bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social Disruption: Sublethal pesticides in pollen lead toApis melliferaqueen events and brood loss
Authors: Traynor Kirsten S. , vanEngelsdorp Dennis , Lamas Zachary S. 
Published: October 2020

AbstractEusocialApis melliferacolonies depend on queen longevity and brood viability to survive, as the queen is the sole reproductive individual and the maturing brood replenishes the shorter lived worker bees. Production of many crops rely on both pesticides and bee pollination to improve crop quantity and quality. We looked at the resiliency of queens and their brood after one month of sublethal exposure to field relevant doses of pesticides that mimic exposure during commercial pollination contracts. We exposed full size colonies to pollen contaminated with field-relevant doses of the fungicides (chlorothalonil and propicanizole), insecticides (chlorypyrifos and fenpropathrin) or both, noting a significant reduction in pollen consumption in colonies exposed to fungicides compared to control. While we found no difference in the total amount of pollen collected per colony, a higher proportion of pollen to non-pollen foragers was detected in all pesticide exposed colonies. After ceasing treatments we measured brood development, discovering a significant increase in brood loss and/or cannibalism across all pesticide exposed groups. Sublethal pesticide exposure in general was linked to reduced production of replacement workers and a change in protein acquisition (pollen vs. non-pollen foraging). Fungicide exposure also resulted in increased loss of the reproductive queen.
Assessing short- and long-term variations in diversity, timing, and body condition of migratory frugivorous birds
Authors: Campo-Celada María , Mendoza Irene , Benítez-López Ana , Gutiérrez-Expósito Carlos , Rabadán-González Julio , Jordano Pedro 
Published: October 2020

AbstractUnder current global change context, climate change is driving substantial phenological mismatches between plant species and the organisms that rely on them. Given that frugivorous birds are fundamental for forest regeneration, and most of them are migrant species, identifying the effect of global change over them must be a priority. In this study we have analysed changes in the composition, morphometry, and physical condition in an avian community at long- (40 years) and short time (seasonal) spans. Our findings indicate a profound transformation at practically every level of analysis. In 40 years, the avian community shows a 66% and 13% decrease of the wintering and seed-disperser species, respectively. Seasonal abundance peaks were advanced in 13 out of 15 species. In addition, we have found a significant 1.5% increase in the morphometric measurements of certain species, supporting findings in previous studies, and also a remarkable general decrease of body condition. Our results point towards land use changes and climate change as the main causes. If this influence continues to rise, biodiversity will likely be irreversibly altered, damaging crucial ecosystem functions such as animal-mediated seed dispersal and forest regeneration in particular.
ASTER: A Method to Predict Clinically Actionable Synthetic Lethal Genetic Interactions
Authors: Liany Herty , Jeyasekharan Anand , Rajan Vaibhav 
Published: October 2020

ABSTRACTA Synthetic Lethal (SL) interaction is a functional relationship between two genes or functional entities where the loss of either entity is viable but the loss of both is lethal. Such pairs can be used to develop targeted anticancer therapies with fewer side effects and reduced overtreatment. However, finding clinically actionable SL interactions remains challenging. Leveraging unified gene expression data of both disease-free and cancerous samples, we design a new technique based on statistical hypothesis testing, called ASTER, to identify SL pairs. We empirically find that the patterns of mutually exclusivity ASTER finds using genomic and transcriptomic data provides a strong signal of SL. For large-scale multiple hypothesis testing, we develop an extension called ASTER++ that can utilize additional input gene features within the hypothesis testing framework. Our extensive experiments demonstrate the efficacy of ASTER in identifying SL pairs with potential therapeutic benefits.CCS CONCEPTS• Applied computing→Computational genomics;Health informatics; •Mathematics of computing→Hypothesis testing and confidence interval computation.ACM Reference FormatHerty Liany, Anand Jeyasekharan, and Vaibhav Rajan. 2021. ASTER: A Method to Predict Clinically Actionable Synthetic Lethal Genetic Interactions. InProceedings of ACM Conference. ACM, New York, NY, USA, 10 pages.https://doi.org/10.1145/nnnnnnn.nnnnnnn
Multiple ligand recognition sites in free fatty acid receptor 2 (FFAR2) direct distinct neutrophil activation patterns
Authors: Lind Simon , Holdfeldt André , Mårtensson Jonas , Granberg Kenneth L. , Forsman Huamei , Dahlgren Claes 
Published: October 2020

