bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermocline Circulation in the Solomon Sea: A Modeling Study*
Authors: Melet Angélique , Gourdeau Lionel , Kessler William S. , Verron Jacques , Molines Jean-Marc 
Published: January 2010

Abstract
In the southwest Pacific, thermocline waters connecting the tropics to the equator via western boundary currents (WBCs) transit through the Solomon Sea. Despite its importance in feeding the Equatorial Undercurrent (EUC) and its related potential influence on the low-frequency modulation of ENSO, the circulation inside the Solomon Sea is poorly documented. A model has been implemented to analyze the mean and the seasonal variability of the Solomon Sea thermocline circulation. The circulation involves an inflow from the open southern Solomon Sea, which is distributed via WBCs between the three north exiting straits of the semiclosed Solomon Sea. The system of WBCs is found to be complex. Its main feature, the New Guinea Coastal Undercurrent, splits in two branches: one flowing through Vitiaz Strait and the other one, the New Britain Coastal Undercurrent (NBCU), exiting at Solomon Strait. East of the Solomon Sea, the encounter of the South Equatorial Current (SEC) with the Solomon Islands forms a previously unknown current, which the authors call the Solomon Islands Coastal Undercurrent (SICU). The NBCU, SEC, and SICU participate in the feeding of the New Ireland Coastal Undercurrent (NICU), which retroflects to the Equatorial Undercurrent, providing the most direct western boundary EUC connection, which is particularly active in June–August. The Solomon Sea WBC seasonal variability results from the combination of equatorial dynamics, remotely forced Rossby waves north of 10°S, and the spinup and spindown of the subtropical gyre as a response of Rossby waves forced south of 10°S.
The Evaluation of CloudSat and CALIPSO Ice Microphysical Products Using Ground-Based Cloud Radar and Lidar Observations
Authors: Protat A. , Delanoë J. , O’Connor E. J. , L’Ecuyer T. S. 
Published: January 2010

Abstract
In this paper, the statistical properties of tropical ice clouds (ice water content, visible extinction, effective radius, and total number concentration) derived from 3 yr of ground-based radar–lidar retrievals from the U.S. Department of Energy Atmospheric Radiation Measurement Climate Research Facility in Darwin, Australia, are compared with the same properties derived using the official CloudSat microphysical retrieval methods and from a simpler statistical method using radar reflectivity and air temperature. It is shown that the two official CloudSat microphysical products (2B-CWC-RO and 2B-CWC-RVOD) are statistically virtually identical. The comparison with the ground-based radar–lidar retrievals shows that all satellite methods produce ice water contents and extinctions in a much narrower range than the ground-based method and overestimate the mean vertical profiles of microphysical parameters below 10-km height by over a factor of 2. Better agreements are obtained above 10-km height. Ways to improve these estimates are suggested in this study. Effective radii retrievals from the standard CloudSat algorithms are characterized by a large positive bias of 8–12 μm. A sensitivity test shows that in response to such a bias the cloud longwave forcing is increased from 44.6 to 46.9 W m−2 (implying an error of about 5%), whereas the negative cloud shortwave forcing is increased from −81.6 to −82.8 W m−2. Further analysis reveals that these modest effects (although not insignificant) can be much larger for optically thick clouds. The statistical method using CloudSat reflectivities and air temperature was found to produce inaccurate mean vertical profiles and probability distribution functions of effective radius. This study also shows that the retrieval of the total number concentration needs to be improved in the official CloudSat microphysical methods prior to a quantitative use for the characterization of tropical ice clouds. Finally, the statistical relationship used to produce ice water content from extinction and air temperature obtained by the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) satellite is evaluated for tropical ice clouds. It is suggested that the CALIPSO ice water content retrieval is robust for tropical ice clouds, but that the temperature dependence of the statistical relationship used should be slightly refined to better reproduce the radar–lidar retrievals.
Directed differentiation of hematopoietic precursors and functional osteoclasts from human ES and iPS cells
Authors: Grigoriadis Agamemnon E. , Kennedy Marion , Bozec Aline , Brunton Fiona , Stenbeck Gudrun , Park In-Hyun , Wagner Erwin F. , Keller Gordon M. 
Published: January 2010

