bluuebunny/crossref_metadata_2025_split huggingface dataset:
A small membrane protein critical to both the offensive and defensive capabilities of Staphylococcus aureus
Authors: Duggan Seána , Laabei Maisem , Alnahari Alaa , O’Brien Eóin C. , Lacey Keenan A. , Bacon Leann , Heesom Kate , Fu Chih-Lung , Otto Michael , Skaar Eric , McLoughlin Rachel M. , Massey Ruth C. 
Published: July 2019

AbstractStaphylococcus aureus is a major human pathogen, where the widespread emergence of antibiotic resistance is making infections more challenging to treat. Toxin induced tissue damage and resistance to the host’s immune system are well established as critical to its ability to cause disease. However, recent attempts to study S. aureus pathogenicity at a population level have revealed significant complexity and hierarchical levels of regulation. In an effort to better understand this we have identified and characterized a principle effector protein, MasA. The inactivation of this small highly-conserved membrane protein simultaneously disrupts toxin production and impairs S. aureus’ ability to resist several aspects of the innate immune system. These pleiotropic effects are mediated by both a change in the stability of the bacterial membrane and the dysregulation of iron homeostasis, which results in a significant impairment in the ability of S. aureus to cause infection in both a subcutaneous and a sepsis model of infection. That proteins with such major effects on pathogenicity remain unidentified in a bacterium as well studied as S. aureus demonstrates how incomplete our understanding of their ability to cause disease is, an issue that needs to be addressed if effective control and treatment strategies are to be developed.
Composite plants for a composite plant: An efficient protocol for root studies in the sunflower using composite plants approach
Authors: Parks Tyler , Yordanov Yordan S. 
Published: July 2019

AbstractSunflower (Helianthus annuus L.) is important oilseed crop in the world and the sunflower oil is prized for its’ exceptional quality and flavor. The recent availability of the sunflower genome can allow genome-wide characterization of genes and gene families. With plant transformation usually being the rate limiting step for gene functional studies of sunflower, composite plants can alleviate this bottleneck. Composite plants, produced using Agrobacterium rhizogenes, are plants with transgenic roots and wild type shoots. Composite plants offer benefits over creating fully transgenic plants, namely time and cost. Here we outlined the critical steps and parameters for a protocol for the sunflower composite plants production. We use more than a dozen genotypes and three constitutive promoters to validates the utility and efficiency of this protocol. Moreover, functional gene characterization by overexpression and RNAi silencing of a root related transcription factor HaLBD16 further emphasize the value of the system in the sunflower studies. With the protocol developed here an experiment can be carried out with efficiency and in only two months. This procedure adds to arsenal of approaches for the functional genetics/genomics in sunflower for characterization candidate genes involved in root development and stress adaptation.Key messageComposite plants technique described here is fast and efficient approach for roots functional studies in sunflower.
Prophylactic efficacy of 5-HT4R agonists against stress
Authors: Chen Briana K. , Mendez-David Indira , Faye Charlene , Gardier Alain M. , David Denis J. , Denny Christine A. 
Published: July 2019

ABSTRACTEnhancing stress resilience could protect against stress-induced psychiatric disorders in at-risk populations. We and others have previously reported that (R,S)-ketamine acts as a resilience enhancing drug (e.g., prophylactic) against stress when administered 1 week before stress. While we have shown that the selective 5-hydroxytryptamine (5-HT) (serotonin) reuptake inhibitor (SSRI) fluoxetine (Flx) is ineffective as a prophylactic, it remains to be determined if other serotonergic drugs could be effective prophylactics. Here, we hypothesized that serotonin 4 receptor (5-HT4R) agonists could be prophylactic against fear, depressive-like, and/or anxiety-like behavior. We tested if three 5-HT4R agonists with varying affinity (e.g., partial or selective agonists) could protect against stress in two mouse strains by utilizing a chronic corticosterone (CORT) administration or a contextual fear conditioning (CFC) paradigm. Mice were administered RS-67,333, prucalopride, or PF-04995274 at varying doses and then 1 week later were subjected to chronic CORT or CFC. Chronic administration of RS-67,333, but not Flx was efficacious as a prophylactic against CORT in C57BL/6NTac mice. A single injection of RS-67,333 attenuated learned fear in male, but not female 129S6/SvEv mice. RS-67,333 was ineffective against stress-induced depressive-like behavior in the forced swim test (FST). A single injection of either prucalopride or PF-04995274 attenuated learned fear and decreased stress-induced depressive-like behavior. These data show that in addition to (R,S)-ketamine, 5-HT4R agonists are also effective prophylactics against stress, suggesting that the 5-HT4R may be a novel target for prophylactic drug development.
ROCK Inhibitor Increases Proacinar Cells in Adult Salivary Gland Organoids
Authors: Koslow Matthew , O’Keefe Kevin J. , Nelson Deirdre A. , Larsen Melinda 
Published: July 2019

