bluuebunny/crossref_metadata_2025_split huggingface dataset:
Future Change of Western North Pacific Typhoons: Projections by a 20-km-Mesh Global Atmospheric Model*
Authors: Murakami Hiroyuki , Wang Bin , Kitoh Akio 
Published: October 2010

Abstract
Projected future changes in tropical cyclone (TC) activity over the western North Pacific (WNP) under the Special Report on Emissions Scenarios (SRES) A1B emission scenario were investigated using a 20-km-mesh, very-high-resolution Meteorological Research Institute (MRI)–Japan Meteorological Agency (JMA) atmospheric general circulation model. The present-day (1979–2003) simulation yielded reasonably realistic climatology and interannual variability for TC genesis frequency and tracks.
The future (2075–99) projection indicates (i) a significant reduction (by about 23%) in both TC genesis number and frequency of occurrence primarily during the late part of the year (September–December), (ii) an eastward shift in the positions of the two prevailing northward-recurving TC tracks during the peak TC season (July–October), and (iii) a significant reduction (by 44%) in TC frequency approaching coastal regions of Southeast Asia.
The changes in occurrence frequency are due in part to changes in large-scale steering flows, but they are due mainly to changes in the locations of TC genesis; fewer TCs will form in the western portion of the WNP (west of 145°E), whereas more storms will form in the southeastern quadrant of the WNP (10°–20°N, 145°–160°E). Analysis of the genesis potential index reveals that the reduced TC genesis in the western WNP is due mainly to in situ weakening of large-scale ascent and decreasing midtropospheric relative humidity, which are associated with the enhanced descent of the tropical overturning circulation. The analysis also indicates that enhanced TC genesis in the southeastern WNP is due to increased low-level cyclonic vorticity and reduced vertical wind shear. These changes appear to be critically dependent on the spatial pattern of future sea surface temperature; therefore, it is necessary to conduct ensemble projections with a range of SST spatial patterns to understand the degree and distribution of uncertainty in future projections.
Evaluation of the established non-MHC multiple sclerosis loci in an Indian population
Authors: Pandit Lekha , Ban Maria , Sawcer Stephen , Singhal Bhim , Nair Shyam , Radhakrishnan Kurupath , Shetty Rajesh , Misri Z , Hegde Suresh , Bhat Irruvathur Gopalakrishna 
Published: October 2010

Background: Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disorder with a strong genetic component. Objective: The prevalence of MS in India is low compared with white populations of Northern European descent. Methods: In order to ascertain whether disease susceptibility genes are the same across different populations, we completed the first investigation in the Indian MS population of 15 MS loci outside of the major histocompatibility (MHC) region that were previously identified and validated with MS susceptibility through genome-wide association and replication studies in white populations. Results: In total, 197 Indian patients and 197 unrelated controls were analyzed. The most associated single nucleotide polymorphism (SNP) within this study was rs6897932 in the IL7R gene, which showed a strong protective effect in this data set (rs 6897932, OR = 0.5543, 95% CI = 0.37–0.78, p = 0.0009727). Two other SNPs were nominally associated with MS in this dataset, namely CLEC16A rs 12708716 (p = 0.0082, OR = 1.478, 95% CI = 1.106–1.975) and CD226 rs763361 ( p = 0.03971, OR = 1.353, CI = 1.014–1.805). For the majority of the remaining SNPs (7/14), the trend for association was in the same direction as in previous studies in the white population. Conclusions: Although the power of this study was limited, our preliminary data suggest that disease susceptibility genes in MS in the Indian population may be similar to those of western populations.
Opposing roles for HIF-1α and HIF-2α in the regulation of angiogenesis by mononuclear phagocytes
Authors: Eubank Tim D. , Roda Julie M. , Liu Haowen , O'Neil Todd , Marsh Clay B. 
Published: October 2010

