bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pluronic gel-based burrowing assay for rapid assessment of neuromuscular health inC. elegans
Authors: Lesanpezeshki Leila , Hewitt Jennifer E. , Laranjeiro Ricardo , Antebi Adam , Driscoll Monica , Szewczyk Nathaniel J. , Blawzdziewicz Jerzy , Lacerda Carla M.R. , Vanapalli Siva A. 
Published: May 2019

AbstractWhole-organism phenotypic assays are central to the assessment of neuromuscular function and health in model organisms such as the nematodeC. elegans. In this study, we report a new assay format for engagingC. elegansin burrowing that enables rapid assessment of nematode neuromuscular health. In contrast to agar environments that pose specific drawbacks for characterization ofC. elegansburrowing ability, here we use the optically transparent and biocompatible Pluronic F-127 gel that transitions from liquid to gel at room temperature, enabling convenient and safe handling of animals. The burrowing assay methodology involves loading animals at the bottom of well plates, casting a liquid-phase of Pluronic on top that solidifies via a modest temperature upshift, enticing animals to reach the surface via chemotaxis to food, and quantifying the relative success animals have in reaching the chemoattractant. We study the influence of Pluronic concentration, gel height and chemoattractant choice to optimize assay performance. To demonstrate the simplicity of the assay workflow and versatility, we show its novel application in multiple areas including (i) evaluating muscle mutants with defects in dense bodies and/or M-lines (pfn-3, atn-1, uig-1, dyc-1, zyx-1, unc-95andtln-1), (ii) tuning assay conditions to reveal changes in the mutantgei- 8, (iii) sorting of fast burrowers in a genetically-uniform wild-type population for later quantitation of their distinct muscle gene expression, and (iv) testing proteotoxic animal models of Huntington and Parkinson’s disease. Results from our studies show that stimulating animals to navigate in a dense environment that offers mechanical resistance to three- dimensional locomotion challenges the neuromuscular system in a manner distinct from standard crawling and thrashing assays. Our simple and high throughput burrowing assay can provide insight into molecular mechanisms for maintenance of neuromuscular health and facilitate screening for therapeutic targets.
Molecular competition in G1 controls when cells simultaneously commit to terminally differentiate and exit the cell-cycle
Authors: Zhao Michael L. , Rabiee Atefeh , Kovary Kyle M. , Bahrami-Nejad Zahra , Taylor Brooks , Teruel Mary N. 
Published: May 2019

SUMMARYTerminal differentiation is essential for the development and maintenance of tissues in all multi-cellular organisms and is associated with a permanent exit from the cell cycle. Failure to permanently exit the cell cycle can result in cancer and disease. However, the molecular mechanisms and timing that coordinates differentiation commitment and cell cycle exit are not yet understood. Here using adipogenesis as a model system to track differentiation commitment in live cells, we show that a rapid switch mechanism engages exclusively in G1 to trigger a simultaneous commitment to differentiate and permanently exit from the cell cycle. We identify a signal integration mechanism whereby the strengths of both mitogen and differentiation stimuli control a molecular competition between cyclin D1 and PPARG-induced expression of the CDK inhibitor p21 which in turn regulates if and when the differentiation switch is triggered and when the proliferative window closes. In this way, the differentiation control system is able to couple mitogen and differentiation stimuli to sustain a long-term balance between terminally differentiating cells and maintaining the progenitor cell pool, a parameter of critical importance for enabling proper development of tissue domains and organs.HIGHLIGHTSProgenitor cells both commit to terminally differentiate and permanently exit the cell cycle at a precise time in G1 as a result of a competition process that can last over multiple cell cycles.Positive-feedback driven expression of PPARG and the parallel induction of p21 triggers a rapid commitment to terminally differentiate and then maintains a postmitotic adipocyte state.Opposing mitogen and adipogenic signals are funneled into a molecular competition in G1 phase that controls if and when cells commit to differentiate, which in turn regulates the number of differentiated cells produced while allowing for the maintenance of sufficient progenitor cells.
Population genetic simulation study of power in association testing across genetic architectures and study designs
Authors: Ming Hay Tong Dominic , Hernandez Ryan D. 
Published: May 2019