AbstractThe directed differentiation of human pluripotent stem cells offers the unique opportunity to generate a broad spectrum of human cell types and tissues for transplantation, drug discovery, and studying disease mechanisms. Here, we report the stepwise generation of bone-resorbing osteoclasts from human embryonic and induced pluripotent stem cells. Generation of a primitive streak-like population in embryoid bodies, followed by specification to hematopoiesis and myelopoiesis by vascular endothelial growth factor and hematopoietic cytokines in serum-free media, yielded a precursor population enriched for cells expressing the monocyte-macrophage lineage markers CD14, CD18, CD11b, and CD115. When plated in monolayer culture in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL), these precursors formed large, multinucleated osteoclasts that expressed tartrate-resistant acid phosphatase and were capable of resorption. No tartrate-resistant acid phosphatase-positive multinucleated cells or resorption pits were observed in the absence of RANKL. Molecular analyses confirmed the expression of the osteoclast marker genes NFATc1, cathepsin K, and calcitonin receptor in a RANKL-dependent manner, and confocal microscopy demonstrated the coexpression of the αvβ3 integrin, cathepsin K and F-actin rings characteristic of active osteoclasts. Generating hematopoietic and osteoclast populations from human embryonic and induced pluripotent stem cells will be invaluable for understanding embryonic bone development and postnatal bone disease.
Genetic copy number variants in sib pairs both affected with schizophrenia
Authors: Lee Chia-Huei , Liu Chih-Min , Wen Chun-Chiang , Chang Shun-Min , Hwu Hai-Gwo 
Published: January 2010

Abstract

Background
Schizophrenia is a complex disorder with involvement of multiple genes.

Methods
In this study, genome-wide screening for DNA copy-number variations (CNVs) was conducted for ten pairs, a total of 20 cases, of affected siblings using oligonucleotide array-based CGH.

Results
We found negative symptoms were significantly more severe (p < 0.05) in the subgroup that harbored more genetic imbalance (n ≧ 13, n = number of CNV-disrupted genes) as compared with the subgroup with fewer CNVs (n ≦ 6), indicating that the degree of genetic imbalance may influence the severity of the negative symptoms of schizophrenia. Four central nervous system (CNS) related genes including CCAAT/enhancer binding protein, delta (CEBPD, 8q11.21), retinoid × receptor, alpha (RXRA, 9q34.2), LIM homeobox protein 5 (LHX5, 12q24.13) and serine/threonine kinase 11 (STK11, 19p13.3) are recurrently (incidence ≧ 16.7%) disrupted by CNVs. Two genes, PVR (poliovirus receptor) and BU678720, are concordantly deleted in one and two, respectively, pairs of co-affected siblings. However, we did not find a significant association of this BU678720 deletion and schizophrenia in a large case-control sample.

Conclusions
We conclude that the high genetic loading of CNVs may be the underlying cause of negative symptoms of schizophrenia, and the CNS-related genes revealed by this study warrant further investigation.
Molecular evolution of the three short PGRPs of the malaria vectors Anopheles gambiae and Anopheles arabiensisin East Africa
Authors: Mendes Cristina , Felix Rute , Sousa Ana-Margarida , Lamego Joana , Charlwood Derek , do Rosário Virgílio E , Pinto João , Silveira Henrique 
Published: January 2010

Abstract

Background
Immune responses to parasites, which start with pathogen recognition, play a decisive role in the control of the infection in mosquitoes. Peptidoglycan recognition proteins (PGRPs) are an important family of pattern recognition receptors that are involved in the activation of these immune reactions. Pathogen pressure can exert adaptive changes in host genes that are crucial components of the vector's defence. The aim of this study was to determine the molecular evolution of the three short PGRPs (PGRP-S1, PGRP-S2 and PGRP-S3) in the two main African malaria vectors - Anopheles gambiae and Anopheles arabiensis.

Results
Genetic diversity of An. gambiae and An. arabiensis PGRP-S1, PGRP-S2 and PGRP-S3 was investigated in samples collected from Mozambique and Tanzania. PGRP-S1 diversity was lower than for PGRP-S2 and PGRP-S3. PGRP-S1 was the only gene differentiated between the two species. All the comparisons made for PGRP-S1 showed significant P-values for Fst estimates and AMOVA confirming a clear separation between species. For PGRP-S2 and PGRP-S3 genes it was not possible to group populations either by species or by geographic region. Phylogenetic networks reinforced the results obtained by the AMOVA and Fst values. The ratio of nonsynonymous substitutions (Ka)/synonymous substitutions (Ks) for the duplicate pair PGRP-S2 and PGRP-S3 was very similar and lower than 1. The 3D model of the different proteins coded by these genes showed that amino acid substitutions were concentrated at the periphery of the protein rather than at the peptidoglycan recognition site.