AbstractMacrophages contribute to tumor growth through the secretion of the proangiogenic molecule vascular endothelial growth factor (VEGF). We previously observed that monocytes treated with the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) produce a soluble form of the VEGF receptor-1 (sVEGFR-1), which neutralizes VEGF biologic activity. The VEGF and VEGFR-1 promoters both contain a hypoxia regulatory element, which binds the hypoxia-inducible factor (HIF) transcription factors under hypoxic conditions. Based on this observation, we examined VEGF and sVEGFR-1 production from monocytes cultured at various O2 concentrations. The amount of sVEGFR-1 production observed from GM-CSF-treated monocytes increased with decreasing levels of O2. This sVEGFR-1 was biologically active and sequestered VEGF. To evaluate the role of the HIFs in sVEGFR-1 production, we used macrophages with a genetic deletion of HIF-1α. HIF-1α−/− macrophages cultured with GM-CSF at hypoxia secreted diminished amounts of VEGF compared with HIF-1α+/+ macrophages, whereas sVEGFR-1 secretion was unaffected. In contrast, siRNA-mediated knockdown of HIF-2α inhibited the production of sVEGFR-1 in response to GM-CSF and low O2, whereas VEGF production was unaffected. These studies suggest that hypoxia, generally thought to promote angiogenesis, can induce antiangiogenic behavior from macrophages within a GM-CSF–rich environment. Furthermore, these results suggest specific and independent roles for HIF-1α and HIF-2α in hypoxic macrophages.
AKAP9 regulation of microtubule dynamics promotes Epac1-induced endothelial barrier properties
Authors: Sehrawat Seema , Ernandez Thomas , Cullere Xavier , Takahashi Mikiko , Ono Yoshitaka , Komarova Yulia , Mayadas Tanya N. 
Published: October 2010

AbstractAdhesive forces at endothelial cell-cell borders maintain vascular integrity. cAMP enhances barrier properties and controls cellular processes through protein kinase A bound to A-kinase anchoring proteins (AKAPs). It also activates exchange protein directly activated by cAMP (Epac1), an exchange factor for Ras-related protein 1 (Rap1) GTPases that promotes cadherin- and integrin-mediated adhesion through effects on the actin cytoskeleton. We demonstrate that AKAP9 facilitates the microtubule polymerization rate in endothelial cells, interacts with Epac1, and is required for Epac1-stimulated microtubule growth. AKAP9 is not required for maintaining barrier properties under steady-state conditions. Rather, it is essential when the cell is challenged to make new adhesive contacts, as is the case when Epac activation enhances barrier function through a mechanism that, surprisingly, requires integrin adhesion at cell-cell contacts. In the present study, defects in Epac-induced responses in AKAP9-silenced cells were evident despite an intact Epac-induced increase in Rap activation, cortical actin, and vascular endothelial-cadherin adhesion. We describe a pathway that integrates Epac-mediated signals with AKAP9-dependent microtubule dynamics to coordinate integrins at lateral borders.
The prolyl isomerase Pin1 acts as a novel molecular switch for TNF-α–induced priming of the NADPH oxidase in human neutrophils
Authors: Boussetta Tarek , Gougerot-Pocidalo Marie-Anne , Hayem Gilles , Ciappelloni Silvia , Raad Houssam , Arabi Derkawi Riad , Bournier Odile , Kroviarski Yolande , Zhou Xiao Zhen , Malter James S. , Lu Ping K. , Bartegi Aghleb , Dang Pham My-Chan , El-Benna Jamel 
Published: October 2010

AbstractNeutrophils play a key role in host defense by releasing reactive oxygen species (ROS). However, excessive ROS production by neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase can damage bystander tissues, thereby contributing to inflammatory diseases. Tumor necrosis factor-α (TNF-α), a major mediator of inflammation, does not activate NADPH oxidase but induces a state of hyperresponsiveness to subsequent stimuli, an action known as priming. The molecular mechanisms by which TNF-α primes the NADPH oxidase are unknown. Here we show that Pin1, a unique cis-trans prolyl isomerase, is a previously unrecognized regulator of TNF-α–induced NADPH oxidase hyperactivation. We first showed that Pin1 is expressed in neutrophil cytosol and that its activity is markedly enhanced by TNF-α. Inhibition of Pin1 activity with juglone or with a specific peptide inhibitor abrogated TNF-α–induced priming of neutrophil ROS production induced by N-formyl-methionyl-leucyl-phenylalanine peptide (fMLF). TNF-α enhanced fMLF-induced Pin1 and p47phox translocation to the membranes and juglone inhibited this process. Pin1 binds to p47phox via phosphorylated Ser345, thereby inducing conformational changes that facilitate p47phox phosphorylation on other sites by protein kinase C. These findings indicate that Pin1 is critical for TNF-α–induced priming of NADPH oxidase and for excessive ROS production. Pin1 inhibition could potentially represent a novel anti-inflammatory strategy.
Histone deacetylase inhibitors impair innate immune responses to Toll-like receptor agonists and to infection
Authors: Roger Thierry , Lugrin Jérôme , Le Roy Didier , Goy Geneviève , Mombelli Matteo , Koessler Thibaud , Ding Xavier C. , Chanson Anne-Laure , Reymond Marlies Knaup , Miconnet Isabelle , Schrenzel Jacques , François Patrice , Calandra Thierry 
Published: October 2010

