bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social environment drives sex and age-specific variation inDrosophila melanogastermicrobiome composition and predicted function
Authors: Leech Thomas , McDowall Laurin , Hopkins Kevin P , Sait Steven M , Harrison Xavier A. , Bretman Amanda 
Published: January 2020

AbstractSocial environments influence multiple traits of individuals including immunity, stress and ageing, often in sex-specific ways. The composition of the microbiome (the assemblage of symbiotic microorganisms within a host) is determined by environmental factors and the host’s immune, endocrine and neural systems. The social environment could alter host microbiomes extrinsically by affecting transmission between individuals, likely promoting homogeneity in the microbiome of social partners. Alternatively, intrinsic effects arising from interactions between the microbiome and host physiology (the microbiota-gut-brain axis) could translate social stress into dysbiotic microbiomes, with consequences for host health. We investigated how manipulating social environments during larval and adult life-stages altered the microbiome composition ofDrosophila melanogasterfruit flies. We used social contexts that particularly alter the development and lifespan of males, predicting that any intrinsic social effects on the microbiome would therefore be sex-specific. The presence of adult males during the larval stage significantly altered the microbiome of pupae of both sexes. In adults, same-sex grouping increased bacterial diversity in both sexes. Importantly, the microbiome community structure of males was more sensitive to social contact at older ages, an effect partially mitigated by housing focal males with young rather than co-aged groups. Functional analyses suggest that these microbiome changes impact ageing and immune responses. This is consistent with the hypothesis that the substantial effects of the social environment on individual health are mediated through intrinsic effects on the microbiome, and provides a model for understanding the mechanistic basis of the microbiota-gut-brain axis.Significance statementThe social environment has pervasive, multifaceted effects on individual health and fitness. If a host’s microbiome is sensitive to the social environment then it could be an important mediator of social effects, as the reciprocal relationships between hosts and their microbiomes have substantial implications for host health. Using aDrosophila melanogasterfruit fly model we show that the fly microbiome is sensitive to the social environment in a sex, age and life-stage dependent manner. In particular, older adult male microbiome communities are altered by same-sex social contact, but this depends on the age of the social partners. These changes have functional effects on fly immunity and lifespan, evidence that indeed this is an influential mediator of social effects on health.
Phylogenomics supported by geometric morphometrics reveals delimitation of sexual species within the polyploid apomicticRanunculus auricomuscomplex (Ranunculaceae)
Authors: Karbstein Kevin , Tomasello Salvatore , Hodac Ladislav , Dunkel Franz G. , Daubert Mareike , Hörandl Elvira 
Published: January 2020

AbstractSpecies are the basic units of biodiversity and evolution. Nowadays, they are widely considered as ancestor-descendant lineages. Their definition remains a persistent challenge for taxonomists due to lineage evolutionary role and circumscription, i.e., persistence in time and space, ecological niche or a shared phenotype of a lineage. Recognizing and delimiting species is particularly methodically challenging in fast-evolving, evolutionary young species complexes often characterized by low genetic divergence, hybrid origin, introgression and incomplete lineage sorting (ILS).Ranunculus auricomusis a large Eurasian apomictic polyploid complex that probably has arisen from the hybridization of a few sexual progenitor species. However, even delimitation and relationships of diploid sexual progenitors have been unclearly ranging from two to twelve species. Here, we present an innovative workflow combining phylogenomic methods based on 86,782 parameter-optimized RADseq loci and target enrichment of 663 nuclear genes together with geometric morphometrics to delimit sexual species in this evolutionary young complex (< 1 Mya). For the first time, we revealed a fully resolved and well-supported maximum likelihood (ML) tree phylogeny congruent to neighbor-net network and STRUCTURE results based on RADseq data. In a few clades, we found evidence of discordant patterns indicated by quartet sampling (QS) and reticulation events in the neighbor-net network probably caused by introgression and ILS. Together with coalescent-based species delimitation approaches based on target enrichment data, we found five main genetic lineages, with an allopatric distribution in Central and Southern Europe. A concatenated geometric morphometric data set including basal and stem leaves, as well as receptacles, revealed the same five main clusters. We accept those five morphologically differentiated, geographically isolated, genetic main lineages as species:R. cassubicifoliuss.l. (incl.R. carpaticola),R. flabellifolius,R. envalirensiss.l. (incl.R. cebennensis),R. marsicusandR. notabiliss.l. (incl.R. austroslovenicus,R. calapius,R. mediocompositus, R. peracrisandR. subcarniolicus). Our comprehensive workflow combing phylogenomic methods supported by geometric morphometrics proved to be successful in delimiting closely related sexual taxa and applying an evolutionary species concept, which is also transferable to other evolutionarily young species complexes.
Lysine Acetylation Reshapes The Downstream Signaling Landscape of Vav1 in Lymphocytes
Authors: Rodríguez-Fdez Sonia , Nevado Lucía F. , Lorenzo-Martín L. Francisco , Bustelo Xosé R. 
Published: January 2020