AbstractWhile it is well established that genetics can be a major contributor to population variation of complex traits, the relative contributions of rare and common variants to phenotypic variation remains a matter of considerable debate. Here, we simulate rare variant association studies across different case/control panel sampling strategies, sequencing methods, and genetic architecture models based on evolutionary forces to determine the statistical performance of RVATs widely in use. We find that the highest statistical power of RVATs is achieved by sampling case/control individuals from the extremes of an underlying quantitative trait distribution. We also demonstrate that the use of genotyping arrays, in conjunction with imputation from a whole genome sequenced (WGS) reference panel, recovers the vast majority (90%) of the power that could be achieved by sequencing the case/control panel using current tools. Finally, we show that for dichotomous traits, the statistical performance of RVATs decreases as rare variants become more important in the trait architecture. Our results extend previous work to show that RVATs are insufficiently powered to make generalizable conclusions about the role of rare variants in dichotomous complex traits.
Sphingolipid production by gut Bacteroidetes regulates glucose homeostasis
Authors: Johnson Elizabeth L. , Heaver Stacey L. , Waters Jillian L. , Kim Benjamin I. , Bretin Alexis , Goodman Andrew L. , Gewirtz Andrew T. , Worgall Tilla S. , Ley Ruth E. 
Published: May 2019

AbstractLevels of Bacteroidetes in the gut microbiome are positively associated with insulin resistance (IR) in humans. Considering that IR is promoted by elevations in hepatic sphingolipids (SL), particularly ceramides, and that Bacteroidetes are the only microbiome phylum possessing genes encoding serine palmitoyltransferase (SPT), which mediates SL synthesis, we investigated a potential link between bacterial SL production, host SL metabolism, and IR.In vitro, bacterial SLs entered colonocytes and were metabolized into complex SL, including ceramides. In mice, administration of WTBacteroides thetaiotaomicron, but not a SPT-deficient mutant, resulted in elevated levels of liver ceramides and reduced responsiveness to exogenously administered insulin. This work establishes bacterial SLs as a new class of microbiome-derived molecule capable of impacting host metabolism.One Sentence SummarySL production by gut Bacteroidetes regulates liver ceramide levels and insulin sensitivity.
Biogeographic patterns of ectomycorrhizal fungal communities associated withCastanopsis sieboldiiacross the Japanese archipelago
Authors: Matsuoka Shunsuke , Iwasaki Takaya , Sugiyama Yoriko , Kawaguchi Eri , Doi Hideyuki , Osono Takashi 
Published: May 2019

AbstractBiogeographic patterns in ectomycorrhizal (ECM) fungal communities and their drivers have been elucidated, including effects of host tree species and abiotic (climatic and edaphic) conditions. At these geographic scales, genotypic diversity and composition of single host tree species change with spatial and environmental gradients, reflecting their historical dispersal events. However, whether the host genotypes can be associated with the biogeographic patterns of ECM communities remains unclear. We investigated the biogeographic pattern of ECM fungal community associated with the single host speciesCastanopsis sieboldii(Fagaceae), whose genotypic diversity and composition across the Japanese archipelago has already been evaluated, and we quantified the effect of host genotypes on the biogeographic pattern. Richness and community composition of ECM fungi changed with latitude and longitude; these biogeographic changes of ECM community were significantly explained by host genotypic variables. Quantitative analyses showed a higher relative explanatory power of climatic and spatial variables than that of host genotypic variables for the biogeographic patterns in the ECM community. Our results suggest the importance of historical events of host dispersal in determining the biogeographic patterns of the ECM fungal community, while their explanation power was lower than that for climatic filtering and/or fungal dispersal.
Analysis of soybean germination, emergence, and prediction of a possible northward expansion of the crop under climate change
Authors: Lamichhane Jay Ram , Constantin Julie , Schoving Céline , Maury Pierre , Debaeke Philippe , Aubertot Jean-Noël , Dürr Carolyne 
Published: May 2019

