bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Analysis of Gene Expression Identifies Distinct Molecular Signatures of Bone Marrow- and Periosteal-Skeletal Stem/Progenitor Cells
Authors: Deveza Lorenzo , Ortinau Laura , Lei Kevin , Park Dongsu 
Published: October 2017

AbstractPeriosteum and bone marrow (BM) both contain skeletal stem/progenitor cells (SSCs) that participate in fracture repair. However, the functional difference and selective regulatory mechanisms of SSCs in different location are unknown due to the lack of specific markers. Here, we report a comprehensive gene expression analysis of bone marrow SSCs (BM-SSCs), periosteal SSCs (P-SSCs), and more differentiated osteoprogenitors by using reporter mice expressing Interferon-inducible Mx1 and NestinGFP, previously known SSC markers. We first defined that the BM-SSCs can be enriched by the combination of Mx1 and NestinGFP expression, while endogenous P-SSCs can be isolated by positive selection of Mx1, CD105 and CD140a (known SSC markers) combined with the negative selection of CD45, CD31, and osteocalcinGFP (a mature osteolineage marker). Comparative gene experession analysis with FACS-sorted BM-SSCs, P-SSCs, Osterix+ (OSX) preosteoblasts, CD51+ stroma cells and CD45+ hematopoietic cells as controls revealed that BM-SSCs and P-SSCs have high similarity with few potential differences without statistical significance. We also found that CD51+ cells are highly heterogeneous and little overlap with SSCs. This was further supported by the microarray cluster analysis, and the two populations clustered together. However, when comparing SSC population to controls, we found several genes that were uniquely upregulated in endogenous SSCs. Amongst these genes, we found KDR (aka Flk1 or VEGFR2) to be most interesting and discovered that it is highly and selectively expressed in P-SSCs. This finding suggests that endogenous P-SSCs are functionally very similar to BM-SSCs with undetectable significant differences in gene expression but there are distinct molecular signatures in P-SSCs, which can be useful to specify P-SSC subset in vivo.
Stochastic character mapping of state-dependent diversification reveals the tempo of evolutionary decline in self-compatible Onagraceae lineages
Authors: Freyman William A. , Höhna Sebastian 
Published: October 2017

AbstractA major goal of evolutionary biology is to identify key evolutionary transitions that correspond with shifts in speciation and extinction rates. Stochastic character mapping has become the primary method used to infer the timing, nature, and number of character state transitions along the branches of a phylogeny. The method is widely employed for standard substitution models of character evolution. However, current approaches cannot be used for models that specifically test the association of character state transitions with shifts in diversification rates such as state-dependent speciation and extinction (SSE) models. Here we introduce a new stochastic character mapping algorithm that overcomes these limitations, and apply it to study mating system evolution over a time-calibrated phylogeny of the plant family Onagraceae. Utilizing a hidden state SSE model we tested the association of the loss of self-incompatibility with shifts in diversification rates. We found that self-compatible lineages have higher extinction rates and lower net-diversification rates compared to self-incompatible lineages. Furthermore, these results provide empirical evidence for the “senescing” diversification rates predicted in highly selfing lineages: our mapped character histories show that the loss of self-incompatibility is followed by a short-term spike in speciation rates, which declines after a time lag of several million years resulting in negative net-diversification. Lineages that have long been self-compatible, such as Fuchsia and Clarkia, are in a previously unrecognized and ongoing evolutionary decline. Our results demonstrate that stochastic character mapping of SSE models is a powerful tool for examining the timing and nature of both character state transitions and shifts in diversification rates over the phylogeny.
Combinatorial Drug Discovery in Nanoliter Droplets
Authors: Kulesa Anthony , Kehe Jared , Hurtado Juan , Tawde Prianca , Blainey Paul C. 
Published: October 2017

