bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk taking to obtain reward: gender differences and associations with emotional and depressive symptoms in a nationally representative cohort of UK adolescents
Authors: Lewis Gemma , Srinivasam Ramya , Roiser Jonathan , Blakemore Sarah-Jayne , Flouri Eirini , Lewis Glyn 
Published: May 2019

AbstractBackgroundLarge population-based studies of neuropsychological factors that characterize or precede depressive symptoms are rare and we know little about gender differences in these associations.MethodsThe Millennium Cohort is a representative UK birth cohort of children born between 2000 and 2002. The Cambridge Gambling Task (CGT) was completed at ages 11 (n=12,355) and 14 (n=10,578). Our main exposure was proportion of points gambled, when odds of winning were above chance (risk taking to obtain reward). We also examined how much adolescents adjusted bets as odds of winning increased (risk adjustment). Outcomes were emotional symptoms at age 11 (SDQ) and depressive symptoms at age 14 (sMFQ). We calculated cross-sectional associations, and a longitudinal association from age 11 to 14, using linear regressions before and after adjusting for confounders.ResultsFemales were less risk taking than males (e.g. females bet 9.22, 95% CI 8.65 to 9.80, percentage points lower at age 11). In univariable models there were cross-sectional associations between risk taking and emotional (age 11) or depressive (age 14) symptoms (e.g. at age 14, a 20-percentage point increase in risk taking was associated with a 0.52 reduction in sMFQ points, 95% CI -.71 to -.33). However, cross-sectional associations were explained by gender differences (at age 14 the association adjusted for gender was: .05, 95% CI -.15 to .25). Longitudinally, there was weak evidence of an association between risk taking and depressive symptoms in females only (a 20-point increase in risk taking at age 11 was associated with a reduction of 0.31 sMFQ points at age 14 (95% CI -.60 to -.02).ConclusionsWe found evidence that adolescent females were less likely to take risks than adolescent males. There was no strong evidence of an association between risk taking and emotional and depressive symptoms, after accounting for gender.AbbreviationsCGT: Millennium Cohort Study (MCS); Cambridge Gambling Task (CGT); Strengths and Difficulties Questionnaire (SDQ); sMFQ: short Mood and Feelings Questionnaire.
The rodent vaginal microbiome across the estrous cycle and the effect of genital nerve electrical stimulation
Authors: Levy Micah , Bassis Christine M. , Kennedy Eric , Yoest Katie E. , Becker Jill B. , Bell Jason , Berger Mitchell B. , Bruns Tim M. 
Published: May 2019

AbstractTreatment options are limited for the approximately 40% of postmenopausal women worldwide who suffer from female sexual dysfunction (FSD). Neural stimulation has shown potential as a treatment for genital arousal FSD, however the mechanisms for its improvement are unknown. One potential cause of some cases of genital arousal FSD are changes to the composition of the vaginal microbiota, which is associated with vulvovaginal atrophy. The primary hypothesis of this study was that neural stimulation may induce healthy changes in the vaginal microbiome, thereby improving genital arousal FSD symptoms. In this study we used healthy rats, which are a common animal model for sexual function, however the rat vaginal microbiome is understudied. Thus this study also sought to examine the composition of the rat vaginal microbiota. Treatment rats (n=5) received 30 minutes of cutaneous electrical stimulation targeting the genital branch of the pudendal nerve, and Control animals (n=4) had 30-minute sessions without stimulation. Vaginal lavage samples were taken during a 14-day baseline period including multiple estrous periods and after twice-weekly 30-minute sessions across a six-week trial period. Analysis of 16S rRNA gene sequences was used to characterize the rat vaginal microbiota in baseline samples and determine the effect of stimulation. We found that the rat vaginal microbiota is dominated by Proteobacteria, Firmicutes, and Actinobacteria, which changed in relative abundance during the estrous cycle and in relationship to each other. While the overall stimulation effects were unclear in these healthy rats, some Treatment animals had less alteration in microbiota composition between sequential samples than Control animals, suggesting that stimulation may help stabilize the vaginal microbiome. Future studies may consider additional physiological parameters, in addition to the microbiome composition, to further examine vaginal health and the effects of stimulation.
Pooled CRISPR screening in pancreatic cancer cells implicates co-repressor complexes as a cause of multiple drug resistance via regulation of epithelial-to-mesenchymal transition
Authors: Ramaker Ryne C. , Hardigan Andrew A. , Gordon Emily R. , Wright Carter A. , Myers Richard M. , Cooper Sara J. 
Published: May 2019

