bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dirhodium Catalysts That Bear Redox Noninnocent Chelating Dicarboxylate Ligands and Their Performance in Intra‐ and Intermolecular C–H Amination
Authors: Kornecki Katherine P. , Berry John F. 
Published: November 2011

AbstractWe report two new analogues of the well‐known C–H amination catalyst [Rh2(esp)2] (1) (esp = α,α,α′,α′‐tetramethyl‐1,3‐benzenedipropanoate) that bear redox‐active supporting ligands that are structurally similar to esp. The redox‐active ligands are 2‐[3‐(1‐carboxy‐1‐methylethoxy)phenoxy]‐2‐methylpropanoic acid (H2L1) and (3‐methoxycarbonyl‐2,5‐di‐tert‐butylphenoxy)ethanoic acid (H2L2), which react with Rh2(OAc)4 to form the catalysts [Rh2(L1)2] (2) and [Rh2(L2)2] (3). Both 2 and 3 have been characterized by X‐ray crystallography and cyclic voltammetry, inter alia. Compounds 2 and 3 are structurally similar to 1 but show more complex electrochemical features. Whereas 1 has a single reversible redox wave that corresponds to the Rh2II,II/Rh2II,III couple, 2 and 3 show multiple oxidations that are characteristic of ligand‐centered oxidation. Catalysts 1, 2, and 3 perform well in a model intramolecular C–H amination reaction, and all three catalysts perform equally well during the first four hours of a model intermolecular reaction. After this point, 2 and 3 cease to function, whereas 1 continues to be active. These results support the hypothesis that intermolecular C–H amination utilizes two distinct mechanisms: (1) a nitrene interception/insertion mechanism that is fast but ceases to be operative after four hours, and (2) a one‐electron mechanism that is more robust over extended time periods, but requires the catalyst to be able to undergo Rh2‐centered oxidation.
A Route to “all‐cis” 2‐Methyl‐6‐Substituted Piperidin‐3‐ol Alkaloids from syn‐(2R,1′S)‐2‐(1‐Dibenzylaminomethyl)epoxide: Rapid Total Synthesis of (+)‐Deoxocassine
Authors: Géant Pierre‐Yves , Martínez Jean , Salom‐Roig Xavier J. 
Published: November 2011

AbstractA general strategy leading to the synthesis of two cis‐2‐methyl‐6‐substituted piperidin‐3‐ols is described. syn‐(2R,1′S)‐2‐(1‐Dibenzylaminomethyl) epoxide (13) was used as common building block. The key step involved oxirane ring opening of 13 by the nucleophilic lithium aza‐enolate of hydrazones 12a and 12b. Subsequent hydrazone hydrolysis and intramolecular reductive amination afforded the alkaloid (+)‐deoxocassine and a new C‐6 ethyl analogue of this substance in good yields.
A Halide‐for‐Anion Swap Using an Anion‐Exchange Resin (A– Form) Method: Revisiting Imidazolium‐Based Anion Receptors and Sensors
Authors: Alcalde Ermitas , Mesquida Neus , Ibáñez Anna , Dinarès Immaculada 
Published: November 2011

AbstractFaced with an extensive pool of imidazolium‐based systems, the present study was based on selected examples of bis(imidazolium) models for anion recognition to broaden the applicability of counteranion exchange by using the anion‐exchange resin (AER) (A– form) method in nonaqueous media. Relying on the hydrophobicity of the quaternary imidazolium salt for counteranion exchange, the AER (A– form) method was performed in organic solvents of different polarity, such as CH3OH and CH3CN. Anion exchange proceeded in excellent to quantitative yields, simultaneously removing halide impurities―often a troublesome purification task. The results of electrospray mass spectrometry [ESI(+)‐MS] analysis focused on the gas‐phase behavior of the dicationic cyclophane prototype 5·2Cl and the open‐chain compound pairs 4·2Br and 15·2Br are briefly described.
Synthetic applications of 3H‐1,2,4‐dithiazoles: Structure and reactivity studies
Authors: Islam Md. Rafiqul , Takikawa Yuji , Lim Kwon Taek 
Published: November 2011