ABSTRACTVav1 works both as a catalytic Rho GTPase activator and an adaptor molecule. These functions, which are critical for T cell development and antigenic responses, are tyrosine phosphorylation-dependent. However, it is not known whether other posttranslational modifications can modulate the signaling output of this protein. Here, we show that Vav1 becomes acetylated in a stimulation- and SH2 domain-dependent manner. We also demonstrate that the acetylation of four residues located in the catalytic, lysine rich and SH2 domains preferentially buffers the Vav1 adaptor function that favors the stimulation of the nuclear factor of activated T cells. As a result, it modifies the signaling diversification properties normally exhibited by Vav1 in lymphocytes. This new regulatory layer is not shared by Vav family paralogs.
Quantifying Tensile Forces at Cell–Cell Junctions with a DNA-based Fluorescent Probe
Authors: Zhao Bin , Li Ningwei , Xie Tianfa , Liang Chungwen , Bagheri Yousef , Sun Yubing , You Mingxu 
Published: January 2020

SUMMARYCells are physically contacting with each other. Direct and precise quantification of forces at cell–cell junctions is still challenging. Herein, we have developed a DNA-based ratiometric fluorescent probe, termed DNAMeter, to quantify intercellular tensile forces. These lipid-modified DNAMeters can spontaneously anchor onto live cell membranes. The DNAMeter consists of two self-assembled DNA hairpins of different force tolerance. Once the intercellular tension exceeds the force tolerance to unfold a DNA hairpin, a specific fluorescence signal will be activated, which enables the real-time imaging and quantification of tensile forces. Using E-cadherin-modified DNAMeter as an example, we have demonstrated an approach to quantify, at the molecular level, the magnitude and distribution of E-cadherin tension among epithelial cells. Compatible with readily accessible fluorescence microscopes, these easy-to-use DNA tension probes can be broadly used to quantify mechanotransduction in collective cell behaviors.
Identification of QTLs for high grain yield and component traits in New Plant Types of rice
Authors: Donde Ravindra , Mohapatra S. , Baksh S. Y. , Padhy B. , Mukherjee M. , Roy S. , Chattopadhyay K. , Anandan A. , Swain P. , Sahoo K. K. , Singh O. N. , Behera L. , Dash S. K. 
Published: January 2020

