bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain
Authors: Zou Gang-Ming , Luo Mei-Hua , Reed April , Kelley Mark R. , Yoder Mervin C. 
Published: October 2006

AbstractApe1 is a molecule with dual functions in DNA repair and redox regulation of transcription factors. In Ape1-deficient mice, embryos do not survive beyond embryonic day 9, indicating that this molecule is required for normal embryo development. Currently, direct evidence of the role of Ape1 in regulating hematopoiesis is lacking. We used the embryonic stem (ES) cell differentiation system and an siRNA approach to knockdown Ape1 gene expression to test the role of Ape1 in hematopoiesis. Hemangioblast development from ES cells was reduced 2- to 3-fold when Ape1 gene expression was knocked down by Ape1-specific siRNA, as was primitive and definitive hematopoiesis. Impaired hematopoiesis was not associated with increased apoptosis in siRNA-treated cells. To begin to explore the mechanism whereby Ape1 regulates hematopoiesis, we found that inhibition of the redox activity of Ape1 with E3330, a specific Ape1 redox inhibitor, but not Ape1 DNA repair activity, which was blocked using the small molecule methoxyamine, affected cytokine-mediated hemangioblast development in vitro. In summary, these data indicate Ape1 is required in normal embryonic hematopoiesis and that the redox function, but not the repair endonuclease activity, of Ape1 is critical in normal embryonic hematopoietic development.
The shape of human gene family phylogenies
Authors: Cotton James A , Page Roderic DM 
Published: October 2006

Abstract

Background
The shape of phylogenetic trees has been used to make inferences about the evolutionary process by comparing the shapes of actual phylogenies with those expected under simple models of the speciation process. Previous studies have focused on speciation events, but gene duplication is another lineage splitting event, analogous to speciation, and gene loss or deletion is analogous to extinction. Measures of the shape of gene family phylogenies can thus be used to investigate the processes of gene duplication and loss. We make the first systematic attempt to use tree shape to study gene duplication using human gene phylogenies.

Results
We find that gene duplication has produced gene family trees significantly less balanced than expected from a simple model of the process, and less balanced than species phylogenies: the opposite to what might be expected under the 2R hypothesis.

Conclusion
While other explanations are plausible, we suggest that the greater imbalance of gene family trees than species trees is due to the prevalence of tandem duplications over regional duplications during the evolution of the human genome.
Reduction in psychotic symptoms as a predictor of patient satisfaction with antipsychotic medication in schizophrenia: Data from a randomized double-blind trial
Authors: Gharabawi Georges M , Greenspan Andrew , Rupnow Marcia FT , Kosik-Gonzalez Colette , Bossie Cynthia A , Zhu Young , Kalali Amir H , Awad A George 
Published: October 2006

Abstract

Background
Patient satisfaction with antipsychotic treatment is important. Limited evidence suggests that satisfaction is associated with symptom improvement and compliance. Predictors of patient satisfaction with antipsychotic medication were examined in a study of patients with a recent exacerbation of schizophrenia.

Methods
Data are from a randomized, double-blind trial comparing risperidone (n = 152), quetiapine (n = 156), and placebo (n = 73). Medication Satisfaction Questionnaire (MSQ) was completed after 14 days of treatment and after 6 weeks at last study visit.

Results
Medication satisfaction at both time points was significantly associated in multiple regression analysis with improvement on 3 Positive and Negative Syndrome Scale (PANSS) factor scores (positive symptoms p < .01; uncontrolled hostility/excitement, p < .0005; anxiety/depression, p < .04) and treatment with risperidone (p < .03); at day 14, significant association was also found with older age (p = .01). At both time points, predictor variables explained over 30% of the variance in medication satisfaction. Change in Hamilton Depression Scale, prolactin levels, sex, and reported adverse events of extrapyramidal symptoms, sedation, and movement disorders were not significant predictors of satisfaction. Lower level of medication satisfaction at day 14 was associated with earlier discontinuation in the trial at week 6 end point. A focused principal components analysis of PANSS factors and MSQ suggested that medication satisfaction relates to 3 groups of factors in descending order of magnitude: lower levels of (a) uncontrolled hostility/excitement, (b) positive symptoms, and (c) negative symptoms, disorganized thoughts, and anxiety/depression.

