bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitive periods for the effect of childhood adversity on DNA methylation: Results from a prospective, longitudinal study
Authors: Dunn Erin C. , Soare Thomas W. , Simpkin Andrew J. , Suderman Matthew J. , Zhu Yiwen , Klengel Torsten , Smith Andrew D.A.C. , Ressler Kerry , Relton Caroline L. 
Published: February 2018

AbstractBackgroundExposure to “early life” adversity is known to predict DNA methylation (DNAm) patterns that may be related to prolonged psychiatric risk. However, few studies have investigated whether adversity has time-dependent effects based on the age at exposure.MethodsUsing a two-stage structured life course modeling approach (SLCMA), we tested the hypothesis that there are sensitive periods when adversity induced greater DNAm changes. We tested this hypothesis in relation to two alternative explanations: an accumulation hypothesis, in which the effect of adversity on DNAm increases with the number of occasions exposed, regardless of timing, and a recency model, in which the effect of adversity is stronger for more proximal events. Data came from the Accessible Resource for Integrated Epigenomics Studies (ARIES), a subsample of mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC; n=670-776).ResultsAfter covariate adjustment and multiple testing correction, we identified 40 CpG sites that were differentially methylated at age 7 following exposure to adversity. Most loci (n=32) were predicted by the timing of adversity, namely exposures during infancy. Neither the accumulation nor recency of the adversity explained considerable variability in DNAm. A standard EWAS of lifetime exposure (vs. no exposure) failed to detect these associations.ConclusionsThe developmental timing of adversity explains more variability in DNAm than the accumulation or recency of exposure. Infancy appears to be a sensitive period when exposure to adversity predicts differential DNAm patterns. Classification of individuals as exposed vs. unexposed to “early life” adversity may dilute observed effects.
Nicotinic cholinergic receptors in VTA glutamate neurons modulate excitatory transmission
Authors: Yan Yijin , Peng Can , Arvin Matthew C. , Jin Xiao-Tao , Kim Veronica J. , Ramsey Matthew D. , Wang Yong , Banala Sambashiva , Wokosin David L. , McIntosh J. Michael , Lavis Luke D. , Lavis Luke D. , Drenan Ryan M. 
Published: February 2018

SummaryVentral tegmental area (VTA) glutamate neurons are important components of brain reward circuitry, but whether they are subject to cholinergic modulation is unknown. To study this, we used an array of molecular, physiological, and photostimulation techniques to examine nicotinic acetylcholine receptors (nAChRs) in VTA glutamate neurons. VTA neurons positive for the vesicular glutamate transporter 2 (VGLUT2+) are responsive to acetylcholine (ACh) released from mesopontine cholinergic axons. VTA VGLUT2+ neurons express mRNA and protein subunits known to comprise typical heteromeric nAChRs. Electrophysiology, coupled with 2-photon microscopy and laser flash photolysis of a photoactivatable nicotine probe, was used to demonstrate nAChR functional activity in the somatodendritic subcellular compartment of VTA VGLUT2+ neurons. Finally, optogenetic isolation of intrinsic VTA glutamatergic microcircuits demonstrated that nicotine potently modulates excitatory transmission within the VTA. These results indicate that VTA glutamate neurons are modulated by cholinergic mechanisms and participate in the cascade of physiological responses to nicotine exposure.
The contraction in inverted repeat regions in the complete plastome sequence ofCressa creticaL
Authors: Bhatt Pritesh P. , Thaker Vrinda S. 
Published: February 2018