AbstractCombinatorial drug treatment strategies perturb biological networks synergistically to achieve therapeutic effects and represent major opportunities to develop advanced treatments across a variety of human disease areas. However, the discovery of new combinatorial treatments is challenged by the sheer scale of combinatorial chemical space. Here we report a high-throughput system for nanoliter-scale phenotypic screening that stabilizes a chemical library in nanoliter droplet emulsions and automates the formulation of chemical combinationsen massusing parallel droplet processing. We apply this system to predict synergy between more than 4,000 investigational and approved drugs and a panel of 10 antibiotics againstE. coli, a model Gram-negative pathogen. We found a range of drugs not previously indicated for infectious disease that synergize with antibiotics. Our validated hits include drugs that synergize with the antibiotics vancomycin, erythromycin, and novobiocin, which are used against Gram-positive bacteria but are not effective by themselves to resolve Gram-negative infections.
The Association of Externalizing and Internalizing Problems with Indicators of Intelligence in a Sample of At-Risk Children
Authors: Kavish Nicholas , Helton Jesse , Vaughn Michael G. , Boutwell Brian B. 
Published: October 2017

AbstractTo date, a substantial body of research exists suggesting an association between indicators of intelligence and various deleterious outcomes, including externalizing and internalizing behavioral problems. Much of this research, however, has focused on samples drawn from the general population, thus it remains less clear how (and if) intelligence relates to problem behaviors in samples of highly at-risk individuals. The current study seeks to contribute to this knowledge base by examining the associations between intelligence and internalizing, externalizing, and total scores on the Child Behavioral Checklist in a sample of approximately 2,500 highly disadvantaged respondents considered by Child Protective Services as at-risk for abuse or neglect. While the two measures of intelligence performed differently, there emerged some association between overall lower IQ and higher total behavioral problem scores. There was some evidence that low IQ also predicted higher internalizing scores, but this relationship varied greatly by measure and model. Results, limitations, and implications of the current study are discussed.
Distinct stimulatory mechanisms regulate the catalytic activity of Polycomb Repressive Complex 2 (PRC2)
Authors: Lee Chul-Hwan , Holder Marlene , Grau Daniel , Saldana-Meyer Ricardo , Ganai Rais Ahmad , Zhang Jenny , Wang Miao , Dobenecker Marc-Werner , Reinberg Danny , Armache Karim-Jean 
Published: October 2017

AbstractThe maintenance of gene expression patterns during metazoan development is carried out, in part, by the actions of the Polycomb Repressive Complex 2 (PRC2). PRC2 catalyzes mono-, di-and trimethylation of histone H3 at lysine 27 (H3K27), with H3K27me2/3 being strongly associated with silenced genes. We demonstrate that EZH1 and EZH2, the two mutually exclusive catalytic subunits of PRC2, are differentially activated by various mechanisms. While both PRC2-EZH1 and PRC2-EZH2 are able to catalyze monomethylation, only PRC2-EZH2 is strongly activated by allosteric modulators and specific chromatin substrates to catalyze di-and trimethylation of H3K27. However, we also show that a PRC2 associated protein, AEBP2, can stimulate the activity of both complexes through a mechanism independent of and additive to allosteric activation. These results have strong implications regarding the cellular requirements for and accompanying adjustments in PRC2 activity, given the difference in the expression of EZH1 and EZH2 upon cellular differentiation.
Rolling a mycobiome down a hill: endophytes in the Taiwanese Cloud Forest
Authors: Thomas Dan , Vandegrift Roo , Ju Yu-Ming , Hsieh Monica , Roy Bitty 
Published: October 2017

AbstractFungal endophytes of plants are ubiquitous and important to host plant health. Despite their ecological importance, landscape-level patterns of microbial communities in plant hosts are not well-characterized. Fungal wood-inhabiting and foliar endophyte communities from multiple tree hosts were sampled at multiple spatial scales across a 25 ha subtropical research plot in northern Taiwan, using culture-free, community DNA amplicon sequencing methods. Fungal endophyte communities were distinct between leaves and wood, but the mycobiomes were highly variable across and within tree species. Of the variance that could be explained, host tree species was the most important driver of mycobiome community-composition. Within a single tree species, “core” mycobiomes were characterized using cooccurrence analysis. These core groups of endophytes in leaves and wood show divergent spatial patterns. For wood endophytes, a more consistent, “minimal” core mycobiome coexisted with the host across the extent of the study. For leaf endophytes, the core fungi resembled a more dynamic, “gradient” model of the core microbiome, changing across the topography and distance of the study.
Accelerated Epigenetic Ageing in Major Depressive Disorder
Authors: Whalley Heather C , Gibson Jude , Marioni Riccardo , Walker Rosie M , Clarke Toni-Kim , Howard David M , Adams Mark J , Hall Lynsey , Morris Stewart , Deary Ian J , Porteous David ,   23andMe Research Team,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Evans Kathryn L , McIntosh Andrew M 
Published: October 2017