Conclusion
Results give further support that treatment satisfaction is positively associated with symptom improvement, particularly psychotic symptoms, and suggest that satisfaction may also be related to compliance, as those who were more satisfied remained in the trial for a longer period of time.

Trial registration number
Trial registration number NCT00061802
Transcriptional response to alcohol exposure in Drosophila melanogaster
Authors: Morozova Tatiana V , Anholt Robert RH , Mackay Trudy FC 
Published: October 2006

Abstract
Background
Alcoholism presents widespread social and human health problems. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Genetic factors that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance.

Results
We assessed whole-genome transcriptional responses following alcohol exposure and demonstrate immediate down-regulation of genes affecting olfaction, rapid upregulation of biotransformation enzymes and, concomitant with development of tolerance, altered transcription of transcriptional regulators, proteases and metabolic enzymes, including biotransformation enzymes and enzymes associated with fatty acid biosynthesis. Functional tests of P-element disrupted alleles corresponding to genes with altered transcription implicated 75% of these in the response to alcohol, two-thirds of which have human orthologues.

Conclusion
Expression microarray analysis is an efficient method for identifying candidate genes affecting complex behavioral and physiological traits, including alcohol abuse. Drosophila provides a valuable genetic model for comparative genomic analysis, which can inform subsequent studies in human populations. Transcriptional analyses following alcohol exposure in Drosophila implicate biotransformation pathways, transcriptional regulators, proteolysis and enzymes that act as metabolic switches in the regulation of fatty acid metabolism as important targets for future studies of the physiological consequences of human alcohol abuse.
CD16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells
Authors: Ancuta Petronela , Wang Jianbin , Gabuzda Dana 
Published: October 2006

Abstract
The CD16+ subset of peripheral blood monocytes (Mo) is expanded dramatically during inflammatory conditions including sepsis, HIV-1 infection, and cancer. CD16+ express high levels of CX3CR1, which mediates arrest onto CX3CL1-expressing endothelial cells (EC) under flow conditions. In contrast, attachment of CD16− Mo onto cytokine-activated EC is independent of CX3CL1. Here, we investigate the ability of CD16+ and CD16− Mo to produce proinflammatory cytokines upon interaction with CX3CL1-expressing HUVEC. We demonstrate that CD16+ but not CD16− Mo produce high levels of IL-6, CCL2, and matrix metalloproteinase (MMP)-9 when cocultured with TNF/IFN-γ-activated HUVEC or nonactivated HUVEC expressing CX3CL1. Furthermore, supernatants from Mo cocultured with cytokine-activated HUVEC induce neuronal death in vitro. These results suggest that membrane-bound CX3CL1 stimulates production of IL-6, CCL2, and MMP-9 by CD16+ Mo, likely via engagement of CX3CR1. Thus, expansion of CD16+ Mo and their accumulation onto CX3CL1-expressing EC may result in recruitment of Mo and T cell subsets at sites of inflammation in response to CCL2, IL-6-induced cell activation and/or differentiation, and MMP-9-mediated vascular and tissue injury.
Intervention of MAdCAM-1 or fractalkine alleviates graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effects
Authors: Ueha Satoshi , Murai Masako , Yoneyama Hiroyuki , Kitabatake Masahiro , Imai Toshio , Shimaoka Takeshi , Yonehara Shin , Ishikawa Sho , Matsushima Kouji 
Published: October 2006

