bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory assessment of new anticoagulants
Authors: Samama Meyer M. , Guinet Céline 
Published: February 2011

AbstractWith the introduction of new anticoagulant agents, there is a need for information on which coagulation tests are most suitable. These agents react differently to assays used to monitor older anticoagulant agents because they have alternative modes of action. Therefore, other tests, or modifications of existing tests which are more appropriate for newer agents, are needed. The prothrombin time test (with conversion to the international normalized ratio) is usually used to monitor warfarin. However, conversion to the international normalized ratio is not appropriate for measuring the effects of fondaparinux, dabigatran, rivaroxaban or apixaban. Instead, chromogenic assays, one-step prothrombinase-induced clotting time test and the HepTest with reduced incubation time, are among the different or modified tests that appear to give the most reproducible and accurate results. The tests show variations in response to anticoagulants – some of which have clinical relevance. Thus, it is important to be aware of the observed variations in order to prevent the misinterpretation of test results.
Glycosylation of proteins in healthy and neoplastic human salivary glands – a preliminary study
Authors: Borzym-Kluczyk Małgorzata , Radziejewska Iwona , Cechowska-Pasko Marzanna 
Published: February 2011

Abstract

Background: In cancer tissue, altered glycosylation of proteins is observed. There are some typical changes; for example, sialyl-Lewisa/x glycoforms are more abundant in many types of cancers. The current study investigated the differences in glycosylation of proteins between neoplastic and healthy human salivary glands.

Methods: Sugar structures on proteins with a molecular mass above 30 kDa were determined by enzyme-linked immunosorbent assay (ELISA) with biotinylated lectins.

Results: The expression of sialic acid in cancer tissues was higher in comparison with healthy ones. The same observations were revealed for Fuc α1-6, α1-2, T, Tn antigens and α1-6 mannose.

Conclusions: Glycosylation of proteins in cancer salivary gland tissues is altered in comparison with healthy tissue.
The effect of timing of teriparatide treatment on the circadian rhythm of bone turnover in postmenopausal osteoporosis
Authors: Luchavova Maria , Zikan Vit , Michalska Dana , Raska Ivan , Kubena Ales A , Stepan Jan J 
Published: February 2011

BackgroundWe hypothesized that with the administration of teriparatide (TPTD) treatment at different times, we would be able to modify the physiological circadian rhythm of bone turnover.MethodsThe concentration of serum C-terminal telopeptide of collagen type I (βCTX), serum N-terminal propeptide of procollagen type I (P1NP), serum ionized calcium (iCa), and plasma PTH were measured every 3 h over a 24 h period in 14 postmenopausal osteoporotic women (aged 72.4±9.3 years) treated with 20 μg TPTD for long term, given at different times of the day. General linear model-repeated measurements (GLM RM) were performed to analyze the circadian rhythms as well as intergroup comparisons.ResultsGLM-RM for both related groups showed a significant influence of time of day on all measured variables except P1NP. The analysis for each group separately provided a powerful model for βCTX (P<0.001, η2=0.496), serum iCa (P<0.001, η2=0.423), plasma PTH (P<0.001, η2=0.283), and serum PINP (P<0.001, η2=0.248). While the evening TPTD treatment showed a marked circadian rhythm for serum βCTX, the morning TPTD treatment rather suggested circasemidian rhythm. The P1NP rhythm followed a much smaller amplitude of the rhythm than βCTX. Changes in serum iCa were positively related to changes in serum βCTX (P<0.001) and negatively related to changes in PTH (P<0.001).ConclusionTiming of TPTD administration may significantly change the 24 h variation in bone turnover markers as well as calcium-parathyroid axis in postmenopausal osteoporotic women.
Role of Elongator Subunit Elp3 in Drosophila melanogaster Larval Development and Immunity
Authors: Walker Jane , Kwon So Yeon , Badenhorst Paul , East Phil , McNeill Helen , Svejstrup Jesper Q 
Published: February 2011