AbstractSoybean (Glycine max (L.) Merr.) has potential to improve sustainability of agricultural production systems. A higher focus on this crop is needed to re-launch its production in the EU. A better understanding of key determinants affecting soybean establishment represents a first step to facilitate its adoption in cropping systems. To this objective, we conducted laboratory and field experiments in order to better characterize seed germination and seedling growth in relation to temperatures, water content, and soil structure. We then used these data to parametrize the SIMPLE crop emergence model and to evaluate its prediction quality, by comparing observed field germination and emergence data with the predicted ones. Finally, we performed a simulation study over the 2020-2100 period, for three sowing dates, from mid-March to mid-April, in the northern climate of France to evaluate whether future climate change will help expand soybean from Southern to Northern part of the country. Soybean germination was very fast, taking only 15 °C days to reach 50% germination at optimal conditions. The base, optimum and maximum temperatures were determined as 4, 30 and 40°C, respectively while the base water potential was −0.7 MPa, indicating a high sensitivity to water stress. The SIMPLE model well-predicted germination and emergence courses and their final rates, compared with the observed field data. The simulation study showed average emergence rate ranging from 61 to 78% with little variability among sowing dates and periods, but a high variability between years. Main causes of non-emergence were seedling mortality due to clods or soil surface crust followed by non-germination and seedling mortality due to drought, especially for mid-April sowing. These results provide a better knowledge of soybean establishment that are encouraging to introduce soybean with early sowings to diversify current cropping systems.
Cornelia-de Lange syndrome-associated mutations cause a DNA damage signalling and repair defect
Authors: Olley Gabrielle , Pradeepa Madapura M. , FitzPatrick David R. , Bickmore Wendy A. , Boumendil Charlene 
Published: May 2019

SummaryCornelia de Lange Syndrome is a multisystem developmental disorder typically caused by mutations in the gene encoding the cohesin loader NIPBL. The associated phenotype is generally assumed to be the consequence of aberrant transcriptional regulation. Recently, we identified a residue substitution in BRD4 associated with a Cornelia de Lange-like syndrome, that reduces BRD4 binding to acetylated histones. Here we show that, although this mutation reduces BRD4-occupancy at enhancers in mouse embryonic stem cells, it does not affect transcription. Rather it delays the cell cycle, increases DNA damage signalling, and perturbs regulation of DNA repair in mutant cells. This uncovers a new role for BRD4 in DNA repair pathway choice. Furthermore, we find evidence of a similar increase in DNA damage signalling in cells derived from NIPBL-deficient individuals, suggesting that defective DNA damage signalling and repair is also a feature of typical Cornelia de Lange Syndrome.
Sustained perturbation in functional connectivity induced by cold pain
Authors: Makovac Elena , Dipasquale Ottavia , Jackson Jade B , Medina Sonia , O’Daly Owen , O’Muircheartaigh Jonathan , de Lara Rubio Alfonso , Williams Steven CR , McMahon Stephen B , Howard Matthew A 
Published: May 2019

AbstractFunctional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes is varied and inconsistent between cohorts. Increases and decreases in connectivity strength in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how other networks are effected, for example, descending pain control networks, remains unknown. Whether connectivity changes relate to peripherally-mediated nociceptive afferent input, represent coping strategies or are sequelae of chronic pain, e.g. anxiety/depression, is also unknown. Here, we examined FC changes in response to experimentally-administered tonic cold pain in healthy volunteers as a means of disambiguating the nature of connectivity changes. We assessed FC prior to, during, and following tonic cold painful stimulation in four seed regions: ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG) and recorded subjectively reported pain using a computerised visual analogue scale. We saw DMN FC changes during painful stimulation and that inter-network communication between the rAI and sgACC seeds with the vmPFC became less anti-correlated during pain, whereas PAG-precuneus FC decreased. Pain-induced FC alterations largely persisted during a 6-minute recovery period following cessation of the painful stimulus. Observed FC changes related to the magnitude of individuals’ subjectively reported pain. We provide new insights into FC changes during and following tonic cold-pain and suggest that some FC changes observed in chronic pain patients may relate to the presence of an ongoing afferent peripheral drive.
Deep serum proteomics reveal biomarkers and causal candidates for type 2 diabetes
Authors: Gudmundsdottir Valborg , Emilsson Valur , Aspelund Thor , Ilkov Marjan , Gudmundsson Elias F , Zilhão Nuno R , Lamb John R , Jennings Lori L , Gudnason Vilmundur 
Published: May 2019

