bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Foxo1 Protects Pancreatic Islet β-Cells Against Fatty Acid and Endoplasmic Reticulum Stress–Induced Apoptosis
Authors: Martinez Sara C. , Tanabe Katsuya , Cras-Méneur Corentin , Abumrad Nada A. , Bernal-Mizrachi Ernesto , Permutt M. Alan 
Published: January 2008

OBJECTIVE—β-Cells are particularly susceptible to fatty acid–induced apoptosis associated with decreased insulin receptor/phosphatidylinositol-3 kinase/Akt signaling and the activation of stress kinases. We examined the mechanism of fatty acid–induced apoptosis of mouse β-cells especially as related to the role played by endoplasmic reticulum (ER) stress–induced Foxo1 activation and whether decreasing Foxo1 activity could enhance cell survival.RESEARCH DESIGN AND METHODS—Mouse insulinoma (MIN6) cells were administered with fatty acids, and the role of Foxo1 in mediating effects on signaling pathways and apoptosis was examined by measuring Foxo1 activity and using dominant-negative Foxo1.RESULTS—Increasing fatty acid concentrations (100–400 μmol/l palmitate or oleate) led to early Jun NH2-terminal kinase (JNK) activation that preceded induction of ER stress markers and apoptosis. Foxo1 activity was increased with fatty acid administration and by pharmacological inducers of ER stress, and this increase was prevented by JNK inhibition. Fatty acids induced nuclear localization of Foxo1 at 4 h when Akt activity was increased, indicating that FoxO1 activation was not mediated by JNK inhibition of Akt. In contrast, fatty acid administration for 24 h was associated with decreased insulin signaling. A dominant-negative Foxo1 adenovirus (Adv-DNFoxo) conferred cells with protection from ER stress and fatty acid–mediated apoptosis. Microarray analysis revealed that fatty acid induction of gene expression was in most cases reversed by Adv-DNFoxo, including the proapoptotic transcription factor CHOP (C/EBP [CCAAT/enhancer binding protein] homologous protein).CONCLUSIONS—Early induction of JNK and Foxo1 activation plays an important role in fatty acid–induced apoptosis. Expressing a dominant-negative allele of Foxo1 reduces expression of apoptotic and ER stress markers and promotes β-cell survival from fatty acid and ER stress, identifying a potential therapeutic target for preserving β-cells in type 2 diabetes.
mTOR Inhibition by Rapamycin Prevents β-Cell Adaptation to Hyperglycemia and Exacerbates the Metabolic State in Type 2 Diabetes
Authors: Fraenkel Merav , Ketzinel-Gilad Mali , Ariav Yafa , Pappo Orit , Karaca Melis , Castel Julien , Berthault Marie-France , Magnan Christophe , Cerasi Erol , Kaiser Nurit , Leibowitz Gil 
Published: January 2008

OBJECTIVE—Mammalian target of rapamycin (mTOR) and its downstream target S6 kinase 1 (S6K1) mediate nutrient-induced insulin resistance by downregulating insulin receptor substrate proteins with subsequent reduced Akt phosphorylation. Therefore, mTOR/S6K1 inhibition could become a therapeutic strategy in insulin-resistant states, including type 2 diabetes. We tested this hypothesis in the Psammomys obesus (P. obesus) model of nutrition-dependent type 2 diabetes, using the mTOR inhibitor rapamycin.
RESEARCH DESIGN AND METHODS—Normoglycemic and diabetic P. obesus were treated with 0.2 mg · kg−1 · day−1 i.p. rapamycin or vehicle, and the effects on insulin signaling in muscle, liver and islets, and on different metabolic parameters were analyzed.
RESULTS—Unexpectedly, rapamycin worsened hyperglycemia in diabetic P. obesus without affecting glycemia in normoglycemic controls. There was a 10-fold increase of serum insulin in diabetic P. obesus compared with controls; rapamycin completely abolished this increase. This was accompanied by weight loss and a robust increase of serum lipids and ketone bodies. Rapamycin decreased muscle insulin sensitivity paralleled by increased glycogen synthase kinase 3β activity. In diabetic animals, rapamycin reduced β-cell mass by 50% through increased apoptosis. Rapamycin increased the stress-responsive c-Jun NH2-terminal kinase pathway in muscle and islets, which could account for its effect on insulin resistance and β-cell apoptosis. Moreover, glucose-stimulated insulin secretion and biosynthesis were impaired in islets treated with rapamycin.
CONCLUSIONS—Rapamycin induces fulminant diabetes by increasing insulin resistance and reducing β-cell function and mass. These findings emphasize the essential role of mTOR/S6K1 in orchestrating β-cell adaptation to hyperglycemia in type 2 diabetes. It is likely that treatments based on mTOR inhibition will cause exacerbation of diabetes.
Omentin-1, a Novel Adipokine, Is Decreased in Overweight Insulin-Resistant Women With Polycystic Ovary Syndrome
Authors: Tan Bee K. , Adya Raghu , Farhatullah S. , Lewandowski Kris C. , O’Hare Paul , Lehnert Hendrik , Randeva Harpal S. 
Published: January 2008

