bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Fluorescent Calix Crown Ethers, Part II: Synthesis and Complex Formation in Solution and the Solid State
Authors: Stoll Ion , Brodbeck Ralf , Wiegmann Sebastian , Eberhard Jens , Kerruth Silke , Neumann Beate , Stammler Hans‐Georg , Mattay Jochen 
Published: September 2008

AbstractNew luminescent 1‐aza‐15‐crown‐5 ethers bearing a coumarin unit were synthesised leading to the cavitand‐based calix crown ether 9. The solid‐state structures of crown ethers 5 and 6 and the solid‐state structures of the sodium and potassium iodide complexes of crown ether 5 are presented. The association constants for the complex formation with alkali metal ions in methanol were determined. Only weak complexes were formed (KNa = 286 M–1, KK = 392 M–1). The aza‐15‐crown‐5 ether was attached by a methylene unit to a cavitand to give the new fluorescent calix crown ether 9. The association constants for the sodium and potassium complexes in methanol were investigated as well, and an enhancement for the association constant of the sodium complex was found (KNa = 1215 M–1, KK = 497 M–1). Selected equilibrium structures of the complexes of 9 were examined by Kohn–Sham density functional calculations to give a detailed understanding of the interplay between the two involved building blocks. Based on these results, a sidewise cation binding of the host 9 can be assumed. These complex geometries are distinct from our findings in our previous work for a larger crown ether attached to a cavitand.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
A New Class of Fluorescent Dye for Sensing Water in Organic Solvents by Photo‐Induced Electron Transfer – A (Phenylamino)naphtho[1,2‐d]oxazol‐2‐yl‐Type Fluorophore with both Proton‐Binding and Proton‐Donating Sites
Authors: Ooyama Yousuke , Egawa Haruka , Yoshida Katsuhira 
Published: September 2008

AbstractA new class of fluorescent dye for sensing water in organic solvents by photo‐induced electron transfer (PET), based on a (phenylamino)naphtho[1,2‐d]oxazol‐2‐yl‐type fluorophore with both proton binding and proton donating sites, has been designed developed. The fluorophore exhibits a weak emission in organic solvents but a drastic enhancement in the fluorescence intensity is observed with increasing water content in organic solvents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Domino Heck–Aza‐Michael Reactions: A One‐Pot, Sequential Three‐Component Approach to 1,1‐Dioxido‐1,2‐benzisothiazoline‐3‐acetic Acid
Authors: Rolfe Alan , Young Kyle , Hanson Paul R. 
Published: September 2008

AbstractThe development of a new method for the synthesis of 1,1‐dioxido‐1,2‐benzisothiazoline‐3‐acetic acid by a domino process is reported whereby a classical Heck reaction is coupled to an intramolecular aza‐Michael reaction. Ultimately, this method has been expanded to a one‐pot, sequential three‐component protocol to generate diverse benzofused γ‐sultams from a range of commercially available α‐bromobenzenesulfonyl chlorides, amines and Michael acceptors. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
2‐Methoxy‐Δ3‐1,3,4‐oxadiazoline, a Multipurpose Precursor for the Generation of a Carbene, an Ylide, or a Diazo Compound
Authors: Mieusset Jean‐Luc , Billing Peter , Abraham Michael , Arion Vladimir B. , Brecker Lothar , Brinker Udo H. 
Published: September 2008

AbstractIn the course of our investigation of the intermolecular reactions of foiled carbenes of the norborn‐2‐en‐7‐ylidene type, we have investigated the decomposition of methoxyoxadiazoline 1 in alcohols. Most of the reactions performed lead to products with an anti configuration confirming the participation of the double bond to the stabilization of the transition states. The thermal behavior of spirooxadiazoline 1 is quite different from the behavior of the parent 2‐methoxy‐2,5,5‐trimethyl‐Δ3‐1,3,4‐oxadiazoline. Photolysis of 1 leads to the carbene after prior formation of the diazo compound whereas thermolysis cleanly generates an extremely unstable carbonyl ylide 4 that immediately decomposes to the stabilized‐nucleophilic carbene 5 and methyl acetate without generation of 1‐methoxyethylidene. Both conformers of 4 do not interconvert and, therefore, they have different life times. Nevertheless, we were able to trap syn ylide 4a with methanol. Calculations show that nonbonding interactions between an alkyl carbene and an ester are more significant than ylide formation. Synthetically, photolysis of oxadiazoline 1 in ethyl acetate has proven to give anti ethers in excellent yields. Moreover, we report the first reactions of a norbornenylidene derivative with O–H bonds in which no products resulting from a cationic rearrangement are formed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Power consequences of linkage disequilibrium variation between populations
Authors: Teo Yik Y. , Small Kerrin S. , Fry Andrew E. , Wu Yumeng , Kwiatkowski Dominic P. , Clark Taane G. 
Published: September 2008

