bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of metabolite identity from accurate mass, migration time prediction and isotopic pattern information in CE‐TOFMS data
Authors: Sugimoto Masahiro , Hirayama Akiyoshi , Robert Martin , Abe Shinobu , Soga Tomoyoshi , Tomita Masaru 
Published: June 2010

AbstractCE‐TOFMS is a powerful method for profiling charged metabolites. However, the limited availability of metabolite standards hinders the process of identifying compounds from detected features in CE‐TOFMS data sets. To overcome this problem, we developed a method to identify unknown peaks based on the predicted migration time (tm) and accurate m/z values. We developed a predictive model using 375 standard cationic metabolites and support vector regression. The model yielded good correlations between the predicted and measured tm (R=0.952 and 0.905 using complete and cross‐validation data sets, respectively). Using the trained model, we subsequently predicted the tm for 2938 metabolites available from the public databases and assigned tentative identities to noise‐filtered features in human urine samples. While 38.9% of the peaks were assigned metabolite names by matching with the standard library alone, the proportion increased to 52.2%. The proposed methodology increases the value of metabolomic data sets obtained from CE‐TOFMS profiling.
A field study on the fusion of terrestrial and satellite location methods in urban cellular networks
Authors: Barcelo‐Arroyo Francisco , Martin‐Escalona Israel , Manente Cyrille 
Published: June 2010

AbstractThis work studies the improvement in service coverage obtained by three different approaches to combining two triangulation (terrestrial and satellite) location methods for cellular networks in an urban environment. The paper assumes that the terrestrial cellular network uses enhanced observed time difference (E‐OTD) in 2G or observed time difference of arrival (OTDOA) in 3G, while the satellite GNSS uses the assisted global positioning system (A‐GPS), but the analysis can be easily generalised to other triangulation methods. A straightforward analytical model is presented to evaluate the service coverage resulting from each of the three approaches. The model is fed with actual coverage figures, gathered from test measurements carried out in Paris (France) for several urban scenarios. Numerical results show that the three approaches lead to improvements in all the tested scenarios, and that the improvement obtained by the increasing complexity of the fusion approach depends highly on the coverage of each individual method and on the joint probability function of individual performances. Copyright © 2010 John Wiley & Sons, Ltd.
Ordered subset analysis for case‐control studies
Authors: Qin Xuejun , Hauser Elizabeth R. , Schmidt Silke 
Published: June 2010

AbstractGenetic heterogeneity, which may manifest on a population level as different frequencies of a specific disease susceptibility allele in different subsets of patients, is a common problem for candidate gene and genome‐wide association studies of complex human diseases. The ordered subset analysis (OSA) was originally developed as a method to reduce genetic heterogeneity in the context of family‐based linkage studies. Here, we have extended a previously proposed method (OSACC) for applying the OSA methodology to case‐control datasets. We have evaluated the type I error and power of different OSACC permutation tests with an extensive simulation study. Case‐control datasets were generated under two different models by which continuous clinical or environmental covariates may influence the relationship between susceptibility genotypes and disease risk. Our results demonstrate that OSACC is more powerful under some disease models than the commonly used trend test and a previously proposed joint test of main genetic and gene‐environment interaction effects. An additional unique benefit of OSACC is its ability to identify a more informative subset of cases that may be subjected to more detailed molecular analysis, such as DNA sequencing of selected genomic regions to detect functional variants in linkage disequilibrium with the associated polymorphism. The OSACC‐identified covariate threshold may also improve the power of an additional dataset to replicate previously reported associations that may only be detectable in a fraction of the original and replication datasets. In summary, we have demonstrated that OSACC is a useful method for improving SNP association signals in genetically heterogeneous datasets. Genet. Epidemiol. 34: 407–417, 2010. © 2010 Wiley‐Liss, Inc.
Effect of including environmental data in investigations of gene‐disease associations in the presence of qualitative interactions
Authors: Williamson Elizabeth , Ponsonby Anne‐Louise , Carlin John , Dwyer Terry 
Published: June 2010

