bluuebunny/crossref_metadata_2025_split huggingface dataset:
A variable selection method for genome-wide association studies
Authors: He Qianchuan , Lin Dan-Yu 
Published: October 2010

AbstractMotivation: Genome-wide association studies (GWAS) involving half a million or more single nucleotide polymorphisms (SNPs) allow genetic dissection of complex diseases in a holistic manner. The common practice of analyzing one SNP at a time does not fully realize the potential of GWAS to identify multiple causal variants and to predict risk of disease. Existing methods for joint analysis of GWAS data tend to miss causal SNPs that are marginally uncorrelated with disease and have high false discovery rates (FDRs).Results: We introduce GWASelect, a statistically powerful and computationally efficient variable selection method designed to tackle the unique challenges of GWAS data. This method searches iteratively over the potential SNPs conditional on previously selected SNPs and is thus capable of capturing causal SNPs that are marginally correlated with disease as well as those that are marginally uncorrelated with disease. A special resampling mechanism is built into the method to reduce false positive findings. Simulation studies demonstrate that the GWASelect performs well under a wide spectrum of linkage disequilibrium patterns and can be substantially more powerful than existing methods in capturing causal variants while having a lower FDR. In addition, the regression models based on the GWASelect tend to yield more accurate prediction of disease risk than existing methods. The advantages of the GWASelect are illustrated with the Wellcome Trust Case-Control Consortium (WTCCC) data.Availability: The software implementing GWASelect is available at http://www.bios.unc.edu/~lin.Access to WTCCC data: http://www.wtccc.org.uk/Contact: lin@bios.unc.eduSupplementary information: Supplementary data are available at Bioinformatics Online.
Benchmarking the performance of human antibody gene alignment utilities using a 454 sequence dataset
Authors: Jackson Katherine J. L. , Boyd Scott , Gaëta Bruno A. , Collins Andrew M. 
Published: October 2010

Abstract
Motivation: Immunoglobulin heavy chain genes are formed by recombination of genes randomly selected from sets of IGHV, IGHD and IGHJ genes. Utilities have been developed to identify genes that contribute to observed VDJ rearrangements, but in the absence of datasets of known rearrangements, the evaluation of these utilities is problematic. We have analyzed thousands of VDJ rearrangements from an individual (S22) whose IGHV, IGHD and IGHJ genotype can be inferred from the dataset. Knowledge of this genotype means that the Stanford_S22 dataset can serve to benchmark the performance of IGH alignment utilities.
Results: We evaluated the performance of seven utilities. Failure to partition a sequence into genes present in the S22 genome was considered an error, and error rates for different utilities ranged from 7.1% to 13.7%.
Availability: Supplementary data includes the S22 genotypes and alignments. The Stanford_S22 dataset and an evaluation tool is available at http://www.emi.unsw.edu.au/~ihmmune/IGHUtilityEval/.
Contact: katherine.jackson@unsw.edu.au
Supplementary information: Supplementary data are available at Bioinformatics online.
Submaximal exercise gas exchange is an important prognostic tool to predict adverse outcomes in heart failure
Authors: Woods Paul R. , Bailey Kent R. , Wood Christina M. , Johnson Bruce D. 
Published: October 2010

AimsTraditionally, VO2peak has been used to determine prognosis in heart failure; however, this measure has limitations. Hence, other exercise and gas exchange parameters measured submaximally, e.g. breathing efficiency (VE/VCO2), end‐tidal CO2 (PETCO2), oxygen uptake efficiency slope (OUES), and circulatory power [ systolic blood pressure (SBP)], have been investigated. The aim of this study was to investigate the prognostic relevance of submaximal exercise gas exchange in heart failure patients.Method and resultsOne hundred and thirty‐two consecutive heart failure patients (mean age 56 ± 12 years, ejection fraction 29 ± 11%) performed peak treadmill testing. Gas exchange and haemodynamic variables were measured continuously. Gas exchange data obtained from the first 2 min of exercise and at a respiratory exchange ratio (RER) of 0.9 were the measurements of interest. Over a median follow‐up period of 62.4 (range 0–114) months, there were 44 endpoints (death or transplant). Univariate analysis demonstrated submaximal predictors of survival, which included VE/VCO2 slope and ratio, PETCO2, OUES, and circulatory power (P≤ 0.01). When these and additional submaximal variables were included together in the multivariable analysis, the strongest submaximal exercise predictive model (C‐statistic 0.75) comprised data from the first stage of exercise (VE and circulatory power) and at an RER of 0.9 (VE/VCO2 ratio). The inclusion of VO2peak and demographic data, with submaximal data (VE/VCO2 ratio at an RER = 0.9), increased the predictiveness of the model (C‐statistic 0.78).ConclusionSubmaximal exercise measures provide useful prognostic information for predicting survival in heart failure. This form of testing is logistically easier, cheaper, and safer for patients compared with maximal exercise.
Use of B‐type natriuretic peptide in the management of hypoxaemic respiratory failure
Authors: Noveanu Markus , Pargger Hans , Breidthardt Tobias , Reichlin Tobias , Schindler Christian , Heise Antje , Schoenenberger Ronald , Manndorff Patricia , Siegemund Martin , Mebazaa Alexandre , Marsch Stephan , Mueller Christian 
Published: October 2010