AbstractA panel of 60 genotypes consisting of New Plant Types (NPTs) along withindica,tropicalandtemperate japonicagenotypes were phenotypically evaluated for four seasons in irrigated situation for grain yieldper seand component traits. Twenty NPT genotypes were found to be promising with an average grain yield of 5.45 to 8.8 t/ha. A total of 85 SSR markers were used in the study to identify QTLs associated with grain yieldper seand related traits. Sixty-six (77.65%) markers were found to be polymorphic. The PIC values varied from 0.516 to 0.92 with an average of 0.704. A moderate level of genetic diversity (0.39) was detected among genotypes. Variation to the tune of 8% within genotypes, 68% among the genotypes within the population and 24% among the populations were observed (AMOVA). The association analysis using GLM and MLM models led to the identification of 30 and 10 SSR markers were associated with 70 and 16 QTLs, respectively. Thirty novel QTLs linked with 16 SSRs were identified to be associated with eleven traits, namely, tiller number (qTL-6.1, qTL-11.1, qTL-4.1), panicle length (qPL-1.1, qPL-5.1,qPL-7.1, qPL-8.1), flag leaf length (qFLL-8.1, qFLL-9.1), flag leaf width (qFLW-6.2, qFLW-5.1,qFLW-8.1, qFLW-7.1), total no. of grains (qTG-2.2, qTG-a7.1), thousand-grain weight (qTGW-a1.1, qTGW-a9.2, qTGW-5.1, qTGW-8.1), fertile grains (qFG-7.1), seed length-breadth ratio (qSlb-3.1), plant height (qPHT-6.1, qPHT-9.1), days to 50% flowering (qFD-1.1) and grain yield per se (qYLD-5.1, qYLD-6.1a, qYLD-11.1). This information could be useful for identification of highly potential parents for development of transgressive segregants. Moreover, super rice genotypes could be developed through pyramiding of these QTLS for important yield traits for prospective increment in yield potentiality and breaking yield ceiling.
Computed tomography reveals hip dysplasia in the extinct Pleistocene saber-tooth catSmilodon
Authors: Balisi Mairin A. , Sharma Abhinav K. , Howard Carrie M. , Shaw Christopher A. , Klapper Robert , Lindsey Emily L. 
Published: January 2020

AbstractReconstructing the behavior of extinct species is challenging, particularly for those with no living analogues. However, damage preserved as paleopathologies on bone can record how an animal moved in life, potentially reflecting behavioral patterns. Here, we assess hypothesized etiologies of pathology in a pelvis and associated right femur of aSmilodon fatalissaber-toothed cat, one of the best-studied species from the Pleistocene-age Rancho La Brea asphalt seeps, California, USA, using visualization by computed tomography (CT). The pelvis exhibits massive destruction of the right hip socket that was interpreted, for nearly a century, to have developed from trauma and infection. CT imaging reveals instead that the pathological distortions characterize chronic remodeling that began at birth and led to degeneration of the joint over the animal’s life. These results suggest that this individual suffered from hip dysplasia, a congenital condition common in domestic dogs and cats. This individual reached adulthood but could not have hunted properly nor defended territory on its own, likely relying on a social group for feeding and protection. While extant social felids are rare, these fossils and others with similar pathologies are consistent with a spectrum of social strategies inSmilodonsupported by a predominance of previous studies.
Mimicry of dopamine 1 receptor signaling with Cell-Penetrating Peptides
Authors: Lorenzon Nicola , Gestin Maxime , Langel Ülo 
Published: January 2020

AbstractIn this study, through the use of protein mimicry, a peptide was developed to activate the dopamine 1 receptor signaling pathway in substitution of L-DOPA. The peptide proved to be capable of efficiently ubiquitously penetrating the cell without the need for transfection agents or chiral recognition by specific pathways. Furthermore, the peptide induced the cellular response normally achieved through the activation of the receptor in cells that had not been treated with the natural ligand. The peptide could work as a candidate substitute to L-DOPA, leading the way for a peptides-based treatment for Parkinson’s disease.
Local retinoic acid directs emergence of the extraocular muscle functional unit
Authors: Comai Glenda , Tesarova Marketa , Dupé Valerie , Rhinn Muriel , Vallecillo Garcia Pedro , da Silva Fabio , Feret Betty , Exelby Katherine , Dollé Pascal , Carlsson Leif , Pryce Brian , Spitz Francois , Stricker Sigmar , Zikmund Tomas , Kaiser Jozef , Briscoe James , Schedl Andreas , Ghyselinck Norbert B. , Schweitzer Ronen , Tajbakhsh Shahragim 
Published: January 2020