AbstractSalisphere-derived adult epithelial cells enriched for progenitor cells have been used to improve saliva production of irradiated mouse salivary glands. Importantly, optimization of the cellular composition of salispheres could improve their regenerative capabilities. The Rho Kinase (ROCK)1 inhibitor, Y27632, has been used to increase the proliferation and reduce apoptosis of progenitor cells grown in vitro. In this study, we investigated whether Y27632 in different cell media contexts could be used to improve expansion of adult epithelial progenitor cells or to affect their differentiation potential. Application of Y27632 in medium used previously to grow salispheres promoted expansion of Kit+ cells, while in simple serum-containing medium Y27632 increased the number of cells that expressed the K5 basal progenitor marker. When tested in a 3D organoid assay, Y27632 enhanced the contribution of adult salispheres to salivary organoids expressing the secretory proacinar marker Aquaporin 5 (AQP5) in response to FGF2 dependent mesenchymal signals. Optimization of epithelial-mesenchymal interactions organoids can be used to improve application of adult salivary progenitor cells in regenerative medicine strategies.HighlightsY27632 promotes Kit+ salisphere cell proliferation in salisphere media.Y27632 promotes K5 expression in salispheres cultured in serum containing media.Y27632 treated Kit+ salispheres form salivary organoids expressing AQP5.
Dynamic changes in RNA-chromatin interactome promote endothelial dysfunction
Authors: Calandrelli Riccardo , Xu Lixia , Luo Yingjun , Wu Weixin , Fan Xiaochen , Nguyen Tri , Chen Chienju , Sriram Kiran , Natarajan Rama , Bouman-Chen Zhen , Zhong Sheng 
Published: July 2019

AbstractChromatins are pervasively attached by RNAs. Here, we asked whether global RNA-chromatin contacts are altered in a given cell type in a disease context, and whether these alterations impact gene expression and cell function. In endothelial cells (ECs) treated by high-glucose and TNFα, we employed single-cell RNA-sequencing and in situ mapping of RNA-genome interaction (iMARGI) assay to delineate temporal changes in transcriptome and RNA-chromatin interactome. ECs displayed dramatic and heterogeneous changes in single cell transcriptome, accompanied by a dynamic and strong increase in inter-chromosomal RNA-DNA interactions, particularly among super enhancers (SEs). These SEs overlap with genes contributing to inflammatory response and endothelial mesenchymal transition (EndoMT), two key aspects of endothelial dysfunction. Perturbation of a high-glucose and TNFα-activated interaction involving SEs overlapping LINC00607 and SERPINE1 attenuated the pro-inflammatory and pro-EndoMT gene induction and EC dysfunction. Our findings highlight RNA-chromatin contacts as a crucial regulatory feature in biological and disease processes, exemplified by endothelial dysfunction, a major mediator of numerous diseases.
Diverse biological processes coordinate the transcriptional response to nutritional changes in aDrosophila melanogastermultiparent population
Authors: Ng’oma E. , Williams-Simon P.A. , Rahman A. , King E.G. 
Published: July 2019