AbstractThe prevalence of type 2 diabetes mellitus (T2DM) is expected to increase rapidly in the next decades, posing a major challenge to societies worldwide. The emerging era of precision medicine calls for the discovery of biomarkers of clinical value for prediction of disease onset, where causal biomarkers can furthermore provide actionable targets. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach measuring serum levels of 4,137 proteins in 5,438 Icelanders to discover novel biomarkers for incident T2DM and describe the serum protein profile of prevalent T2DM. We identified 536 proteins associated with incident or prevalent T2DM. Through LASSO penalized logistic regression analysis combined with bootstrap resampling, a panel of 20 protein biomarkers that accurately predicted incident T2DM was identified with a significant incremental improvement over traditional risk factors. Finally, a Mendelian randomization analysis provided support for a causal role of 48 proteins in the development of T2DM, which could be of particular interest as novel therapeutic targets.
Microbial communities profiling in intensive care units expose limitations in current sanitary standards
Authors: Ribeiro Lucas Ferreira , Lopes Erica M. , Kishi Luciano T. , Ribeiro Liliane Fraga Costa , Menegueti Mayra Gonçalves , Gaspar Gilberto Gambero , Silva-Rocha Rafael , Guazzaroni María Eugenia 
Published: May 2019

ABSTRACTHospital-associated infections (HAIs) are the leading cause of morbidity and mortality in intensive care units (ICUs) and neonatal intensive care units (NICUs). Organisms causing these infections are often present on surfaces around the patient. Given that microbiotas may vary across different ICUs, the HAI-related microbial signatures within these units remain underexplored. In this study, we use deep-sequencing analyses to explore and compare the structure of bacterial communities at inanimate surfaces of the ICU and NICU wards of The Medical School Clinics Hospital (Brazil). The data revealed that NICU presents higher biodiversity than ICU and surfaces closest to the patient showed a peculiar microbiota, distinguishing one unit from the other. Several facultative anaerobes or obligate anaerobes HAI-related genera were classified as biomarkers for the NICU, whereasPseudomonaswas the main biomarker for ICU. Correlation analyses revealed a distinct pattern of microbe-microbe interactions for each unit, including bacteria able to form multi-genera biofilms. Furthermore, we evaluated the effect of concurrent cleaning over the ICU bacterial community. The results showed that, although some bacterial populations decreased after cleaning, various HAI-related genera were quite stable to sanitization, suggesting being well-adapted to the ICU environment. Overall, these results enabled identification of discrete ICU and NICU reservoirs of potentially pathogenic bacteria and provided evidence for the presence of a set of biomarkers that distinguish these units. Moreover, the study exposed the inconsistencies of the routine cleaning to minimize HAI-related genera contamination.IMPORTANCEDue to the high impact of HAIs, there is an urgent need for the development of robust policies on microbial surveillance to help guide procedures, improving infection control. To the best of our knowledge, this is the first comprehensive study, using a high-throughput approach, focused on comparing the microbiota peculiarities of the ICU and NICU in one of the largest public hospitals in Brazil. The work highlighted bacteria associated with nosocomial infections, identifying the most potent reservoirs of contamination, and evaluated the microbiota changes related to the cleaning procedure. Therefore, this study contributes to increase the knowledge about (N)ICUs microbiomes and may help to reduce health-care-associated infections, especially in developing countries.
A global screen for assembly state changes of the mitotic proteome by SEC-SWATH-MS
Authors: Heusel Moritz , Frank Max , Köhler Mario , Amon Sabine , Frommelt Fabian , Rosenberger George , Bludau Isabell , Aulakh Simran , Linder Monika I. , Liu Yansheng , Collins Ben C. , Gstaiger Matthias , Kutay Ulrike , Aebersold Ruedi 
Published: May 2019