ABSTRACTPancreatic ductal adenocarcinoma (PDAC) patients suffer poor outcomes in part due to therapeutic resistance. We conducted four genome-wide CRISPR activation (CRISPRact) and CRISPR knock out (CRISPRko) screens to identify novel resistance mechanisms to four cytotoxic chemotherapies (gemcitabine, 5-fluorouracil, irinotecan, and oxaliplatin). ABCG2, a well-described efflux pump was the strongest mediator of resistance. We showed that overexpressing HDAC1 altered promoter occupancy and expression of genes involved in the epithelial-to-mesenchymal transition. Using the results of our CRISPR screens, we predicted drug sensitivity for patients and cell lines based on gene expression profiles. These predictions could be clinically useful for treatment selection.
Cohesin promotes stochastic domain intermingling to ensure proper regulation of boundary-proximal genes
Authors: Luppino Jennifer M. , Park Daniel S. , Nguyen Son C. , Lan Yemin , Xu Zhuxuan , Joyce Eric F. 
Published: May 2019

AbstractThe mammalian genome can be segmented into thousands of topologically associated domains (TADs) based on chromosome conformation capture studies, such as Hi-C. TADs have been proposed to act as insulated neighborhoods, spatially sequestering and insulating the enclosed genes and regulatory elements through chromatin looping and self-association. Recent results indicate that inter-TAD interactions can also occur, suggesting boundaries may be semi-permissible. However, the nature, extent, and function, if any, of these inter-TAD interactions remains unclear. Here, we combine super-and high-resolution microscopy with Oligopaint technology to precisely quantify the interaction frequency within and between neighboring domains in human cells. We find that intermingling across domain boundaries is a widespread feature of the human genome, with varying levels of interactions across different loci that correlate with their differing boundary strengths by Hi-C. Moreover, we find that cohesin depletion, which is known to abolish TADs at the population-average level, does not induce ectopic interactions but instead reduces both intra- and inter-domain interactions to a similar extent. Reduced chromatin intermixing due to cohesin loss affects domain incorporation and transcriptional bursting frequencies of genes close to architectural boundaries, potentially explaining the gene expression changes observed in the cohesinopathy Cornelia de Lange syndrome. Together, our results provide a mechanistic explanation for stochastic domain intermingling, arguing that cohesin partially bypasses boundaries to promote alternating incorporation of boundary-proximal genes into neighboring regulatory domains.
Patterns of annual and seasonal immune investment in a temporal reproductive opportunist
Authors: Schultz Elizabeth M. , Gunning Christian E. , Cornelius Jamie M. , Reichard Dustin G. , Klasing Kirk C. , Hahn Thomas P. 
Published: May 2019

AbstractHistorically, investigations of how organisms’ investments in immunity fluctuate in response to environmental and physiological changes have focused on seasonally breeding organisms that confine reproduction to seasons with mild environmental conditions and abundant resources. Consequently, knowledge of how harsh environmental conditions and reproductive effort may interact to shape investment in immunity remains limited. The red crossbill,Loxia curvirostra, is a songbird that can breed on both short, cold and long, warm days if conifer seeds are abundant. This species provides an ideal system to investigate the influence of environmental fluctuations, reproductive investment, and their potential interactions on patterns of immune investment. In this study, we measured inter- and intra-annual immune variation in crossbills across four consecutive summers (2010-2013) and multiple seasons within one year (summer 2011-spring 2012) to explore how physiological and environmental factors impact this immune variation. Overall, the data suggest that immunity varies seasonally, among years, and in response to environmental fluctuations in food resources, precipitation, and temperature, but less in response to physiological measures such as reproduction. Collectively, this system demonstrates that a reproductively flexible organism may breed when conditions allow simultaneous investment in survival-related processes rather than at the expense of them.
Transcriptomic insights into the establishment of coral-algal symbioses from the symbiont perspective
Authors: Mohamed Amin R , Andrade Natalia , Moya Aurelie , Chan Cheong Xin , Negri Andrew P. , Bourne David G. , Ball Eldon E , Miller David J 
Published: May 2019