AbstractSynthetic applications of 3H‐1,2,4‐dithiazoles have been studied extensively. The facile synthesis of hitherto unknown 3H‐1,2,4‐dithiazole S‐oxides was realized by the mCPBA oxidation of 3H‐1,2,4‐dithiazoles. The structural information of the 1,2,4‐dichalcogenazole ring system was revealed by the ORTEP analysis of 3‐tert‐butyl‐5‐4‐chloro‐phenyl‐3H‐1,2,4‐dithiazole S‐oxide. The reactivities of 3H‐1,2,4‐dithiazoles are also discussed. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:154–159, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20764
Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy
Authors: Lange Christian M. , Kutalik Zoltan , Morikawa Kenichi , Bibert Stéphanie , Cerny Andreas , Dollenmaier Günter , Dufour Jean-François , Gerlach Tilman J. , Heim Markus H. , Malinverni Raffaele , Müllhaupt Beat , Negro Francesco , Moradpour Darius , Bochud Pierre-Yves 
Published: November 2011

Abstract

Elevated serum ferritin levels may reflect a systemic inflammatory state as well as increased iron storage, both of which may contribute to an unfavorable outcome of chronic hepatitis C (CHC). We therefore performed a comprehensive analysis of the role of serum ferritin and its genetic determinants in the pathogenesis and treatment of CHC. To this end, serum ferritin levels at baseline of therapy with pegylated interferon-alpha and ribavirin or before biopsy were correlated with clinical and histological features of chronic hepatitis C virus (HCV) infection, including necroinflammatory activity (N = 970), fibrosis (N = 980), steatosis (N = 886), and response to treatment (N = 876). The association between high serum ferritin levels (>median) and the endpoints was assessed by logistic regression. Moreover, a candidate gene as well as a genome-wide association study of serum ferritin were performed. We found that serum ferritin ≥ the sex-specific median was one of the strongest pretreatment predictors of treatment failure (univariate P < 0.0001, odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.34–0.60). This association remained highly significant in a multivariate analysis (P = 0.0002, OR = 0.35, 95% CI = 0.20–0.61), with an OR comparable to that of interleukin (IL)28B genotype. When patients with the unfavorable IL28B genotypes were stratified according to high versus low ferritin levels, SVR rates differed by >30% in both HCV genotype 1- and genotype 3–infected patients (P < 0.001). Serum ferritin levels were also independently associated with severe liver fibrosis (P < 0.0001, OR = 2.67, 95% CI = 1.68–4.25) and steatosis (P = 0.002, OR = 2.29, 95% CI = 1.35–3.91), but not with necroinflammatory activity (P = 0.3). Genetic variations had only a limited impact on serum ferritin levels. Conclusion: In patients with CHC, elevated serum ferritin levels are independently associated with advanced liver fibrosis, hepatic steatosis, and poor response to interferon-alpha-based therapy. (Hepatology 2012)
Rosmarinic acid and baicalin epigenetically derepress peroxisomal proliferator-activated receptor γ in hepatic stellate cells for their antifibrotic effect
Authors: Yang Melissa D. , Chiang Yi-Ming , Higashiyama Reiichi , Asahina Kinji , Mann Derek A. , Mann Jelena , Wang Clay C.C. , Tsukamoto Hidekazu 
Published: November 2011