AbstractBackgroundMajor depressive disorder (MDD) is a severe, heritable psychiatric disorder associated with shortened lifespan and comorbidities of advancing age. It is unknown however whether MDD is associated with accelerated biological ageing relative to chronological age. This hypothesis was tested using the epigenetic clock as a measure of biological age.MethodsTo address the main hypothesis, using peripheral blood, we derived measures of Epigenetic Age Acceleration (EAA) in 3,833 controls and 1,219 MDD cases based on Hannum and Horvath epigenetic clocks in Generation Scotland (GS:SFHS, mean age 48 years, std dev 14.5). Models controlled for relatedness, sex, cell counts, and processing batch (basic model), as well as additional covariates of smoking and drinking status, and body mass index (BMI) (full models).ResultsAccelerated epigenetic ageing was found in MDD cases versus controls using the Horvath clock (β=0.0804, p=0.012 equivalent to 0.20 years) in both the basic and full models. Significant MDD*age interactions indicated greatest effects at younger age ranges. No significant differences were observed for the Hannum clock. BMI was the only additional covariate found to attenuate the relationship between EAAHorvathand MDD. Further, genetic correlation analysis indicated significant overlap in the genetic aetiology of EAAHorvathwith BMI (rG=0.20, p=0.03), between MDD with BMI (rG=0.10, p=9.86×10−6), but not between EAAHorvathand MDD (rG=0.14, p=0.125). Mediation analysis indicated partial mediation of the relationship between EAAHorvathand depression status through BMI (β =0.0028; p=0.0248, ~13%).ConclusionThese data imply that accelerated biological ageing is associated with MDD and partially mediated through BMI.
runibic: a Bioconductor package for parallel row-based biclustering of gene expression data
Authors: Orzechowski Patryk , Pańszczyk Artur , Huang Xiuzhen , Moore Jason H. 
Published: October 2017

AbstractMotivationBiclustering (called also co-clustering) is an unsupervised technique of simultaneous analysis of rows and columns of input matrix. From the first application to gene expression data, multiple algorithms have been proposed. Only a handful of them were able to provide accurate results and were fast enough to be suitable for large-scale genomic datasets.ResultsIn this paper we introduce a Bioconductor package with parallel version of UniBic biclustering algorithm: one of the most accurate biclustering methods that have been developed so far. For the convenience of usage, we have wrapped the algorithm in an R package calledrunibic. The package includes: (1) a couple of times faster parallel version of the original sequential algorithm,(2) muchmore efficient memory management, (3) modularity which allows to build new methods on top of the provided one, (4) integration with the modern Bioconductor packages such asSummarizedExperiment,ExpressionSetandbiclust.AvailabilityThe package is implemented in R (3.4) and will be available in the new release of Bioconductor (3.6). Currently it could be downloaded from the following URL:http://github.com/athril/runibic/Contactpatryk.orzechowski@gmail.com,jhmoore@upenn.eduSupplementary informationSupplementary informations are available in vignette of the package.
An empirical test of the temperature dependence of carrying capacity
Authors: Bernhardt Joey R. , Sunday Jennifer M. , O’Connor Mary I. 
Published: October 2017