AbstractPlastome studies have been the focus of research in plant molecular evolution and systematics.C. creticaL. (Convolvulaceae) is a halophyte, habitat in the ecologically challenged area with high salinity and drought. The complete physical map of plastome revealed that it is 141,419bp long, circular molecule. It contains typical quadripartite structure of large single copy region (LSC 94,808bp), small single copy region (SSC 32,527bp) separated by a pair of inverted repeat regions (IRs 7042bp). This plastome is compared with the complete plastomes of other members of Convolvulaceae showed notable distinctions. An exceptional shift in IRs to SC regions is experienced inC. creticaled to many genes shift in both SC regions and contraction in IRs. The size of IRs reduced to 2 to 4 times as compared to those of the Convolvulaceae members studied. The shifted IRs regions showed remarkable variation in nucleotides patterns. Further, the shift was from the IR boundaries and in between the IR regions led to segment IRs. It is concluded that the shift in IRs may be the strategic move for adaptation in the harsh environment.
Yeast heterochromatin regulators Sir2 and Sir3 act directly at euchromatic DNA replication origins
Authors: Hoggard Timothy A , Chang FuJung , Perry Kelsey Rae , Subramanian Sandya , Kenworthy Jessica , Chueng Julie , Shor Erika , Cosgrove Michael , Boeke Jef D. , Fox Catherine A , Weinreich Michael 
Published: February 2018

ABSTRACTMost active DNA replication origins are found within euchromatin, while origins within heterochromatin are often inactive or inhibited. In yeast, origin activity within heterochromatin is negatively controlled by the histone H4K16 deacetylase, Sir2, and at some heterochromatic loci also by the nucleosome binding protein, Sir3. The prevailing view has been that direct functions of Sir2 and Sir3 are confined to heterochromatin. However, growth defects in yeast mutants compromised for loading the MCM helicase, such ascdc6-4, are robustly suppressed by deletion of eitherSIR2orSIR3. While this and other observations indicate thatSIR2,3can have a negative impact on at least some euchromatic origins, the genomic scale of this effect was unknown. It was also unknown whether this suppression resulted from direct functions of Sir2,3 within euchromatin, or was an indirect effect of their previously established roles within heterochromatin. Using both MCM ChIP-Seq and MNase-H4K16ac ChIP-Seq data, we show that aSIR2deletion rescues MCM complex loading at ~80% of euchromatic origins incdc6-4cells. Therefore, Sir2 exhibits a pervasive effect at the majority of euchromatic origins. Importantly, in wild type (i.e.CDC6) cells, origin-adjacent nucleosomes were depleted for H4K16 acetylation in aSIR2-dependent manner. In addition, both Sir2 and Sir3 directly bound to nucleosomes adjacent to euchromatic origins. The relative levels of each of these molecular hallmarks of yeast heterochromatin –SIR2-dependent H4K16 hypoacetylation, Sir2, and Sir3 – correlated with how strongly aSIR2deletion suppressed the MCM loading defect incdc6-4cells. Finally, a screen for histone H3 and H4 mutants that could suppress thecdc6-4growth defect identified amino acids that map to a surface of the nucleosome important for Sir3 binding. We conclude that heterochromatin proteins directly bind euchromatic DNA replication origins and modify their local chromatin environment.
One man’s trash is another man’s treasure - the effect of bacteria on phytoplankton-zooplankton interactions in chemostat systems
Authors: Raatz M , Schälicke S , Sieber M , Wacker A , Gaedke U 
Published: February 2018

