bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cadmium Exposure Increases the Risk of Juvenile Obesity: A Human and Zebrafish Comparative Study
Authors: Green Adrian J. , Hoyo Cathrine , Mattingly Carolyn J. , Luo Yiwen , Tzeng Jung-Ying , Murphy Susan , Planchart Antonio 
Published: August 2017

OBJECTIVEHuman obesity is a complex metabolic disorder disproportionately affecting people of lower socioeconomic strata, and ethnic minorities, especially African Americans and Hispanics. Although genetic predisposition and a positive energy balance are implicated in obesity, these factors alone do not account for the excess prevalence of obesity in lower socioeconomic populations. Therefore, environmental factors, including exposure to pesticides, heavy metals, and other contaminants, are agents widely suspected to have obesogenic activity, and they also are spatially correlated with lower socioeconomic status. Our study investigates the causal relationship between exposure to the heavy metal, cadmium (Cd), and obesity in a cohort of children and a zebrafish model of adipogenesis.DESIGNAn extensive collection of first trimester maternal blood samples obtained as part of the Newborn Epigenetics Study (NEST) were analyzed for the presence Cd, and these results were cross analyzed with the weight-gain trajectory of the children through age five years. Next, the role of Cd as a potential obesogen was analyzed in anin vivozebrafish model.RESULTSOur analysis indicates that the presence of Cd in maternal blood during pregnancy is associated with increased risk of juvenile obesity in the offspring, independent of other variables, including lead (Pb) and smoking status. Our results are recapitulated in a zebrafish model, in which exposure to Cd at levels approximating those observed in the NEST study is associated with increased adiposity.CONCLUSIONOur findings identify Cd as potential human obesogen. Moreover, these observations are recapitulated in a zebrafish model, suggesting that the underlying mechanisms may be evolutionarily conserved, and that zebrafish may be a valuable model for uncovering pathways leading to Cd-mediated obesity in human populations.
CarrierSeq: a sequence analysis workflow for low-input nanopore sequencing
Authors: Mojarro Angel , Hachey Julie , Ruvkun Gary , Zuber Maria T. , Carr Christopher E. 
Published: August 2017

AbstractMotivationLong-read nanopore sequencing technology is of particular significance for taxonomic identification at or below the species level. For many environmental samples, the total extractable DNA is far below the current input requirements of nanopore sequencing, preventing “sample to sequence” metagenomics from low-biomass or recalcitrant samples.ResultsHere we address this problem by employing carrier sequencing, a method to sequence low-input DNA by preparing the target DNA with a genomic carrier to achieve ideal library preparation and sequencing stoichiometry without amplification. We then use CarrierSeq, a sequence analysis workflow to identify the low-input target reads from the genomic carrier. We tested CarrierSeq experimentally by sequencing from a combination of 0.2 ngBacillus subtilisATCC 6633 DNA in a background of 1 μgEnterobacteria phage λDNA. After filtering of carrier, low quality, and low complexity reads, we detected target reads (B. subtilis), contamination reads, and “high quality noise reads” (HQNRs) not mapping to the carrier, target or known lab contaminants. These reads appear to be artifacts of the nanopore sequencing process as they are associated with specific channels (pores). By treating reads as a Poisson arrival process, we implement a statistical test to reject data from channels dominated by HQNRs while retaining target reads.AvailabilityCarrierSeq is an open-source bash script with supporting python scripts which leverage a variety of bioinformatics software packages on macOS and Ubuntu. Supplemental documentation is available from Github -https://github.com/amojarro/carrierseq. In addition, we have compiled all required dependencies in a Docker image available from -https://hub.docker.com/r/mojarro/carrierseq.
Toward Capturing the Exposome: Exposure Biomarker Variability and Co-Exposure Patterns in the Shared Environment
Authors: Chung Ming Kei , Kannan Kurunthachalam , Buck Louis Germaine M. , Patel Chirag J. 
Published: August 2017