AbstractBackgroundEnvironmental variation in the amount of resources available to populations challenge individuals to optimize the allocation of those resources to key fitness functions. This coordination of resource allocation relative to resource availability is commonly attributed to key nutrient sensing gene pathways in laboratory model organisms, chiefly the insulin/TOR signaling pathway. However, the genetic basis of diet-induced variation in gene expression is less clear.ResultsTo describe the natural genetic variation underlying nutrient-dependent differences, we used an outbred panel derived from a multiparental population, theDrosophilaSynthetic Population Resource. We analyzed RNA sequence data from multiple female tissue samples dissected from flies reared in three nutritional conditions: high sugar (HS), dietary restriction (DR), and control (C) diets. A large proportion of genes in the experiment (19.6% or 2,471 genes) were significantly differentially expressed for the effect of diet, 7.8% (978 genes) for the effect of the interaction between diet and tissue type (LRT,Padj.< 0.05). Interestingly, we observed similar patterns of gene expression relative to the C diet, in the DR and HS treated flies, a response likely reflecting diet component ratios. Hierarchical clustering identified 21 robust gene modules showing intra-modularly similar patterns of expression across diets, all of which were highly significant for diet or diet-tissue interaction effects (false discovery rate, FDRPadj.< 0.05). Gene set enrichment analysis for different diet-tissue combinations revealed a diverse set of pathways and gene ontology (GO) terms (two-sample t-test, FDR < 0.05). GO analysis on individual co-expressed modules likewise showed a large number of terms encompassing a large number of cellular and nuclear processes (Fisher exact test,Padj.< 0.01). Although a handful of genes in the IIS/TOR pathway includingIlp5,Rheb, andSirt2showed significant elevation in expression, known key genes such asInR,chico, insulin peptide genes, and the nutrient-sensing pathways were not observed.ConclusionsOur results suggest that a more diverse network of pathways and gene networks mediate the diet response in our population. These results have important implications for future studies focusing on diet responses in natural populations.
A few stickleback suffice for the transport of alleles to new lakes
Authors: Galloway Jared , Cresko William A. , Ralph Peter 
Published: July 2019

AbstractThreespine stickleback populations provide a striking example of local adaptation to divergent habitats in populations that are connected by recurrent gene flow. These small fish occur in marine and freshwater habitats throughout the Northern Hemisphere, and in numerous cases the smaller freshwater populations have been established “de novo” from marine colonists. Independently evolved freshwater populations show similar phenotypes that have been shown to derive largely from the same standing genetic variants. Geographic isolation prevents direct migration between the freshwater populations, strongly suggesting that these shared locally adaptive alleles are transported through the marine population. However it is still largely unknown how gene flow, recombination, and selection jointly impact the standing variation that might fuel this adaptation. Here we use individual-based, spatially explicit simulations to determine the levels of gene flow that best match observed patterns of allele sharing among habitats in stickleback. We aim to better understand how gene flow and local adaptation in large metapopulations determine the speed of adaptation and re-use of standing genetic variation. In our simulations we find that repeated adaptation uses a shared set of alleles that are maintained at low frequency by migration-selection balance in oceanic populations. This process occurs over a realistic range of intermediate levels of gene flow that match previous empirical population genomic studies in stickleback. Examining these simulations more deeply reveals how lower levels of gene flow leads to slow, independent adaptation to different habitats, whereas higher levels gene flow leads to significant mutation load – but an increased probability of successful population genomic scans for locally adapted alleles. Surprisingly, we find that the genealogical origins of most freshwater adapted alleles can be traced back to the original generation of marine individuals that colonized the lakes, as opposed to subsequent migrants. These simulations provide deeper context for existing studies of stickleback evolutionary genomics, and guidance for future empirical studies in this model. More broadly, our results support existing theory of local adaptation but extend it by more completely documenting the genealogical history of adaptive alleles in a metapopulation.
Genomic phylogeography of the White-crowned ManakinPseudopipra pipra(Aves: Pipridae) illuminates a continental-scale radiation out of the Andes
Authors: Berv Jacob S. , Campagna Leonardo , Feo Teresa J. , Castro-Astor Ivandy , Ribas Camila C. , Prum Richard O. , Lovette Irby J. 
Published: July 2019