Abstract

Hepatic stellate cells (HSCs) undergo myofibroblastic transdifferentiation (activation) to participate in liver fibrosis and identification of molecular targets for this cell fate regulation is essential for development of efficacious therapeutic modalities for the disease. Peroxisomal proliferator-activated receptor γ (PPARγ) is required for differentiation of HSCs and its epigenetic repression underlies HSC activation. The herbal prescription Yang-Gan-Wan (YGW) prevents liver fibrosis, but its active ingredients and molecular mechanisms are unknown. Here we demonstrate YGW prevents and reverses HSC activation by way of epigenetic derepression of Pparγ involving reductions in MeCP2 expression and its recruitment to Pparγ promoter, suppressed expression of PRC2 methyltransferase EZH2, and consequent reduction of H2K27di-methylation at the 3′ exon. High-performance liquid chromatography / mass spectrometry (HPLC/MS) and nuclear magnetic resonance (NMR) analyses identify polyphenolic rosmarinic acid (RA) and baicalin (BC) as active phytocompounds. RA and BC suppress the expression and signaling by canonical Wnts, which are implicated in the aforementioned Pparγ epigenetic repression. RA treatment in mice with existing cholestatic liver fibrosis inhibits HSC activation and progression of liver fibrosis. Conclusion: These results demonstrate a therapeutic potential of YGW and its active component RA and BC for liver fibrosis by way of Pparγ derepression mediated by suppression of canonical Wnt signaling in HSCs. (Hepatology 2012)
Lipid nanoparticle siRNA systems for silencing the androgen receptor in human prostate cancer in vivo
Authors: Lee Justin B. , Zhang Kaixin , Tam Yuen Yi C. , Tam Ying K. , Belliveau Nathan M. , Sung Vanessa Y.C. , Lin Paulo J.C. , LeBlanc Eric , Ciufolini Marco A. , Rennie Paul S. , Cullis Pieter R. 
Published: November 2011

AbstractThe androgen receptor (AR) plays a critical role in the progression of prostate cancer. Silencing this protein using short‐hairpin RNA (shRNA) has been correlated with tumor growth inhibition and decreases in serum prostate specific antigen (PSA). In our study, we have investigated the ability of lipid nanoparticle (LNP) formulations of small‐interfering RNA (siRNA) to silence AR in human prostate tumor cell lines in vitro and in LNCaP xenograft tumors following intravenous (i.v.) injection. In vitro screening studies using a panel of cationic lipids showed that LNPs containing the ionizable cationic lipid 2,2‐dilinoleyl‐4‐(2‐dimethylaminoethyl)‐[1,3]‐dioxolane (DLin‐KC2‐DMA) exhibited the most potent AR silencing effects in LNCaP cells. This is attributed to an optimized ability of DLin‐KC2‐DMA‐containing LNP to be taken up into cells and to release the siRNA into the cell cytoplasm following endocytotic uptake. DLin‐KC2‐DMA LNPs were also effective in silencing the AR in a wild‐type AR expressing cell line, LAPC‐4, and a variant AR expressing cell line, CWR22Rv1. Importantly, it is demonstrated that LNP AR‐siRNA systems containing DLin‐KC2‐DMA can silence AR gene expression in distal LNCaP xenograft tumors and decrease serum PSA levels following i.v. injection. To our knowledge, this is the first report demonstrating the feasibility of LNP delivery of siRNA for silencing AR gene expression in vivo.
Child analysis in a changing world. In the face of a paradigm shift from the mind to the brain: Can we meet the challenge?
Authors: Gauthier Yvon 
Published: November 2011

AbstractChild analysts and child therapists are now practicing in a new environment where an increased emphasis is made on identifying the symptoms and finding the shortest possible way to get rid of them, from the knowledge of brain functioning. From that perspective, the history of the symptom, of the child who owns it, and of the family in which this child is being raised are not emphasized as strongly. Searching for a specific meaning of such symptoms seems to be of no more interest. How can such a heavy trend be met? Major changes also have occurred within the psychoanalytic milieu. Advances from the observational world, from Spitz (1945) to Bowlby's (1987) attachment theory, provide essential knowledge to the field of early child–parent interactions. Longitudinal research in recent decades has shown close ties between early development and future outcomes. Such new knowledge is inspiring child analysis with very young children as well as with severely disturbed, older children. Early intervention with disadvantaged populations is showing the importance of the nonspecific aspects of the therapeutic relationship as a factor of change. In light of recent neurobiologic research on the influence of a specific environment—attachment experiences—on early development of the brain, it is now possible to speak of the social brain (Cozolino, 2006).
On a heuristic point of view concerning the expression of numerous genes during the cell cycle
Authors: Cooper Stephen 
Published: November 2011