AbstractNon-activating positive allosteric modulators specific for free fatty acid receptor 2 (FFAR2) increased the activity induced by orthosteric agonists to trigger a rise in intracellular Ca2+([Ca2+]i) and activate the O2−producing neutrophil NADPH-oxidase. In addition, two allosteric modulators (Cmp58 and AZ1729) recognized by different receptor domains on FFAR2, cooperatively triggered activation without any rise in [Ca2+]i. To gain insights into FFAR2 modulation and signaling, we set out to identify structurally diverse allosteric FFAR2 modulators. Initially, we identified two molecules that directly activate neutrophils and these were classified as an allosteric FFAR2 agonists and an orthosteric agonist, respectively. Based on the sensitizing effect on the neutrophil response to propionate, ten non-direct-activating molecules were classified as allosteric FFAR2 modulators. One of these synergistically activated neutrophils when combined with AZ1729, but not when combined with Cmp58. The remaining nine compounds synergistically induced the same type of biased neutrophil signaling but only when combined with Cmp58. The activation signals down-stream of FFAR2 when stimulated by two allosteric modulators with different binding sites were in most cases biased in that two complementary modulators together triggered an activation of the NADPH-oxidase, but no increase in [Ca2+]i. The neutrophil activation pattern achieved when two functionally “AZ1729- or “Cmp58-like” allosteric FFAR2 modulators were combined, supporting a model for activation in which FFAR2 has two different sites that selectively bind allosteric modulators. The novel neutrophil activation patterns and receptor down-stream signaling mediated by two cross-sensitizing allosteric modulators represent a new regulatory mechanism that controls FFAR2 receptor function.
Spatiotemporal organization of movement-invariant and movement-specific signaling in the output layer of motor cortex
Authors: Currie Stephen P. , Ammer Julian J. , Premchand Brian , Dacre Joshua , Wu Yufei , Eleftheriou Constantinos , Colligan Matt , Clarke Thomas , Mitchell Leah , Faisal Aldo , Hennig Matthias H. , Duguid Ian 
Published: October 2020

AbstractMotor cortex generates descending output necessary for executing a wide range of limb movements. Although movement-related activity has been described throughout motor cortex, the spatiotemporal organization of movement-specific signaling in deep layers remains largely unknown. Here, we recorded layer 5B population dynamics in the caudal forelimb area of motor cortex while mice performed a forelimb push/pull task and found that most neurons show movement-invariant responses, with a minority displaying movement specificity. Cell-type-specific imaging identified that movement-invariant responses dominated pyramidal tract (PT) neuron activity, with a small subpopulation representing movement type, whereas a larger proportion of intratelencephalic (IT) neurons displayed movement-specific signaling. The proportion of IT neurons decoding movement-type peaked prior to movement initiation, while for PT neurons this occurred during movement execution. Our data suggest that layer 5B population dynamics largely reflect movement-invariant signaling, with information related to movement-type being differentially routed through relatively small, distributed subpopulations of projection neurons.
DOUBLER: Unified Representation Learning of Biological Entities and Documents for Predicting Protein–Disease Relationships
Authors: Sztyler Timo , Malone Brandon 
Published: October 2020

AbstractMotivationWe propose a system that learns consistent representations of biological entities, such as proteins and diseases, based on a knowledge graph and additional data modalities, like structured annotations and free text describing the entities. In contrast to similar approaches, we explicitly incorporate the consistency of the representations into the learning process. In particular, we use these representations to identify novel proteins associated with diseases; these novel relationships could be used to prioritize protein targets for new drugs.ResultsWe show that our approach outperforms state-of-the-art link prediction algorithms for predicting unknown protein–disease associations. Detailed analysis demonstrates that our approach is most beneficial when additional data modalities, such as free text, are informative.AvailabilityCode and data are available at:https://github.com/nle-sztyler/research-doublerContacttimo.sztyler@neclab.eu
Root water gates and not changes in root structure provide new insights into plant physiological responses and adaptations to drought, flooding and salinity
Authors: Domec Jean-Christophe , King John S. , Carmichael Mary J. , Overby Anna Treado , Wortemann R Remi , Smith William K. , Miao Guofang , Noormets Asko , Johnson Daniel M. 
Published: October 2020