Abstract
Regulated by histone acetyltransferases and deacetylases (HDACs), histone acetylation is a key epigenetic mechanism controlling chromatin structure, DNA accessibility, and gene expression. HDAC inhibitors induce growth arrest, differentiation, and apoptosis of tumor cells and are used as anticancer agents. Here we describe the effects of HDAC inhibitors on microbial sensing by macrophages and dendritic cells in vitro and host defenses against infection in vivo. HDAC inhibitors down-regulated the expression of numerous host defense genes, including pattern recognition receptors, kinases, transcription regulators, cytokines, chemokines, growth factors, and costimulatory molecules as assessed by genome-wide microarray analyses or innate immune responses of macrophages and dendritic cells stimulated with Toll-like receptor agonists. HDAC inhibitors induced the expression of Mi-2β and enhanced the DNA-binding activity of the Mi-2/NuRD complex that acts as a transcriptional repressor of macrophage cytokine production. In vivo, HDAC inhibitors increased the susceptibility to bacterial and fungal infections but conferred protection against toxic and septic shock. Thus, these data identify an essential role for HDAC inhibitors in the regulation of the expression of innate immune genes and host defenses against microbial pathogens.
Hypoxia inhibits senescence and maintains mesenchymal stem cell properties through down-regulation of E2A-p21 by HIF-TWIST
Authors: Tsai Chih-Chien , Chen Yann-Jang , Yew Tu-Lai , Chen Ling-Lan , Wang Jir-You , Chiu Chao-Hua , Hung Shih-Chieh 
Published: October 2010

Abstract
Although low-density culture provides an efficient method for rapid expansion of human mesenchymal stem cells (MSCs), MSCs enriched by this method undergo senescence and lose their stem cell properties, which could be preserved by combining low-density and hypoxic culture. The mechanism was mediated through direct down-regulation of E2A-p21 by the hypoxia-inducible factor–1α (HIF-1α)–TWIST axis. Expansion under normoxia induced E2A and p21 expression, which were abrogated by overexpression of TWIST, whereas siRNA against TWIST up-regulated E2A and p21 in hypoxic cells. Furthermore, siRNA against p21 in normoxic cells enhanced proliferation and increased differentiation potential, whereas overexpression of p21 in hypoxic cells induced a decrease in proliferation and a loss of differentiation capacity. More importantly, MSCs expanded under hypoxic conditions by up to 100 population doublings, exhibited telomerase activity with maintained telomere length, normal karyotyping, and intact genetic integrity, and did not form tumors. These results support low-density hypoxic culture as a method for efficiently expanding MSCs without losing stem cell properties or increasing tumorigenicity.
Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics
Authors: Brunstein Claudio G. , Miller Jeffrey S. , Cao Qing , McKenna David H. , Hippen Keli L. , Curtsinger Julie , DeFor Todd , Levine Bruce L. , June Carl H. , Rubinstein Pablo , McGlave Philip B. , Blazar Bruce R. , Wagner John E. 
Published: October 2010