AbstractComplex diseases are likely to be caused by the interplay of genetic and environmental factors. Despite this, gene‐disease associations are frequently investigated using models that focus solely on a marginal gene effect, ignoring environmental factors entirely. Failing to take into account a gene‐environment interaction can weaken the apparent gene‐disease association, leading to loss in statistical power and, potentially, inability to identify genuine risk factors. If a gene‐environment interaction exists, therefore, a joint analysis allowing the effect of the gene to differ between groups defined by the environmental exposure can have greater statistical power than a marginal gene‐disease model. However, environmental data are subject to measurement error. Substantial losses in statistical power for detecting gene‐environment interactions can arise from measurement error in the environmental exposure. It is unclear, however, what effect measurement error may have on the power of the joint analysis. We consider the potential benefits, in terms of statistical power, of collecting concurrent environmental data within large cohorts in order to enhance gene detection. We further consider whether these benefits remain in the presence of misclassification in both the gene and the environmental exposure. We find that when an effect of the gene is apparent only in the presence of the environmental exposure, the joint analysis has greater power than a marginal gene‐disease analysis. This comparative increase in power remains in the presence of likely levels of misclassification of either the gene or environmental exposure. Genet. Epidemiol. 34:552–560, 2010. © 2010 Wiley‐Liss, Inc.
Identifying genetic interactions in genome‐wide data using Bayesian networks
Authors: Jiang Xia , Barmada M. Michael , Visweswaran Shyam 
Published: June 2010

AbstractIt is believed that interactions among genes (epistasis) may play an important role in susceptibility to common diseases (Moore and Williams [2002]. Ann Med 34:88–95; Ritchie et al. [2001]. Am J Hum Genet 69:138–147). To study the underlying genetic variants of diseases, genome‐wide association studies (GWAS) that simultaneously assay several hundreds of thousands of SNPs are being increasingly used. Often, the data from these studies are analyzed with single‐locus methods (Lambert et al. [2009]. Nat Genet 41:1094–1099; Reiman et al. [2007]. Neuron 54:713–720). However, epistatic interactions may not be easily detected with single‐locus methods (Marchini et al. [2005]. Nat Genet 37:413–417). As a result, both parametric and nonparametric multi‐locus methods have been developed to detect such interactions (Heidema et al. [2006]. BMC Genet 7:23). However, efficiently analyzing epistasis using high‐dimensional genome‐wide data remains a crucial challenge. We develop a method based on Bayesian networks and the minimum description length principle for detecting epistatic interactions. We compare its ability to detect gene‐gene interactions and its efficiency to that of the combinatorial method multifactor dimensionality reduction (MDR) using 28,000 simulated data sets generated from 70 different genetic models We further apply the method to over 300,000 SNPs obtained from a GWAS involving late onset Alzheimer's disease (LOAD). Our method outperforms MDR and we substantiate previous results indicating that the GAB2 gene is associated with LOAD. To our knowledge, this is the first successful model‐based epistatic analysis using a high‐dimensional genome‐wide data set. Genet. Epidemiol. 34:575–581, 2010. © 2010 Wiley‐Liss, Inc.
Precipitation and temperature trends for the Southwest China: 1960–2007
Authors: Qin Nianxiu , Chen Xi , Fu Guobin , Zhai Jianqing , Xue Xianwu 
Published: June 2010

AbstractDaily temperature and precipitation data from 136 stations of Southwest China (SWC) during the last five decades, from 1960 to 2007, were analysed to determine the spatial and temporal trends by using the Mann–Kendall trend test. Results show that SWC has become warmer over the last five decades, especially in the recent 20–25 years. The increasing trends in winter months are more significant than those in the months of other seasons, and spatially Tibet, Hengduan mountains area and west Sichuan Plateau have larger temperature trend in magnitude than the other regions have. A downward trend was detected in Sichuan Basin also, but the region with cooler temperature was shrinking due to the statistically significant increasing trend of temperature after 1990s. Both annual and seasonal means of daily maximum and minimum temperatures show an increasing trend, but trend magnitude of minimum temperature was larger than that of maximum temperature, resulting in the decrease of diurnal temperature range for SWC in the last 50 years. Annual precipitation showed slightly and statistically insignificant increasing trend, but statistically significant increasing trend has been detected in winter season while autumn witnessed a statistically significant decreasing trend. The results could be a reference for the planning and management of water resources under climate change. Copyright © 2010 John Wiley & Sons, Ltd.
IL‐2‐granzyme A chimeric protein overcomes multidrug resistance (MDR) through a caspase 3‐independent apoptotic pathway
Authors: Grodzovski Inna , Lichtenstein Michal , Galski Hanan , Lorberboum‐Galski Haya 
Published: June 2010

