bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Transfer Alters the DNA Methylation Status of Specific Genes in Fertilized and Parthenogenetically Activated Mouse Embryonic Stem Cells
Authors: Hikichi Takafusa , Kohda Takashi , Wakayama Sayaka , Ishino Fumitoshi , Wakayama Teruhiko 
Published: January 2008

Abstract
Recent cloning technology has been demonstrated successfully using nuclear transfer (NT) techniques to generate embryonic stem (ES) cells. Mice can be cloned from adult somatic cells or ES cells by NT, and such cloned embryos can be used to establish new NT-ES cell lines. However, ES cells derived from parthenogenetic embryos show epigenetic disorders and low potential for normal differentiation unless used to produce subsequent generations of NT-ES lines. Thus, enucleated oocytes can initialize epigenetic modification, but the extent and efficacy of this remain unclear. In this study, our goal was to clarify why the contribution rate of ES cells derived from parthenogenetic embryos (pES) cells appears to improve after NT. We compared gene expression profiles between pES and NT-pES cell lines using DNA microarray analysis and allele-specific DNA methylation analysis. Although changes in expression level were observed for 4% of 34,967 genes, only 81 (0.2%) showed common changes across multiple cell lines. In particular, the expression level of a paternally expressed gene, U2af1-rs1, was significantly increased in all NT-pES cell lines investigated. The methylation status at the upstream differentially methylated region of U2af1-rs1 was also changed significantly after NT. This was observed in NT-pES cells, but also in conventionally produced NT-ES cells, which has never been reported previously. These results suggest that NT affects the epigenetic status of a few gene regions in common and that a change in the methylation status of U2af1-rs1 could be used as a genetic marker to investigate the effects of NT.
Disclosure of potential conflicts of interest is found at the end of this article.
Fibroblast Growth Factor 4 and Its Novel Splice Isoform Have Opposing Effects on the Maintenance of Human Embryonic Stem Cell Self-Renewal
Authors: Mayshar Yoav , Rom Eran , Chumakov Irina , Kronman Achia , Yayon Avner , Benvenisty Nissim 
Published: January 2008

Abstract
Human embryonic stem cells (HESCs) are unique in their capacity to self-renew while remaining pluripotent. This undifferentiated state must be actively maintained by secreted factors. To identify autocrine factors that may support HESC growth, we have taken a global genetic approach. Microarray analysis identified fibroblast growth factor 4 (FGF4) as a prime candidate for autocrine signaling. Furthermore, the addition of recombinant FGF4 to HESCs supports their proliferation. We show that FGF4 is produced by multiple undifferentiated HESC lines, along with a novel fibroblast growth factor 4 splice isoform (FGF4si) that codes for the amino-terminal half of FGF4. Strikingly, although FGF4 supports the undifferentiated growth of HESCs, FGF4si effectively counters its effect. Furthermore, we show that FGF4si is an antagonist of FGF4, shutting down FGF4-induced Erk1/2 phosphorylation. Expression analysis shows that both isoforms are expressed in HESCs and early differentiated cells. However, whereas FGF4 ceases to be expressed in mature differentiated cells, FGF4si continues to be expressed after cell differentiation. Targeted knockdown of FGF4 using small interfering RNA increased differentiation of HESCs, demonstrating the importance of endogenous FGF4 signaling in maintaining their pluripotency. Taken together, these results suggest a growth-promoting role for FGF4 in HESCs and a putative feedback inhibition mechanism by a novel FGF4 splice isoform that may serve to promote differentiation at later stages of development.
Disclosure of potential conflicts of interest is found at the end of this article.
The Common −866G&gt;A Variant in the Promoter of UCP2 Is Associated With Decreased Risk of Coronary Artery Disease in Type 2 Diabetic Men
Authors: Cheurfa Nadir , Dubois-Laforgue Danièle , Ferrarezi Daniela A.F. , Reis André F. , Brenner Guilherme M. , Bouché Clara , Le Feuvre Claude , Fumeron Frédéric , Timsit José , Marre Michel , Velho Gilberto 
Published: January 2008