AbstractThe complex landscape history of the Neotropics has generated opportunities for population isolation and diversification that place this region among the most species-rich in the world. Detailed phylogeographic studies are required to uncover the biogeographic histories of Neotropical taxa, to identify evolutionary correlates of diversity, and to reveal patterns of genetic connectivity, disjunction, and potential differentiation among lineages from different areas of endemism. The White-crowned Manakin (Pseudopipra pipra) is a small suboscine passerine bird that is broadly distributed through the subtropical rainforests of Central America, the lower montane cloud forests of the Andes from Colombia to central Peru, the lowlands of Amazonia and the Guianas, and the Atlantic forest of southeast Brazil.Pseudopiprais currently recognized as a single, polytypic biological species. We studied the effect of the Neotropical landscape on genetic and phenotypic differentiation within this species using genomic data derived from double digest restriction site associated DNA sequencing (ddRAD), and mitochondrial DNA. Most of the genetic breakpoints we identify among populations coincide with physical barriers to gene flow previously associated with avian areas of endemism. The phylogenetic relationships among these populations imply a novel pattern of Andean origination for this group, with subsequent diversification into the Amazonian lowlands. Our analysis of genomic admixture and gene flow reveals a complex history of introgression between some western Amazonian populations. These reticulate processes confound our application of standard concatenated and coalescent phylogenetic methods and raise the question of whether a lineage in the western Napo area of endemism should be considered a hybrid species. Lastly, analysis of variation in vocal and plumage phenotypes in the context of our phylogeny supports the hypothesis thatPseudopiprais a species-complex composed of at least 8, and perhaps up to 17 distinct species which have arisen in the last ∼2.5 Ma.
Identification ofkit-ligand aas the Gene Responsible for the Medaka Pigment Cell Mutantfew melanophore
Authors: Otsuki Yuji , Okuda Yuki , Naruse Kiyoshi , Saya Hideyuki 
Published: July 2019

ABSTRACTThe body coloration of animals is due to pigment cells derived from neural crest cells, which are multipotent and differentiate into diverse cell types. Medaka (Oryzias latipes) possesses four distinct types of pigment cells known as melanophores, xanthophores, iridophores, and leucophores. Thefew melanophore(fm) mutant of medaka is characterized by reduced numbers of melanophores and leucophores. We here identifykit-ligand a(kitlga) as the gene whose mutation gives rise to thefmphenotype. This identification was confirmed by generation ofkitlgaknockout medaka and the findings that these fish also manifest reduced numbers of melanophores and leucophores and fail to rescue thefmmutant phenotype. We also found that expression ofsox5,pax7a,pax3a, andmitfagenes is down-regulated in bothfmandkitlgaknockout medaka, implicating c-Kit signaling in regulation of the expression of these genes as well as the encoded transcription factors in pigment cell specification. Our results may provide insight into the pathogenesis of c-Kit–related pigmentation disorders such as piebaldism in humans, and ourkitlgaknockout medaka may prove useful as a tool for drug screening.
Discovery and Quality Analysis of a Comprehensive Set of Structural Variants and Short Tandem Repeats
Authors: Jakubosky David , Smith Erin N. , D’Antonio Matteo , Bonder Marc Jan , Greenwald William W. Young , D’Antonio-Chronowska Agnieszka , Matsui Hiroko ,   i2QTL Consortium,   HipSci Consortium, Stegle Oliver , Montgomery Stephen B. , DeBoever Christopher , Frazer Kelly A. 
Published: July 2019

AbstractStructural variants (SVs) and short tandem repeats (STRs) are important sources of genetic diversity but are not routinely analyzed in genetic studies because they are difficult to accurately identify and genotype. Because SVs and STRs range in size and type, it is necessary to apply multiple algorithms that incorporate different types of evidence from sequencing data and employ complex filtering strategies to discover a comprehensive set of high-quality and reproducible variants. Here we assembled a set of 719 deep whole genome sequencing (WGS) samples (mean 42x) from 477 distinct individuals which we used to discover and genotype a wide spectrum of SV and STR variants using five algorithms. We used 177 unique pairs of genetic replicates to identify factors that affect variant call reproducibility and developed a systematic filtering strategy to create of one of the most complete and well characterized maps of SVs and STRs to date.
Sub-sampling of cues in associative learning
Authors: Perez Omar D. , Vogel Edgar H. , Narasiwodeyar Sanjay , Soto Fabian A. 
Published: July 2019