AbstractChemostat experiments are employed to study predator-prey and other trophic interactions, frequently using phytoplankton-zooplankton systems. These experiments often use population dynamics as fingerprints of ecological and evolutionary processes, assuming that the contributions of all major actors to these dynamics are known. However, bacteria are often neglected although they are frequently present. We argue that even without external carbon sources bacteria may affect the experimental outcomes depending on experimental conditions and the physiological traits of bacteria, phytoplankton and zooplankton. Using a static carbon flux model and a dynamic simulation model we predict the minimum and maximum impact of bacteria on phytoplankton-zooplankton population dynamics. Under bacteria-suppressing conditions, we find that the effect of bacteria is indeed negligible and their omission justified. Under bacteria-favouring conditions, however, bacteria may strongly affect average biomasses. Furthermore, the population dynamics may become highly complex resulting in wrong conclusions if bacteria are not considered. Our model results provide suggestions to reduce the bacterial impact experimentally. Next to optimizing experimental conditions (e.g. the dilution rate) the appropriate choice of the zooplankton predator is decisive. Counterintuitively, bacteria have a larger impact if they are not ingested by the predator as high bacterial biomasses and complex population dynamics arise via competition for nutrients with the phytoplankton. Only if the predator is at least partly bacterivorous the impact of bacteria is minimized. Our results help to improve both the design of chemostat experiments and their interpretation and thus advance the study of ecological and evolutionary processes in aquatic food webs.
Identification of changing ribosome protein compositions using cryo-EM and mass spectrometry
Authors: Sun Ming , Samir Parimal , Shen Bingxin , Li Wen , Browne Christopher M. , Rahul  , Frank Joachim , Link Andrew J. 
Published: February 2018

SummaryThe regulatory role of the ribosome in gene expression has come into sharper focus. It has been proposed that ribosomes are dynamic complexes capable of changing their protein composition in response to enviromental stimuli. We applied both cryo-EM and mass spectrometry to identify such changes in S. cerevisiae 80S ribosomes. Cryo-EM shows a fraction (17%) of the ribosome population in yeast growing in glucose lack the ribosomal proteins RPL10 (ul16) and RPS1A/B (eS1). Unexpectedly, this fraction rapidly increases to 34% after the yeast are switched to growth in glycerol. Using quantitative mass spectrometry, we found that the paralog yeast ribosomal proteins RPL8A (eL8A) and RPL8B (eL8B) change their relative proportions in the 80S ribosome when yeast are switched from growth in glucose to glycerol. Using yeast genetics and polysome profiling, we show that yeast ribosomes containing either RPL8A or RPL8B are not functionally interchangeable. Our combined cryo-EM and quantitative proteomic data support the hypothesis that ribosomes are dynamic complexes that alter their composition and functional activity in response to changes in growth or environmental conditions.
Hypoarousal non-stationary ADHD biomarker based on echo-state networks
Authors: Ibanez-Soria D. , Soria-Frisch A. , Garcia-Ojalvo J. , Picardo Jacobo , García-Banda Gloria , Servera Mateu , Ruffini Giulio 
Published: February 2018

ABSTRACTAttention-Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity and impulsivity. It is one of the most commonly diagnosed neurodevelopmental and psychiatric disorders of childhood and therefore presents a very high prevalence rate. However the high rate of ADHD misdiagnosis makes the discovery of neurophysiological ADHD biomarkers an important clinical challenge. This study proposes a novel non-stationary ADHD biomarker based on Echo State Networks to quantify EEG dynamical changes between low attention/arousal states (resting with eyes closed, or EC) and normal attention/arousal states (resting with eyes open, or EO). Traditionally, EEG biomarkers have revealed an increase in stationary power in the theta band along with a decrease in beta, with these frequencies largely accepted to be altered in the ADHD population. We successfully verify the hypothesis that measured differences between these two conditions are altered in the ADHD population. Statistically significant differences between a group of ADHD subjects and an aged-matched control population were obtained in theta and beta rhythms. Our network discriminates between EO/EC EEG regimes in the ADHDs better than in controls, suggesting that differences in EEG patterns between low and normal arousal/attention states are larger in the ADHD population.
Sex-specific additive genetic variances and correlations for fitness in a song sparrow (Melospiza melodia) population subject to natural immigration and inbreeding
Authors: Wolak Matthew E. , Arcese Peter , Keller Lukas F. , Nietlisbach Pirmin , Reid Jane M. 
Published: February 2018