AimsEvaluation and management of patients with hypoxaemic respiratory failure in the intensive care unit (ICU) are difficult. The use of B‐type natriuretic peptide (BNP), a quantitative marker of cardiac stress and heart failure (HF), may be helpful. The purpose of this study is to describe the prevalence of causative disorders of hypoxaemic respiratory failure in the ICU and to determine the impact of a BNP‐guided diagnostic strategy.Methods and resultsThis prospective, multi‐centre, randomized, single‐blind, controlled trial included 314 ICU patients with hypoxaemic respiratory failure: 159 patients were randomly assigned to a diagnostic strategy involving the measurement of BNP and 155 were assessed in a standard manner. The time to discharge and the total cost of treatment were the primary endpoints. Hypoxaemic respiratory failure was multi‐causal in 27% of the patients. Heart failure was the most common diagnosis in both groups. The use of BNP levels, in conjunction with other clinical information, significantly increased the detection of HF in combination with an additional diagnosis (32 vs. 16%, P = 0.001) and also increased the application of HF‐specific medical therapy (nitrates: 32 vs. 23%, P < 0.05 and diuretics: 65 vs. 50%, P < 0.01). Time to discharge (median, 13 vs.14 days, P = 0.50) and total cost of treatment (median, US‐$6190 vs. 7155, P = 0.24) were comparable in both groups.ConclusionHypoxaemic respiratory failure in the ICU is often a multi‐causal disorder. The use of BNP increased the detection of HF, but did not significantly improve patient management as quantified by time to discharge or treatment cost. ClinicalTrials.gov Identifier: NCT00130559.
A Further Examination of the Relation Between Trait Anger and Alcohol‐Related Aggression: The Role of Anger Control
Authors: Parrott Dominic J. , Giancola Peter R. 
Published: November 2010

Background: Trait anger has been identified as a risk factor for alcohol‐related aggression. However, to develop a more accurate risk profile, it is necessary to examine the interactive relations between trait anger and other key personality variables. The present study examined the influence of anger control on alcohol‐related aggression.Methods: Participants were 164 social drinking men age 21–35 years old. Trait anger and anger control were assessed with the State‐Trait Anger Expression Inventory (Spielberger, 1996). Following consumption of an alcoholic or placebo beverage, participants competed in an aggression paradigm in which electric shocks were received from and administered to a fictitious opponent during a competitive reaction time task. Aggression was operationalized as shock intensities administered to the opponent under conditions of low and high provocation.Results: Analyses indicated that trait anger significantly predicted aggression, but only among men who were intoxicated and reported low levels of anger control.Conclusions: The present findings suggest that anger control may be a crucial risk factor in determining whether one's anger proneness will lead to intoxicated aggression following provocation.
Controlled and Behaviorally Relevant Levels of Oral Ethanol Intake in Rhesus Macaques Using a Flavorant‐Fade Procedure
Authors: Katner Simon N. , Flynn Claudia T. , Von Huben Stefani N. , Kirsten Amber J. , Davis Sophia A. , Lay Christopher C. , Cole Maury , Roberts Amanda J. , Fox Howard S. , Taffe Michael A. 
Published: November 2010