ABSTRACTCoordinated development of muscles, tendons, and their attachment sites ensures emergence of functional musculoskeletal units that are adapted to diverse anatomical demands among different species. How these different tissues are patterned and functionally assembled during embryogenesis is poorly understood. Here, we investigated the morphogenesis of extraocular muscles (EOMs), an evolutionary conserved cranial muscle group that is crucial for the coordinated movement of the eyeballs and for visual acuity. By means of lineage analysis, we redefined the cellular origins of periocular connective tissues interacting with the EOMs, which do not arise exclusively from neural crest mesenchyme as previously thought. Using 3D imaging approaches, we established an integrative blueprint for the EOM functional unit. By doing so, we identified a developmental time window where individual EOMs emerge from a unique muscle anlage and establish insertions in the sclera, which sets these muscles apart from classical muscle-to-bone type of insertions. Further, we demonstrate that the eyeballs are a source of diffusible retinoic acid that allow their targeting by the EOMs in a temporal and dose dependent manner. Using genetically modified mice and inhibitor treatments, we find that endogenous local variations in the concentration of retinoids contribute to the establishment of tendon condensations and attachment sites that precede the initiation of muscle patterning. Collectively, our results highlight how global and site-specific programs are deployed for the assembly of muscle functional units with precise definition of muscle shapes and topographical wiring of their tendon attachments.
Nephrotic Syndrome-Associated Hypercoagulopathy is Alleviated by Nuclear Receptor Agonist Therapy with both Pioglitazone and Glucocorticoids
Authors: Waller Amanda P. , Agrawal Shipra , Wolfgang Katelyn J. , Kino Jiro , Chanley Melinda A. , Smoyer William E. , Kerlin Bryce A. ,   the Pediatric Nephrology Research Consortium (PNRC)
Published: January 2020

ABSTRACTBackgroundThrombosis is a potentially life-threatening nephrotic syndrome (NS) complication. We have previously demonstrated that hypercoagulopathy is proportional to NS severity in rat models and that pioglitazone (Pio) reduces proteinuria both independently and in combination with methylprednisolone (MP), a glucocorticoid (GC). However, the effect of these treatments on NS-associated hypercoagulopathy remains unknown. We thus sought to determine the ability of Pio and GC to alleviate NS-associated hypercoagulopathy.MethodsPuromycin aminonucleoside-induced rat NS was treated with sham, Low- or High-dose MP, Pio, or combination (Pio+Low-MP) and plasma was collected at day 11. Plasma samples were collected from children with steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS) upon presentation and after 7 weeks of GC therapy. Plasma endogenous thrombin potential (ETP), antithrombin (AT) activity, and albumin (Alb) were measured using thrombin generation, amidolytic, and colorimetric assays, respectively.ResultsIn a rat model of NS, both High-MP and Pio improved proteinuria and corrected hypoalbuminemia, ETP and AT activity (P<0.05). Proteinuria (P=0.005) and hypoalbuminemia (P<0.001) were correlated with ETP. In childhood NS, while ETP was not different at presentation, GC therapy improved proteinuria, hypoalbuminemia, and ETP in children with SSNS (P<0.001) but not SRNS (P=0.330).ConclusionsBoth Pio and GC diminish proteinuria and significantly alleviate hypercoagulopathy. Both Pio and MP improved hypercoagulopathy in rats, and successful GC therapy (SSNS) also improved hypercoagulopathy in childhood NS. These data suggest that even a partial reduction in proteinuria may reduce NS-associated thrombotic risk.SIGNIFICANCE STATEMENTNephrotic syndrome (NS) is characterized by massive proteinuria and is complicated by a complex, acquired hypercoagulopathy that markedly increases the risk for potentially life-threatening venous thromboembolism (VTE). This study demonstrates a strong correlation between proteinuria reduction and improvement of an established VTE-risk biomarker, in both a well-established animal model and in childhood NS before and after steroid treatment. We show that nuclear receptor agonists with known disparate mechanisms of action successfully reduce proteinuria and simultaneously improve NS-associated hypercoagulopathy. These data suggest that complete or partial proteinuria reduction by any therapeutic modality may concurrently reduce NS-associated thrombotic risk.
Identifying novel B-cell targets for chronic inflammatory autoimmune disease by screening of chemical probes in a patient-derived cell assay
Authors: Sundström Yvonne , Shang Ming-Mei , Panda Sudeepta Kumar , Grönwall Caroline , Wermeling Fredrik , Gunnarsson Iva , Lundberg Ingrid E , Sundström Michael , Jakobsson Per-Johan , Berg Louise 
Published: January 2020