AbstractDespite the ecological significance of the mutualistic relationship between Symbiodiniaceae and reef-building corals, the molecular machinery underpinning the establishment of this relationship is not well understood. This is especially true of the symbiont side, as previous attempts to understand the interaction between coral larvae and Symbiodiniaceae have focused nearly exclusively on the host. In the current study, Acropora tenuis planula larvae were exposed to a compatible strain of Symbiodiniaceae (Cladocopium) and the transcriptomic landscape of the symbiont profiled at 3, 12, 48 and 72 h post-exposure using RNA-Seq. The transcriptomic response of Cladocopium to the symbiotic state was complex, the most obvious feature being an extensive and generalised downregulation of gene expression. Included in this “symbiosis-derived transcriptional repression” were a range of stress response and immune-related genes. In contrast, genes implicated in metabolism were upregulated in the symbiotic state. Consistent with previous ecological studies, this transcriptomic response of Cladocopium implied that active translocation of metabolites to the host occurred, and thus that the mutualistic relationship can be established at the larval stage. This study provides novel insights into the transcriptomic remodelling that occurs in Symbiodiniaceae, with important implications for understanding the establishment of symbiosis between corals and their dinoflagellate partners.
SEQdata-BEACON: a comprehensive database of sequencing performance and statistical tools for performance evaluation and yield simulation in BGISEQ-500
Authors: Zhou Yanqiu , Liu Chen , Zhou Rongfang , Lu Anzhi , Huang Biao , Liu Liling , Chen Ling , Luo Bei , Huang Jin , Tian Zhijian 
Published: May 2019

AbstractBackgroundBGISEQ-500 is based on DNBSEQ™ technology and superior in providing high outputs and requiring less cost. This sequencer has been widely used in various areas of scientific and clinical research. A better understanding of the sequencing process and sequencer performance is essential for stabilizing sequencing process, accurately interpreting sequencing results and efficiently solving sequencing troubles. To solve these problems, a comprehensive database SEQdata-BEACON was constructed to accumulate sequencing performance data in BGISEQ-500.MethodsTotally 60 BGISEQ-500 sequencers in BGI-Wuhan lab were used to collect the sequencing performance data. Those lanes in paired-end 100 sequencing using 10bp barcode were chosen, and each lane containing 66 metrics was assigned a unique entry number as ID. The database was constructed in MySQL server 8.0 and the website was built on Apache (2.4.33 win64 VC15 server). The statistical analysis and linear regression models were generated by R program based on the data from November 2018 to April 2019.ResultsA total of 2236 entries were recorded in the database, including sample ID, yield, quality, machine state and supplies information. According to correlation matrix, the 52 numerical metrics were clustered into three groups signifying yield-quality, machine state and sequencing calibration. The metrics distributions also delivered some patterns and rendered clues for further explanation or analysis of the sequencing process. Using the data of total 200 cycles, the linear regression model well simulated the final outputs. Moreover, the predicted final yield could be provided in the 15th cycle of the early stage of sequencing and the corresponding coefficient of determination R2 of the 200th and 15th cycle models were 0.97 and 0.81 respectively. The data source, statistical findings and application tools were all available in our website http://seqBEACON.genomics.cn:443/home.html. These resources can be used as a constantly updated reference for BGISEQ-500 users to comprehensively understand DNBSEQ™ technology, solve sequencing problems and optimize the sequencing process.
Genome sequence of the model rice variety KitaakeX
Authors: Jain Rashmi , Jenkins Jerry , Shu Shengqiang , Chern Mawsheng , Martin Joel A. , Copetti Dario , Duong Phat Q. , Pham Nikki T. , Kudrna David A. , Talag Jayson , Schackwitz Wendy S. , Lipzen Anna M. , Dilworth David , Bauer Diane , Grimwood Jane , Nelson Catherine R. , Xing Feng , Xie Weibo , Barry Kerrie W. , Wing Rod A. , Schmutz Jeremy , Li Guotian , Ronald Pamela C. 
Published: May 2019