AbstractBACKGROUND:Along with time, variation in the exposome is dependent on the location and sex of study participants. One specific factor that may influence exposure co-variations is a shared household environment.OBJECTIVES:To examine the influence of shared household and partner’s sex in relation to the variation in 128 endocrine disrupting chemical (EDC) exposures among couples.METHODS:In a cohort comprising 501 couples trying for pregnancy, we measured 128 (13 chemical classes) persistent and non-persistent EDCs and estimated 1) sex-specific differences; 2) variance explained by shared household; and 3) Spearman’s rank correlation coefficients (rs) for females, males, and couples’ exposures.RESULTS:Sex was correlated with 8 EDCs including polyfluoroalkyl substances (PFASs) (p< 0.05). Shared household explained 43% and 41% of the total variance for PFASs and blood metals, respectively, but less than 20% for the remaining 11 EDC classes. Co-exposure patterns of the exposome were similar between females and males, with within-classrs higher for persistent and lower for non-persistent chemicals. Medianrss of polybrominated compounds and urine metalloids were 0.45 and 0.09, respectively, for females (0.41 and 0.08 for males), whereas lowerrss for these 2 classes were found for couples (0.21 and 0.04).CONCLUSIONS:Overall, sex did not significantly affect EDC levels in couples. Individual, rather than shared environment, could be a major factor influencing the co-variation of 128 markers of the exposome. Correlations between exposures are lower in couples than in individual partners and have important analytical and sampling implications for epidemiological study.
Use of whole genome sequencing to investigate an outbreak of gonorrhoea among females in urban New South Wales, Australia, 2012 to 2014
Authors: Buckley Cameron , Forde Brian M. , Trembizki Ella , Lahra Monica M. , Beatson Scott A. , Whiley David M. 
Published: August 2017

AbstractIncreasing rates of gonorrhoea have been observed among urban heterosexuals within the Australian state of New South Wales (NSW). Here, we applied whole genome sequencing (WGS) to better understand transmission dynamics. Ninety-four isolates of a particularN. gonorrhoeaegenotype (G122) associated with female patients (years 2012 to 2014) underwent phylogenetic analysis using core single nucleotide polymorphisms (SNPs). Context for genetic variation was provided by including an unbiased selection of 1,870N. gonorrhoeaegenomes from a recent United Kingdom (UK) study. NSW genomes formed a single clade, with the majority of isolates belonging to one of five clusters, and comprised patients of varying age groups. Intra-patient variability was less than 7 core SNPs. Several patients had indistinguishable core SNPs, suggesting a common infection source. These data have provided an enhanced understanding of transmission ofN. gonorrhoeaeamong urban heterosexuals in NSW, Australia, and highlight the value of using WGS inN. gonorrhoeaeoutbreak investigations.
Comparing colours using visual models
Authors: Maia Rafael , White Thomas E. 
Published: August 2017

Lay SummaryAn outstanding challenge for the study of colour traits is how best to use “colour spaces” to represent their visual perception, particularly when asking questions of colour-difference (e.g. the (dis)similarity of males and females, mimics and models, or sister species, to a given viewer). We use simulations to show that existing methods fail to statistically and biologically estimate the separation of groups in colour space, and we suggest a flexible, robust, alternative that avoids those pitfalls.AbstractColour in nature presents a striking dimension of variation, though understanding its function and evolution largely depends on our ability to capture the perspective of relevant viewers. This goal has been radically advanced by the development and widespread adoption of colour spaces, which allow for the viewer-subjective estimation of colour appearance. Most studies of colour in camouflage, aposematism, sexual selection, and other signalling contexts draw on these models, with the shared analytical objective of estimating how similar (or dissimilar) colour samples are to a given viewer. We summarise popular approaches for estimating the separation of samples in colour space, and use a simulation-based approach to test their efficacy with common data structures. We show that these methods largely fail to estimate the separation of colour samples by neglecting (i) the statistical distribution and within-group variation of the data, and/or (ii) the discriminability of groups relative to the observer’s visual capabilities. Instead, we formalize the two questions that must be answered to establish both the statistical presence and theoretical magnitude of colour differences, and propose a two-step, permutation-based approach that achieves this goal. Unlike previous methods, our suggested approach accounts for the multidimensional nature of visual model data, and is robust against common colour-data features such as heterogeneity and outliers. We demonstrate the pitfalls of current methods and the flexibility of our suggested framework using an example from the literature, with recommendations for future inquiry.
Ligand-regulated entry into the HRD ERAD pathway—the dark side of allostery
Authors: Wangeline Margaret A , Hampton Randolph Y 
Published: August 2017