ABSTRACTQuantifying sex-specific additive genetic variance (VA) in fitness, and the cross-sex genetic correlation (rA), is pre-requisite to predicting evolutionary dynamics and the magnitude of sexual conflict. Quantifying VAand rAin underlying fitness components, and multiple genetic consequences of immigration and resulting gene flow, is required to identify mechanisms that maintain VAin fitness. However, these key parameters have rarely been estimated in wild populations experiencing natural environmental variation and immigration. We used comprehensive pedigree and life-history data from song sparrows (Melospiza melodia) to estimate VAand rAin sex-specific fitness and underlying fitness components, and to estimate additive genetic effects of immigrants as well as inbreeding depression. We found substantial VAin female and male fitness, with a moderate positive cross-sex rA. There was also substantial VAin adult reproductive success in males but not females, and moderate VAin juvenile survival but not adult survival. Immigrants introduced alleles for which additive genetic effects on local fitness were negative, potentially reducing population mean fitness through migration load, yet alleviating expression of inbreeding depression. Substantial VAfor fitness can consequently be maintained in the wild, and be concordant between the sexes despite marked sex-specific VAin reproductive success.
Linking international experience and cultural intelligence development
Authors: Michailova Snejina , Ott Dana L. 
Published: February 2018

PurposeThe purpose of this paper is to critically examine the literature on the relationship between international experience (IE) and cultural intelligence (CQ) development, and advocate for the utilization of theory to explain this relationship.Design/methodology/approachOn the basis of the premise that CQ can be developed through IE, the authors review existing empirical research in regards to this relationship. The authors conducted a search of the main business, education, and psychology databases for articles published from 2003, the year when the CQ construct was introduced, through 2017. The search focused on studies where CQ was tested as a dependent variable or as a mediator between IE and a dependent variable, and resulted in 15 empirical articles and three book chapters.FindingsA critical analysis of the relationship between IE and CQ reveals considerable variation and inconsistencies among findings within the extant empirical literature. The authors argue that this is mainly because most studies fail to apply a theory to explain the link between these two constructs. The authors draw from social learning theory (SLT) to illustrate how it can be utilized to detail the relationship between IE and CQ development. The authors also suggest how future research can advance the understanding of this relationship, and outline the implications of such examinations for practice.Originality/valueWhile substantive knowledge has been generated to understand CQ as an antecedent, the authors investigate CQ development as the dependent variable. The critical review of this literature identifies a specific weakness within previous research and the authors offer a way to resolve it. SLT, which views learning as being affected by both observation and experience, and includes attention, retention, and participative reproduction, is one potentially powerful tool that can explain why and how IE can lead to CQ development. This is a far more fine- grained and detailed approach to understanding and explaining the relationship between the two constructs than provided by previous studies.
A Bayesian Nonparametric Approach to Causal Inference on Quantiles
Authors: Xu Dandan , Daniels Michael J. , Winterstein Almut G. 
Published: February 2018

Summary
We propose a Bayesian nonparametric approach (BNP) for causal inference on quantiles in the presence of many confounders. In particular, we define relevant causal quantities and specify BNP models to avoid bias from restrictive parametric assumptions. We first use Bayesian additive regression trees (BART) to model the propensity score and then construct the distribution of potential outcomes given the propensity score using a Dirichlet process mixture (DPM) of normals model. We thoroughly evaluate the operating characteristics of our approach and compare it to Bayesian and frequentist competitors. We use our approach to answer an important clinical question involving acute kidney injury using electronic health records.
Both sarcopenia and frailty determine suitability of patients for liver transplantation—A systematic review and meta‐analysis of the literature
Authors: Kahn Judith , Wagner Doris , Homfeld Nicole , Müller Helmut , Kniepeiss Daniela , Schemmer Peter 
Published: February 2018