Background: Flavorant‐fading procedures can initiate and maintain oral ethanol intake in rodents. The present study developed a similar procedure to achieve controlled and behaviorally relevant levels of ethanol intake in monkeys.Methods: Male rhesus macaques (N= 13) were initially given the opportunity to consume 0.5 g/kg of a 1% (w/v) ethanol plus 4% (w/v) Tang solution in 1‐hr limited‐access sessions without the requirement of an operant response. Once consumption was stable at a particular concentration (%) and/or amount (g/kg), animals were given access to higher concentrations and/or amounts of ethanol. Animals were tested on a bimanual motor skill (BMS) task 20 and 90 min after consumption to assess behavioral impairment. Blood alcohol levels (BALs) were assessed after a session in which animals had the opportunity to consume up to 3.0 g/kg of 6% (w/v) ethanol.Results: The gradual fading up of higher concentrations and amounts of ethanol resulted in controlled and robust levels (>2.0 g/kg) of ethanol intake in half of the subjects. Increasing the concentration of the sweetener from 4 to 6% (w/v) was effective in initiating consumption in three animals. Two monkeys required the additional step of presenting the increased‐sweetener solutions after a meal (postprandial consumption) to initiate significant ethanol intake. Animals were significantly impaired on the BMS task after consumption of 2.0, 2.5, and 3.0 g/kg of ethanol. Individual consumption ranging from 0.8 to 3.0 g/kg of ethanol produced BALs of 18 to 269 mg/dl.Conclusions: The flavorant‐fading procedure was effective in producing behaviorally relevant levels of ethanol consumption in rhesus macaques. This model facilitated a randomized‐dose procedure to determine the behavioral effects of 0.5 to 3.0 g/kg of ethanol. This procedure therefore is of significant utility in determining behavioral or physiologic effects of specific doses of consumed ethanol in monkeys.
Interactions of Alcohol Dehydrogenase to p‐Hydroxyacetophenone–sepharose and p‐Acetamidophenol‐sepharose
Authors: Negoro Munetaka , Wakabayashi Ichiro 
Published: November 2010

Abstract: Background: p‐Hydroxyacetophenone (HAP)‐sepharose is known to be an effective ligand for isolation of aldehyde dehydrogenase and chloramphenicol acetyltransferase. In this study, we investigated ligand specificities to alcohol dehydrogenase (ADH) using p‐HAP‐sepharose and p‐acetamidophenol (AAP)‐sepharose.Methods: p‐HAP and p‐AAP were coupled to epoxy‐activated sepharose and used as ligands for affinity chromatography to detect binding proteins. Fractions of affinity chromatography were collected and separated by SDS‐PAGE. Commassie brilliant blue staining was carried out for detecting proteins. For determining protein sequences, polypeptide was separated by HPLC after cleavage of Lys‐specific protease digestion.Results: p‐HAP ligands have the ability to bind to seven proteins, including class I ADH extracted from a rat cytosolic fraction as well as HLADH (horse liver ADH). p‐HAP, p‐AAP and benzaldehyde (10 mM each) could elute HLADH from the complex of HLADH‐pHAP‐sepharose column. On the other hand, p‐AAP‐sepharose has no ability to bind to HLADH, although three proteins from a rat liver cytosolic fraction were found to be able to bind to p‐AAP‐sepharose.Conclusions: p‐HAP binds to ADH in a structure‐specific manner and this binding is nonspecific to species of origin of ADH.
Unexpected Presence of Graminan- and Levan-Type Fructans in the Evergreen Frost-Hardy Eudicot Pachysandra terminalis (Buxaceae): Purification, Cloning, and Functional Analysis of a 6-SST/6-SFT Enzyme
Authors: Van den Ende Wim , Coopman Marlies , Clerens Stefan , Vergauwen Rudy , Le Roy Katrien , Lammens Willem , Van Laere André 
Published: October 2010