Abstract
Acute graft-versus-host disease (aGVHD) is associated with high risk of morbidity and mortality and is a common complication after double umbilical cord blood (UCB) transplantation. To reduce these risks, we established a method of CD4+CD25+FoxP3+ T regulatory cell (Treg) enrichment from cryopreserved UCB followed by a 18 + 1-day expansion culture including anti-CD3/anti-CD28 antibody-coated beads and recombinant human interleukin-2. In a “first-in-human” clinical trial, we evaluated the safety profile of UCB Treg in 23 patients. Patients received a dose of 0.1-30 × 105UCB Treg/kg after double UCB transplantation. The targeted Treg dose was achieved in 74% of cultures, with all products being suppressive in vitro (median 86% suppression at a 1:4 ratio). No infusional toxicities were observed. After infusion, UCB Treg could be detected for 14 days, with the greatest proportion of circulating CD4+CD127−FoxP3+ cells observed on day +2. Compared with identically treated 108 historical controls without Treg, there was a reduced incidence of grade II-IV aGVHD (43% vs 61%, P = .05) with no deleterious effect on risks of infection, relapse, or early mortality. These results set the stage for a definitive study of UCB Treg to determine its potency in preventing allogeneic aGVHD. This study is registered at http://www.clinicaltrials.gov as NCT00602693.
Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma
Authors: Chen Yingtai , Zheng Tongzhang , Lan Qing , Foss Francine , Kim Christopher , Chen Xuezhong , Dai Min , Li Yumin , Holford Theodore , Leaderer Brian , Boyle Peter , Chanock Stephen J. , Rothman Nathaniel , Zhang Yawei 
Published: October 2010

AbstractWe conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m2, women with BMI more than or equal to 25 kg/m2 had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 Pforinteraction = .034) and IL7R (rs1494555 Pforinteraction = .016) for NHL overall; IL7R (rs1494555 Pforinteraction = .016) and TNF (1799724 Pforinteraction = .031) for B-cell lymphoma; and IL5 (rs2069812 Pforinteraction = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 Pforinteraction = .006), IL13 (rs20541 Pforinteraction = .019), and IL7R (rs1494555 Pforinteraction = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 Pforinteraction = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 Pforinteraction = .013) and TNF (1799724 Pforinteraction = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.
A fast and cost-effective approach to develop and map EST-SSR markers: oak as a case study
Authors: Durand Jérôme , Bodénès Catherine , Chancerel Emilie , Frigerio Jean-Marc , Vendramin Giovanni , Sebastiani Federico , Buonamici Anna , Gailing Oliver , Koelewijn Hans-Peter , Villani Fiorella , Mattioni Claudia , Cherubini Marcello , Goicoechea Pablo G , Herrán Ana , Ikaran Ziortza , Cabané Cyril , Ueno Saneyoshi , Alberto Florian , Dumoulin Pierre-Yves , Guichoux Erwan , de Daruvar Antoine , Kremer Antoine , Plomion Christophe 
Published: October 2010

Abstract

Background
Expressed Sequence Tags (ESTs) are a source of simple sequence repeats (SSRs) that can be used to develop molecular markers for genetic studies. The availability of ESTs for Quercus robur and Quercus petraea provided a unique opportunity to develop microsatellite markers to accelerate research aimed at studying adaptation of these long-lived species to their environment. As a first step toward the construction of a SSR-based linkage map of oak for quantitative trait locus (QTL) mapping, we describe the mining and survey of EST-SSRs as well as a fast and cost-effective approach (bin mapping) to assign these markers to an approximate map position. We also compared the level of polymorphism between genomic and EST-derived SSRs and address the transferability of EST-SSRs in Castanea sativa (chestnut).

Results
A catalogue of 103,000 Sanger ESTs was assembled into 28,024 unigenes from which 18.6% presented one or more SSR motifs. More than 42% of these SSRs corresponded to trinucleotides. Primer pairs were designed for 748 putative unigenes. Overall 37.7% (283) were found to amplify a single polymorphic locus in a reference full-sib pedigree of Quercus robur. The usefulness of these loci for establishing a genetic map was assessed using a bin mapping approach. Bin maps were constructed for the male and female parental tree for which framework linkage maps based on AFLP markers were available. The bin set consisting of 14 highly informative offspring selected based on the number and position of crossover sites. The female and male maps comprised 44 and 37 bins, with an average bin length of 16.5 cM and 20.99 cM, respectively. A total of 256 EST-SSRs were assigned to bins and their map position was further validated by linkage mapping. EST-SSRs were found to be less polymorphic than genomic SSRs, but their transferability rate to chestnut, a phylogenetically related species to oak, was higher.