Abstract
The Elongator complex has been implicated in several cellular processes, including gene expression and tRNA modification. We investigated the biological importance of the Elp3 gene in Drosophila melanogaster. Deletion of Elp3 results in larval lethality at the pupal stage. During early development, larval growth is dramatically impaired, with progression to the third instar delayed for ∼24 hr, and pupariation occurring only at day 14 after egg laying. Melanotic nodules appear after 4 days. Microarray analysis shows that stress response genes are induced and ecdysone-induced transcription factors are severely repressed in the mutant. Interestingly, the phenotypes of Elp3 flies are similar to those of flies lacking the domino gene, encoding a SWI/SNF-like ATP-dependent chromatin-remodeling enzyme. Indeed, the gene expression profiles of these mutants are also remarkably similar. Together, these data demonstrate that Drosophila Elp3 is essential for viability, normal development, and hematopoiesis and suggest a functional overlap with the chromatin remodeler Domino.
Inference of Mutation Parameters and Selective Constraint in Mammalian Coding Sequences by Approximate Bayesian Computation
Authors: Keightley Peter D , Eöry Lél , Halligan Daniel L , Kirkpatrick Mark 
Published: February 2011

Abstract
We develop an inference method that uses approximate Bayesian computation (ABC) to simultaneously estimate mutational parameters and selective constraint on the basis of nucleotide divergence for protein-coding genes between pairs of species. Our simulations explicitly model CpG hypermutability and transition vs. transversion mutational biases along with negative and positive selection operating on synonymous and nonsynonymous sites. We evaluate the method by simulations in which true mean parameter values are known and show that it produces reasonably unbiased parameter estimates as long as sequences are not too short and sequence divergence is not too low. We show that the use of quadratic regression within ABC offers an improvement over linear regression, but that weighted regression has little impact on the efficiency of the procedure. We apply the method to estimate mutational and selective constraint parameters in data sets of protein-coding genes extracted from the genome sequences of primates, murids, and carnivores. Estimates of CpG hypermutability are substantially higher in primates than murids and carnivores. Nonsynonymous site selective constraint is substantially higher in murids and carnivores than primates, and autosomal nonsynonymous constraint is higher than X-chromsome constraint in all taxa. We detect significant selective constraint at synonymous sites in primates, carnivores, and murid rodents. Synonymous site selective constraint is weakest in murids, a surprising result, considering that murid effective population sizes are likely to be considerably higher than the other two taxa.
The Effects of Weak Genetic Perturbations on the Transcriptome of the Wing Imaginal Disc and Its Association With Wing Shape in Drosophila melanogaster
Authors: Dworkin Ian , Anderson Julie A , Idaghdour Youssef , Parker Erin Kennerly , Stone Eric A , Gibson Greg 
Published: February 2011

Abstract
A major objective of genomics is to elucidate the mapping between genotypic and phenotypic space as a step toward understanding how small changes in gene function can lead to elaborate phenotypic changes. One approach that has been utilized is to examine overall patterns of covariation between phenotypic variables of interest, such as morphology, physiology, and behavior, and underlying aspects of gene activity, in particular transcript abundance on a genome-wide scale. Numerous studies have demonstrated that such patterns of covariation occur, although these are often between samples with large numbers of unknown genetic differences (different strains or even species) or perturbations of large effect (sexual dimorphism or strong loss-of-function mutations) that may represent physiological changes outside of the normal experiences of the organism. We used weak mutational perturbations in genes affecting wing development in Drosophila melanogaster that influence wing shape relative to a co-isogenic wild type. We profiled transcription of 1150 genes expressed during wing development in 27 heterozygous mutants, as well as their co-isogenic wild type and one additional wild-type strain. Despite finding clear evidence of expression differences between mutants and wild type, transcriptional profiles did not covary strongly with shape, suggesting that information from transcriptional profiling may not generally be predictive of final phenotype. We discuss these results in the light of possible attractor states of gene expression and how this would affect interpretation of covariation between transcriptional profiles and other phenotypes.
Epistasis Increases the Rate of Conditionally Neutral Substitution in an Adapting Population
Authors: Draghi Jeremy A , Parsons Todd L , Plotkin Joshua B 
Published: February 2011