AbstractOne of the main problems of conventional anticancer therapy is multidrug resistance (MDR), whereby cells acquire resistance to structurally and functionally unrelated drugs following chemotherapeutic treatment. One of the main causes of MDR is overexpression of the P‐glycoprotein transporter. In addition to extruding the chemotherapeutic drugs, it also inhibits apoptosis through the inhibition of caspases. To overcome MDR, we constructed a novel chimeric protein, interleukin (IL)‐2 granzyme A (IGA), using IL‐2 as a targeting moiety and granzyme A as a killing moiety, fused at the cDNA level. IL‐2 binds to the high‐affinity IL‐2 receptor that is expressed in an array of abnormal cells, including malignant cells. Granzyme A is known to cause caspase 3‐independent cell death. We show here that the IGA chimeric protein enters the target sensitive and MDR cancer cells overexpressing IL‐2 receptor and induces caspase 3‐independent cell death. Specifically, after its entry, IGA causes a decrease in the mitochondrial potential, triggers translocation of nm23‐H1, a granzyme A‐dependent DNase, from the cytoplasm to the nucleus, where it causes single‐strand DNA nicks, thus causing cell death. Moreover, IGA is able to overcome MDR and kill cells resistant to chemotherapeutic drugs. We believe that overcoming MDR with targeted molecules such as IGA chimeric protein that causes caspase‐independent apoptotic cell death could be applied to many other resistant types of tumors using the appropriate targeting moiety. Thus, this novel class of targeted molecules could open up new vistas in the fight against human cancer.
APC mutations are associated with increased bone mineral density in patients with familial adenomatous polyposis
Authors: Miclea Razvan L , Karperien Marcel , Langers Alexandra M , Robanus-Maandag Els C , van Lierop Antoon , van der Hiel Bernies , Stokkel Marcel P , Ballieux Bart E , Oostdijk Wilma , Wit Jan M , Vasen Hans F , Hamdy Neveen A 
Published: June 2010

Abstract
The canonical Wnt pathway plays a key regulatory role in osteoblastogenesis and bone mass acquisition through its main effector, β-catenin. Adenomatous polyposis coli (APC) represents the key intracellular gatekeeper of β-catenin turnover, and heterozygous germ-line mutations in the APC gene cause familial adenomatous polyposis (FAP). Whether APC mutations affect bone mass has not been previously investigated. We conducted a cross-sectional study evaluating skeletal status in FAP patients with a documented APC mutation. Twenty-two FAP patients with a mean age of 42 years (54.5% women) were included in this study. Mean bone mineral density (BMD) Z-scores were significantly increased above normal at all measured sites: lumbar spine (p &lt; .01), total hip (p &lt; .01), femoral neck (p &lt; .05), and trochanter (p &lt; .01). Z-scores were +1 or greater in 14 patients (63.6%) and +2 or greater in 5 (22.7%). Mean values of bone turnover markers were within normal ranges. There was a significant positive correlation between procollagen type I N-terminal propeptide (P1NP) and β-crosslaps (β-CTX) (r = 0.70, p &lt; .001) and between these markers and sclerostin and BMD measurements. We demonstrate that FAP patients display a significantly higher than normal mean BMD compared with age- and sex-matched healthy controls in the presence of a balanced bone turnover. Our data suggest a state of “controlled” activation of the Wnt signaling pathway in heterozygous carriers of APC mutations, most likely owing to upregulation of cytoplasmic β-catenin levels. © 2010 American Society for Bone and Mineral Research.
Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK-mediated Runx2 activation
Authors: Lin Kuan-Liang , Chou Ching-Heng , Hsieh Shu-Chen , Hwa Su-Yang , Lee Ming-Ta , Wang Fung-Fang 
Published: June 2010

Abstract
Deficiency of the collagen receptor discoidin domain receptor tyrosine kinase (DDR2) in mice and humans results in dwarfism and short limbs, of which the mechanism remains unknown. Here we report that DDR2 is a key regulator of osteoblast differentiation. DDR2 mRNA expression was increased at an early stage of induced osteoblast differentiation. In the subchondral bone of human osteoarthritic knee, DDR2 was detected in osteoblastic cells. In mouse embryos, DDR2 expression was found from E11 to E15, preceding osteocalcin (OCN) and coinciding with Runx2 expression. Activating transcription factor 4 (ATF4) enhanced DDR2 mRNA expression, and knockdown of ATF4 expression delayed DDR2 induction during osteoblast differentiation. A CCAAT/enhancer binding protein (C/EBP) binding site at −1150 bp in the DDR2 promoter was required for ATF4-mediated DDR2 activation. C/EBPβ bound to and cooperated with ATF4 in stimulating DDR2 transcription; accordingly, the ATF4 mutants deficient of C/EBPβ binding were incapable of transactivating DDR2. Overexpression of DDR2 increased osteoblast-specific gene expression. Conversely, knockdown of DDR2 suppressed osteogenic marker gene expression and matrix mineralization during the induced osteogenesis. The stimulation of p38 MAPK by DDR2 was required for DDR2-induced activation of Runx2 and OCN promoters. Together our findings uncover a pathway in which ATF4, by binding to C/EBPβ transcriptionally upregulates DDR2 expression, and DDR2, in turn, activates Runx2 through p38 MAPK to promote osteoblast differentiation. © 2010 American Society for Bone and Mineral Research.
Role of trabecular microarchitecture and its heterogeneity parameters in the mechanical behavior of ex vivo human L3 vertebrae
Authors: Wegrzyn Julien , Roux Jean-Paul , Arlot Monique E , Boutroy Stéphanie , Vilayphiou Nicolas , Guyen Olivier , Delmas Pierre D , Chapurlat Roland , Bouxsein Mary L 
Published: June 2010