OBJECTIVE—Uncoupling protein 2 (UCP2) is a physiological downregulator of reactive oxygen species generation and plays an antiatherogenic role in the vascular wall. A common variant in the UCP2 promoter (−866G&gt;A) modulates mRNA expression, with increased expression associated with the A allele. We investigated association of this variant with coronary artery disease (CAD) in two cohorts of type 2 diabetic subjects.
RESEARCH DESIGN AND METHODS—We studied 3,122 subjects from the 6-year prospective Non–Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events, and Ramipril (DIABHYCAR) Study (14.9% of CAD incidence at follow-up). An independent, hospital-based cohort of 335 men, 52% of whom had CAD, was also studied.
RESULTS—We observed an inverse association of the A allele with incident cases of CAD in a dominant model (hazard risk 0.88 [95% CI 0.80–0.96]; P = 0.006). Similar results were observed for baseline cases of CAD. Stratification by sex confirmed an allelic association with CAD in men, whereas no association was observed in women. All CAD phenotypes considered—myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), and sudden death—contributed significantly to the association. Results were replicated in a cross-sectional study of an independent cohort (odds ratio 0.47 [95% CI 0.25–0.89]; P = 0.02 for a recessive model).
CONCLUSIONS—The A allele of the −866G&gt;A variant of UCP2 was associated with reduced risk of CAD in men with type 2 diabetes in a 6-year prospective study. Decreased risk of myocardial infarction, angina pectoris, CABG, and sudden death contributed individually and significantly to the reduction of CAD risk. This association was independent of other common CAD risk factors.
Adiponectin, Change in Adiponectin, and Progression to Diabetes in the Diabetes Prevention Program
Authors: Mather Kieren J. , Funahashi Tohru , Matsuzawa Yuji , Edelstein Sharon , Bray George A. , Kahn Steven E. , Crandall Jill , Marcovina Santica , Goldstein Barry , Goldberg Ronald ,   for the Diabetes Prevention Program
Published: January 2008

OBJECTIVE— To determine whether baseline adiponectin levels or intervention-associated change in adiponectin levels were independently associated with progression to diabetes in the Diabetes Prevention Program (DPP).
RESEARCH DESIGN AND METHODS— Cox proportional hazards analysis was used to evaluate the contribution of adiponectin and treatment-related change in adiponectin to risk of progression to diabetes.
RESULTS— Baseline adiponectin was a strong independent predictor of incident diabetes in all treatment groups (hazard ratio per ∼3 μg/ml higher level; 0.61 in the lifestyle, 0.76 in the metformin, and the 0.79 in placebo groups; all P &lt; 0.001, P = 0.13 comparing groups). Baseline differences in adiponectin between sexes and race/ethnicity groups were not reflected in differences in diabetes risk. DPP interventions increased adiponectin levels ([means ± SE] 0.83 ± 0.05 μg/ml in the lifestyle group, 0.23 ± 0.05 μg/ml in the metformin group, and 0.10 ± 0.05 μg/ml in the placebo group; P &lt; 0.001 for increases versus baseline, P &lt; 0.01 comparing groups). These increases were associated with reductions in diabetes incidence independent of baseline adiponectin levels in the lifestyle and placebo groups but not in the metformin subjects (hazard ratio 0.72 in the lifestyle group (P &lt; 0.001), 0.92 in the metformin group (P = 0.18), and 0.89 in the placebo group; P = 0.02 per ∼1 μg/ml increase, P = 0.02 comparing groups). In the lifestyle group, adjusting for change in weight reduced, but did not remove, the effect of increased adiponectin.
CONCLUSIONS— Adiponectin is a powerful marker of diabetes risk in subjects at high risk for diabetes, even after adjustment for weight. An increase in adiponectin in the lifestyle and placebo groups was associated with a reduction in diabetes risk. However, these changes in adiponectin were comparatively small and less strongly related to diabetes outcome than baseline adiponectin levels.
Highly Enantioselective Allylation of Aromatic α‐Keto Phosphonates Catalyzed by Chiral N,N′‐Dioxide‐Indium(III) Complexes
Authors: Huang Jinglun , Wang Jing , Chen Xiaohong , Wen Yuehong , Liu Xiaohua , Feng Xiaoming 
Published: January 2008

AbstractThe ramipril derivative N,N′‐dioxide 3g‐indium(III) complex was found to be an efficient catalyst for the allylation of the aromatic α‐keto phosphonates. The corresponding α‐hydroxy phosphonates were obtained with high yields (up to 98 %) and high enantioselectivities (up to 91 % ee). A bifunctional catalyst system was described with an N‐oxide as Lewis base activating tetraallyltin and indium as Lewis acid activating aromatic α‐keto phosphonates. A possible catalytic cycle has been proposed to explain the mechanism of the reaction.
A scoring system for the classification of β‐thalassemia/Hb E disease severity
Authors: Sripichai Orapan , Makarasara Wattanan , Munkongdee Thongperm , Kumkhaek Chutima , Nuchprayoon Issarang , Chuansumrit Ampaiwan , Chuncharunee Suporn , Chantrakoon Nawarat , Boonmongkol Piathip , Winichagoon Pranee , Fucharoen Suthat 
Published: January 2008