AbstractWe quantify the degree to which LD differences exist in the human genome and investigates the consequences that variations in patterns of LD between populations can have on the power of case‐control or family‐trio association studies. Although only a small proportion of SNPs show significant LD differences (0.8–5%), these can introduce artificial signals of associations and reduce the power to detect true associations in case‐control designs, even when meta‐analytic approaches are used to account for stratification. We show that combining trios from different populations in the presence of significant LD differences can adversely affect power even though the number of trios has increased. Our results have implications on genetic studies conducted in populations with substantial population structure and show that the use of meta‐analytic approaches or family‐based designs to protect Type 1 error does not prevent loss of power due to differences in LD across populations. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.
Blocking the hedgehog pathway inhibits hepatoblastoma growth #
Authors: Eichenmüller Melanie , Gruner Ivonne , Hagl Beate , Häberle Beate , Müller-Höcker Josef , von Schweinitz Dietrich , Kappler Roland 
Published: September 2008

Abstract
Recent evidence has indicated that Hedgehog (Hh) signaling significantly contributes to liver development and regeneration and that activation of the pathway may contribute to growth of hepatocellular carcinoma (HCC) in adults. However, the role of Hh signaling in pediatric liver tumors remains to be elucidated. In this study, we show that Hh signaling is activated in hepatoblastoma (HB), the most common liver tumor in childhood, with most occurrences before the age of 3 years. The Hh target genes glioma-associated oncogene homolog 1 (GLI1) and Patched (PTCH1) showed increased transcript levels in 65% and 30% of HB samples, respectively, compared with normal liver tissues. Most interestingly, the gene encoding the hedgehog interacting protein (HHIP) is transcriptionally silenced by cytosine-phospho-guanosine (CpG) island promoter hypermethylation in 26% of HB cases and treatment with the DNA-demethylating agent 5-aza-2′-deoxycytidine partially restored HHIP expression. Blocking Hh signaling with the antagonist cyclopamine had a strong inhibitory effect on cell proliferation of HB cell lines with an activated pathway. We further demonstrate that this decrease in cell viability is caused by a massive induction of apoptosis, as shown by morphological changes and phosphatidylserine membrane asymmetry. In cyclopamine-exposed HB cells, caspase 3 and poly(adenosine diphosphate-ribose) polymerase proteins were specifically activated by their proteolytic cleavage. Conclusion: This study demonstrates, for the first time, the frequent occurrence of GLI1 and PTCH1 overexpression and HHIP promoter methylation in early childhood HB, thus indicating a key role for Hh signaling activation in the malignant transformation of embryonal liver cells. (Hepatology 2009;49:482–490.)
Deficiency in regulatory T cells results in development of antimitochondrial antibodies and autoimmune cholangitis #
Authors: Zhang Weici , Sharma Rahul , Ju Shyr-Te , He Xiao-Song , Tao Yanyan , Tsuneyama Koichi , Tian Zhigang , Lian Zhe-Xiong , Fu Shu Man , Gershwin Eric M. 
Published: September 2008

Abstract
There have been several descriptions of mouse models that manifest select immunological and clinical features of autoimmune cholangitis with similarities to primary biliary cirrhosis in humans. Some of these models require immunization with complete Freund's adjuvant, whereas others suggest that a decreased frequency of T regulatory cells (Tregs) facilitates spontaneous disease. We hypothesized that antimitochondrial antibodies (AMAs) and development of autoimmune cholangitis would be found in mice genetically deficient in components essential for the development and homeostasis of forkhead box 3 (Foxp3)+ Tregs. Therefore, we examined Scurfy (Sf) mice, animals that have a mutation in the gene encoding the Foxp3 transcription factor that results in a complete abolition of Foxp3+ Tregs. At 3 to 4 weeks of age, 100% of animals exhibit high-titer serum AMA of all isotypes. Furthermore, mice have moderate to severe lymphocytic infiltrates surrounding portal areas with evidence of biliary duct damage, and dramatic elevation of cytokines in serum and messenger RNAs encoding cytokines in liver tissue, including tumor necrosis factor α, interferon-γ, interleukin (IL)-6, IL-12, and IL-23. Conclusion: The lack of functional Foxp3 is a major predisposing feature for loss of tolerance that leads to autoimmune cholangitis. These findings reflect on the importance of regulatory T cells in other murine models as well as in patients with primary biliary cirrhosis. (Hepatology 2008.)
Autochthonous liver tumors induce systemic T cell tolerance associated with T cell receptor down-modulation #
Authors: Ney Jasmin T. , Schmidt Thomas , Kurts Christian , Zhou Qi , Eckert Dawid , Felsher Dean W. , Schorle Hubert , Knolle Percy , Tüting Thomas , Barchet Winfried , Büttner Reinhard , Limmer Andreas , Gütgemann Ines 
Published: September 2008