Abstract
Low bone mineral density (BMD) is a strong risk factor for vertebral fracture risk in osteoporosis. However, many fractures occur in people with moderately decreased or normal BMD. Our aim was to assess the contributions of trabecular microarchitecture and its heterogeneity to the mechanical behavior of human lumbar vertebrae. Twenty-one human L3 vertebrae were analyzed for BMD by dual-energy X-ray absorptiometry (DXA) and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) and then tested in axial compression. Microarchitecture heterogeneity was assessed using two vertically oriented virtual biopsies—one anterior (Ant) and one posterior (Post)—each divided into three zones (superior, middle, and inferior) and using the whole vertebral trabecular volume for the intraindividual distribution of trabecular separation (Tb.Sp*SD). Heterogeneity parameters were defined as (1) ratios of anterior to posterior microarchitectural parameters and (2) the coefficient of variation of microarchitectural parameters from the superior, middle, and inferior zones. BMD alone explained up to 44% of the variability in vertebral mechanical behavior, bone volume fraction (BV/TV) up to 53%, and trabecular architecture up to 66%. Importantly, bone mass (BMD or BV/TV) in combination with microarchitecture and its heterogeneity improved the prediction of vertebral mechanical behavior, together explaining up to 86% of the variability in vertebral failure load. In conclusion, our data indicate that regional variation of microarchitecture assessment expressed by heterogeneity parameters may enhance prediction of vertebral fracture risk. © 2010 American Society for Bone and Mineral Research.
Effect of chronic intermittent hypoxia on biological behavior and hypoxia‐associated gene expression in lung cancer cells
Authors: Liu Yonglei , Song Xianrang , Wang Xingwu , Wei Ling , Liu Xiuju , Yuan Shuanghu , Lv Liyan 
Published: June 2010

AbstractHypoxia plays an important role in the development of solid tumors and is associated with their therapeutic resistance. There exist three major forms of hypoxia: acute, chronic, and intermittent hypoxia. Previous studies have shown that cancer cells could behave in the form of adaptation to hypoxia in tumor growth, which could result in their biological changes and determine their responses to the therapies. To investigate the tumor cells' adaptation to hypoxia, we recreated two models using two lung cancer cell lines in the presence of intermittent hypoxia, which is characterized by changes in oxygen pressure within the disorganized vascular network. We investigated biological behaviors such as cell cycle, proliferation, radiation sensitivity, apoptosis and migration, hypoxia signal pathway in the lung cancer cells treated with chronic intermittent hypoxia, as well as the role of hypoxia inducible factor 1 there, hypoxia‐inducible genes analyzed by real‐time RT‐PCR chip in H446 cells treated with the model. The results indicated the changes of some hypoxia target gene expressions of those induced by hypoxia, some of which were confirmed by real‐time RT‐PCR. The cells mediated by irradiation induced resistance to radiation and apoptosis and increased metastasis in lung cancer cells. It was found that such changes were related to hypoxia inducible factor 1, alpha subunit (HIF‐1α). J. Cell. Biochem. 111: 554–563, 2010. © 2010 Wiley‐Liss, Inc.
Transcription activation of myostatin by trichostatin A in differentiated C2C12 myocytes via ASK1‐MKK3/4/6‐JNK and p38 mitogen‐activated protein kinase pathways
Authors: Han Der‐Sheng , Huang Hsiang‐Po , Wang Tyng‐Guey , Hung Meng‐Yu , Ke Jia‐Yu , Chang Kuei‐Ting , Chang Hsin‐Yu , Ho Yu‐Ping , Hsieh Wei‐Yuan , Yang Wei‐Shiung 
Published: June 2010