AbstractHere, we report the de novo genome sequencing and analysis of Oryza sativa ssp. japonica variety KitaakeX, a Kitaake plant carrying the rice XA21 immune receptor. Our KitaakeX sequence assembly contains 377.6 Mb, consisting of 33 scaffolds (476 contigs) with a contig N50 of 1.4 Mb. Complementing the assembly are detailed gene annotations of 35,594 protein coding genes. We identified 331,335 genomic variations between KitaakeX and Nipponbare (ssp. japonica), and 2,785,991 variations between KitaakeX and Zhenshan97 (ssp. indica). We also compared Kitaake resequencing reads to the KitaakeX assembly and identified 219 small variations. The high-quality genome of the model rice plant KitaakeX will accelerate rice functional genomics.
Modeling hepatitis C micro-elimination among people who inject drugs with direct-acting antivirals in metropolitan Chicago
Authors: Tatara Eric , Gutfraind Alexander , Collier Nicholson T. , Echevarria Desarae , Cotler Scott J. , Major Marian , Ozik Jonathan , Dahari Harel , Boodram Basmattee 
Published: May 2019

ABSTRACTHepatitis C virus (HCV) infection is a leading cause of chronic liver disease and mortality worldwide. Direct-acting antiviral (DAA) therapy leads to high cure rates. However, persons who inject drugs (PWID) are at risk for reinfection after cure and may require multiple DAA treatments to reach the World Health Organization’s (WHO) goal of HCV elimination by 2030. Using an agent-based model (ABM) that accounts for the complex interplay of demographic factors, risk behaviors, social networks, and geographic location for HCV transmission among PWID, we examined the combination(s) of DAA enrollment (2.5%, 5%, 7.5%, 10%), adherence (60%, 70%, 80%, 90%) and frequency of DAA treatment courses needed to achieve the WHO’s goal of reducing incident chronic infections by 90% by 2030 among a large population of PWID from Chicago, IL and surrounding suburbs. We also estimated the economic DAA costs associated with each scenario. Our results indicate that a DAA treatment rate of >7.5% per year with 90% adherence results in 75% of enrolled PWID requiring only a single DAA course; however19% would require 2 courses, 5%, 3 courses and <2%, 4 courses), with an overall DAA cost of $325 million to achieve the WHO goal in metropolitan Chicago. We estimate a 28% increase in the overall DAA cost under low adherence (70%) compared to high adherence (90%). Our modeling results have important public health implications for HCV elimination among U.S. PWID. Using a range of feasible treatment enrollment and adherence rates, we report robust findings supporting the need to address re-exposure and reinfection among PWID to reduce HCV incidence.
Saving Old Bones: a non-destructive method for bone collagen prescreening
Authors: Sponheimer Matt , Ryder Christina M. , Fewlass Helen , Smith Erin K. , Pestle William J. , Talamo Sahra 
Published: May 2019

AbstractBone collagen is an important material for radiocarbon, paleodietary, and paleoproteomic analyses, but it degrades over time. Various methods have been employed to prescreen bone for collagen preservation, but these are often destructive and/or require exportation for analysis. Here we show that near-infrared spectroscopy can be used to determine bone collagen content quickly and non-destructively on site.r
Restored tactile sensation improves neuroprosthetic arm control
Authors: Flesher Sharlene N , Downey John E , Weiss Jeffrey M , Hughes Christopher L , Herrera Angelica J , Tyler-Kabara Elizabeth C , Boninger Michael L , Collinger Jennifer L , Gaunt Robert A 
Published: May 2019