Abstractβ‐Thalassemia intermediate patients show a remarkable clinical heterogeneity. We examined the phenotypic diversity of 950 β‐thalassemia/Hb E patients in an attempt to construct a system for classifying disease severity. A novel scoring system based on six independent parameters, hemoglobin level, age at disease presentation, age at receiving first blood transfusion, requirement for transfusion, spleen size, and growth and development, was able to separate patients into three distinctive severity categories: mild, moderate, and severe courses. This system, therefore, can increase the accuracy of studies of genotype–phenotype interactions and facilitate decisions for appropriate patient management. Am. J. Hematol. 2008. © 2008 Wiley‐Liss, Inc.
Diabetes and overweight associate with non‐APOE4 genotype in an alzheimer's disease population
Authors: Profenno Louis A. , Faraone Stephen V. 
Published: January 2008

AbstractType 2 diabetes is a risk factor for late‐onset Alzheimer's disease (AD), and studies suggest that pathogenic effects of diabetes and insulin resistance may be associated with non‐APOE4 AD. Therefore, we examined association of the APOE4 allele with diabetes in an AD population. Retrospective and cross‐sectional clinical and APOE‐genotype data on 465 cases with probable or definite AD previously ascertained by the National Institute of Mental Health Genetics Initiative were analyzed by regression analysis. Dependent variables included presence of APOE4 alleles and AD onset age. Diabetes was the independent variable and covariates included gender, hypertension, and other potentially confounding variables. We also examined for interactions involving weight status as overweight and obesity are independent risk factors for insulin resistance, diabetes and AD. Prevalence of diabetes was 13% among AD cases without an APOE4 allele and 5–6% among AD cases with one or two APOE4 alleles. Odds ratio for diabetes was 0.26 [95% CI: 0.09–0.73; P = 0.011] by APOE4 status after adjusting for all covariates. Diabetes did not associate with AD onset age. Among other independent variables included in the model, APOE4 and diuretic medication treatment were associated with AD onset age. In a subset of cases with body mass index determinations, overweight also exhibited an inverse association with APOE4 and associated with decreased non‐APOE4 AD onset age. Pathogenic mechanisms associated with diabetes and overweight are enriched in AD cases without an APOE4 allele. © 2008 Wiley‐Liss, Inc.
Geographic access to cancer care in the U.S.
Authors: Onega Tracy , Duell Eric J. , Shi Xun , Wang Dongmei , Demidenko Eugene , Goodman David 
Published: January 2008

AbstractBACKGROUNDAlthough access to cancer care is known to influence patient outcomes, to the authors' knowledge, little is known regarding geographic access to cancer care, and how it may vary by population characteristics. This study estimated travel time to specialized cancer care settings for the continental U.S. population and calculated per capita oncologist supply.METHODSThe closest travel times were estimated using a network analysis of the road distance weighted by travel speeds from the population or geographic centroid of every ZIP area in the continental U.S. to that of the nearest cancer care setting under consideration: National Cancer Institute (NCI)‐designated Cancer Centers, academic medical centers, and oncologists. Alaska and Hawaii were excluded because travel in these states is often not road‐based. Population and geographic characteristics including race/ethnicity, income, education, and region were derived from U.S. Census 2000 data and from rural‐urban commuting area classifications. Oncologist supply per 100,000 residents in Hospital Referral Regions (pHRRs) was estimated by region.RESULTSTravel times of ≤1 hour were estimated for 45.2% of the population to the nearest NCI Cancer Center, 69.4% to the nearest academic‐based care, and 91.8% to any specialized cancer care. Native Americans, nonurban dwellers, and residents in the South had the longest travel times to the nearest NCI Cancer Center compared with the overall U.S. population (median [interquartile range (IQR)] in minutes: 155 [62–308], 173 [111–257], and 164 [70–272], vs 78 [27–172], respectively). Travel burdens persisted for Native Americans and nonurban populations across all 3 cancer care settings. For all population strata, travel times markedly increased as the degree of cancer care specialization increased. The median oncologist supply for pHRRs was 2.83 per 100,000 individuals.CONCLUSIONSThere are population groups with limited access to the most specialized cancer care settings. Cancer 2008. © 2008 American Cancer Society.
Dispersive Effects in Chemomechanical Reactions with Polyallylamine‐Derived Hydrogels
Authors: Kato Kazuaki , Schneider Hans‐Jörg 
Published: January 2008