AbstractThe influence of aquaporin (AQP) activity on plant water movement remains unclear, especially in plants subject to unfavorable conditions. We applied a multitiered approach at a range of plant scales to (i) characterize the resistances controlling water transport under drought, flooding and flooding plus salinity conditions; (ii) quantify the respective effects of AQP activity and xylem structure on root (Kroot), stem (Kstem) and leaf (Kleaf) conductances, and (iii) evaluate the impact of AQP-regulated transport capacity on gas exchange. We found that drought, flooding and flooding-salinity reduced Krootand root AQP activity inPinus taeda, whereas Krootof the flood-tolerantTaxodium distichumdid not decline under flooding. The extent of the AQP-control of transport efficiency varied among organs and species, ranging from 35%-55% in Krootto 10%-30% in Kstemand Kleaf. In response to treatments, AQP-mediated inhibition of Krootrather than changes in xylem acclimation controlled the fluctuations in Kroot. The reduction in stomatal conductance and its sensitivity to vapor pressure deficit were direct responses to decreased whole-plant conductance triggered by lower Krootand larger resistance belowground. Our results provide new mechanistic and functional insights on plant hydraulics that are essential to quantifying the influences of future stress on ecosystem function.
The mutability of demographic noise in microbial range expansions
Authors: Yu QinQin , Gralka Matti , Duvernoy Marie-Cécilia , Sousa Megan , Harpak Arbel , Hallatschek Oskar 
Published: October 2020

AbstractDemographic noise, the change in the composition of a population due to random birth and death events, is an important driving force in evolution because it reduces the efficacy of natural selection. Demographic noise is typically thought to be set by the population size and the environment, but recent experiments with microbial range expansions have revealed substantial strain-level differences in demographic noise under the same growth conditions. Many genetic and phenotypic differences exist between strains; to what extent do single mutations change the strength of demographic noise? To investigate this question, we developed a high-throughput method for measuring demographic noise in colonies without the need for genetic manipulation. By applying this method to 191 randomly-selected single gene deletion strains from theE. coliKeio collection, we find that a typical single gene deletion mutation decreases demographic noise by 8% (maximal decrease: 81%). We find that the strength of demographic noise is an emergent trait at the population level that can be predicted by colony-level traits but not cell-level traits. The observed differences in demographic noise from single gene deletions can increase the establishment probability of beneficial mutations by almost an order of magnitude higher than the wild type. Our results show that single mutations can substantially alter adaptation through their effects on demographic noise and suggest that demographic noise can be an evolvable phenotype of a population.
Graded titin cleavage progressively reduces tension and uncovers the source of A-band stability in contracting muscle
Authors: Li Yong , Hessel Anthony L. , Unger Andreas , Ing David , Recker Jannik , Koser Franziska , Freundt Johanna K. , Linke Wolfgang A. 
Published: October 2020

AbstractThe giant muscle protein titin is a major contributor to passive force; however, its role in active force generation is unresolved. Here, we use a novel titin-cleavage (TC) mouse model that allows specific and rapid cutting of elastic titin to quantify how titin-based forces define myocyte ultrastructure and mechanics. We show that under mechanical strain, as titin cleavage doubles from heterozygous to homozygous TC muscles, Z-disks become increasingly out of register while passive and active forces are reduced. Interactions of elastic titin with sarcomeric actin filaments are revealed. Strikingly, when titin-cleaved muscles contract, myosin-containing A-bands become split and adjacent myosin filaments move in opposite directions while also shedding myosins. This establishes intact titin filaments as critical force-transmission networks, buffering the forces observed by myosin filaments during contraction. To perform this function, elastic titin must change stiffness or extensible length, unveiling its fundamental role as an activation-dependent spring in contracting muscle.
IDENTIFICATION OF A NOVEL MECHANISM FOR LFA-1 ORGANIZATION DURING NK CYTOLYTIC RESPONSE
Authors: Pariani Alejandro P. , Almada Evangelina , Hidalgo Florencia , Borini-Etichetti Carla , Vena Rodrigo , Marín Leandra , Favre Cristián , Goldenring James R. , Larocca M. Cecilia 
Published: October 2020