Summary paragraphThe sense of touch is critical for skillful hand control1–3, but is largely missing for people who use prosthetic devices. Instead, prosthesis users rely heavily on visual feedback, even though state transitions that are necessary to skillfully interact with objects, such as object contact, are relayed more precisely through tactile feedback4–6. Here we show that restoring tactile sensory feedback, through intracortical microstimulation of the somatosensory cortex7, enables a person with a bidirectional intracortical brain-computer interface to improve their performance on functional object transport tasks completed with a neurally-controlled prosthetic limb. The participant had full visual feedback and had practiced the task for approximately two years prior to these experiments. Nevertheless, successful trial times on a commonly used clinical upper limb assessment task were reduced from a median time of 20.9 s (13.1 - 40.5 s interquartile range) to 10.2 s (5.4 - 18.1 s interquartile range) when vision was supplemented with microstimulation-evoked cutaneous percepts that were referred to different fingers and were graded in intensity based on real-time prosthesis contact forces. Faster completion times were primarily due to a reduction in the amount of time spent attempting to grasp objects. These results demonstrate the importance of tactile sensations in upper-limb control and the utility of creating bidirectional brain-computer interfaces to restore this stream of information using intracortical microstimulation.
Intertwined Functions of Separase and Caspase in Cell Division and Programmed Cell Death
Authors: Jeong Pan-Young , Kumar Ashish , Joshi Pradeep , Rothman Joel H. 
Published: May 2019

AbstractTimely sister chromatid separation, promoted by separase, is essential for faithful chromosome segregation. Separase is a member of the CD clan of cysteine proteases, which also includes the pro-apoptotic enzymes known as caspases. We report that theC. elegansseparase SEP-1, primarily known for its role in cell division, is required for apoptosis when the predominant pro-apoptotic caspase CED-3 is compromised. Loss of SEP-1 results in extra surviving cells in a weakced-3(−)mutant, and suppresses the embryonic lethality of a mutant defective for the apoptotic suppressorced-9/Bcl-2. We also report apparent non-apoptotic roles for CED-3 in promoting germ cell proliferation and germline meiotic chromosome disjunction and the normal rate of embryonic development. Moreover, loss of the soma-specific (CSP-3) and germline-specific (CSP-2) caspase inhibitors results in CED-3-dependent suppression of embryonic lethality and meiotic chromosome non-disjunction respectively, when separase function is compromised. Thus, while caspases and separases have evolved different substrate specificities associated with their specialized functions in apoptosis and cell division respectively, they appear to have retained the residual ability to participate in both processes, supporting the view that co-option of components in cell division may have led to the innovation of programmed cell suicide early in metazoan evolution.
A protein-centric approach for exome variant aggregation enables sensitive association analysis with clinical outcomes
Authors: Li Ginny X.L. , Munro Dan , Fermin Damian , Vogel Christine , Choi Hyungwon 
Published: May 2019

AbstractSomatic mutations are early drivers of tumorigenesis and tumor progression. However, the mutations typically occur at variable positions across different individuals, resulting in the data being too sparse to test meaningful associations between variants and phenotypes. To overcome this challenge, we devised a novel approach called Gene-to-Protein-to-Disease (GPD) which accumulates variants into new sequence units as the degree of genetic assault on structural or functional units of each protein. The variant frequencies in the sequence units were highly reproducible between two large cancer cohorts. Survival analysis identified 247 sequence units in which somatic mutations had deleterious effects on overall survival, including consensus driver mutations obtained from multiple calling algorithms. By contrast, around 75% of the survival predictive units had been undetected by conventional gene-level analysis. We demonstrate the ability of these signatures to separate patient groups according to overall survival, therefore providing novel prognostic tools for various cancers. GPD also identified sequence units with somatic mutations whose impact on survival was modified by the occupancy of germline variants in the surrounding regions. The findings indicate that a patient’s genetic predisposition interacts with the effect of somatic mutations on survival outcome in some cancers.