Conclusions
PGRP-S1 is less diverse and showed higher divergence between An. gambiae and An. arabiensis regardless of geographic location. This probably relates to its location in the chromosome-X, while PGRP-S2 and PGRP-S3, located in chromosome-2L, showed signs of autosomal introgression. The two short PGRP genes located in the chromosome-2L were under purifying selection, which suggests functional constraints. Different types of selection acting on PGRP-S1 and PGRP-S2 and S3 might be related to their different function and catalytic activity.
Gene expression profiling in C57BL/6J and A/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background
Authors: de Jong Simone , Fuller Tova F , Janson Esther , Strengman Eric , Horvath Steve , Kas Martien JH , Ophoff Roel A 
Published: January 2010

AbstractBackgroundWe performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL/6J and A/J. The selected brain areas are implicated in neurobehavioral traits while these mouse strains are known to differ widely in behavior. Consequently, we hypothesized that comparing gene expression profiles for specific brain regions in these strains might provide insight into the molecular mechanisms of human neuropsychiatric traits. We performed a whole-genome gene expression experiment and applied a systems biology approach using weighted gene co-expression network analysis.ResultsWe were able to identify modules of co-expressed genes that distinguish a strain or brain region. Analysis of the networks that are most informative for hippocampus and amygdala revealed enrichment in neurologically, genetically and psychologically related pathways. Close examination of the strain-specific gene expression profiles, however, revealed no functional relevance but a significant enrichment of single nucleotide polymorphisms in the probe sequences used for array hybridization. This artifact was not observed for the modules of co-expressed genes that distinguish amygdala and hippocampus.ConclusionsThe brain-region specific modules were found to be independent of genetic background and are therefore likely to represent biologically relevant molecular networks that can be studied to complement our knowledge about pathways in neuropsychiatric disease.
Transcriptomic profiling of bovine IVF embryos revealed candidate genes and pathways involved in early embryonic development
Authors: Huang Wen , Yandell Brian S , Khatib Hasan 
Published: January 2010

AbstractBackgroundEarly embryonic loss is a large contributor to infertility in cattle. Although genetic factors are known to affect early embryonic development, the discovery of such factors has been a serious challenge. The objective of this study was to identify genes differentially expressed between blastocysts and degenerative embryos at early stages of development.ResultsUsing microarrays, genome-wide RNA expression was profiled and compared for in vitro fertilization (IVF) - derived blastocysts and embryos undergoing degenerative development up to the same time point. Surprisingly similar transcriptomic profiles were found in degenerative embryos and blastocysts. Nonetheless, we identified 67 transcripts that significantly differed between these two groups of embryos at a 15% false discovery rate, including 33 transcripts showing at least a two-fold difference. Several signaling and metabolic pathways were found to be associated with the developmental status of embryos, among which were previously known important steroid biosynthesis and cell communication pathways in early embryonic development.ConclusionsThis study presents the first direct and comprehensive comparison of transcriptomes between IVF blastocysts and degenerative embryos, providing important information for potential genes and pathways associated with early embryonic development.
Genetic analysis of the Staphylococcus epidermidis Macromolecular Synthesis Operon: Serp1129 is an ATP binding protein and sigA transcription is regulated by both σA- and σB-dependent promoters
Authors: Bryant Kendall A , Kinkead Lauren C , Larson Marilynn A , Hinrichs Steven H , Fey Paul D 
Published: January 2010

Abstract

Background
The highly conserved macromolecular synthesis operon (MMSO) contains both dnaG (primase) and sigA (primary sigma factor). However, in previously evaluated gram-positive species, the MMSO is divergent upstream of dnaG. The MMSO of Bacillus subtilis contains three open reading frames (ORFs) that are differentially regulated by multiple promoters. In conjunction with studies to determine the expression profile of dnaG, the MMSO of Staphylococus epidermidis was characterized.

Results
The ORFs of S. epidermidis were compared to the previously described MMSO of B. subtilis and two additional ORFs in S. epidermidis, serp1129 and serp1130, were identified. The largest transcript, 4.8 kb in length, was expressed only in exponential growth and encompassed all four ORFs (serp1130, serp1129, dnaG, and sigA). A separate transcript (1.5 kb) comprising serp1130 and serp1129 was expressed in early exponential growth. Two smaller transcripts 1.3 and 1.2 kb in size were detected with a sigA probe in both exponential and post-exponential phases of growth. Western blot analysis correlated with the transcriptional profile and demonstrated that Serp1129 was detected only in the exponential phase of growth. Computational analysis identified that Serp1130 contained a CBS motif whereas Serp1129 contained an ATP/GTP binding motif. Functional studies of Serp1129 demonstrated that it was capable of binding both ATP and GTP. Comparisons with a sigB:dhfr mutant revealed that the 1.3 kb sigA transcript was regulated by a σB-dependent promoter.

