bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosing Land–Atmosphere Interaction from a Regional Climate Model Simulation over West Africa
Authors: van den Hurk Bart J. J. M. , van Meijgaard Erik 
Published: December 2009

Abstract
Land–atmosphere interaction at climatological time scales in a large area that includes the West African Sahel has been explicitly explored in a regional climate model (RegCM) simulation using a range of diagnostics. First, areas and seasons of strong land–atmosphere interaction were diagnosed from the requirement of a combined significant correlation between soil moisture, evaporation, and the recycling ratio. The northern edge of the West African monsoon area during June–August (JJA) and an area just north of the equator (Central African Republic) during March–May (MAM) were identified. Further analysis in these regions focused on the seasonal cycle of the lifting condensation level (LCL) and the convective triggering potential (CTP), and the sensitivity of CTP and near-surface dewpoint depressions HIlow to anomalous soil moisture. From these analyses, it is apparent that atmospheric mechanisms impose a strong constraint on the effect of soil moisture on the regional hydrological cycle.
A Climatology of Midlatitude Mesoscale Convective Vortices in the Rapid Update Cycle
Authors: James Eric P. , Johnson Richard H. 
Published: December 2009

Abstract
Climatological characteristics of mesoscale convective vortices (MCVs) occurring in the state of Oklahoma during the late spring and summer of four years are investigated. The MCV cases are selected based on vortex detection by an objective algorithm operating on analyses from the Rapid Update Cycle (RUC) model. Consistent with a previous study, true MCVs represent only about 20% of the mesoscale relative vorticity maxima detected by the algorithm. The MCVs have a broad range of radii and intensities, and their longevities range between 1 and 54 h. Their median radius is about 200 km, and their median midlevel relative vorticity is 1.2 × 10−4 s−1. There appears to be no significant relationship between MCV longevity and intensity. Similar to past estimates, approximately 40% of the MCVs generate secondary convection within their circulations.
The mean synoptic-scale MCV environment is determined by the use of a RUC-based composite analysis at four different stages in the MCV life cycle, defined based on vortex detection by the objective algorithm. MCV initiation is closely tied to the diurnal cycle of convection over the Great Plains, with MCVs typically forming in the early morning, near the time of maximum extent of nocturnal mesoscale convective systems (MCSs). Features related to the parent MCSs, including upper-level divergent outflow, midlevel convergence, and a low-level jet, are prominent in the initiating MCV composite. The most significant feature later in the MCV life cycle is a persistent mesoscale trough in the midlevel height field. The potential vorticity (PV) structure of the composite MCV consists of a midlevel maximum and an upper-level minimum, with some extension of elevated PV into the lower troposphere as the vortex matures. The environment immediately downshear of the MCV is more conducive to secondary convection than the environment upshear of the MCV.
This midlatitude MCV climatology represents an extension of past individual case studies by providing mean characteristics of a large MCV population; these statistics are suitable for the verification of MCV simulations. Also presented is the first high-resolution composite analysis of the MCV environment at different stages of the MCV life cycle, which will aid in identifying and forecasting these systems.
Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis
Authors: Simon K. Claire , Munger Kassandra L , Xing Yang  , Ascherio Alberto 
Published: December 2009