AbstractKimura observed that the rate of neutral substitution should equal the neutral mutation rate. This classic result is central to our understanding of molecular evolution, and it continues to influence phylogenetics, genomics, and the interpretation of evolution experiments. By demonstrating that neutral mutations substitute at a rate independent of population size and selection at linked sites, Kimura provided an influential justification for the idea of a molecular clock and emphasized the importance of genetic drift in shaping molecular evolution. But when epistasis among sites is common, as numerous empirical studies suggest, do neutral mutations substitute according to Kimura's expectation? Here we study simulated, asexual populations of RNA molecules, and we observe that conditionally neutral mutations—i.e., mutations that do not alter the fitness of the individual in which they arise, but that may alter the fitness effects of subsequent mutations—substitute much more often than expected while a population is adapting. We quantify these effects using a simple population-genetic model that elucidates how the substitution rate at conditionally neutral sites depends on the population size, mutation rate, strength of selection, and prevalence of epistasis. We discuss the implications of these results for our understanding of the molecular clock, and for the interpretation of molecular variation in laboratory and natural populations.
Functional Relevance of CpG Island Length for Regulation of Gene Expression
Authors: Elango Navin , Yi Soojin V 
Published: February 2011

Abstract
CpG islands mark CpG-enriched regions in otherwise CpG-depleted vertebrate genomes. While the regulatory importance of CpG islands is widely accepted, it is little appreciated that CpG islands vary greatly in lengths. For example, CpG islands in the human genome vary ∼30-fold in their lengths. Here we report findings suggesting that the lengths of CpG islands have functional consequences. Specifically, we show that promoters associated with long CpG islands (long-CGI promoters) are distinct from other promoters. First, long-CGI promoters are uniquely associated with genes with an intermediate level of gene expression breadths. Notably, intermediate expression breadths require the most complex mode of gene regulation, from the standpoint of information content. Second, long-CGI promoters encode more RNA polymerase II (Polr2a) binding sites than other promoters. Third, the actual binding patterns of Polr2a occur in a more tissue-specific manner in long-CGI promoters compared to other CGI promoters. Moreover, long-CGI promoters contain the largest numbers of experimentally characterized transcription start sites compared to other promoters, and the types of transcription start sites in them are biased toward tissue-specific patterns of gene expression. Finally, long-CGI promoters are preferentially associated with genes involved in development and regulation. Together, these findings indicate that functionally relevant variations of CpG islands exist. By investigating consequences of certain CpG island traits, we can gain additional insights into the mechanism and evolution of regulatory complexity of gene expression.
A Screenable in vivo Assay to Study Proteostasis Networks in Caenorhabditis elegans
Authors: Segref Alexandra , Torres Serena , Hoppe Thorsten 
Published: February 2011

Abstract
In eukaryotic cells, the ubiquitin/proteasome system (UPS) is a key determinant of proteostasis as it regulates the turnover of damaged proteins. However, it is still unclear how the UPS integrates intrinsic and environmental challenges to promote organismal development and survival. Here, we set up an in vivo degradation assay to facilitate the genetic identification of ubiquitin-dependent proteolysis pathways in the multicellular organism Caenorhabditis elegans. Using this assay, we found that mild induction of protein-folding stress, which is nontoxic for wild-type worms, strongly reduces ubiquitin-dependent protein turnover. Ubiquitin-mediated degradation is also reduced by metabolic stress, which correlates with life-span extension. Unlike other stress conditions, however, acute heat stress results in enhanced rather than reduced proteolysis. Intriguingly, our study provides the first evidence for the existence of tissue-specific degradation requirements because loss of key regulators of the UPS, such as proteasomal subunits, causes accumulation of the model substrate, depending on the tissue type. Thus, here we establish a screenable degradation assay that allows diverse genetic screening approaches for the identification of novel cell-type-specific proteostasis networks important for developmental processes, stress response, and aging, thereby substantially extending the work on recently described mechanistic UPS reporter studies.
Sourcing Premia with Incomplete Contracts: Theory and Evidence
Authors: Kohler Wilhelm K , Smolka Marcel 
Published: February 2011

Abstract
Drawing on Grossman & Helpman (2004) and Antràs & Helpman (2004), we identify general conditions that result in an unambiguous mapping of a firm’s productivity level into the organizational form and location of its input sourcing. Using a detailed 2006-2008 data set for Spanish manufacturing firms, we then establish a number of stylized facts about firm-level heterogeneity in sourcing strategies that have largely gone unnoticed in existing literature on input sourcing. Finally, we explore this heterogeneity through econometric estimation of productivity premia associated with different sourcing strategies. We find a robustly significant premium on a strategy that features offshore production of intermediate inputs through a related party (vertical integration). Lower productivity premia are found for strategies that rely on outsourcing to unrelated parties abroad or on vertical integration within the home economy. Across all specifications employed, estimated mean productivity is lowest for domestic-outsourcing firms.
Differential Expression of Novel Adiponectin Receptor-1 Transcripts in Skeletal Muscle of Subjects With Normal Glucose Tolerance and Type 2 Diabetes
Authors: Ashwal Reut , Hemi Rina , Tirosh Amir , Gordin Reut , Yissachar Eleanor , Cohen-Dayag Anat , Rosenberg Avi , Karasik Avraham , Blüher Matthias , Kanety Hannah 
Published: February 2011