AbstractLiver grafts are allocated based on both urgency and utility. Due to a tremendous shortage of suitable organs for liver transplantation (LT), a careful selection of suitable recipients is of utmost importance. While the sickest first principle for organ allocation based on MELD score goes along with poor utility, other parameters reflecting the general health condition like frailty and sarcopenia might be essential to detect suitable patients for the waiting list. Thus, this study was designed to evaluate both frailty and sarcopenia in LT. A systematic review of the literature on sarcopenia and frailty measurements in liver transplant recipients was performed. Thirteen of 238 studies were selected for full paper review. Six of the studies investigating the impact of frailty on waitlist mortality were subjected to a meta‐analysis. Despite the different methodologies to assess sarcopenia, reports showed that sarcopenia was highly related to waitlist mortality with a sum of all that highly favored negative outcome in case of sarcopenia. The existing literature clearly underlines that frailty and sarcopenia are important to determine in LT candidates. One unique index for transplant candidates reflecting frailty should be developed and be used as a standard in all transplant centers to facilitate comparability.
Impact of early reoperation on graft survival after liver transplantation: Univariate and multivariate analysis
Authors: Elsabbagh Ahmed M. , Girlanda Raffaele , Hawksworth Jason , Pichert Matthew D. , Williams Cassie , Pozzi Agostino , Kroemer Alexander , Nookala Anupama , Smith Coleman , Matsumoto Cal S. , Fishbein Thomas M. 
Published: February 2018

AbstractBackgroundData on rate, risk factors, and consequences of early reoperation after liver transplantation are still limited.Study designSingle‐center retrospective analysis of data of 428 patients, who underwent liver transplantation in period between January 2009 and December 2014. Univariate and multivariate analysis were used to study the risk factors of early reoperation and its impact on graft survival.ResultsOf 428 patients, 74 (17.3%) underwent early reoperation. Of them, 46 (62.2%) underwent reoperation within the first week and 28 (37.8%) underwent reoperation later than 1 week after transplantation. With multivariate analysis, significant risk factors of early reoperation included pretransplant ICU admission, previous abdominal surgery and diabetes. Early reoperation itself was not found to be an independent predictor of graft loss. However, early reoperation later than 7 days from transplant was found to be independent predictor of graft loss (odds ratio [OR] = 5.125; 95% CI, 1.358‐19.552; P = .016). In our series, other independent predictors of graft loss were MELD score (P = .010) and operative time (P = .048).ConclusionsThis analysis demonstrates that early reoperations later than a week appear to negatively impact the graft survival. The timing of early reoperation should be a focus of additional studies.
Use of glucagon‐like peptide‐1 receptor agonists among individuals on basal insulin requiring treatment intensification
Authors: Trautmann M. E. , Vora J. 
Published: February 2018

AbstractAs Type 2 diabetes progresses, treatment is intensified with additional therapies in an effort to manage hyperglycaemia effectively and therefore avoid complications. When greater efficacy is required, options for injectable treatments include glucagon‐like peptide‐1 receptor agonists and insulin, which may be added on to oral glucose‐lowering treatments. Among individuals receiving long‐acting basal insulin as their first injectable treatment, ~40−60% are unable to achieve or maintain their target HbA1c goals. For these people, treatment intensification options are relatively limited and include the addition of short‐acting prandial insulin or a glucagon‐like peptide‐1 receptor agonist. Glucagon‐like peptide‐1 receptor agonists vary in their effects, with short‐ and long‐acting agents having a greater impact on postprandial and fasting hyperglycaemia, respectively. Studies comparing treatment intensification options have found both glucagon‐like peptide‐1 receptor agonists and prandial insulin to be effective in reducing HbA1c concentrations; however, recipients of glucagon‐like peptide‐1 receptor agonists lost weight and had a greater frequency of gastrointestinal adverse events, whereas those receiving prandial insulin gained weight and had a greater incidence of hypoglycaemia. In addition to the separate administration of a glucagon‐like peptide‐1 receptor agonist and basal insulin, fixed‐ratio combinations of a glucagon‐like peptide‐1 receptor agonist and basal insulin offer a single administration for both treatments but have less flexibility in dose titration than treatment with their individual components. For individuals who require treatment intensification beyond basal insulin, use of these various options allows physicians to target the individual needs of their patients for the achievement of optimal long‐term glycaemic control.