Abstract
The reason the adaptive immune system fails in advanced liver tumors is largely unclear. To address this question, we have developed a novel murine model that combines c-myc–induced autochthonous tumorigenesis with expression of a cognate antigen, ovalbumin (OVA). When c-myc/OVA transgenic mice were crossed with liver-specific inducer mice, multifocal hepatocellular carcinomas co-expressing OVA developed in a tetracycline-dependent manner with a short latency and 100% penetrance. Transferred OVA-specific T cells, although infiltrating the tumor at high numbers, were hyporesponsive, as evidenced by a lack of in vivo cytotoxicity and interferon gamma production. This allowed the tumor to progress even in the presence of large numbers of antigen-specific T cells and even after vaccination (OVA+CpG-DNA). Interestingly, T cell receptor down-modulation was observed, which may explain antigen-specific hyporesponsiveness. This model is helpful in understanding liver cancer–specific mechanisms of T cell tolerance and dissection of antigen-specific and nonspecific mechanisms of immunotherapies in the preclinical phase. (Hepatology 2009.)
Recruitment of host progenitor cells in rat liver transplants #
Authors: Sun Zhaoli , Zhang Xiuying , Locke Jayme E. , Zheng Qizhi , Tachibana Shingo , Diehl Anna Mae , Williams George Melville 
Published: September 2008

Abstract
Despite major histocompatibility complex incompatibility, liver transplants from Lewis rats to dark agouti (DA) rats survive indefinitely without immunosuppression, and the studies we report sought the mechanism(s) responsible for this. At 1 year, most of the liver reacted positively to host anti-DA antibody. When small (50%) grafts were transplanted, recruitment was more rapid because most of the organ assumed the host phenotype at 3 months. After transplantation, the Y chromosome was detected in the hepatocytes of XX to XY grafts by both in situ hybridization and polymerase chain reaction. Further, livers from transgenic Lewis rats carrying strong green fluorescent protein (GFP) markers lost the marker with time after transplantation to DA, GFP-negative hosts. Few liver cells contained the Y chromosome in syngeneic XX to XY liver grafts or when the hosts of Lewis XX to DA XY allografts were treated with cyclosporine A at 10 mg/kg/day. This dosage also impeded enlargement of the liver at 10 days. Using GFP-positive XX Lewis donors transplanted to GFP-negative XY DA hosts, we found little Y DNA in GFP-positive cells at 10 days. Host-derived OV-6–positive and c-kit–positive, albumin-positive cells were present at 3-10 days, but cells with the CD34 marker were less common and some clearly still had the donor phenotype at 10 days. Cells positive for chemokine cysteine-X-cysteine receptor-4 increased with time and were abundant 1 month after transplantation. We conclude: (1) extrahepatic cells can differentiate into liver tissues; (2) regenerative stimuli accelerate stem cell recruitment; (3) both regeneration and recruitment are impeded by cyclosporine A immunosuppression, and (4) donor GFP-positive cells contained little host Y chromosome after transplantation, suggesting that cell fusion was uncommon and, therefore, unlikely to be the mechanism leading to the changes in genotype and phenotype we observed. (Hepatology 2008.)
The tyrosine kinase receptor HER2 (erbB‐2): From oncogenesis to adipogenesis
Authors: Vazquez‐Martin Alejandro , Ortega‐Delgado Francisco Jose , Fernandez‐Real Jose Manuel , Menendez Javier A. 
Published: September 2008