Conclusion
We have generated a bin map for oak comprising 256 EST-SSRs. This resource constitutes a first step toward the establishment of a gene-based map for this genus that will facilitate the dissection of QTLs affecting complex traits of ecological importance.
Identification of expression QTL (eQTL) of genes expressed in porcine M. longissimus dorsi and associated with meat quality traits
Authors: Ponsuksili Siriluck , Murani Eduard , Schwerin Manfred , Schellander Karl , Wimmers Klaus 
Published: October 2010

Abstract

Background
Genetic analysis of transcriptional profiles is a promising approach for identifying and dissecting the genetics of complex traits like meat performance. Accordingly, expression levels obtained by microarray analysis were taken as phenotypes in a linkage analysis to map eQTL. Moreover, expression levels were correlated with traits related to meat quality and principle components with high loadings of these traits. By using an up-to-date annotation and localization of the respective probe-sets, the integration of eQTL mapping data and information of trait correlated expression finally served to point to candidate genes for meat quality traits.

Results
Genome-wide transcriptional profiles of M. longissimus dorsi RNAs samples of 74 F2 animals of a pig resource population revealed 11,457 probe-sets representing genes expressed in the muscle. Linkage analysis of expression levels of these probe-sets provided 9,180 eQTL at the suggestive significance threshold of LOD > 2. We mapped 653 eQTL on the same chromosome as the corresponding gene and these were designated as 'putative cis- eQTL'. In order to link eQTL to the traits of interest, probe-sets were addressed with relative transcript abundances that showed correlation with meat quality traits at p ≤ 0.05. Out of the 653 'putative cis- eQTL', 262 transcripts were correlated with at least one meat quality trait. Furthermore, association of expression levels with composite traits with high loadings for meat quality traits generated by principle component analysis were taken into account leading to a list of 85 genes exhibiting cis- eQTL and trait dependent expression.

Conclusion
Holistic expression profiling was integrated with QTL analysis for meat quality traits. Correlations between transcript abundance and meat quality traits, combined with genetic positional information of eQTL allowed us to prioritise candidate genes for further study.
Quantitative trait loci mapping reveals candidate pathways regulating cell cycle duration in Plasmodium falciparum
Authors: Reilly Ayala Heather B , Wacker Mark A , Siwo Geoffrey , Ferdig Michael T 
Published: October 2010

Abstract

Background
Elevated parasite biomass in the human red blood cells can lead to increased malaria morbidity. The genes and mechanisms regulating growth and development of Plasmodium
falciparum through its erythrocytic cycle are not well understood. We previously showed that strains HB3 and Dd2 diverge in their proliferation rates, and here use quantitative trait loci mapping in 34 progeny from a cross between these parent clones along with integrative bioinformatics to identify genetic loci and candidate genes that control divergences in cell cycle duration.

Results
Genetic mapping of cell cycle duration revealed a four-locus genetic model, including a major genetic effect on chromosome 12, which accounts for 75% of the inherited phenotype variation. These QTL span 165 genes, the majority of which have no predicted function based on homology. We present a method to systematically prioritize candidate genes using the extensive sequence and transcriptional information available for the parent lines. Putative functions were assigned to the prioritized genes based on protein interaction networks and expression eQTL from our earlier study. DNA metabolism or antigenic variation functional categories were enriched among our prioritized candidate genes. Genes were then analyzed to determine if they interact with cyclins or other proteins known to be involved in the regulation of cell cycle.

Conclusions
We show that the divergent proliferation rate between a drug resistant and drug sensitive parent clone is under genetic regulation and is segregating as a complex trait in 34 progeny. We map a major locus along with additional secondary effects, and use the wealth of genome data to identify key candidate genes. Of particular interest are a nucleosome assembly protein (PFL0185c), a Zinc finger transcription factor (PFL0465c) both on chromosome 12 and a ribosomal protein L7Ae-related on chromosome 4 (PFD0960c).