Conclusions
These studies demonstrated that the S. epidermidis 1457 MMSO contains two ORFs (serp1129 and serp1130) not described within the B. subtilis MMSO and at least three promoters, one of which is σβ-dependent. The transcriptional regulation of sigA by σB provides evidence that the staphylococcal σB-dependent response is controlled at both the transcriptional and post-transcriptional level. The conservation of serp1129 across multiple gram-positive organisms and its capability to bind ATP and GTP support the need for further investigation of its role in bacterial growth.
XIAP is not required for human tumor cell survival in the absence of an exogenous death signal
Authors: Sensintaffar John , Scott Fiona L , Peach Robert , Hager Jeffrey H 
Published: January 2010

AbstractBackgroundThe X-linked Inhibitor of Apoptosis (XIAP) has attracted much attention as a cancer drug target. It is the only member of the IAP family that can directly inhibit caspase activityin vitro, and it can regulate apoptosis and other biological processes through its C-terminal E3 ubiquitin ligase RING domain. However, there is controversy regarding XIAP's role in regulating tumor cell proliferation and survival under normal growth conditionsin vitro.MethodsWe utilized siRNA to systematically knock down XIAP in ten human tumor cell lines and then monitored both XIAP protein levels and cell viability over time. To examine the role of XIAP in the intrinsic versus extrinsic cell death pathways, we compared the viability of XIAP depleted cells treated either with a variety of mechanistically distinct, intrinsic pathway inducing agents, or the canonical inducer of the extrinsic pathway, TNF-related apoptosis-inducing ligand (TRAIL).ResultsXIAP knockdown had no effect on the viability of six cell lines, whereas the effect in the other four was modest and transient. XIAP knockdown only sensitized tumor cells to TRAIL and not the mitochondrial pathway inducing agents.ConclusionsThese data indicate that XIAP has a more central role in regulating death receptor mediated apoptosis than it does the intrinsic pathway mediated cell death.
Rac1 and Cdc42 are regulators of HRasV12-transformation and angiogenic factors in human fibroblasts
Authors: Appledorn Daniel M , Dao Kim-Hien T , O'Reilly Sandra , Maher Veronica M , McCormick J Justin 
Published: January 2010

AbstractBackgroundThe activities of Rac1 and Cdc42 are essential for HRas-induced transformation of rodent fibroblasts. What is more, expression of constitutively activated mutants of Rac1 and/or Cdc42 is sufficient for their malignant transformation. The role for these two Rho GTPases in HRas-mediated transformation of human fibroblasts has not been studied. Here we evaluated the contribution of Rac1 and Cdc42 to maintaining HRas-induced transformation of human fibroblasts, and determined the ability of constitutively activated mutants of Rac1 or Cdc42 to induce malignant transformation of a human fibroblast cell strain.MethodsUnder the control of a tetracycline regulatable promoter, dominant negative mutants of Rac1 and Cdc42 were expressed in a human HRas-transformed, tumor derived fibroblast cell line. These cells were used to determine the roles of Rac1 and/or Cdc42 proteins in maintaining HRas-induced transformed phenotypes. Similarly, constitutively active mutants were expressed in a non-transformed human fibroblast cell strain to evaluate their potential to induce malignant transformation. Affymetrix GeneChip arrays were used for transcriptome analyses, and observed expression differences were subsequently validated using protein assays.ResultsExpression of dominant negative Rac1 and/or Cdc42 significantly altered transformed phenotypes of HRas malignantly transformed human fibroblasts. In contrast, expression of constitutively active mutants of Rac1 or Cdc42 was not sufficient to induce malignant transformation. Microarray analysis revealed that the expression of 29 genes was dependent on Rac1 and Cdc42, many of which are known to play a role in cancer. The dependence of two such genes,uPAandVEGFwas further validated in both normoxic and hypoxic conditions.Conclusion(s)The results presented here indicate that expression of both Rac1 and Cdc42 is necessary for maintaining several transformed phenotypes in oncogenic HRas transformed human cells, including their ability to form tumors in athymic mice. Our data also indicate that expression of either activated Rac1 or Cdc42 alone is not sufficient for malignant transformation of human fibroblasts, although each is required for specific transformed phenotypes. Furthermore, our study elucidates that the expression of several highly significant cancer related genes require the activities of Rac1 and/or Cdc42 which may also play a critical role in cellular transformation.
Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues
Authors: Curtis Carol D , Thorngren Daniel L , Nardulli Ann M 
Published: January 2010

AbstractBackgroundDuring the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).MethodsImmunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue.ResultsWe found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue.ConclusionsOur studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.