AbstractCoincidence of the beneficial graft-vs.-tumor (GVT) effects and the detrimental graft-vs.-host disease (GVHD) remains the major obstacle against the widespread use of allogeneic bone marrow transplantation (BMT) as tumor immunotherapy. We here demonstrate that intervention of MAdCAM-1 (mucosal vascular addressin cell adhesion molecule-1) or fractalkine/CX3CL1 after the expansion of allo-reactive donor CD8 T cells selectively inhibits the recruitment of effector donor CD8 T cells to the intestine and alleviates the graft-vs.-host reaction (GVHR) associated intestinal injury without impairing GVT effects. In a nonirradiated acute GVHD model, donor CD8 T cells up-regulate the expression of intestinal homing receptor α4β7 and chemokine receptors CXCR6 and CX3CR1, as they differentiate into effector cells and subsequently infiltrate into the intestine. Administration of anti-MAdCAM-1 antibody or anti-fractalkine antibody, even after the expansion of alloreactive donor CD8 T cells, selectively reduced the intestine-infiltrating donor CD8 T cells and the intestinal crypt cell apoptosis without affecting the induction of donor derived anti-host CTL or the infiltration of donor CD8 T cells in the hepatic tumor. Moreover, in a clinically relevant GVHD model with myeloablative conditioning, these antibodies significantly improved the survival and loss of weight without impairing the beneficial GVT effects. Thus, interruption of α4β7-MAdCAM-1 or CX3CR1-fractalkine interactions in the late phase of GVHD would be a novel therapeutic approach for the separation of GVT effects from GVHR-associated intestinal injury.
Mechanisms underlying TGF-β1-induced expression of VEGF and Flk-1 in mouse macrophages and their implications for angiogenesis
Authors: Jeon Seong-Hyun , Chae Byung-Chul , Kim Hyun-A , Seo Goo-Young , Seo Dong-Wan , Chun Gie-Taek , Kim Nam-Soo , Yie Se-Won , Byeon Woo-Hyeon , Eom Seok-Hyun , Ha Kwon-Soo , Kim Young-Myeong , Kim Pyeung-Hyeun 
Published: October 2006

AbstractTGF-β induces vascular endothelial growth factor (VEGF), a potent angiogenic factor, at the transcriptional and protein levels in mouse macrophages. VEGF secretion in response to TGF-β1 is enhanced by hypoxia and by overexpression of Smad3/4 and hypoxia-inducible factor-1α/β (HIF-1α/β). To examine the transcriptional regulation of VEGF by TGF-β1, we constructed mouse reporters driven by the VEGF promoter. Overexpression of HIF-1α/β or Smad3/4 caused a slight increase of VEGF promoter activity in the presence of TGF-β1, whereas cotransfection of HIF-1α/β and Smad3/4 had a marked effect. Smad2 was without effect on this promoter activity, whereas Smad7 markedly reduced it. Analysis of mutant promoters revealed that the one putative HIF-1 and two Smad-binding elements were critical for TGF-β1-induced VEGF promoter activity. The relevance of these elements was confirmed by chromatin immunoprecipitation assay. p300, which has histone acetyltransferase activity, augmented transcriptional activity in response to HIF-1α/β and Smad3/4, and E1A, an inhibitor of p300, inhibited it. TGF-β1 also increased the expression of fetal liver kinase-1 (Flk-1), a major VEGF receptor, and TGF-β1 and VEGF stimulated pro-matrix metalloproteinase 9 (MMP-9) and active-MMP-9 expression, respectively. The results from the present study indicate that TGF-β1 can activate mouse macrophages to express angiogenic mediators such as VEGF, MMP-9, and Flk-1.
Definition of the Molecular Basis for Estrogen Receptor-Related Receptor-α-Cofactor Interactions
Authors: Gaillard Stéphanie , Dwyer Mary A. , McDonnell Donald P. 
Published: October 2006

Abstract
Estrogen receptor-related receptor-α (ERRα) is an orphan nuclear receptor that does not appear to require a classical small molecule ligand to facilitate its interaction with coactivators and/or hormone response elements within target genes. Instead, the apo-receptor is capable of interacting in a constitutive manner with coactivators that stimulate transcription by acting as protein ligands. We have screened combinatorial phage libraries for peptides that selectively interact with ERRα to probe the architecture of the ERRα-coactivator pocket. In this manner, we have uncovered a fundamental difference in the mechanism by which this receptor interacts with peroxisome proliferator-activated receptor-γ coactivator-1α, as compared with members of the steroid receptor coactivator subfamily of coactivators. Our findings suggest that it may be possible to develop ERRα ligands that exhibit different pharmacological activities as a consequence of their ability to differentially regulate coactivator recruitment. In addition, these findings have implications beyond ERRα because they suggest that subtle alterations in the structure of the activation function-2 pocket within any nuclear receptor may enable differential recruitment of coactivators, an observation of notable pharmaceutical importance.
Diagnosis of α-1-Antitrypsin Deficiency: An Algorithm of Quantification, Genotyping, and Phenotyping
Authors: Snyder Melissa R , Katzmann Jerry A , Butz Malinda L , Yang Ping , Dawson D Brian , Halling Kevin C , Highsmith W Edward , Thibodeau Stephen N 
Published: October 2006