The extent to which potential genetic determinants of vitamin D levels may be related to multiple sclerosis (MS) risk has not been thoroughly explored. The objective of this study was to determine whether polymorphisms in VDR, CYP27B1, CYP24A1, CYP2R1 and DBP are associated with the risk of MS and whether these variants may modify associations between environmental or dietary vitamin D on MS risk. A nested case-control study was conducted in two, large cohorts of US nurses, including 214 MS cases and 428 age-matched controls. Conditional logistic regression models were used to calculate relative risks (RR) and 95% confidence intervals (CIs) and to assess the significance of gene—environment interactions. No associations were observed for any of the single-nucleotide polymorphisms (SNPs) in VDR, CYP27B1, CYP24A1, CYP2R1 or DBP (p > 0.05 for all). The authors did observe an interaction (p = 0.04) between dietary intake of vitamin D and the vitamin D receptor FokI polymorphism on MS risk. The protective effect of increasing vitamin D was evident only in individuals with the ‘ff ’ genotype (RR = 0.2, 95% CI: 0.06, 0.78; p = 0.02 for 400 IU/day increase). It was concluded that this does not support a role for the selected SNPs involved in vitamin D metabolism in the etiology of MS. The finding of a marginally significant gene—environment interaction requires replication in larger datasets, but suggests future genetic studies may benefit from considering relevant environmental context.
Redesigning a large-scale clinical trial in response to negative external trial results: the CAMUS study of Phytotherapy for Benign Prostatic Hyperplasia
Authors: Lee Jeannette , Andriole Gerald , Avins Andrew , Crawford E David , Foster Harris , Kaplan Steven , Kreder Karl , Kusek John , McCullough Andrew , McVary Kevin , Meleth Sreelatha , Naslund Michael , Nickel J Curtis , Nyberg Leroy , Roehrborn Claus , Dale Williams O. , Barry Michael 
Published: December 2009

Background Benign prostatic hyperplasia (BPH), a common condition among older men, confers its morbidity through potentially bothersome lower urinary tract symptoms. Treatments for BPH include drugs such as alpha-adrenergic receptor blockers and 5-alpha reductase inhibitors, minimally invasive therapies that use heat to damage or destroy prostate tissue, and surgery including transurethral resection of the prostate. Complementary and alternative medicines are gaining popularity in the US. Two phytotherapies commonly used for BPH are extracts of the fruit of Serenoa repens, the Saw palmetto dwarf palm that grows in the Southeastern US, and extracts of the bark of Pygeum africanum, the African plum tree. Purpose The objective of the Complementary and Alternative Medicines for Urological Symptoms (CAMUS) clinical trial is to determine if phytotherapy is superior to placebo in the treatment of BPH. Methods CAMUS was originally designed as a 3300-participant, four-arm trial of S. repens, P. africanum, an alpha-adrenergic blocking drug, and placebo with time to clinical progression of BPH, a measure of long-term efficacy, as the primary endpoint. Before enrollment started, a randomized, double-blind, placebo-controlled, single institution clinical trial showed that S. repens at the usual dose did not demonstrate any benefit over placebo with respect to symptom relief at 1 year. Consequently, the focus of CAMUS shifted from evaluating long-term efficacy to determining if any short-term (6—18 months) symptom relief could be achieved with increasing doses of S. repens, the phytotherapy most commonly used in the US for BPH. Results Results are anticipated in 2011. Conclusions Trial design occurs in an environment of continually evolving information. In this case, emerging results from another trial suggested that a study of long-term efficacy was premature, and that an effective dose and preparation of S. repens had to be established before proceeding to a long-term clinical trial. Clinical Trials 2009; 6: 628—636. http://ctj.sagepub.com
Transient Epstein-Barr virus reactivation in CD3 monoclonal antibody-treated patients
Authors: Keymeulen Bart , Candon Sophie , Fafi-Kremer Samira , Ziegler Anette , Leruez-Ville Marianne , Mathieu Chantal , Vandemeulebroucke Evy , Walter Markus , Crenier Laurent , Thervet Eric , Legendre Christophe , Pierard Denis , Hale Geoff , Waldmann Herman , Bach Jean-François , Seigneurin Jean Marie , Pipeleers Daniel , Chatenoud Lucienne 
Published: December 2009