Abstract
About 15% of flowering plants accumulate fructans. Inulin-type fructans with β(2,1) fructosyl linkages typically accumulate in the core eudicot families (e.g. Asteraceae), while levan-type fructans with β(2,6) linkages and branched, graminan-type fructans with mixed linkages predominate in monocot families. Here, we describe the unexpected finding that graminan- and levan-type fructans, as typically occurring in wheat (Triticum aestivum) and barley (Hordeum vulgare), also accumulate in Pachysandra terminalis, an evergreen, frost-hardy basal eudicot species. Part of the complex graminan- and levan-type fructans as accumulating in vivo can be produced in vitro by a sucrose:fructan 6-fructosyltransferase (6-SFT) enzyme with inherent sucrose:sucrose 1-fructosyltransferase (1-SST) and fructan 6-exohydrolase side activities. This enzyme produces a series of cereal-like graminan- and levan-type fructans from sucrose as a single substrate. The 6-SST/6-SFT enzyme was fully purified by classic column chromatography. In-gel trypsin digestion led to reverse transcription-polymerase chain reaction-based cDNA cloning. The functionality of the 6-SST/6-SFT cDNA was demonstrated after heterologous expression in Pichia pastoris. Both the recombinant and native enzymes showed rather similar substrate specificity characteristics, including peculiar temperature-dependent inherent 1-SST and fructan 6-exohydrolase side activities. The finding that cereal-type fructans accumulate in a basal eudicot species further confirms the polyphyletic origin of fructan biosynthesis in nature. Our data suggest that the fructan syndrome in P. terminalis can be considered as a recent evolutionary event. Putative connections between abiotic stress and fructans are discussed.
Signaling Pathways Mediating the Induction of Apple Fruitlet Abscission
Authors: Botton Alessandro , Eccher Giulia , Forcato Claudio , Ferrarini Alberto , Begheldo Maura , Zermiani Monica , Moscatello Stefano , Battistelli Alberto , Velasco Riccardo , Ruperti Benedetto , Ramina Angelo 
Published: October 2010

AbstractApple (Malus × domestica) represents an interesting model tree crop for studying fruit abscission. The physiological fruitlet drop occurring in this species can be easily magnified by using thinning chemicals, such as benzyladenine (BA), to obtain fruits with improved quality and marketability. Despite the economic importance of this process, the molecular determinants of apple fruitlet abscission are still unknown. In this research, BA was used to obtain fruitlet populations with different abscission potentials to be analyzed by means of a newly released 30K oligonucleotide microarray. RNAs were extracted from cortex and seed of apple fruitlets sampled over a 4-d time course, during which BA triggers fruit drop, and used for microarray hybridization. Transcriptomic profiles of persisting and abscising fruitlets were tested for statistical association with abscission potential, allowing us to identify molecular signatures strictly related to fruit destiny. A hypothetical model for apple fruitlet abscission was obtained by putting together available transcriptomic and metabolomic data. According to this model, BA treatment would establish a nutritional stress within the tree that is primarily perceived by the fruitlet cortex whose growth is blocked by resembling the ovary growth inhibition found in other species. In weaker fruits, this stress is soon visible also at the seed level, likely transduced via reactive oxygen species/sugar and hormones signaling cross talk, and followed by a block of embryogenesis and the consequent activation of the abscission zone.
Inactivation of a DNA Methylation Pathway in Maize Reproductive Organs Results in Apomixis-Like Phenotypes
Authors: Garcia-Aguilar Marcelina , Michaud Caroline , Leblanc Olivier , Grimanelli Daniel 
Published: October 2010

AbstractApomictic plants reproduce asexually through seeds by avoiding both meiosis and fertilization. Although apomixis is genetically regulated, its core genetic component(s) has not been determined yet. Using profiling experiments comparing sexual development in maize (Zea mays) to apomixis in maize-Tripsacum hybrids, we identified six loci that are specifically downregulated in ovules of apomictic plants. Four of them share strong homology with members of the RNA-directed DNA methylation pathway, which in Arabidopsis thaliana is involved in silencing via DNA methylation. Analyzing loss-of-function alleles for two maize DNA methyltransferase genes belonging to that subset, dmt102 and dmt103, which are downregulated in the ovules of apomictic plants and are homologous to the Arabidopsis CHROMOMETHYLASEs and DOMAINS REARRANGED METHYLTRANSFERASE families, revealed phenotypes reminiscent of apomictic development, including the production of unreduced gametes and formation of multiple embryo sacs in the ovule. Loss of DMT102 activity in ovules resulted in the establishment of a transcriptionally competent chromatin state in the archesporial tissue and in the egg cell that mimics the chromatin state found in apomicts. Interestingly, dmt102 and dmt103 expression in the ovule is found in a restricted domain in and around the germ cells, indicating that a DNA methylation pathway active during reproduction is essential for gametophyte development in maize and likely plays a critical role in the differentiation between apomictic and sexual reproduction.
Norcoclaurine Synthase Is a Member of the Pathogenesis-Related 10/Bet v1 Protein Family
Authors: Lee Eun-Jeong , Facchini Peter 
Published: October 2010