OBJECTIVE—Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Recent studies have shown that plasma omentin-1 levels decrease with obesity. Currently, no data exist on the relative expression and regulation of omentin-1 in adipose tissue of women with PCOS. The objective of this study was to assess mRNA and protein levels of omentin-1, including circulating omentin-1, in omental adipose tissue of women with PCOS and matched control subjects. Ex vivo and in vivo regulation of adipose tissue omentin-1 was also studied.
RESEARCH DESIGN AND METHODS—Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of omentin-1. Plasma omentin-1 was measured by enzyme-linked immunosorbent assay. The effects of d-glucose, insulin, and gonadal and adrenal steroids on adipose tissue omentin-1 were analyzed ex vivo. The in vivo effects of insulin (hyperinsulinemia) on omentin-1 levels were also assessed by a prolonged insulin-glucose infusion.
RESULTS—In addition to decreased plasma omentin-1 levels in women with PCOS (P &lt; 0.05), compared with control subjects, there was significantly lower levels of omentin-1 mRNA (P &lt; 0.01) and protein (P &lt; 0.05) in omental adipose tissue of women with PCOS (P &lt; 0.01). Furthermore, in omental adipose tissue explants, insulin and glucose significantly dose-dependently decreased omentin-1 mRNA expression, protein levels, and secretion into conditioned media (P &lt; 0.05, P &lt; 0.01). Also, hyperinsulinemic induction in healthy subjects significantly reduced plasma omentin-1 levels (P &lt; 0.01).
CONCLUSIONS—Our novel findings reveal that omentin-1 is downregulated by insulin and glucose. These may, in part, explain the decreased omentin-1 levels observed in our overweight women with PCOS.
Modified Constraint-Induced Therapy in Chronic Stroke: Results of a Single-Blinded Randomized Controlled Trial
Authors: Page Stephen J , Levine Peter , Leonard Anthony , Szaflarski Jerzy P , Kissela Brett M 
Published: January 2008

Background and PurposeThis single-blinded randomized controlled trial compared the efficacy of a reimbursable, outpatient, modified constraint-induced therapy (mCIT) protocol (half-hour therapy sessions occurring 3 days per week in which subjects used the more affected arm combined with less affected arm restriction 5 days per week for 5 hours; both of these regimens were administered during a 10-week period) with that of a time-matched exercise program for the more affected arm or a no-treatment control regimen.SubjectsThirty-five subjects with chronic stroke participated in the study.MethodsThe Action Research Arm Test (ARAT), Fugl-Meyer Assessment of Motor Recovery After Stroke (FM), and Motor Activity Log (MAL) were administered to the subjects.ResultsAfter intervention, significant differences were observed on the ARAT and MAL Amount of Use and Quality of Movement scales, all in favor of the mCIT group.Discussion and ConclusionThe data affirm previous findings suggesting that this reimbursable, outpatient protocol increases more affected arm use and function. Magnitude of changes was consistent with those reported in more intense protocols, such as constraint-induced therapy.
Reusable, Polymer‐Supported, Palladium‐Catalyzed, Atom‐ Efficient Coupling Reaction of Aryl Halides with Sodium Tetraphenylborate in Water by Focused Microwave Irradiation
Authors: Bai Lin , Wang Jin‐Xian 
Published: January 2008

AbstractA rapid and efficient cross‐coupling reaction of sodium tetraphenylborate with aryl bromides was carried out in water at 120 °C in the presence of a polymer‐supported palladium catalyst and potassium carbonate under focused microwave irradiation. All four phenyl groups of sodium tetraphenylborate participated in the reaction and produced polyfunctional biaryls in excellent yields. The polymeric catalyst can be easily separated from the reaction mixture and reused more than 10 times without showing any decrease in activity.
Enantioselective Cobalt‐Catalyzed [6+2] Cycloadditions of Cycloheptatriene with Alkynes
Authors: Toselli Nicolas , Martin David , Achard Mathieu , Tenaglia Alphonse , Bürgi Thomas , Buono Gerard 
Published: January 2008