AbstractHere we report a unique situation in which an early and synchronized Epstein-Barr virus (EBV) reactivation was induced by a 6-day course of treatment with a humanized CD3-specific monoclonal antibody in patients with recent onset of type 1 diabetes. The virologic and immunologic analysis demonstrated that this reactivation was transient, self-limited, and isolated, associated with the rapid advent of an EBV-specific T-cell response. The anti-CD3 antibody administration induced short-lasting immunosuppression and minor yet clear-cut signs of T-cell activation that preceded viral reactivation. Early posttransplant monitoring of renal and islet allograft recipients showed that no comparable phenomenon was observed after the administration of full-dose immunosuppressive therapy. This EBV reactivation remains of no apparent clinical concern over the long term and should not preclude further development of therapeutic anti-CD3 antibodies. This phenomenon may also direct new research avenues to understand the still ill-defined nature of stimuli triggering EBV reactivation in vivo.
EF-hand domains of MCFD2 mediate interactions with both LMAN1 and coagulation factor V or VIII
Authors: Zheng Chunlei , Liu Hui-hui , Zhou Jiahai , Zhang Bin 
Published: December 2009

AbstractCombined deficiency of factor V and factor VIII (F5F8D) is a bleeding disorder caused by mutations in either LMAN1 or MCFD2. LMAN1 (ERGIC-53) and MCFD2 form a Ca2+-dependent cargo receptor that cycles between the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment for efficient transport of FV/FVIII from the ER to the Golgi. Here we show that the C-terminal EF-hand domains are both necessary and sufficient for MCFD2 to interact with LMAN1. MCFD2 with a deletion of the entire N-terminal non-EF hand region still retains the LMAN1-binding function. Deletions that disrupt core structure of the EF-hand domains abolish LMAN1 binding. Circular dichroism spectroscopy studies on missense mutations localized to different structural elements of the EF-hand domains suggest that Ca2+-induced folding is important for LMAN1 interaction. The EF-hand domains also mediate the interaction with FV and FVIII. However, mutations in MCFD2 that disrupt the tertiary structure and abolish LMAN1 binding still retain the FV/FVIII binding activities, suggesting that this interaction is independent of Ca2+-induced folding of the protein. Our results suggest that the EF-hand domains of MCFD2 contain separate binding sites for LMAN1 and FV/FVIII that are essential for cargo receptor formation and cargo loading in the ER.
The P2X7-nonmuscle myosin membrane complex regulates phagocytosis of nonopsonized particles and bacteria by a pathway attenuated by extracellular ATP
Authors: Gu Ben J. , Saunders Bernadette M. , Jursik Claudia , Wiley James S. 
Published: December 2009

AbstractPhagocytosis of nonopsonized bacteria is central to innate immunity, but its regulation is less defined. We show that overexpression of the P2X7 receptor greatly augments the phagocytosis of nonopsonized beads and heat-killed bacteria by transfected HEK-293 cells, whereas blocking P2X7 expression by siRNA significantly reduces the phagocytic ability of human monocytic cells. An intact P2X7-nonmuscle myosin complex is required for phagocytosis of nonopsonized beads because activation of P2X7 receptors by adenosine triphosphate (ATP), which dissociates myosin IIA from the P2X7 complex, inhibits this phagocytic pathway. Fresh human monocytes rapidly phagocytosed live and heat-killed Staphylococcus aureus and Escherichia coli in the absence of serum, but the uptake was reduced by prior incubation with ATP, or P2X7 monoclonal antibody, or recombinant P2X7 extracellular domain. Injection of beads or bacteria into the peritoneal cavity of mice resulted in their brisk phagocytosis by macrophages, but injection of ATP before particles markedly decreased this uptake. These data demonstrate a novel pathway of phagocytosis of nonopsonized particles and bacteria, which operate in vivo and require an intact P2X7-nonmuscle myosin IIA membrane complex. The inhibitory effect of ATP on particle uptake by the macrophage is regulated by the P2X7 receptor and defines this phagocytic pathway.
The emerging role of cardiovascular risk factor-induced mitochondrial dysfunction in atherogenesis
Authors: Puddu Paolo , Puddu Giovanni M , Cravero Eleonora , De Pascalis Susanna , Muscari Antonio 
Published: December 2009