AbstractThe current model of the eukaryotic cell cycle proposes that numerous genes are expressed at different times during the cell cycle. The existence of myriad control points for gene expression leads to theoretical and logical problems for cell cycle control. Each expressed gene requires a control element to appear in a cell‐cycle specific manner; this control element requires another control element and so on, ad infinitum. There are also experimental problems with the current model based on ineffective synchronization methods and problems with microarray measurements of mRNA. Equally important, the efficacy of mRNA variation in affecting changes in protein content is negligible. An alternative view of the cell cycle proposes cycle‐independent, invariant accumulation of mRNA during the cell cycle with decreases of specific proteins occurring only during the mitotic period of the cell cycle. © 2011 IUBMB IUBMB Life, 2011.
Off‐target immune cell toxicity caused by AG‐012986, a pan‐CDK inhibitor, is associated with inhibition of p38 MAPK phosphorylation
Authors: Lee Dong U. , Jessen Bart 
Published: November 2011

AbstractAG‐012986 is a pan‐CDK (cyclin‐dependent kinase) inhibitor that has in vitro and in vivo antitumor properties but was stopped in development due in part to rapid bone‐marrow‐independent white blood cell toxicity in preclinical studies and the potential for acute and delayed immunosuppression in humans. Because peripheral lymphocytes are largely nonproliferating, it was hypothesized the toxicity of AG‐012986 was due to an off‐target mechanism and not driven by the intended pharmacology. We show the toxicity mechanism in primary human immune cells is caspase driven. T‐cells treated with AG‐012986 and acutely stimulated through the T‐cell receptor exhibited decreased toxicity while still maintaining cell division inhibition. This indicated that the pharmacology of AG‐012986 functioned as expected but the toxicity had now been decoupled through activation. Induced phosphorylation of p38 and IL‐2 production was impaired with AG‐012986. Thus, AG‐012986 could cause apoptosis of T‐cells by targeting upstream kinases in the p38 Mitogen‐activated protein kinase (MAPK) pathway and impairing cellular survival. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:101–108 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20415
Development, characterization, and applications of a novel estrogen receptor beta monoclonal antibody
Authors: Wu Xianglin , Subramaniam Malayannan , Negron Vivian , Cicek Muzaffer , Reynolds Carol , Lingle Wilma L. , Goetz Matthew P. , Ingle James N. , Spelsberg Thomas C. , Hawse John R. 
Published: November 2011

AbstractThe role of estrogen receptor alpha (ERα) in breast cancer has been studied extensively, and its protein expression is prognostic and a primary determinant of endocrine sensitivity. However, much less is known about the role of ERβ and its relevance remains unclear due to the publication of conflicting reports. Here, we provide evidence that much of this controversy may be explained by variability in antibody sensitivity and specificity and describe the development, characterization, and potential applications of a novel monoclonal antibody targeting full‐length human ERβ and its splice variant forms. Specifically, we demonstrate that a number of commercially available ERβ antibodies are insensitive for ERβ and exhibit significant cross‐reaction with ERα. However, our newly developed MC10 ERβ antibody is shown to be highly specific and sensitive for detection of full‐length ERβ and its variant forms. Strong and variable staining patterns for endogenous levels of ERβ protein were detected in normal human tissues and breast tumors using the MC10 antibody. Importantly, ERβ was shown to be expressed in a limited cohort of both ERα positive and ERα negative breast tumors. Taken together, these data demonstrate that the use of poorly validated ERβ antibodies is likely to explain much of the controversy in the field with regard to the biological relevance of ERβ in breast cancer. The use of the MC10 antibody, in combination with highly specific antibodies targeting only full‐length ERβ, is likely to provide additional discriminatory features in breast cancers that may be useful in predicting response to therapy. J. Cell. Biochem. 113: 711–723, 2012. © 2011 Wiley Periodicals, Inc.
Cross‐talk between endothelial and breast cancer cells regulates reciprocal expression of angiogenic factors in vitro
Authors: Buchanan Cara F. , Szot Christopher S. , Wilson Tia D. , Akman Steven , Metheny‐Barlow Linda J. , Robertson John L. , Freeman Joseph W. , Rylander Marissa Nichole 
Published: November 2011