AbstractMyostatin is a negative regulator of skeletal muscle mass. The pathways employed in modulating myostatin gene expression are scarcely known. We aimed to determine the signaling pathway of myostatin induction by a histone deacetylase (HDAC) inhibitor–trichostatin A (TSA) in differentiated C2C12 myocytes. TSA increased myostatin mRNA expression up to 40‐fold after treatment for 24 h, and induced myostatin promoter activity up to 3.8‐fold. Pretreatment with actinomycin D reduced the TSA‐induced myostatin mRNA by 93%, suggesting TSA‐induced myostatin expression mainly at the transcriptional level. Pretreatment with p38 MAPK (SB203580) and JNK (SP600125) inhibitors, but not ERK (PD98059) inhibitor, blocked TSA‐induced myostatin expression, respectively, by 72% and 43%. Knockdown of p38 MAPK by RNAi inhibited the TSA‐induced myostatin expression by 77% in C2C12 myoblasts. The protein levels of phosphorylated p38 MAPK, JNK, but not ERK, increased with TSA treatment in differentiated C2C12 cells. Direct activation of p38 MAPK and JNK by anisomycin in the absence of TSA increased myostatin mRNA by fourfold. The phosphorylated form of the kinase MKK3/4/6 and ASK1, upstream cascades of p38 MAPK and JNK, also increased with TSA treatment. We concluded that the induction of myostatin by TSA treatment in differentiated C2C12 cells is in part through ASK1‐MKK3/6‐p38 MAPK and ASK1‐MKK4‐JNK signaling pathways. Activation of p38 MAPK and JNK axis is necessary, but not sufficient for TSA‐induced myostatin expression. J. Cell. Biochem. 111: 564–573, 2010. © 2010 Wiley‐Liss, Inc.
Cigarette smoke extract induces HO‐1 expression in mouse cerebral vascular endothelial cells: Involvement of c‐Src/NADPH oxidase/PDGFR/JAK2/STAT3 pathway
Authors: Shih Ruey‐Horng , Lee I‐Ta , Hsieh Hsi‐Lung , Kou Yu Ru , Yang Chuen‐Mao 
Published: June 2010

AbstractSeveral chemicals present in cigarette smoke (CS) have been reported to induce heme oxygenase‐1 (HO‐1) expression, which represents a prime defense mechanism in protecting the cells from stress‐dependent adverse effects on peripheral vascular system. However, the effects of cigarette smoke extract (CSE) on HO‐1 induction and the mechanisms underlying CSE‐induced HO‐1 expression in brain vessels are not completely understood. Here, we used a mouse brain endothelial cell culture (bEnd.3) to investigate the effect of CSE on HO‐1 induction and the mechanisms underlying CSE‐induced HO‐1 expression in cerebral vessels. We demonstrated that sublethal concentrations of CSE (30 µg/ml) induced submaximal HO‐1 expression in bEnd.3 cells. NADPH oxidase‐dependent ROS generation played a key role in CSE‐induced HO‐1 expression. CSE‐induced HO‐1 expression was mediated through PDGFR/JAK2/STAT3 cascade, which was observed by pretreatment with the respective pharmacological inhibitors or transfection with PDGFR shRNA. CSE activated NADPH oxidase through c‐Src in bEnd.3 cells. Taken together, these results suggested that, in bEnd.3 cells, CSE‐induced HO‐1 expression was mediated through PDGFR/JAK2/STAT3 cascade, which was regulated by c‐Src or c‐Src activated‐NADPH oxidase/ROS. J. Cell. Physiol. 225: 741–750, 2010. © 2010 Wiley‐Liss, Inc.
Origin of cardiac progenitor cells in the developing and postnatal heart
Authors: Kuhn Elizabeth N. , Wu Sean M. 
Published: June 2010

AbstractThe mammalian heart lacks the capacity to replace the large numbers of cardiomyocytes lost due to cardiac injury. Several different cell‐based routes to myocardial regeneration have been explored, including transplantation of cardiac progenitors and cardiomyocytes into injured myocardium. As seen with cell‐based therapies in other solid organ systems, inherent limitations, such as host immune response, cell death and long‐term graft instability have hampered meaningful cardiac regeneration. An understanding of the cell biology of cardiac progenitors, including their developmental origin, lineage markers, renewal pathways, differentiation triggers, microenvironmental niche, and mechanisms of homing and migration to the site of injury, will enable further refinement of therapeutic strategies to enhance clinically meaningful cardiac repair. J. Cell. Physiol. 225: 321–325, 2010. © 2010 Wiley‐Liss, Inc.