AbstractVolume changes of polyallylamine‐derived hydrogels crosslinked with glutaraldehyde are determined with a large variety of effector compounds. Monocarboxylic effectors lead to smaller contractions, in contrast to dicarboxylate structures, which allow more effective non‐covalent crosslinking between the positively charged nitrogen centers of the polymer backbone. Electroneutral compounds lead to negligible changes, whereas effectors with either a large p‐moiety like in naphthoic acid or phenyl derivatives with polarizable substituents induce large contractions. This finding is in line with significant contributions of van der Waals interactions between the effectors within the hydrogel. Chemomechanical differences between regioisomeric effectors such as p‐ and o‐nitrobenzoic acid are in agreement with independent results of dispersive interactions in related complexes. The volume decrease corresponds almost entirely to the gravimetrically determined water content of the gels. The acidity profile shows a strong contraction above pH 10, which is consistent with the known pK value of such polyamines. NMR spectra of the gels indicate strong binding of the effectors by line broadening, which is significant only for the chemomechanically active compounds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
(Dimethoxy‐ and Dihalopyridyl)boronic Acids and Highly Functionalized Heteroarylpyridines by Suzuki Cross‐Coupling Reactions
Authors: Smith Amy E. , Clapham Kate M. , Batsanov Andrei S. , Bryce Martin R. , Tarbit Brian 
Published: January 2008

AbstractWe report the synthesis of (2,6‐dimethoxy‐3‐pyridyl)boronic acid (2), (2,3‐dimethoxy‐4‐pyridyl)boronic acid (4), (2,6‐difluoro‐3‐pyridyl)boronic acid (6), (2,6‐dichloro‐3‐pyridyl)boronic acid (8) and (2,3‐dichloro‐4‐pyridyl)boronic acid (10) by directed ortho‐metalation reactions on the corresponding disubstituted pyridine precursor, followed by the reaction with triisopropyl borate (TPB) or trimethyl borate. Thereactivity of the pyridylboronic acids with heteroaryl halides in Suzuki–Miyaura cross‐coupling reactions has been evaluated. New highly functionalized heteroarylpyridine derivatives have thereby been obtained in moderate to high yields. The reaction of 8 and 3‐amino‐2‐chloropyridine yielded the rare 5H‐pyrrolo[2,3‐b:4,5‐b′]dipyridine (i.e. 1,5‐diazacarbazole) ring system by sequential cross‐coupling and intramolecular cyclisation reactions. The X‐ray crystal structures are reported for the pyridylboronic acids 2, 4, 8 and 10. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
High‐resolution 2‐DE for resolving proteins, protein adducts and complexes in plasma
Authors: Candiano Giovanni , Santucci Laura , Petretto Andrea , Pavone Barbara , Del Boccio Piero , Musante Luca , Bruschi Maurizio , Federici Giorgio , Gusmano Rosanna , Urbani Andrea , Ghiggeri Gian M. 
Published: January 2008

AbstractA 2‐DE system has been devised in which proteins are first separated in their native state followed by separation according to mass under denaturing conditions (Nat/SDS‐PAGE). Hydrophilic properties of the gel and the presence of dihydroxybisacrylamide in the first dimension allowed a good resolution for high‐molecular‐weight proteins and maintained interactions. With this method 252 plasma spots have been resolved and 140 have been characterized by MS as isoforms of 60 proteins, a relevant part of which (12) were not detected by traditional 2‐D gels or by other nondenaturing 2‐D techniques. The list includes complement factors (C4d, C7), coagulation factors (coagulation factor II, fibrin β), apolipoproteins (apolipoprotein B) and cell debris (vinculin, gelsolin, tropomyosin, dystrobrevin β, fibrinectin I). Nat/SDS PAGE also allowed separation of nicked forms of albumin, Apo B100 and α2‐macroglobulin and showed the presence of atypical albumin adducts corresponding to post‐translational and oxidation products. Our system provides therefore new tools for resolving proteins, protein aggregates and complexes and amplifies the potentiality of traditional electrophoretic analysis.
Biofiltration of a methanol containing air stream in a dry tubular biofilm reactor using ceramic rings as carrier
Authors: Omil F. , Rojas H. , Thalasso F. , Lema J.M. 
Published: January 2008