OBJECTIVE
Adiponectin receptor-1 (AdipoR1) expression in skeletal muscle has been suggested to play an important role in insulin resistance and diabetes. We aimed at evaluating the presence of novel AdiopR1 splice variants in human muscle and their regulation under physiological and pathophysiological states.

RESEARCH DESIGN AND METHODS
AdipoR1 5′UTR mRNA transcripts, predicted from bioinformatics data, were evaluated in fetal and adult human tissues. Expression and function of the identified transcripts were assessed in cultured human skeletal muscle cells and in muscle biopsies obtained from individuals with normal glucose tolerance (NGT) and type 2 diabetes (n = 49).

RESULTS
Screening of potential AdipoR1 5′UTR splice variants revealed a novel highly abundant muscle transcript (R1T3) in addition to the previously described transcript (R1T1). Unlike R1T1, R1T3 expression was significantly increased during fetal development and myogenesis, paralleled with increased AdipoR1 protein expression. The 5′UTR of R1T3 was found to contain upstream open reading frames that repress translation of downstream coding sequences. Conversely, AdipoR1 3′UTR was associated with enhanced translation efficiency during myoblast-myotube differentiation. A marked reduction in muscle expression of R1T3, R1T1, and R1T3-to-R1T1 ratio was observed in individuals with type 2 diabetes compared with expression levels of NGT subjects, paralleled with decreased expression of the differentiation marker myogenin. Among NGT subjects, R1T3 expression was positively correlated with insulin sensitivity.

CONCLUSIONS
These results indicate that AdipoR1 receptor expression in human skeletal muscle is subjected to posttranscriptional regulation, including alternative splicing and translational control. These mechanisms play an important role during myogenesis and may be important for whole-body insulin sensitivity.
Hemoglobin A1c as a Predictor of Incident Diabetes
Authors: Cheng Peiyao , Neugaard Britta , Foulis Philip , Conlin Paul R. 
Published: February 2011

OBJECTIVE
Several studies have suggested that HbA1c levels may predict incident diabetes. With new recommendations for use of HbA1c in diagnosing diabetes, many patients with HbA1c results below the diagnostic threshold will be identified. Clinicians will need to categorize risk for a subsequent diabetic diagnosis in such patients. The objective of this study was to determine the ability of HbA1c to predict the incidence of a diabetic diagnosis.

RESEARCH DESIGN AND METHODS
We performed a historical cohort study using electronic medical record data from two Department of Veterans Affairs Medical Centers. Patients (n = 12,589) were identified with a baseline HbA1c &lt;6.5% between January 2000 and December 2001 and without a diagnosis of diabetes. Patients (12,375) had at least one subsequent follow-up visit. These patients were tracked for 8 years for a subsequent diagnosis of diabetes.

RESULTS
During an average follow-up of 4.4 years, 3,329 (26.9%) developed diabetes. HbA1c ≥5.0% carried a significant risk for developing diabetes during follow-up. When compared with the reference group (HbA1c &lt;4.5%), HbA1c increments of 0.5% between 5.0 and 6.4% had adjusted odds ratios of 1.70 (5.0–5.4%), 4.87 (5.5–5.9%), and 16.06 (6.0–6.4%) (P &lt; 0.0001). Estimates of hazard ratios similarly showed significant increases for HbA1c ≥5.0%. A risk model for incident diabetes within 5 years was developed and validated using HbA1c, age, BMI, and systolic blood pressure.

CONCLUSIONS
The incidence of diabetes progressively and significantly increased among patients with an HbA1c ≥5.0%, with substantially expanded risk for those with HbA1c 6.0–6.4%.
Inflammatory Genes in Epicardial Fat Contiguous With Coronary Atherosclerosis in the Metabolic Syndrome and Type 2 Diabetes
Authors: Sacks Harold S. , Fain John N. , Cheema Paramjeet , Bahouth Suleiman W. , Garrett Edward , Wolf Rodney Y. , Wolford David , Samaha Joseph 
Published: February 2011

OBJECTIVE
To determine changes in gene expression in epicardial adipose tissue (EAT) associated with coronary atherosclerosis (CAD) and effects of pioglitazone therapy.

