in G1 phase. However, LADs on the distal ∼25 Mb of most chromosomes tend to contact the NL first and then gradually detach, while centromere-proximal LADs accumulate gradually at the NL. Furthermore, our data indicate that S-phase chromatin shows transiently increased lamin interactions. These findings highlight a dynamic choreography of LAD – NL contacts during interphase progression, and illustrate the usefulness of pA-DamID to study the dynamics of genome compartmentalization.
Repeatability analysis improves the reliability of behavioral data
Authors: Rudeck Juliane , Vogl Silvia , Banneke Stefanie , Schönfelder Gilbert , Lewejohann Lars 
Published: December 2019

AbstractReliability of data has become a major concern in the course of the reproducibility crisis. Especially when studying animal behavior, confounding factors such as novel test apparatus can lead to a wide variability of data. At worst, effects of novelty or stress related behavior can mask treatment effects and the behavioral data may be misinterpreted. Habituation to the test situation is a common practice to circumvent novelty induced increases in variance and to improve the reliability of the respective measurements. However, there is a lack of published empirical knowledge regarding reasonable habituation procedures and a method validation seems to be overdue.This study aimed at setting up a simple strategy to increase reliability of behavioral data. Therefore, exemplary data from mice tested in an Open Field (OF) arena were used to elucidate the potential of habituation and how reliability of measures can be confirmed by means of a repeatability analysis using the software R. On seven consecutive days, male C57BL/6J, BALB/cJ and 129S1/SvImJ mice were tested in an OF arena once daily and individual mouse behavior (distance travelled, average activity) was recorded. A repeatability analysis was conducted in order to estimate the reliability of measured animal behavior with regard to repeated trials of habituation.Our data analysis revealed that monitoring animal behavior during habituation is important to determine when individual differences of the measurements are stable. Here, the mixed effect model framework proved to be a powerful tool for estimating repeatability values. Repeatability values from distance travelled and average activity increased over the habituation period, revealing that around 60 % of the variance of the data can be explained by individual differences between mice. The first day of habituation was statistically significantly different from the following 6 days in terms of distance travelled and average activity. A habituation period of three days appeared to be sufficient in this study. Overall these results emphasize the importance of habituation and in depth analysis of habituation data to define the correct starting point of the experiment for improving the reliability and reproducibility of experimental data.
Dancing bees evaluate agricultural forage resources as inferior to central urban land
Authors: Samuelson Ash E. , Schürch Roger , Leadbeater Ellouise 
Published: December 2019

AbstractRecent evidence suggests that flower-rich areas within cities could play an important role in pollinator conservation, but direct comparison of agricultural and urban areas has proved challenging to perform over large scales. Here we use the waggle dances of honeybees (Apis melliferaL.) to evaluate floral resource availability over the entire season at deeply urban or agricultural sites. Through analysis of 3378 dances that were performed over two years by 20 colonies in SE England, we show that foraging trip distance is consistently lower at urban sites across the entire season, implying a higher availability of forage in heavily urbanized areas. Urban bees also collected nectar with a higher mean sugar content. From the self-reported perspective of a generalist pollinator, the modern agricultural landscapes that we studied provided insufficient and transient resources relative to heavily urbanised areas, which may represent important refuges within an impoverished landscape.