Abstract
An important role in atherogenesis is played by oxidative stress, which may be induced by common risk factors. Mitochondria are both sources and targets of reactive oxygen species, and there is growing evidence that mitochondrial dysfunction may be a relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Mitochondrial DNA is probably the most sensitive cellular target of reactive oxygen species. Damage to mitochondrial DNA correlates with the extent of atherosclerosis. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. Oxidized low density lipoprotein and hyperglycemia may induce the production of reactive oxygen species in mitochondria of macrophages and endothelial cells. Conversely, reactive oxygen species may favor the development of type 2 diabetes mellitus, mainly through the induction of insulin resistance. Similarly - in addition to being a cause of endothelial dysfunction, reactive oxygen species and subsequent mitochondrial dysfunction - hypertension may develop in the presence of mitochondrial DNA mutations. Finally, other risk factors, such as aging, hyperhomocysteinemia and cigarette smoking, are also associated with mitochondrial damage and an increased production of free radicals. So far clinical studies have been unable to demonstrate that antioxidants have any effect on human atherogenesis. Mitochondrial targeted antioxidants might provide more significant results.
An improved empirical bayes approach to estimating differential gene expression in microarray time-course data: BETR (Bayesian Estimation of Temporal Regulation)
Authors: Aryee Martin J , Gutiérrez-Pabello José A , Kramnik Igor , Maiti Tapabrata , Quackenbush John 
Published: December 2009

AbstractBackgroundMicroarray gene expression time-course experiments provide the opportunity to observe the evolution of transcriptional programs that cells use to respond to internal and external stimuli. Most commonly used methods for identifying differentially expressed genes treat each time point as independent and ignore important correlations, including those within samples and between sampling times. Therefore they do not make full use of the information intrinsic to the data, leading to a loss of power.ResultsWe present a flexible random-effects model that takes such correlations into account, improving our ability to detect genes that have sustained differential expression over more than one time point. By modeling the joint distribution of the samples that have been profiled across all time points, we gain sensitivity compared to a marginal analysis that examines each time point in isolation. We assign each gene a probability of differential expression using an empirical Bayes approach that reduces the effective number of parameters to be estimated.ConclusionsBased on results from theory, simulated data, and application to the genomic data presented here, we show that BETR has increased power to detect subtle differential expression in time-series data. The open-source R packagebetris available through Bioconductor. BETR has also been incorporated in the freely-available, open-source MeV software tool available fromhttp://www.tm4.org/mev.html.
Disruption of occludin function in polarized epithelial cells activates the extrinsic pathway of apoptosis leading to cell extrusion without loss of transepithelial resistance
Authors: Beeman Neal E , Baumgartner Heidi K , Webb Patricia G , Schaack Jerome B , Neville Margaret C 
Published: December 2009

AbstractBackgroundOccludin is a tetraspanin protein normally localized to tight junctions. The protein interacts with a variety of pathogens including viruses and bacteria, an interaction that sometimes leads to its extrajunctional localization.ResultsHere we report that treatment of mammary epithelial monolayers with a circularized peptide containing a four amino acid sequence found in the second extracellular loop of occludin, LHYH, leads to the appearance of extrajunctional occludin and activation of the extrinsic apoptotic pathway. At early times after peptide treatment endogenous occludin and the LYHY peptide were co-localized in extrajunctional patches, which were also shown to contain components of the death inducing signaling complex (DISC), caspases 8 and 3, the death receptor FAS and the adaptor molecule FADD. After this treatment occludin could be immunoprecipitated with FADD, confirming its interaction with the DISC. Extrusion after LYHY treatment was accomplished with no loss of epithelial resistance.ConclusionThese observations provide strong evidence that, following disruption, occludin forms a complex with the extrinsic death receptor leading to extrusion of apoptotic cells from the epithelial monolayer. They suggest that occludin has a protective as well as a barrier forming role in epithelia; pathogenic agents which utilize this protein as an entry point into the cell might set off an apoptotic reaction allowing extrusion of the infected cell before the pathogen can gain entry to the interstitial space.
An experimental assessment of in silico haplotype association mapping in laboratory mice
Authors: Burgess-Herbert Sarah L , Tsaih Shirng-Wern , Stylianou Ioannis M , Walsh Kenneth , Cox Allison J , Paigen Beverly 
Published: December 2009

Abstract

Background
To assess the utility of haplotype association mapping (HAM) as a quantitative trait locus (QTL) discovery tool, we conducted HAM analyses for red blood cell count (RBC) and high density lipoprotein cholesterol (HDL) in mice. We then experimentally tested each HAM QTL using published crosses or new F2 intercrosses guided by the haplotype at the HAM peaks.