AbstractA 13.4 L dry tubular biofilm reactor (DTB), with ceramics rings as carrier, was used to treat a polluted air stream using methanol as a model pollutant. The design of this reactor was based on the creation of a mist by contacting the waste gas and a liquid nutrient solution inside an atomizing nozzle. The liquid was supplied intermittently (16 s every 3 min) in order to minimize water addition (91% of reactor operational time corresponded to “dry” conditions). The reactor was operated at empty bed residence times (EBRT) of 42 s and volumetric loading rates of 1.5–3.0 kg/m3/d. Biofilm growth was observed first on the walls of the reactor, and subsequently growth developed on the surface of the rings. Methanol was completely removed from the gas phase at low loading rates and the removal efficiency was around 83–93% at a loading of 3.0 kg/m3/d. Organic carbon mass balances showed that, in the presence of the carrier, up to 73% methanol was biodegraded; nondegraded methanol and other metabolites constituted the remaining fraction in the liquid and gas effluent. © 2008 American Institute of Chemical Engineers Environ Prog, 2008
Modulation of several waves of gene expression during FGF‐1 induced epithelial‐mesenchymal transition of carcinoma cells
Authors: Billottet Clotilde , Tuefferd Marianne , Gentien David , Rapinat Audrey , Thiery Jean‐Paul , Broët Philippe , Jouanneau Jacqueline 
Published: January 2008

AbstractDuring epithelial‐mesenchymal transition (EMT), epithelial cells are converted into isolated motile and invasive mesenchymal cells. In model systems, EMT is induced most often by the activation of tyrosine kinase receptors through signaling pathways involving translational and post‐translational regulation. In this study, we have used the NBT‐II bladder carcinoma cell system to investigate in vitro Fibroblast Growth Factor‐1 (FGF‐1)‐induced EMT. Transcriptome analyses were performed on NBT‐II cells stimulated for 2, 6, 24, and 48 h with FGF‐1. As some phenotypic changes occurred around 6 h post‐stimulation, a supervised analysis was designed to identify transcript variations across defined time‐periods. Our results clearly indicate that immediately after FGF‐1 stimulation a set of genes assigned to transcriptional regulation (e.g., jun‐B and v‐ets) and to EMT induction (e.g., Notch 1) is transiently up‐regulated. A set of genes involved in proteolytic systems (e.g., MMP‐13 and uPAR) is immediately up‐regulated but subsequently maintained throughout FGF‐1 stimulation. Then follows a second wave of gene expression that includes a strong but transient up‐regulation of ephrin B1 and arginase I. Finally, a third group of genes is stably modulated over 48 h which consists primarily of down‐regulated genes specifically associated with the EMT‐based loss of the epithelial phenotype and maintenance of the mesenchymal and invasive phenotype of carcinoma cells. Using genome‐wide oligoarray technology, we have identified novel expressions of immediate, immediate‐early and later EMT biomarkers that are specifically activated downstream of the FGF/FGFR pathway and which might be significant prognostic factors for tumor progression of carcinoma. J. Cell. Biochem. 104: 826–839, 2008. © 2008 Wiley‐Liss, Inc.
MicroRNAs play a role in the development of human hematopoietic stem cells
Authors: Liao Rongxia , Sun Jianguo , Zhang Liang , Lou Guiyu , Chen Min , Zhou Dujin , Chen Zhengtang , Zhang Shaoxiang 
Published: January 2008

AbstractMicroRNAs (miRNAs) are a class of recently discovered noncoding RNA genes that post‐transcriptionally regulate gene expression. It is becoming clear that miRNAs play an important role in the regulation of gene translation during development. However, in mammals, expression data are principally based on whole tissue analysis and are still very incomplete. We isolated CD34+CD38− hematopoietic stem cells (HSCs) from human umbilical cord blood, on the basis of cell‐surface markers using fluorescence‐activated cell sorting (FACS). Also, CD34+ subpopulation was FACS isolated as the control. Next, using microarray containing oligonucleotides corresponding to 517 miRNAs from human, mouse, and rat genomes, we obtained miRNA gene expression profiles of both subpopulations. We focused on the HSCs correlative miRNAs with comparison to the control. The miRNAs of particular interest were confirmed by real‐time RT‐PCR. HSCs‐overexpressed hsa‐miR‐520h and underexpressed hsa‐miR‐129 were selected for target prediction and analysis. The result showed that EIF2C3 and CAMTA1, genes related to miRNAs processing or transcription regulation, were proved to be real targets for hsa‐miR‐129. And ABCG2, involved in stemness maintaining, a real target for hsa‐miR‐520h. Finally, we chose hsa‐miR‐520h, enriched in HSCs but low in CD34+ cells, for functional characterization, because of its possible role in differentiation of HSCs by regulating ABCG2. As a result, hsa‐miR‐520h transduction into CD34+ cells greatly increased number of different progenitor colonies in Colony‐Forming‐Cell assays, suggesting that hsa‐miR‐520h may promote differentiation of HSCs into progenitor cells by inhibiting ABCG2 expression. This study paves the way for identifying HSC‐specific miRNAs and their roles in HSC development. J. Cell. Biochem. 104: 805–817, 2008. © 2008 Wiley‐Liss, Inc.