AbstractThe elimination of transformed and viral infected cells by natural killer (NK) cells requires the formation of a specialized junction between NK and target cells, generally denominated immunological synapse (IS). After initial recognition, the IS enables the directed secretion of lytic granules content into the susceptible target cell. The lymphocyte function–associated antigen (LFA)-1 regulates NK effector function by enabling NK-IS assembly and maturation. The pathways underlying LFA-1 accumulation at the IS in NK cells have not been elucidated so far. A kinase anchoring protein 350 (AKAP350) is a centrosome/Golgi associated protein with a central role in the regulation of Golgi organization and microtubule dynamics. In T cells, AKAP350 participates in LFA-1 activation by mechanisms that remain elusive. We first investigated AKAP350 participation in NK cytolytic activity. Our results showed that the decrease in AKAP350 levels by expression of specific shRNAs (AKAP350KD) inhibited NK-YTS cytolytic activity, without affecting NK:target cell conjugate formation. The impairment of NK effector function in AKAP350KD cells correlated with decreased LFA-1 clustering and defective IS maturation. AKAP350KD cells that were exclusively activatedviaLFA-1 showed impaired LFA-1 organization and deficient lytic granule translocation as well. In NK AKAP350KD cells, activation signaling through Vav1 was preserved up to 10 min of interaction with target cells, but significantly decreased afterwards. Experiments in YTS and inex vivoNK cells revealed the existence of an intracellular pool of LFA-1 vesicles, which partially associated with the Golgi apparatus. Upon NK cell activation, this LFA-1 pool redistributed to the IS in a Golgi-AKAP350-dependent manner. Disruption of Golgi integrity or alteration of microtubule dynamics impaired LFA-1 localization at the IS. Therefore, this study reveals the existence of a Golgi/AKAP350 dependent trafficking pathway for LFA-1, which is relevant for LFA-1 organization at NK-lytic IS and, concomitantly, for NK cytolytic function.
Resilience in a Natural Model of Metabolic Dysfunction Through Changes in Longevity and Ageing-Related Metabolites
Authors: Medley J Kyle , Persons Jenna , Biswas Tathagata , Olsen Luke , Peuß Robert , Krishnan Jaya , Xiong Shaolei , Rohner Nicolas 
Published: October 2020