RESEARCH DESIGN AND METHODS
Genes were quantified by RT-PCR in EAT and thoracic subcutaneous adipose tissue (SAT) obtained during surgery in CAD patients with metabolic syndrome (MS) or type 2 diabetes and control subjects with minimal or no CAD and no MS or type 2 diabetes.

RESULTS
Increased expression of interleukin-1 receptor antagonist (IL-1Ra) and IL-10, a trend for higher IL-1β, and no change in peroxisome proliferator–activated receptor-γ (PPARγ) was found in EAT from MS or type 2 diabetes. Only PPARγ mRNA was reduced in SAT. Pioglitazone therapy in type 2 diabetes was associated with decreased expression of IL-1β, IL-1Ra, and IL-10 in EAT; decreased IL-10 in SAT; and increased PPARγ in SAT.

CONCLUSIONS
In MS and type 2 diabetes with CAD, proinflammatory and anti-inflammatory genes were differentially increased in EAT and selectively reduced in association with pioglitazone treatment.
Brownian motor moving in a fluctuating tube in the presence of a load
Authors: Ou Zhi-e , Yi Shu-ting , Huang Xiao-qun , Xiong Jian-wen , Ai Bao-quan 
Published: February 2011

Abstract
The transport of Brownian particles moving along a three-dimensional fluctuating tube is investigated in the presence of a load. The tube wall can fluctuate between two states. Coarsening the description of a process for the sake of simplifying the dynamic will result in an entropic barrier and an effective diffusion coefficient. It is found that we can control the asymmetric parameter and the load force to control the current direction and there is an optimized transition rate at which the current takes a maximum value.
Comparing hyoscine and drotaverine effects on colon in CT colonography
Authors: Kristev Athanas , Sirakov Nikolay , Getova Damianka , Katcarov Vasil , Sirakov Vladimir , Stefanov Rumen , Turiiski Valentin , Velkova Kichka 
Published: February 2011

AbstractHyoscine and drotaverine effectiveness was compared for the purposes of achieving optimum distension following insufflation in CT colonography. The in vitro effects of hyoscine and drotaverine on tone and contractility of SM preparations isolated from different areas of human colon were studied by isometric registration of contractile activity. Both medications have a relaxing effect on SM preparations and inhibit their spontaneous contractions. The drotaverine-induced effects were reliably more marked than the hyoscine-induced ones. CT colonography was performed in 70 patients who were injected with equal doses of either hyoscine (n=32) or drotaverine (n=38). The degree of drug-induced distension in both groups was determined by measuring the lumen of the colon on a 2D reconstruction. In most colon areas the width of the distended lumen was greater in the drotaverine-treated patients. We concluded that drotaverine can be used as a means to facilitate colonic distension.
Spectroscopic investigations and physico-chemical characterization of newly synthesized mixed-ligand complexes of 2-methylbenzimidazole with metal ions
Authors: Shaker Shayma , Khaledi Hamid , Ali Hapipah 
Published: February 2011

AbstractSome mixed ligand complexes containing 2-methylbenzimidazole and thiocyanate ion were synthesized. Free ligands and their metal complexes were characterized using elemental analysis, determination of metal, magnetic susceptibility, molar conductivity, infrared, UV-VIS, and (1H, 13C) NMR spectra, and X-ray structure analysis. The results suggest that the Ag(I) complex has linear geometry, Fe(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) have tetrahedral geometry, Pd(II) complex has square planar geometry, VO(IV) square pyramidal geometry, Pb(II) irregular tetrahedral geometry, and that the Cr(III) and Mn(II) complexes have octahedral geometry. The following general formulae were proposed for the prepared complexes: [AgBX], [CrB3X3], (HB)2[MnB2X4] · 2B and [MB2X2], where B = 2-methylbenzimidazole, HB = 2-methylbenzimidazolium, X = thiocyanate ion, and M = VO(IV), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Pd(II), Cd(II), and Pb(II). Molar conductance of a 10−3 M solution in N,N-dimethyl formamide (DMF) indicates that all the complexes are non-electrolytes except the Mn(II) complex which is an electrolyte because the molar conductivity of its solution in DMF is high.