AbstractPredicting population persistence and dynamics in the context of global change is a major challenge for ecology. A widely held prediction is that population abundance at carrying capacity decreases with warming, assuming no change in resource supply, due to increased individual resource demands associated with higher metabolic rates. However, this prediction, which is based on metabolic scaling theory (MST), has not been tested empirically. Here we experimentally tested whether effects of temperature on short-term metabolic performance (rates of photosynthesis and respiration) translate directly to effects of temperature on population rates in a phytoplankton species. We found that effects of temperature on organismal metabolic rates matched theoretical predictions, and that the temperature dependence of individual metabolic performance translated to population abundance. Population abundance at carrying capacity,K, decreased with temperature less than expected based on the temperature dependence of photosynthesis. Concurrent with declines in abundance, we observed a linear decline in cell size of approximately 2.3% °C−1, which is consistent with broadly observed patterns in unicellular organisms, known as the temperature-size rule. When theoretical predictions include higher densities allowed by shifts toward smaller individual size, observed declines inKwere quantitatively consistent with theoretical predictions. Our results indicate that outcomes of population dynamics across a range of temperatures reflect organismal responses to temperature via metabolic scaling, providing a general basis for forecasting population responses to global change.
Sharing genetic admixture and diversity of public biomedical datasets
Authors: Harismendy Olivier , Kim Jihoon , Xu Xiaojun , Ohno-Machado Lucila 
Published: October 2017

AbstractGenetic ancestry and admixture are critical co-factors to study phenotype-genotype associations using cohorts of human subjects. Most publically available molecular datasets – genomes, exomes or transcriptomes - are however missing this information or only share self-reported ancestry. This represents a limitation to identify and re-purpose datasets to investigate the contribution of race and ethnicity to diseases and traits. we propose an analytical framework to enrich the meta-data from publically available cohorts with admixture information and a resulting diversity score at continental resolution, calculated directly from the data. We illustrate the utility and versatility of the framework using The Cancer Genome Atlas datasets indexed and searched through the DataMed Data Discovery Index. Data repositories or data contributors can use this framework to provide, as metadata, admixture for controlled access datasets, minimizing the work involved in requesting a dataset that may ultimately prove inadequate for a researcher’s purpose. With the increasingly global scale of human genetics research, research on disease risk and susceptibility would benefit greatly from the adequate estimation and sharing of admixture data following a framework such as the one presented.
Ustekinumab treatment of pityriasis rubra pilaris: A report of five cases
Authors: Napolitano Monica , Lembo Luigi , Fania Luca , Abeni Damiano , Didona Dario , Didona Biagio 
Published: October 2017

AbstractPityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory skin disease of unknown etiology. Patients refractory to conventional therapies have been treated successfully with biologic drugs such as anti‐tumor necrosis factor agents. Recently, a role of the interleukin‐23/T‐helper 17 axis in PRP has been described. Our objective was to assess the effectiveness of ustekinumab in five patients with adult‐onset PRP refractory to conventional therapies. In the present study, four patients had type I and one patient type II adult‐onset PRP. They were treated with three s.c. doses of ustekinumab at weeks 0, 4 and 16. Clinical response was evaluated monthly during treatment up to a 15‐month follow‐up period. All patients promptly showed a decrease in erythema, follicular hyperkeratosis and scaling. After three injections, complete remission of skin lesions was achieved in four out of five cases and a significant clinical improvement was shown in one case. To the best of our knowledge, this is the largest case series reported on ustekinumab treatment in PRP. Our results, in addition to previous studies from other groups, suggest that ustekinumab may be a possible first‐line treatment for PRP patients refractory to conventional therapies.
PARENTHOOD AS A TURNING POINT IN THE LIFE COURSE FOR MALE AND FEMALE GANG MEMBERS: A STUDY OF WITHIN‐INDIVIDUAL CHANGES IN GANG MEMBERSHIP AND CRIMINAL BEHAVIOR
Authors: PYROOZ DAVID C. , MCGLOIN JEAN MARIE , DECKER SCOTT H. 
Published: October 2017

AbstractThe impact of parenthood on leaving a street gang is not well understood. This is likely because researchers in prior studies have not accounted for multiple dimensions of gang exit, possible gender differences, and potential selection bias. In this study, we use a sample of 466 male and 163 female gang members from the National Longitudinal Study of Youth 1997 to consider the within‐individual relationship between changes in parenthood and changes in claiming gang membership and offending. These data offer the opportunity to consider gender differences and birth parity (i.e., first or second child). The results from a series of fixed‐effects models reveal that motherhood is associated with enduring reductions in both the odds of claiming gang membership and the rate of offending, whereas fatherhood has a temporary beneficial impact on gang membership and offending only for those fathers who reside with their children. In most cases, the beneficial effect of having a child rests in becoming a parent for the first time. On the whole, our study findings demonstrate that parenthood serves as a turning point for a particular group of noteworthy offenders—gang members.
Congested bile can predict the outcomes of endoscopic stenting for hilar biliary malignancies
Authors: Xia Ming Xing , Sun Bo , Xing Ling , Gao Dao Jian , Ye Xin , Wu Jun , Wang Tian Tian , Hu Bing 
Published: October 2017