Abstract
Norcoclaurine synthase (NCS) catalyzes the first committed step in the biosynthesis of benzylisoquinoline alkaloids (BIAs). NCS from Thalictrum flavum (Tf NCS), Papaver somniferum (Ps NCS1 and Ps NCS2), and Coptis japonica (Cj PR10A) share substantial identity with pathogen-related 10 (PR10) and Bet v1 proteins, whose functions are not well understood. A distinct enzyme (Cj NCS1) with similarity to 2-oxoglutarate–dependent dioxygenases was suggested as the bona fide NCS in C. japonica. Here, we validate the exclusive role of PR10/Bet v1-type NCS enzymes in BIA metabolism. Immunolocalization of Ps NCS2 revealed its cell type–specific occurrence in phloem sieve elements, which contain all other known BIA biosynthetic enzymes. In opium poppy, NCS transcripts and proteins were abundant in root and stem, but at low levels in leaf and carpel. Silencing of NCS in opium poppy profoundly reduced alkaloid levels compared with controls. Immunoprecipitation of NCS from total protein extracts of T. flavum cells resulted in a nearly complete attenuation of NCS activity. A Ps NCS2–green fluorescent protein fusion introduced by microprojectile bombardment into opium poppy cells initially localized to the endoplasmic reticulum but subsequently sorted to the vacuole. In our hands, Cj NCS1 did not catalyze the formation of (S)-norcoclaurine from dopamine and 4-hydroxyphenylacetaldehyde.
Arabidopsis SET DOMAIN GROUP2Is Required for H3K4 Trimethylation and Is Crucial for Both Sporophyte and Gametophyte Development
Authors: Berr Alexandre , McCallum Emily J. , Ménard Rozenn , Meyer Denise , Fuchs Jörg , Dong Aiwu , Shen Wen-Hui 
Published: October 2010

AbstractHistone H3 lysine 4 trimethylation (H3K4me3) is abundant in euchromatin and is in general associated with transcriptional activation in eukaryotes. Although some Arabidopsis thaliana SET DOMAIN GROUP (SDG) genes have been previously shown to be involved in H3K4 methylation, they are unlikely to be responsible for global genome-wide deposition of H3K4me3. Most strikingly, sparse knowledge is currently available about the role of histone methylation in gametophyte development. In this study, we show that the previously uncharacterized SDG2 is required for global H3K4me3 deposition and its loss of function causes wide-ranging defects in both sporophyte and gametophyte development. Transcriptome analyses of young flower buds have identified 452 genes downregulated by more than twofold in the sdg2-1 mutant; among them, 11 genes, including SPOROCYTELESS/NOZZLE (SPL/NZZ) and MALE STERILITY1 (MS1), have been previously shown to be essential for male and/or female gametophyte development. We show that both SPL/NZZ and MS1 contain bivalent chromatin domains enriched simultaneously with the transcriptionally active mark H3K4me3 and the transcriptionally repressive mark H3K27me3 and that SDG2 is specifically required for the H3K4me3 deposition. Our data suggest that SDG2-mediated H3K4me3 deposition poises SPL/NZZ and MS1 for transcriptional activation, forming a key regulatory mechanism in the gene networks responsible for gametophyte development.
Farmers' relationship with hospitality businesses: a preliminary study
Authors: Duarte Alonso Abel 
Published: October 2010

PurposeNumerous advantages exist for farmers as food producers and for restaurateurs as food sellers to be engaged in business relationships. While in many situations such relationships would seem a very “natural” process that would also benefit consumers, to date very little research has been conducted in examining the extent to which farmers are engaged in such relationships. The present paper aims to explore these areas from the farmers' perspective.Design/methodology/approachSemi‐structured telephone interviews and two on‐site face‐to‐face interviews were conducted among 30 farm owners/operators in the state of Alabama, USA.FindingsA very weak relationship was noticed between farms and hotels/restaurants in this study. While geographic distance or isolation could be assumed to be an impediment for both farms and hospitality businesses to interact, only two businesses mentioned such constraint as a reason for not engaging in business relationships. In contrast, not being contacted by hospitality businesses or not starting the contact, as well as concerns of not receiving the “right price”, or convenience by selling their produce by other means (on‐site, farmers' markets) were some of the reasons farmers mentioned.Research limitations/implicationsThe low number of respondents and the selection of only those businesses that were advertised are acknowledged limitations in this study.Practical implicationsEngaging in business relationships with restaurants may help farmers maximize the price they receive for their hard work, have a steady source for their product, or educate a new “breed” of consumers who value the importance of consuming fresher foods. To achieve these benefits, stronger interactions between both industries are needed, especially in cases where both restaurants and farms are geographically close to one another.Originality/valueThe study investigates an area that has been neglected in contemporary research.