AbstractThe enantioselective cobalt‐catalyzed [6+2] cycloadditions of cycloheptatriene 1 with alkynes 2 is reported. Chiral phosphoramidites based on 3,3′‐disubstituted (R)‐BINOL appeared to be efficient ligands, affording the corresponding cycloadducts with good yields and up to 92 % ee. A vibrational circular dichroism study afforded the absolute configuration of new chiral (+)‐(1S,6R)‐7‐phenyl[4.2.1]bicyclo‐ nonatriene 3a and (−)‐(1S,6R)‐7‐trimethylsilyl[4.2.1]bicyclononatriene 3c.
Efficient Heterogeneous Asymmetric Catalysis of the Mukaiyama Aldol Reaction by Silica‐ and Ionic Liquid‐Supported Lewis Acid Copper(II) Complexes of Bis(oxazolines)
Authors: Doherty S. , Goodrich P. , Hardacre C. , Pârvulescu V. , Paun C. 
Published: January 2008

AbstractLewis acid complexes based on copper(II) and an imidazolium‐tagged bis(oxazoline) have been used to catalyse the asymmetric Mukaiyama aldol reaction between methyl pyruvate and 1‐methoxy‐1‐trimethylsilyloxypropene under homogeneous and heterogeneous conditions. Although the ees obtained in ionic liquid were similar to those found in dichloromethane, there was a significant rate enhancement in the ionic liquid with reactions typically reaching completion within 2 min compared with only 55 % conversion after 60 min in dichloromethane. However, this rate enhancement was offset by lower chemoselectivity in ionic liquids due to the formation of 3‐hydroxy‐1,3‐diphenylbutan‐1‐one as a by‐product. Supporting the catalyst on silica or an imidazolium‐modified silica using the ionic liquid or in an ionic liquid‐diethyl ether system completely suppressed the formation of this by‐product without reducing the enantioselectivity. Although the heterogeneous systems were characterised by a drop in catalytic activity the system could be recycled up to five times without any loss in conversion or ee.
Tandem Gold(III)‐Catalyzed Amination‐Intramolecular Hydroamination Reactions of 1‐En‐4‐yn‐3‐ols with Sulfonamides: Efficient Approach to Highly Substituted Pyrroles
Authors: Shu Xing‐Zhong , Liu Xue‐Yuan , Xiao Hui‐Quan , Ji Ke‐Gong , Guo Li‐Na , Liang Yong‐Min 
Published: January 2008

AbstractA simple, convenient and efficient synthetic approach to highly substituted pyrroles has been developed by utilizing a gold(III)‐catalyzed tandem amination‐intramolecular hydroamination reaction. The first examples of gold‐catalyzed, selective amination of 1‐en‐4‐yn‐3‐ols have also been disclosed.
A Stereoselective Palladium‐Mediated Reductive Coupling of Electron‐Deficient Terminal Iodoalkenes
Authors: Batsanov Andrei S. , Knowles Jonathan P. , Samsam Benedict , Whiting Andrew 
Published: January 2008

AbstractIodoacrylate esters undergo palladium‐catalysed reductive homocoupling to derive dienyl diester derivatives. This reductive coupling can be extended to ester‐substituted terminal iododienes to derive tetraene diesters. In all cases, the reactions show relatively high levels of stereocontrol, which shows an inversion of stereochemistry about one iodoalkene unit. This process, and the suggestion that the reaction releases diiodine, is consistent with a syn‐1,2‐addition of an iodopalladium(II)‐alkene species across another iodoalkene unit (carbometallation step), followed by reductive syn‐elimination of iodopalladium iodide to derive palladium(II) iodide. It appears that under the reaction conditions employed, palladium(II) iodide may equilibrate to palladium(0) and diiodine, which can be observed or trapped out from the reaction mixture.
Dalton’s Disputed Nitric Oxide Experiments and the Origins of his Atomic Theory
Authors: Usselman Melvyn C. , Leaist Derek G. , Watson Katherine D. 
Published: January 2008

AbstractIn 1808 John Dalton published his first general account of chemical atomic theory, a cornerstone of modern chemistry. The theory originated in his earlier studies of the properties of atmospheric gases. In 1803 Dalton discovered that oxygen combined with either one or two volumes of nitric oxide in closed vessels over water and this pioneering observation of integral multiple proportions provided important experimental evidence for his incipient atomic ideas. Previous attempts to reproduce Dalton’s experiments have been unsuccessful and some commentators have concluded the results were fraudulent. We report a successful reconstruction of Dalton’s experiments and provide an analysis exonerating him of any scientific misconduct. But we conclude that Dalton, already thinking atomistically, adjusted experimental conditions to obtain the integral combining proportions.
Increased TGF‐Beta1 protein expression in patients with advanced colorectal cancer
Authors: Langenskiöld Marcus , Holmdahl Lena , Falk Peter , Angenete Eva , Ivarsson Marie‐Louise 
Published: January 2008