ABSTRACTHMG-CoA reductase (HMGR) undergoes regulated degradation as part of feedback control of the sterol pathway. In yeast the stability of the Hmg2 isozyme of HMGR is controlled by the 20 carbon isoprenoid geranylgeranyl pyrophosphate (GGPP): increasing levels of GGPP causes more efficient degradation by the HRD pathway, allowing feedback regulation of HMGR. The HRD pathway is a conserved quality control pathway critical for the ER-associated degradation of misfolded ER proteins. We have explored the action of GGPP in HRD-dependent Hmg2 degradation. GGPP was highly potent as a regulatory molecule in vivo, andin vitro, GGPP altered Hmg2 folding at nanomolar concentrations. These effects of GGPP were absent in a variety of stabilized or non-regulated Hmg2 mutants. Consistent with its high potency, the effects of GGPP were highly specific; other closely related molecules were ineffective in altering Hmg2 structure. In fact, two close GGPP analogues, 2F-GGPP and GGSPP were completely inactive at all concentrations tested, and GGSPP was an antagonist of GGPPs effectsin vivoandin vitro. The effects of GGPP on Hmg2 structure and degradation were reversed by chemical chaperones, indicating that GGPP caused selective Hmg2 misfolding. These data indicate that GGPP functions in a manner analogous to an allosteric ligand, causing Hmg2 misfolding through interaction with a reversible, specific binding site. Consistent with this, the Hmg2 protein forms mulitmers. We propose that this “allosteric misfolding,” ormallostery, may be a widely used tactic of biological regulation, with potential for development of small molecule pharmaceuticals that induce selective misfolding.
Assessing the performance of real-time epidemic forecasts: A case study of Ebola in the Western Area Region of Sierra Leone, 2014–15
Authors: Funk Sebastian , Camacho Anton , Kucharski Adam J. , Lowe Rachel , Eggo Rosalind M. , Edmunds W. John 
Published: August 2017

AbstractReal-time forecasts based on mathematical models can inform critical decision-making during infectious disease outbreaks. Yet, epidemic forecasts are rarely evaluated during or after the event, and there is little guidance on the best metrics for assessment. Here, we propose an evaluation approach that disentangles different components of forecasting ability using metrics that separately assess the calibration, sharpness and unbiasedness of forecasts. This makes it possible to assess not just how close a forecast was to reality but also how well uncertainty has been quantified. We used this approach to analyse the performance of weekly forecasts we generated in real time in Western Area, Sierra Leone, during the 2013–16 Ebola epidemic in West Africa. We investigated a range of forecast model variants based on the model fits generated at the time with a semi-mechanistic model, and found that good probabilistic calibration was achievable at short time horizons of one or two weeks ahead but models were increasingly inaccurate at longer forecasting horizons. This suggests that forecasts may have been of good enough quality to inform decision making requiring predictions a few weeks ahead of time but not longer, reflecting the high level of uncertainty in the processes driving the trajectory of the epidemic. Comparing forecasts based on the semi-mechanistic model to simpler null models showed that the best semi-mechanistic model variant performed better than the null models with respect to probabilistic calibration, and that this would have been identified from the earliest stages of the outbreak. As forecasts become a routine part of the toolkit in public health, standards for evaluation of performance will be important for assessing quality and improving credibility of mathematical models, and for elucidating difficulties and trade-offs when aiming to make the most useful and reliable forecasts.
Mosaic Turner syndrome shows reduced phenotypic penetrance in an adult population study compared to clinically ascertained cases
Authors: Tuke Marcus A. , Ruth Katherine S. , Wood Andrew R. , Beaumont Robin N. , Tyrrell Jessica , Jones Samuel E. , Yaghootkar Hanieh , Turner Claire L.S. , Donohoe Mollie E. , Brooke Antonia M. , Collinson Morag N. , Freathy Rachel M. , Weedon Michael N. , Frayling Timothy M. , Murray Anna 
Published: August 2017