AbstractReciprocal growth factor exchange between endothelial and malignant cells within the tumor microenvironment may directly stimulate neovascularization; however, the role of host vasculature in regulating tumor cell activity is not well understood. While previous studies have examined the angiogenic response of endothelial cells to tumor‐secreted factors, few have explored tumor response to endothelial cells. Using an in vitro co‐culture system, we investigated the influence of endothelial cells on the angiogenic phenotype of breast cancer cells. Specifically, VEGF, ANG1, and ANG2 gene and protein expression were assessed. When co‐cultured with microvascular endothelial cells (HMEC‐1), breast cancer cells (MDA‐MB‐231) significantly increased expression of ANG2 mRNA (20‐fold relative to MDA‐MB‐231 monoculture). Moreover, MDA‐MB‐231/HMEC‐1 co‐cultures produced significantly increased levels of ANG2 (up to 580 pg/ml) and VEGF protein (up to 38,400 pg/ml) while ANG1 protein expression was decreased relative to MDA‐MB‐231 monocultures. Thus, the ratio of ANG1:ANG2 protein, a critical indicator of neovascularization, shifted in favor of ANG2, a phenomenon known to correlate with vessel destabilization and sprouting in vivo. This angiogenic response was not observed in nonmalignant breast epithelial cells (MCF‐10A), where absolute protein levels of MCF‐10A/HMEC‐1 co‐cultures were an order of magnitude less than that of the MDA‐MB‐231/HMEC‐1 co‐cultures. Results were further verified with a functional angiogenesis assay demonstrating well‐defined microvascular endothelial cell (TIME) tube formation when cultured in media collected from MDA‐MB‐231/HMEC‐1 co‐cultures. This study demonstrates that the angiogenic activity of malignant mammary epithelial cells is significantly enhanced by the presence of endothelial cells. J. Cell. Biochem. 113: 1142–1151, 2012. © 2011 Wiley Periodicals, Inc.
Effect of reconstituted discoidal high‐density lipoproteins on lipid mobilization in RAW 264.7 and CHOK1 cells
Authors: Toledo Juan D. , Cabaleiro Laura V. , Garda Horacio A. , Gonzalez Marina C. 
Published: November 2011

AbstractReconstituted discoidal high‐density lipoproteins (rHDL) resemble nascent HDL, which are formed at the early reverse cholesterol transport steps, and constitute the initial cholesterol (Chol) acceptors from cell membranes. We have used different sized rHDL containing or not Chol, to test their abilities to promote cholesterol and phospholipid efflux from two different cell lines: Raw 264.7 macrophages and CHOK1 cells. All rHDL and lipid‐free apolipoprotein A‐I (apoA‐I) were found to be bound to CHO and RAW cells. In RAW cells, a positive correlation between cellular binding and Chol removal was found for 78 and 96 Å rHDL. Chol‐free rHDL were more effective than Chol‐containing ones in binding to RAW cells and promoting Chol removal. These results were more evident in the 96 Å rHDL. On the other hand, rHDL binding to CHO cells was relatively independent of disc size and Chol content. In spite of the fact that apoA‐I and rHDL promoted Chol efflux from both cellular lines, only in CHOK1 cells this result was also associated to decrease Chol esterification. Among choline‐containing phospholipids, only phosphatidylcholine (PC) (but not sphingomyelin) was detected to be effuxed from both cellular lines. With the only exception of Chol‐free 96 Å discs, the other rHDL as well as apoA‐I promoted PC efflux from RAW cells. Chol‐containing rHDL were more active than Chol‐free ones of comparable size to promote PC efflux from RAW macrophages. Regarding CHO cells, only apoA‐I and Chol‐free 78 Å rHDL were active enough to remove PC. J. Cell. Biochem. 113: 1208–1216, 2012. © 2011 Wiley Periodicals, Inc.
MiR‐17‐92 cluster regulates cell proliferation and collagen synthesis by targeting TGFB pathway in mouse palatal mesenchymal cells
Authors: Li Ling , Shi Jia‐Yu , Zhu Gui‐Quan , Shi Bing 
Published: November 2011