AbstractInsights from extreme-adapted organisms, which have evolved natural strategies for promoting survivability under severe environmental pressures, may help guide future research into novel approaches for enhancing human longevity. The cave-adapted Mexican tetra,Astyanax mexicanus, has attracted interest as a model system formetabolic resilience, a term we use to denote the property of maintaining robust health and longevity under conditions that would have highly deleterious effects in other organisms (Fig 1). Cave-dwelling populations of Mexi-can tetra exhibit elevated blood glucose and possess a mutation in the insulin receptor that in humans has been linked to Rabson-Mendenhall syndrome, a condition characterized by severe insulin resistance that causes numerous developmental abnormalities, is highly associated with debilitating progression, and drastically reduces lifespan. In addition, cavefish develop large numbers of hypertrophic visceral adipocytes and possess vastly enriched stores of body fat compared to surface-dwelling counterparts. However, cavefish appear to avoid the progression of the respective pathologies typically associated with these conditions, such as accumulation of advanced glycation end products (AGEs), chronic tissue inflammation, impaired growth due to insulin dysregulation, and low survivability due to arterial disease. The metabolic strategies underlying the resilience properties ofA. mexicanuscavefish, and how they relate to environmental challenges of the cave environment, are poorly understood. Here, we provide an untargeted metabolomics study of long- and short-term fasting in twoA. mexicanuscave populations and one surface population. We find that, although cave-fish share many similarities with metabolic syndrome normally associated with the human state of obesity, important differences emerge, including a reduction in cholesteryl esters and intermediates of protein glycation, and an increase in antioxidants and metabolites associated with hypoxia and longevity. We find important overlaps between metabolic alterations in cave-dwelling Mexican tetra and other models of resilience and extreme longevity, such as naked mole-rats, including enhanced reliance on sugars as an energy source and a trend toward more potent antioxidant activity. This work suggests that certain metabolic features associated with human pathologies are not intrinsically harmful, but are rather consequences of suboptimal adaptation of humans to survival under adverse metabolic conditions, and suggests promising avenues for future investigation into the role of metabolic strategies in evolutionary adaptation and health. We provide a transparent pipeline for reproducing our analysis and a Shiny app for other researchers to explore and visualize our dataset.
PhyKIT: a UNIX shell toolkit for processing and analyzing phylogenomic data
Authors: Steenwyk Jacob L. , Buida Thomas J. , Labella Abigail L. , Li Yuanning , Shen Xing-Xing , Rokas Antonis 
Published: October 2020

AbstractDiverse disciplines in biology process and analyze multiple sequence alignments (MSAs) and phylogenetic trees to evaluate their information content, infer evolutionary events and processes, and predict gene function. However, automated processing of MSAs and trees remains a challenge due to the lack of a unified toolkit. To fill this gap, we introduce PhyKIT, a toolkit for the UNIX shell environment with 30 functions that process MSAs and trees, including but not limited to estimation of mutation rate, evaluation of sequence composition biases, calculation of the degree of violation of a molecular clock, and collapsing bipartitions (internal branches) with low support. To demonstrate the utility of PhyKIT, we detail three use cases: (1) summarizing information content in MSAs and phylogenetic trees for diagnosing potential biases in sequence or tree data; (2) evaluating gene-gene covariation of evolutionary rates to identify functional relationships, including novel ones, among genes; and (3) identify lack of resolution events or polytomies in phylogenetic trees, which are suggestive of rapid radiation events or lack of data. We anticipate PhyKIT will be useful for processing, examining, and deriving biological meaning from increasingly large phylogenomic datasets. PhyKIT is freely available on GitHub (https://github.com/JLSteenwyk/PhyKIT) and documentation including user tutorials are available online (https://jlsteenwyk.com/PhyKIT).
CharPlant: ADe NovoOpen Chromatin Region (OCR) Prediction Tool for Plant Genomes
Authors: Shen Yin , Chen Ling-Ling , Gao Junxiang 
Published: October 2020

AbstractChromatin accessibility is a highly informative structural feature for understanding gene transcription regulation because it indicates the degree to which nuclear macromolecules such as proteins and RNA can access chromosomal DNA. Studies show that chromatin accessibility is highly dynamic during stress response, stimulus response, and developmental transition. Moreover, physical access to chromosomal DNA in eukaryotes is highly cell-specific. Therefore, current technologies such as DNase-seq, ATAC-seq, and FAIRE-seq reveal only a portion of the open chromatin regions (OCRs) present in a given species. Thus, the genome-wide distribution of OCRs remains unknown. In this study, we developed a bioinformatics tool called CharPlant for thede novoprediction of chromatin accessible regions in plant genomes. To develop this tool, we constructed a three-layer convolutional neural network (CNN) and subsequently trained the CNN using DNase-seq and ATAC-seq datasets of four plant species. The model simultaneously learns the sequence motifs and regulatory logics, which are jointly used to determine DNA accessibility. All of these steps are integrated into CharPlant, which can be run using a simple command line. The results of data analysis using CharPlant in this study demonstrate its prediction power and computational efficiency. To our knowledge, CharPlant is the firstde novoprediction tool that can identify potential OCRs in the whole genome. The source code of CharPlant and supporting files are freely downloadable fromhttps://github.com/Yin-Shen/CharPlant.