AbstractWomen with X chromosome aneuploidy such as 45,X (Turner syndrome) or 47,XXX (Triple X syndrome) present with characteristics including differences in stature, increased cardiovascular disease risk and primary ovarian insufficiency. Many women with X chromosome aneuploidy undergo lifetime clinical monitoring for possible complications. However, ascertainment of cases in the clinic may mean that the phenotypic penetrance is overestimated. Studies of prenatally ascertained X chromosome aneuploidy cases have limited follow-up data and so the long-term consequences into adulthood are often not reported. We aimed to characterise the prevalence and phenotypic consequences of X chromosome aneuploidy in a large population of women over 40 years of age. We detected 30 women with 45,X, 186 with mosaic 45,X/46,XX and 110 with 47,XXX among 244,848 UK Biobank women, using SNP array data. The prevalence of non-mosaic 45,X (1/8,162) and 47,XXX (1/2,226) was lower than expected, but was higher for mosaic 45,X/46,XX (1/1,316). The characteristics of women with 45,X were consistent with the characteristics of a clinically recognised Turner syndrome phenotype, including a 17.2cm shorter stature (SD = 5.72cm;P= 1.5 × 10−53) and 16/30 did not report an age at menarche. The phenotype of women with 47,XXX included taller stature (5.3cm; SD = 5.52cm;P= 5.8 × 10−20), earlier menopause age (5.12 years; SD = 5.1 years;P= 1.2 x 10−14) and a lower fluid intelligence score (24%; SD = 29.7%;P= 3.7 × 10−8). In contrast, the characteristics of women with mosaic 45,X/46,XX were much less pronounced than expected. Women with mosaic 45,X/46,XX were less short, had a normal reproductive lifespan and birth rate, and no reported cardiovascular complications. In conclusion, the availability of data from 244,848 women allowed us to assess the phenotypic penetrance of traits associated with X chromosome aneuploidy in an adult population setting. Our results suggest that the clinical management of women with 45,X/46,XX mosaicism should be minimal, particularly those identified incidentally.FundingNone
Human occipital bone sexual dimorphism in an Archiac period archaeological population
Authors: Hoover Dr. Kara C. 
Published: August 2017

PREPRINT NOTESThis paper was submitted for publication theInternational Journal of Osteoarchaeologyin August of 2003. The paper was rejected roughly a year later due to scope and collection issues. I revisited the paper in 2007 with an eye to updating and resubmitting with additional data but the project was triaged from the publication pipeline due to the work involved relative to other projects more relevant to my research interests at the time. The current preprint paper contains updated references on occipital bone sexual dimorphism—all limited to the condylar region rather than the full suite of variation in the region.I am posting this to the preprint server to contribute the findings to the larger scientific community in the hopes that I might have time to revisit the paper as a student project. A more rigorous study would need to expand the sample either to a study collection that has remains with known sex (either verified via molecular sexing techniques or using a modern study collection) or additional comparative collections from hunter-gatherer populations. If a student is interested in taking up the topic and assuming lead authorship on a co-authored paper, I’d be happy to collaborate and see this piece through the publication pipeline.ABSTRACTThis paper presents the results of a comprehensive study of sexual dimorphism in the human occipital region of the skull using the remains of 39 prehistoric adults from the prehistoric Windover (6,000-8,000 BP). The results of a discriminant analysis classified 64% of the individuals correctly (using osteologically identified sex). Sexual dimorphism in this population may not be prevalent due to environmental stress.
GIVE: toward portable genome browsers for personal websites
Authors: Cao Xiaoyi , Yan Zhangming , Wu Qiuyang , Zheng Alvin , Zhong Sheng 
Published: August 2017

ABSTRACTGrowing popularity and diversity of genomic data demands portable and versatile genome browsers. Here, we present an open source programming library, called GIVE that facilitates creation of personalized genome browsers without requiring a system administrator. By inserting HTML tags, one can add to a personal webpage interactive visualization of multiple types of genomics data, including genome annotation, “linear” quantitative data (wiggle), and genome interaction data. GIVE includes a graphical interface called HUG (HTML Universal Generator) that automatically generates HTML code for displaying user chosen data, which can be copy-pasted into user’s personal website or saved and shared with collaborators. The simplicity of use was enabled by encapsulation of novel data communication and visualization technologies, including new data structures, a memory management method, and a double layer display method. GIVE is available at:http://www.givengine.org/.
LIM Protein Ajuba associates with the RPA complex through direct and cell cycle-dependent interaction with the RPA70 subunit
Authors: Fowler Sandy , Maguin Pascal , Kalan Sampada , Loayza Diego 
Published: August 2017