AbstractIntroductionThere is evidence that TGF‐β1 plays a role as a tumor suppressor in early disease and has pro‐oncogenic effects in advanced tumor stage. The aim of the study was to correlate TGF‐β1 in plasma and tissue to clinical and pathological parameters in patients with various stages of disease progression.MethodsOne hundred sixty‐nine patients who underwent surgery for a colorectal carcinoma were prospectively included. Blood samples, tumor free mucosa and tumor biopsies were assayed.ResultsTGF‐β1 protein expression in tumors increased with increasing T‐stage regardless of whether patients with metastatic disease were included or not (P = 0.0006). Patients with metastatic disease showed elevated TGF‐β1 protein expression in both tumor tissue (P = 0.004) and plasma (P = 0.001) compared to those without metastatic disease. TGF‐β1 protein expression was higher in the colon compared with the rectum in both tumor tissue and tumor‐free bowel (P = 0.03), regardless of whether patients with metastatic disease were included or not. This difference was mainly attributable to a higher TGF‐β1 protein expression in non‐metastatic patients with lymph node positivity (P = 0.005).ConclusionsHigher TGF‐β1 protein expression is associated with increasing T‐stage and metastatic disease, indicating that TGF‐β1 is of importance in tumor progression. The localization of the tumor seems to influence the TGF‐β1 protein expression in patients with tumor cell‐positive lymph nodes. J. Surg. Oncol. 2008;97:409–415. © 2008 Wiley‐Liss, Inc.
Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers
Authors: Wei Yongkun , Xia Weiya , Zhang Zhihong , Liu Jinsong , Wang Huamin , Adsay Nazmi V. , Albarracin Constance , Yu Dihua , Abbruzzese James L. , Mills Gordon B. , Bast Robert C. , Hortobagyi Gabriel N. , Hung Mien‐Chie 
Published: January 2008

AbstractMethylation of lysine 27 on histone H3 (H3K27) by the EZH2 complex is an epigenetic mark that mediates gene silencing. EZH2 is overexpressed in many cancers and correlates with poor prognosis in both breast and prostate cancers. However, the status of H3K27 methylation and its clinical implication in cancer patients have not been reported. We thus examined trimethylation of H3K27 (H3K27me3) by immunohistochemistry and its association with clinical variables and prognosis in breast, ovarian, and pancreatic cancers. We found that H3K27me3 expression was significantly lower in breast, ovarian and pancreatic cancers than in normal tissues (62% in breast cancer vs. 88% in normal breast tissue, P = 0.001; 38.4% in ovarian cancer vs. 83.3% in normal ovarian tissue, P < 0.05; and 26% in pancreatic cancer vs. 89% in normal pancreatic tissue, P < 0.001). H3K27me3 expression showed significant prognostic impact in breast, ovarian and pancreatic cancers in univariate survival analyses. In all three cancer types, patients with low expression of H3K27me3 had significantly shorter overall survival time when compared with those with high H3K27me3 expression. In a multivariate model, H3K27me3 expression was an independent prognostic value for overall survival in all three cancer types. These results suggest that H3K27me3 expression is a prognostic indicator for clinical outcome in patients with breast, ovarian, and pancreatic cancers. © 2008 Wiley‐Liss, Inc.
Biocatalytic hydrogels by template polymerization
Authors: El‐Sherif H. , El‐Masry M. 
Published: January 2008

AbstractNovel ionizable hydrogels were prepared from poly(acrylic acid) and dimethylaminoethyl methacrylate monomer employing template polymerization technique as an alternative to traditional physical and chemical crosslinking. The mode of interaction, as proved by Fourier Transform Infrared Spectroscopy (FTIR), was multiple H‐bonding between the tertiary amino group of the monomer and the carboxylic groups of the polymer. The hydrogels represented suitable matrices for enzyme immobilization. The effect of varying the polymer–monomer molar ratio on the swelling kinetics and parameters was investigated. The dynamic swelling isotherm exhibited a Fickian mode of penetrant sorption and a plateau that increases with the amino group content. A polymer complex of molar ratio (polymer:monomer) 0.5:0.8 had a weight swelling ratio of 10 and 7 at pHs 3 and 8, respectively. The proven pH sensitivity together with the amphoteric character of these hydrogels make them good candidates for another bioapplication such as oral delivery systems of therapeutic peptides and proteins. The structural integrity of the hydrogels was proved by their swelling reversibility. β‐Galactosidase, as an acidic model enzyme, was immobilized covalently on the synthesized hydrogels. The maximum enzyme velocity (Vmax) was enhanced to 19 µmol/min/mg, for polycomplex of molar ratio 0.5:0.8, compared with 3.2 µmol/min/mg for the free enzyme. Copyright © 2008 John Wiley & Sons, Ltd.
Effects of take‐up speed on the structure and properties of melt‐spun poly(L‐lactic acid) fibers
Authors: Kim Min Sup , Kim Jeong Cheol , Kim Young Ho 
Published: January 2008