Results
The HAM for RBC, using 33 classic inbred lines, revealed 8 QTLs; 2 of these were true positives as shown by published crosses. A HAM-guided (C57BL/6J × CBA/J)F2 intercross we carried out verified 2 more as true positives and 4 as false positives. The HAM for HDL, using 81 strains including recombinant inbred lines and chromosome substitution strains, detected 46 QTLs. Of these, 36 were true positives as shown by published crosses. A HAM-guided (C57BL/6J × A/J)F2 intercross that we carried out verified 2 more as true positives and 8 as false positives. By testing each HAM QTL for RBC and HDL, we demonstrated that 78% of the 54 HAM peaks were true positives and 22% were false positives. Interestingly, all false positives were in significant allelic association with one or more real QTL.

Conclusion
Because type I errors (false positives) can be detected experimentally, we conclude that HAM is useful for QTL detection and narrowing. We advocate the powerful and economical combined approach demonstrated here: the use of HAM for QTL discovery, followed by mitigation of the false positive problem by testing the HAM-predicted QTLs with small HAM-guided experimental crosses.
Identifying sexual differentiation genes that affect Drosophila life span
Authors: Shen Jie , Ford Daniel , Landis Gary N , Tower John 
Published: December 2009

Abstract

Background
Sexual differentiation often has significant effects on life span and aging phenotypes. For example, males and females of several species have different life spans, and genetic and environmental manipulations that affect life span often have different magnitude of effect in males versus females. Moreover, the presence of a differentiated germ-line has been shown to affect life span in several species, including Drosophila and C. elegans.

Methods
Experiments were conducted to determine how alterations in sexual differentiation gene activity might affect the life span of Drosophila melanogaster. Drosophila females heterozygous for the tudor[1] mutation produce normal offspring, while their homozygous sisters produce offspring that lack a germ line. To identify additional sexual differentiation genes that might affect life span, the conditional transgenic system Geneswitch was employed, whereby feeding adult flies or developing larvae the drug RU486 causes the over-expression of selected UAS-transgenes.

Results
In this study germ-line ablation caused by the maternal tudor[1] mutation was examined in a long-lived genetic background, and was found to increase life span in males but not in females, consistent with previous reports. Fitting the data to a Gompertz-Makeham model indicated that the maternal tudor[1] mutation increases the life span of male progeny by decreasing age-independent mortality. The Geneswitch system was used to screen through several UAS-type and EP-type P element mutations in genes that regulate sexual differentiation, to determine if additional sex-specific effects on life span would be obtained. Conditional over-expression of transformer female isoform (traF) during development produced male adults with inhibited sexual differentiation, however this caused no significant change in life span. Over-expression of doublesex female isoform (dsxF) during development was lethal to males, and produced a limited number of female escapers, whereas over-expression of dsxF specifically in adults greatly reduced both male and female life span. Similarly, over-expression of fruitless male isoform A (fru-MA) during development was lethal to both males and females, whereas over-expression of fru-MA in adults greatly reduced both male and female life span.

Conclusion
Manipulation of sexual differentiation gene expression specifically in the adult, after morphological sexual differentiation is complete, was still able to affect life span. In addition, by manipulating gene expression during development, it was possible to significantly alter morphological sexual differentiation without a significant effect on adult life span. The data demonstrate that manipulation of sexual differentiation pathway genes either during development or in adults can affect adult life span.