SUMMARYB-cell secretion of autoantibodies drives autoimmune diseases, including systemic lupus erythematosus and idiopathic inflammatory myositis. Few therapies are presently available for treatment of these patients, often resulting in unsatisfactory effects and helping only some of patients. We developed a screening assay for evaluation of novel targets suspending B-cell maturation into antibody secreting cells, which could contribute to future drug development. The assay was employed for testing 43 high quality chemical probes and compounds inhibiting under-explored protein targets, using primary cells from patients with autoimmune disease. Probes inhibiting bromodomain family proteins and histone methyl transferases demonstrated abrogation of B-cell functions to a degree comparable to a positive control, the JAK inhibitor tofacitinib. Inhibition of each target rendered a specific functional cell and potential disease modifying effect, indicating specific epigenetic protein targets as potential new intervention points for future drug discovery and development efforts.
Prediction of contact fatigue life of AT40 ceramic coating based on neural network
Authors: Zhou Renze , Xing Zhiguo , Wang Haidou , Piao Zhongyu , Huang Yanfei , Guo Weiling , Ma Runbo 
Published: January 2020

Purpose
With the development of deep learning-based analytical techniques, increased research has focused on fatigue data analysis methods based on deep learning, which are gaining in popularity. However, the application of deep neural networks in the material science domain is mainly inhibited by data availability. In this paper, to overcome the difficulty of multifactor fatigue life prediction with small data sets,

Design/methodology/approach
A multiple neural network ensemble (MNNE) is used, and an MNNE with a general and flexible explicit function is developed to accurately quantify the complicated relationships hidden in multivariable data sets. Moreover, a variational autoencoder-based data generator is trained with small sample sets to expand the size of the training data set. A comparative study involving the proposed method and traditional models is performed. In addition, a filtering rule based on the R2 score is proposed and applied in the training process of the MNNE, and this approach has a beneficial effect on the prediction accuracy and generalization ability.

Findings
A comparative study involving the proposed method and traditional models is performed. The comparative experiment confirms that the use of hybrid data can improve the accuracy and generalization ability of the deep neural network and that the MNNE outperforms support vector machines, multilayer perceptron and deep neural network models based on the goodness of fit and robustness in the small sample case.

Practical implications
The experimental results imply that the proposed algorithm is a sophisticated and promising multivariate method for predicting the contact fatigue life of a coating when data availability is limited.

Originality/value
A data generated model based on variational autoencoder was used to make up lack of data. An MNNE method was proposed to apply in the small data case of fatigue life prediction.
An empirical analysis of search engines’ response to web search queries associated with the classroom setting
Authors: Anuyah Oghenemaro , Milton Ashlee , Green Michael , Pera Maria Soledad 
Published: January 2020

PurposeThe purpose of this paper is to examine strengths and limitations that search engines (SEs) exhibit when responding to web search queries associated with the grade school curriculumDesign/methodology/approachThe authors employed a simulation-based experimental approach to conduct an in-depth empirical examination of SEs and used web search queries that capture information needs in different search scenarios.FindingsOutcomes from this study highlight that child-oriented SEs are more effective than traditional ones when filtering inappropriate resources, but often fail to retrieve educational materials. All SEs examined offered resources at reading levels higher than that of the target audience and often prioritized resources with popular top-level domain (e.g. “.com”).Practical implicationsFindings have implications for human intervention, search literacy in schools, and the enhancement of existing SEs. Results shed light on the impact on children’s education that result from introducing misconception about SEs when these tools either retrieve no results or offer irrelevant resources, in response to web search queries pertinent to the grade school curriculum.Originality/valueThe authors examined child-oriented and popular SEs retrieval of resources aligning with task objectives and user capabilities–resources that match user reading skills, do not contain hate-speech and sexually-explicit content, are non-opinionated, and are curriculum-relevant. Findings identified limitations of existing SEs (both directly or indirectly supporting young users) and demonstrate the need to improve SE filtering and ranking algorithms.