AbstractBackground: Laboratory testing in suspected α-1-antitrypsin (A1AT) deficiency involves analysis of A1AT concentrations and identification of specific alleles by genotyping or phenotyping. The purpose of this study was to define and evaluate a strategy that provides reliable laboratory evaluation of A1AT deficiency.Methods: Samples from 512 individuals referred for A1AT phenotype analysis were analyzed by quantification, phenotype, and genotype. A1AT concentrations were measured by nephelometry. Phenotype analysis was performed by isoelectric focusing electrophoresis. The genotype assay detected the S and Z deficiency alleles by a melting curve analysis.Results: Of the 512 samples analyzed, 2% of the phenotype and genotype results were discordant. Among these 10 discordant results, 7 were attributed to phenotyping errors. On the basis of these data we formulated an algorithm, according to which we analyzed samples by genotyping and quantification assays, with a reflex to phenotyping when the genotype and quantification results were not concordant. Retrospective analyses demonstrated that 4% of samples submitted for genotype and quantitative analysis were reflexed to phenotyping. Of the reflexed samples, phenotyping confirmed the genotype result in 85% of cases. In the remaining 15%, phenotyping provided further information, including identifying rare deficiency alleles and suggesting the presence of a null allele, and allowed for a more definitive interpretation of the genotype result.Conclusions: The combination of genotyping and quantification, with a reflex to phenotyping, is the optimal strategy for the laboratory evaluation of A1AT deficiency.
Analysis of the VENUS-3 PWR Pressure Vessel Surveillance Benchmark Using TRIPOLI-4.3 Monte Carlo Code
Authors: Lee YK 
Published: October 2006

Abstract
This paper presents the analysis of the VENUS-3 PWR Pressure Vessel Surveillance Dosimetry Benchmark using the three-dimensional (3D) continuous-energy Monte Carlo code TRIPOLI-4.3. VENUS-3 benchmark specifications are taken from the 2004 release of the International Database for Integral Shielding Experiments (SINBAD) of OECD/NEA. Pointwise nuclear data library for TRIPOLI-4.3 transport calculations were prepared from ENDF/B-VI.4. Detector cross sections for 27 Al(n,φ), 58 Ni(n,p), and 115 n(n,n′) from IRDF-2002, IRDF-90.v2, and ENDF/B-VI.4 have been investigated. Two 235 U fission spectra, continuous Watt spectrum and 581 group ENDF/B-VI.4 spectrum have been compared. To speed up the simulation and to predict the axial (50-cm) and azimuthal (0̊-90̊) variation of the reaction rates for core barrel measurement points, variance reduction techniques using cylindrical surface detector and cylindrical biasing meshes have been applied and demonstrated. C/E values at 160 different locations have been evaluated. Without taking into account the uncertainty of the nuclear data in transport calculation and the uncertainty of the 3D neutron source distribution, a 10 % C/E tolerance margin should be accepted.
NG2 and Olig2 Expression Provides Evidence for Phenotypic Deregulation of Cultured Central Nervous System and Peripheral Nervous System Neural Precursor Cells
Authors: Dromard Cecile , Bartolami Sylvain , Deleyrolle Loïc , Takebayashi Hirohide , Ripoll Chantal , Simonneau Lionel , Prome Sylvie , Puech Sylvie , Tran Van Ba Christophe , Duperray Christophe , Valmier Jean , Privat Alain , Hugnot Jean-Philippe 
Published: October 2006