AbstractPoly(L‐lactic acid) (PLLA) filament fibers were prepared by one‐step melt spinning process and the effects of variations in take‐up speed on their thermal properties, mechanical properties, and crystalline structures were investigated. Differential scanning calorimetry (DSC) results revealed that the PLLA fibers showed multiple melting peaks and that the melting peak appearing at a lower temperature moved lower while that at a higher temperature moved higher with increasing take‐up speed. The glass transition temperature (Tg) obtained from dynamic mechanical analysis (DMA) increased with increasing take‐up speed. The tenacity increased and the boiling water shrinkage (BWS) decreased with increasing take‐up speed. However, these mechanical and thermal properties were stabilized at take‐up speeds over 3500 m/min. The melt‐spun PLLA fibers of this study showed an α‐form crystal structure which was not affected by the take‐up speed. The change in the tendency of the thermal and mechanical properties at around 3500 m/min did not appear to result from the change in crystal form but rather from the change in crystallite size and crystallite orientation. Copyright © 2008 John Wiley & Sons, Ltd.
Adsorption of carbaryl using molecularly imprinted microspheres prepared by precipitation polymerization
Authors: Yao Wei , Fang Yanjun , Gao Guoliang Li, Zhixian , Cheng Yiyong 
Published: January 2008

AbstractTo obtain the desired specific adsorbents for carbaryl to enrichment, separation, and analysis of trace pesticide residues in environmental water, molecularly imprinted polymer (MIP) microspheres were prepared by precipitation polymerization using carbaryl, methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), azobisisobutyronitrile (AIBN), and acetonitrile as template, functional monomer, cross‐linker, initiator, and porogen, respectively. Molecular modeling software was used to compute rational interaction between the template molecule and function monomer. The adsorption properties of carbaryl in acetonitrile for imprinted microspheres were evaluated by equilibrium rebinding experiments. Scatchard plot analysis revealed that there was one class of binding sites populated in the imprinted polymer microspheres with dissociation constants of 3.3 × 10−2 mol/l and an apparent maximum number of 1.95 µmol/g. The specificity of the imprinted microspheres was investigated by binding analysis using carbaryl and structurally related carbamate pesticides. The results indicated that the obtained imprinted microspheres showed a good selectivity for carbaryl. Copyright © 2007 John Wiley & Sons, Ltd.
Evaluation of reproducibility of protein identification results after multidimensional human serum protein separation
Authors: Stalder Daniel , Haeberli André , Heller Manfred 
Published: January 2008

AbstractWe developed a gel‐ and label‐free proteomics platform for comparative studies of human serum. The method involves the depletion of the six most abundant proteins, protein fractionation by Off‐Gel™ IEF and RP‐HPLC, followed by tryptic digestion, LC‐MS/MS, protein identification, and relative quantification using probabilistic peptide match score summation (PMSS). We evaluated performance and reproducibility of the complete platform and the individual dimensions, by using chromatograms of the RP‐HPLC runs, PMSS based abundance scores and abundance distributions as objective endpoints. We were interested if a relationship exists between the quantity ratio and the PMSS score ratio. The complete analysis was performed four times with two sets of serum samples containing different concentrations of spiked bovine beta‐lactoglobulin (0.1 and 0.3%, w/w). The two concentrations resulted in significantly differing PMSS scores when compared to the variability in PMSS scores of all other protein identifications. We identified 196 proteins, of which 116 were identified four times in corresponding fractions whereof 73 qualified for relative quantification. Finally, we characterized the PMSS based protein abundance distributions with respect to the two dimensions of fractionation and discussed some interesting patterns representing discrete isoforms. We conclude that combination of Off‐Gel™ electrophoresis (OGE) and HPLC is a reproducible protein fractionation technique, that PMSS is applicable for relative quantification, that the number of quantifiable proteins is always smaller than the number of identified proteins and that reproducibility of protein identifications should supplement probabilistic acceptance criteria.