OBJECTIVEEndoscopic management of malignant hilar biliary obstruction (MHBO) remains challenging, with relatively poor jaundice control and high infectious risk. The factors that affect the outcome of endoscopic therapy are still unclear. This retrospective cohort study aimed to investigate predictive factors for the outcomes of biliary stenting in patients with MHBO.METHODSBetween June 2015 and June 2016, consecutive patients with MHBO who received primary endoscopic stenting and completed follow‐up at our institution were identified and evaluated. All patients received full aspiration of congested bile followed by plastic or metal stent(s) placement. Clinical success was achieved in patients whose total serum bilirubin decreased by over two‐thirds in a month.RESULTSA total of 64 patients were included. Among them, 28 received a single stent placement and 36 received multiple stent placements. Altogether 53 (82.8%) patients attained clinical success and 48 (75.0%) underwent re‐interventions within 6 months. Multivariate analyses showed that only a total bile volume of ≥30 mL aspirated from the intrahepatic ducts predicted clinical success (OR 6.83, 95% CI 1.2–38.4, P = 0.029), absence of early post‐endoscopic retrograde cholangiopancreatography cholangitis (OR 0.03, 95% CI 0.004–0.36, P = 0.001), and lack of re‐intervention within 6 months (HR 0.10, 95% CI 0.05–0.22, P < 0.001) after initial endoscopic stenting.CONCLUSIONThe volume of congested bile may effectively predict treatment outcomes of endoscopic stenting for MHBO and guide the therapeutic strategy.
Contemporary salvage post prostatectomy radiotherapy: Early implementation improves biochemical control
Authors: Kneebone Andrew , Hruby George , Harris Georgia , Rasiah Kris , Vass Justin , Whalley Deborah , McCloud Philip , Louw Sandra , Guo Linxin , Eade Thomas 
Published: October 2017

AbstractIntroductionThe optimal time to commence salvage radiotherapy (SRT) for a rising PSA post radical prostatectomy is not known. We wished to assess the impact of index PSA (iPSA) level prior to SRT on rates of biochemical failure (BCF) post treatment.MethodsPatients referred to our institution for SRT for a rising PSA post surgery were accrued onto a prospective database. Baseline demographic data, tumour and treatment factors were collected including pathologic T and N stage, margin status, Gleason score (GS), lymphovascular space invasion (LVSI), use of androgen deprivation therapy (ADT) and time from surgery to salvage radiotherapy. Our endpoint was time to BCF.ResultsBetween January 2008 and December 2013, 189 patients received SRT to a mean dose of 69.8 Gy in 34 fractions using Intensity Modulated Radiotherapy (IMRT). Median follow‐up was 50 months. For patients with an iPSA of <0.2 ng/mL (n = 92), iPSA ≥ 0.2 to <1.0 ng/mL (n = 75) and ≥ 1.0 ng/mL (n = 22), rates of BCF at 5 years were 28.3%, 44.3% and 73.7% respectively. Compared to the iPSA <0.2 ng/mL group, the hazard ratios for time to BCF for an iPSA ≥ 0.2 to <1.0 ng/mL was 1.73 (P = 0.05) and >1.0 ng/mL was 3.1 (P = 0.002). Factors predicting time to BCF on univariate analysis included iPSA, GS, T stage, PSA nadir post surgery and LVSI. On multivariate analysis, GS, iPSA, use of ADT, T stage, PSA post surgery nadir and margin status remained significant.ConclusionRising iPSA levels are associated with an increasing risk of biochemical failure after adjusting for known prognostic factors and early salvage post prostatectomy radiotherapy is recommended.