AbstractTheories of learning distinguish between elemental and configural stimulus processing depending on whether stimuli are processed independently or as whole configurations. Evidence for elemental processing comes from findings of summation in animals where a compound of two dissimilar stimuli is deemed to be more predictive than each stimulus alone, whereas configural processing is supported by experiments employing similar stimuli in which summation is not found. However, in humans the summation effect is robust and impervious to similarity manipulations. In three experiments in human predictive learning, we show that summation can be obliterated when partially reinforced cues are added to the summands in training and test. This lack of summation only holds when the partially reinforced cues are similar to the reinforced cues (Experiment 1) and seems to depend on participants sampling only the most salient cue in each trial (Experiments 2a and 2b) in a sequential visual search process. Instead of attributing our and other’s instances of lack of summation to the customary idea of configural processing, we offer a formal sub-sampling rule that might be applied to situations in which the stimuli are hard to parse from each other.
Passive transfer of fibromyalgia pain from patients to mice
Authors: Goebel Andreas , Gentry Clive , Cuhadar Ulku , Krock Emerson , Vastani Nisha , Sensi Serena , Sandor Katalin , Jurczak Alexandra , Baharpoor Azar , Brieskorn Louisa , Urbina Carlos Morado , Sandstrom Angelika , Tour Janette , Kadetoff Diana , Kosek Eva , Bevan Stuart , Svensson Camilla I. , Andersson David A. 
Published: July 2019

SUMMARYFibromyalgia syndrome (FMS) is a chronic pain condition characterized by widespread pain and tenderness1,2. The etiology and pathophysiology of fibromyalgia are unknown and there are no effective treatments. Here we show that sensory hypersensitivity in FMS is caused by autoantibodies that act by sensitizing nociceptive sensory neurons. Administration of IgG from FMS patients increased mouse pain sensitivities to stimulation with mechanical pressure and cold. In contrast, transfer of IgG depleted samples from FMS patients or IgG from healthy control subjects had no effect on pain sensitivity. Sensory nerve fibres in ex vivo skin-nerve preparations from mice treated with FMS IgG were hypersensitive to mechanical stimulation. Immunohistochemical analysis revealed that IgG from FMS patients specifically labeled satellite glial cells and myelinated fibre tracts, as well as a small number of macrophages and endothelial cells in mouse dorsal root ganglia but not skin, muscle, spinal cord and brain. Our results demonstrate that fibromyalgia pain is caused by IgG autoantibodies that sensitize peripheral nociceptive afferents neurons and suggest that therapies that reduce patient IgG titres may be effective treatments of fibromyalgia pain.
Structural fuzziness of the RNA-organizing protein SERF1a determines a toxic gain-of-interaction
Authors: Meyer N. Helge , Dellago Hanna , Tam-Amersdorfer Carmen , Merle David A. , Parlato Rosanna , Gesslbauer Bernd , Almer Johannes , Gschwandtner Martha , Leon A. , Franzmann Titus M. , Grillari Johannes , Kungl Andreas J. , Zangger Klaus , Falsone S. Fabio 
Published: July 2019

ABSTRACTMembers of the MOAG/SERF protein family have been attributed a neuropathologic significance because of their ability to enhance the proteotoxic polymerization of amyloidogenic proteins such as alpha-Synuclein (aSyn). However, the cellular function remains unknown. Here, we identify SERF1a as an RNA-organizing protein i) with no structural homology to canonical RNA-binding proteins, ii) with an RNA-chaperoning activity which favours the incorporation of RNA into nucleoli and liquid-like artificial RNA-organelles, and iii) with a high degree of conformational disorder in the RNA-bound state. We demonstrate that this type of structural fuzziness determines an undifferentiated interaction of SERF1a with aSyn and RNA. Both molecules bind to one identical, positively charged site of SERF1a by an analogous electrostatic binding mode, with similar binding affinities, and without any observable disorder-to-order transition. The absence of primary or secondary structure discriminants results in SERF1a being unable to distinguish between nucleic acid and amyloidogenic protein, leading the pro-amyloid aSyn:SERF1a interaction to prevail under conditions of cellular stress. We suggest that structural fuzziness of SERF1a accounts for an adverse gain-of-interaction which favours toxic binding to aSyn at the expense of non-toxic RNA binding, therefore promoting a functionally distorted and pathogenic process. Our results provide a direct link between structural disorder, amyloid aggregation and the malfunctioning of RNA-associated cellular processes, three hallmarks of neurodegenerative diseases.