AbstractDNA damage response pathways are essential for genome stability and cell survival. Specifically, the ATR kinase is activated by DNA replication stress. An early event in this activation is the recruitment and phosphorylation of RPA, a single stranded DNA binding complex composed of three subunits, RPA70,RPA32 and RPA14. We have previously shown that the LIM protein Ajuba associates with RPA, and that depletion of Ajuba leads to potent activation of ATR. In this study, we show evidence that the Ajuba-RPA interaction occurs through direct protein contact with RPA70, and that their association is cell cycle-regulated and is reduced upon DNA replication stress. We propose a model in which Ajuba negatively regulates the ATR pathway by directly interacting with RPA70, thereby preventing an inappropriate ATR activation. Our results provide a framework to understand the mechanism of regulation of ATR in human cells, which is important to prevent cellular transformation and tumorigenesis.
Map-based cloning of the genePm21that confers broad spectrum resistance to wheat powdery mildew
Authors: He Huagang , Zhu Shanying , Ji Yaoyong , Jiang Zhengning , Zhao Renhui , Bie Tongde 
Published: August 2017

AbstractCommon wheat (Triticum aestivumL.) is one of the most important cereal crops. Wheat powdery mildew caused byBlumeria graminisf. sp.tritici(Bgt) is a continuing threat to wheat production. ThePm21gene, originating fromDasypyrum villosum, confers high resistance to all knownBgtraces and has been widely applied in wheat breeding in China. In this research, we identifyPm21as a typical coiled-coil, nucleotide-binding site, leucine-rich repeat gene by an integrated strategy of resistance gene analog (RGA)-based cloning via comparative genomics, physical and genetic mapping, BSMV-induced gene silencing (BSMV-VIGS), large-scale mutagenesis and genetic transformation.
Withdrawal-induced escalated oxycodone self-administration is mediated by kappa opioid receptor function
Authors: Nguyen Jacques D. , Kirson Dean , Steinman Michael Q. , Patel Reesha , Khom Sophia , Varodayan Florence P. , Hedges David M. , Oleata Christopher S. , Grant Yanabel , Roberto Marisa , Taffe Michael A. 
Published: August 2017

ABSTRACTBackground:Prescription opioid addiction is a significant health problem characterized by compulsive drug seeking, withdrawal and chronic relapse. We investigated the neurobiological consequences of escalation of prescription opioid use using extended access to intravenous oxycodone self-administration in rats.Methods:Male Wistar rats acquired oxycodone self-administration (0.15 mg/kg/infusion, i.v.) in 1h or 12h access sessions. Electrophysiological and immunohistochemical studies investigated the effects of oxycodone self-administration on kappa opioid receptor (KOR) regulation of GABAergic signaling and dynorphin expression in the central nucleus of the amygdala (CeA).Results:Rats given 12h access to oxycodone for 5 sessions/week (LgA) escalated their responding more than rats given 1h oxycodone (ShA) or 12h saline access. Slowed escalation of responding was found in rats given 12h access for 7 sessions/week (LgA-7day) or rats pretreated with the KOR antagonist nor-binaltorphamine dihydrochloride (norBNI) before LgA (norBNI+LgA). The KOR agonist U-50488 decreased GABA release in CeA neurons of all groups except LgA. norBNI increased GABA release in control group neurons, suggesting tonic KOR activity. This activity was abolished in ShA, norBNI+LgA, and LgA-7day rat neurons, consistent with decreased CeA dynorphin immunoreactivity observed in LgA-7day rats. However, norBNI effects were reversed (decreased CeA GABA release) in LgA rat neurons.Conclusions:The experience of intermittent extended withdrawal periods accelerates the escalation of oxycodone self-administration and causes greater dysregulation of CeA KOR-mediated GABAergic signaling. A KOR agonist/antagonist switch effect seen with other drugs of abuse was absent, which suggests that oxycodone-induced neuroadaptations may be distinct from those resulting from other drugs of abuse.