SummaryLiving systems integrate biochemical reactions that determine the functional state of each cell. Reactions are primarily mediated by proteins that have in systematic studies been treated as independent entities, disregarding their higher level organization into complexes which affects their activity and/or function and is thus of great interest for biological research. Here, we describe the implementation of an integrated technique to quantify cell state-specific changes in the physical arrangement of protein complexes, concurrently for thousands of proteins and hundreds of complexes. Applying this technique for comparison of human cells in interphase and mitosis, we provide a systematic overview of mitotic proteome reorganization. The results recall key hallmarks of mitotic complex remodeling and discover new events, such as a new model of nuclear pore complex disassembly, validated by orthogonal methods. To support the interpretation of quantitative SEC-SWATH-MS datasets, we extend the software CCprofiler and provide an interactive exploration tool, SECexplorer-cc.HighlightsQuantification of proteome assembly state changes using SEC-SWATH-MSSystems-wide analysis of assembly state changes in the mitotic proteomeDiscovery and validation of a novel mitotic disassembly intermediate of the nuclear pore complexHigher sensitivity and information content compared to thermostability-based approaches for global measurement of proteome statesSECexplorer, an online platform to browse results and investigate proteins newly implicated in cell division
Genomics of sorghum local adaptation to a parasitic plant
Authors: Bellis Emily S. , Kelly Elizabeth A. , Lorts Claire M. , Gao Huirong , DeLeo Victoria L. , Rouhan Germinal , Budden Andrew , Bhaskara Govinal Badiger , Hu Zhenbin , Muscarella Robert , Timko Michael P. , Nebie Baloua , Runo Steven M. , Chilcoat N. Doane , Juenger Thomas E. , Morris Geoffrey P. , dePamphilis Claude W. , Lasky Jesse R. 
Published: May 2019

ABSTRACTHost-parasite coevolution can maintain high levels of genetic diversity in traits involved in species interactions. In many systems, host traits exploited by parasites are constrained by use in other functions, leading to complex selective pressures across space and time. Here, we study genome-wide variation in the staple crop Sorghum bicolor (L.) Moench and its association with the parasitic weed Striga hermonthica (Delile) Benth., a major constraint to food security in Africa. We hypothesize that geographic selection mosaics across gradients of parasite occurrence maintain genetic diversity in sorghum landrace resistance. Suggesting a role in local adaptation to parasite pressure, multiple independent loss-of-function alleles at sorghum LOW GERMINATION STIMULANT 1 (LGS1) are broadly distributed among African landraces and geographically associated with S. hermonthica occurrence. However, low frequency of these alleles within S. hermonthica-prone regions and their absence elsewhere implicate potential tradeoffs restricting their fixation. LGS1 is thought to cause resistance by changing stereochemistry of strigolactones, hormones that control plant architecture and belowground signaling to mycorrhizae and are required to stimulate parasite germination. Consistent with tradeoffs, we find signatures of balancing selection surrounding LGS1 and other candidates from analysis of genome-wide associations with parasite distribution. Experiments with CRISPR-Cas9 edited sorghum further indicate the benefit of LGS1-mediated resistance strongly depends on parasite genotype and abiotic environment and comes at the cost of reduced photosystem gene expression. Our study demonstrates long-term maintenance of diversity in host resistance genes across smallholder agroecosystems, providing a valuable comparison to both industrial farming systems and natural communities.SIGNIFICANCE STATEMENTUnderstanding co-evolution in crop-parasite systems is critical to management of myriad pests and pathogens confronting modern agriculture. In contrast to wild plant communities, parasites in agricultural ecosystems are usually expected to gain the upper hand in co-evolutionary ‘arms races’ due to limited genetic diversity of host crops in cultivation. Here, we develop a framework to characterize associations between genome variants in global landraces (traditional varieties) of the staple crop sorghum with the distribution of the devastating parasitic weed Striga hermonthica. We find long-term maintenance of diversity in genes related to parasite resistance, highlighting an important role of host adaptation for co-evolutionary dynamics in smallholder agroecosystems.