AbstractElongation and elevation of palatal shelves, mainly caused by proliferation and extra‐cellular matrix synthesis of palatal mesenchymal cells (PMCs), are essential for normal palatal development. Transforming growth factor beta (TGFB) pathway could induce proliferation inhibition and collagen synthesis in PMCs. Recent studies found that miRNA‐17‐92 (miR‐17‐92) cluster, including miR‐17, miR‐18a, miR‐19a, miR‐20a, miR‐19b, and miR‐92a, expressed in the 1st bronchial arch of mouse embryos during the period of palatal shelf elongation and elevation, and directly targeted TGFB pathway in cancer cell lines. Whether miR‐17‐92 cluster expresses and targets TGFB pathway in PMCs has not yet been studied. Using quantitative real‐time RT‐PCR, we found that miR‐17‐92 expressed in PMCs and decreased from embryonic day (E) 12 to E14 in palatal shelves. MTT assay and Western blot showed that miR‐17‐92 inhibited TGFB1 induced proliferation inhibition and collagen synthesis in PMCs by decreasing TGFBR2, SMAD2, and SMAD4 protein level. Further luciferase assay showed that miR‐17 and miR‐20a directly targeted 3′UTR of TGFBR2, and that miR‐18a directly targeted 3′UTR of SMAD2 and SMAD4. We thus conclude that miR‐17‐92 cluster could inhibit TGFB pathway induced proliferation inhibition and collagen synthesis in PMCs by directly targeting TGFBR2, SMAD2, and SMAD4. J. Cell. Biochem. 113: 1235–1244, 2012. © 2011 Wiley Periodicals, Inc.
ΔE1 and high‐capacity adenoviral vectors expressing full‐length codon‐optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum
Authors: Zong Shan , Kron Matthias W. , Epp Christian , Engler Tatjana , Bujard Hermann , Kochanek Stefan , Kreppel Florian 
Published: November 2011

AbstractBackgroundThe merozoite surface protein (MSP)‐1 of Plasmodium falciparum, the causative agent of malaria tropica, is considered to be a promising vaccine candidate. Although its stable cloning and expression has been difficult in the past, adenoviral vectors expressing the complex protein are described in the present study.MethodsCodon‐optimized msp‐1 was used to construct a set of first generation (ΔE1Ad) and high‐capacity adenovirus (HC‐Ad) vectors, and cellular and humoral immune responses induced by the vectors were characterized in detail in mice.ResultsGeneration of stable ΔE1Ad and HC‐Ad vectors expressing full‐length MSP‐1 and their production to high vector titers was found to be feasible. Epitope identification and analysis of frequencies of specific CD8 T‐cells revealed that MSP‐1 expressing HC‐Ad vectors induced higher frequencies of interferon‐γ + CD8 T‐cells than ΔE1 vectors. Irrespective of the vector format, higher titers of MSP‐1 specific antibodies were generated by Ad vectors expressing MSP‐1 from a chicken β‐actin (CAG) promoter comprising the cytomegalovirus early enhancer element and the chicken β‐actin promoter.ConclusionsThe findings of the present study suggest that Ad vectors expressing full‐length codon‐optimized MSP‐1 are promising candidate vaccines against P. falciparum infections. Use of the HC‐Ad vector type for delivery, as well as the CAG promoter to control MSP‐1 expression, may further increase the efficacy of this vaccine candidate. Copyright © 2011 John Wiley & Sons, Ltd.