Abstract
Neural stem cells cultured with fibroblast growth factor 2 (FGF2)/epidermal growth factor (EGF) generate clonal expansions called neurospheres (NS), which are widely used for therapy in animal models. However, their cellular composition is still poorly defined. Here, we report that NS derived from several embryonic and adult central nervous system (CNS) regions are composed mainly of remarkable cells coexpressing radial glia markers (BLBP, RC2, GLAST), oligodendrogenic/neurogenic factors (Mash1, Olig2, Nkx2.2), and markers that in vivo are typical of the oligodendrocyte lineage (NG2, A2B5, PDGFR-α). On NS differentiation, the latter remain mostly expressed in neurons, together with Olig2 and Mash1. Using cytometry, we show that in growing NS the small population of multipotential self-renewing NS-forming cells are A2B5+ and NG2+. Additionally, we demonstrate that these NS-forming cells in the embryonic spinal cord were initially NG2− and rapidly acquired NG2 in vitro. NG2 and Olig2 were found to be rapidly induced by cell culture conditions in spinal cord neural precursor cells. Olig2 expression was also induced in astrocytes and embryonic peripheral nervous system (PNS) cells in culture after EGF/FGF treatment. These data provide new evidence for profound phenotypic modifications in CNS and PNS neural precursor cells induced by culture conditions.
Biology of Stem Cells in Human Umbilical Cord Stroma: In Situ and In Vitro Surveys
Authors: Karahuseyinoglu Sercin , Cinar Ozgur , Kilic Emine , Kara Fadil , Akay Guvem Gumus , Demiralp Duygu Özel , Tukun Ajlan , Uckan Duygu , Can Alp 
Published: October 2006

Abstract
Cells in the umbilical cord stroma have gained attention in recent years; however, differentiation to certain lineages in humans has been demonstrated in few studies. Unlike bone marrow MSCs, human umbilical cord stroma cells (HUCSCs) are far from being well characterized. This study attempts to describe proliferation, structural, and differentiation properties of these cells to account for their exceptional nature in many aspects. Cellular dynamics, cellular structure, and the degree of transformations during expansion and differentiation into mesenchymal and neuronal lineages were examined in vitro over a 10-month period. Comparisons with human bone marrow MSCs regarding differentiation were performed. HUCSCs in culture revealed two distinct cell populations, type 1 and type 2 cells, that possessed differential vimentin and cytokeratin filaments. Corresponding cells were encountered in cord sections displaying region-specific localization. α-Smooth muscle actin and desmin filaments, which were evident in cord sections, diminished through passages. No difference was noted regarding type 1 and type 2 cells in differentiation to chondrogenic, adipogenic, and osteogenic lineages, whereas a preferential differentiation was noted in neuronal lineage. Relative success was achieved by production of chondrocytic spheres and osteogenic monolayers, whereas adipocytes were immature compared with bone marrow MSCs. The presence of neuronal markers suggests that they transform into a certain state of maturity under neurogenic induction. Conclusively, HUCSCs retain their original phenotype in culture without spontaneous differentiation, have a limited lifespan, and bear multipotent stem cell characteristics. Given these characteristics, they may be generally considered progenitor cells if manipulated under appropriate conditions and deserve further study to be potentially used in cell-based therapies.
Derivation of Clinically Compliant MSCs from CD105+, CD24− Differentiated Human ESCs
Authors: Lian Qizhou , Lye Elias , Suan Yeo Keng , Khia Way Tan Eileen , Salto-Tellez Manuel , Liu Tong Ming , Palanisamy Nallasivam , El Oakley Reida Menshawe , Lee Eng Hin , Lim Bing , Lim Sai-Kiang 
Published: October 2006

Abstract
Adult tissue-derived mesenchymal stem cells (MSCs) have demonstrated therapeutic efficacy in treating diseases or repairing damaged tissues through mechanisms thought to be mediated by either cell replacement or secretion of paracrine factors. Characterized, self-renewing human ESCs could potentially be an invariable source of consistently uniform MSCs for therapeutic applications. Here we describe a clinically relevant and reproducible manner of generating identical batches of hESC-derived MSC (hESC-MSC) cultures that circumvents exposure to virus, mouse cells, or serum. Trypsinization and propagation of HuES9 or H1 hESCs in feeder- and serum-free selection media generated three polyclonal, karyotypically stable, and phenotypically MSC-like cultures that do not express pluripotency-associated markers but displayed MSC-like surface antigens and gene expression profile. They differentiate into adipocytes, osteocytes, and chondrocytes in vitro. Gene expression and fluorescence-activated cell sorter analysis identified CD105 and CD24 as highly expressed antigens on hESC-MSCs and hESCs, respectively. CD105+, CD24− monoclonal isolates have a typical MSC gene expression profiles and were identical to each other with a highly correlated gene expression profile (r2 &gt; .90). We have developed a protocol to reproducibly generate clinically compliant and identical hESC-MSC cultures.