AbstractRecent experimental evidences begin to support the notion that the proto‐oncogene HER2 (erbB‐2) might unexpectedly function to modulate the adipogenic conversion of preadipocytes. Two opposing scenarios have been proposed, however, to explain the influence of HER2 on adipocyte differentiation. In one hand, down‐modulation of HER2 expression and pharmacological reduction of HER2 activity have been related to enhanced adipocyte differentiation. On the contrary, an increased abundance in HER2 has been described in differentiated adipocytes compared with preadipocytes. Considering that expression and activity of the lipogenic enzyme Fatty Acid Synthase (FASN) become up‐regulated during adipogenic conversion, we recently hypothesized that a “HER2 → FASN axis” ‐a “lipogenic benefit” that has been shown to enhance cancer cell proliferation, survival, chemoresistance and metastasis in biologically aggressive subgroups of breast carcinomas‐might also naturally work during the differentiation of preadipocytes. To definitely clarify if the discrepancy between the opposing theories for a role of HER2 during adipocyte differentiation related to the experimental approach utilized to compare the abundance of HER2 in undifferentiated and differentiated adipocytes (i.e., cell lysates containing equivalent protein content versus cell lysates generated from similar cell numbers), we here took advantage of a high content microscopy approach. Using an automated confocal imaging platform, we monitored the expression status of the adipogenic marker FASN and its timing relationship with HER2 not only in individual 3T3‐L1 cells but further in whole cultures of 3T3‐L1 preadipocytes undergoing adipogenic conversion. Our findings not only confirm a non‐oncogenic role for HER2 in the process of adipose differentiation but further suggest that HER2 might represent a previously unrecognized target to manage obesity via the lipogenic enzyme FASN. J. Cell. Biochem. 105: 1147–1152, 2008. © 2008 Wiley‐Liss, Inc.
The EphA3 receptor is expressed in a subset of rhabdomyosarcoma cell lines and suppresses cell adhesion and migration
Authors: Clifford Noretta , Smith Loraine M. , Powell James , Gattenlöhner Stefan , Marx Alexander , O'Connor Rosemary 
Published: September 2008

AbstractElevated expression of the Eph receptor tyrosine kinase EphA3 is associated with lymphocytic leukaemia, but little is known about its expression or function in solid tumours. Out of a panel of cancer cell lines, we found that EphA3 was expressed only on two rhabdomyosarcoma (RMS) cell lines of the embryonal histological subtype and on one of the alveolar RMS subtype, whereas it was not detected on two other cell lines of the alveolar subtype. Other EphA receptors (1–7) were, either not expressed in any, or expressed in all five RMS cell lines. Stimulation of EphA3‐expressing TE671 and RD RMS cells with ephrinA5 resulted in loss of adhesion to fibronectin, decreased migration towards the stromal cell‐derived growth factor‐I (SDF‐I), increased EphA3 phosphorylation, and increased Rho GTPase activity. In contrast, ectopic expression of EphA3 in the EphA3 negative CRL2061 cell line resulted in decreased cell adhesion. Finally, suppression of EphA3 expression by siRNA in RD cells results in increased SDF‐I‐mediated motility. These data indicate that EphA3 expression may define subsets of RMS tumours, and that EphA3 suppresses motility through regulation of Rho GTPases in RMS cells. J. Cell. Biochem. 105: 1250–1259, 2008. © 2008 Wiley‐Liss, Inc.
Elk‐1, CREB, and MKP‐1 regulate Egr‐1 expression in gonadotropin‐releasing hormone stimulated gonadotrophs
Authors: Mayer Sabine I. , Willars Gary B. , Nishida Eisuke , Thiel Gerald 
Published: September 2008

AbstractStimulation of gonadotropin‐releasing hormone (GnRH) receptors with the GnRH analogue buserelin enhances expression of the zinc finger transcription factor Egr‐1 in a pituitary gonadotroph cell line. The signaling cascade is blocked by overexpression of MAP kinase phosphatase‐1 that dephosphorylates extracellular signal‐regulated protein kinase in the nucleus. Chromatin immunoprecipitation experiments revealed that the phosphorylated form of Elk‐1, a key regulator of gene transcription driven by serum response element (SRE), binds to the 5′‐upstream region of the Egr‐1 gene in buserelin‐stimulated gonadotrophs. Expression of a dominant‐negative mutant of Elk‐1 completely blocked Egr‐1 expression, indicating that Elk‐1 connects the intracellular signaling cascade elicited by activation of GnRH receptors with transcription of the Egr‐1 gene. GnRH receptor activation additionally induced the phosphorylation of CREB, which in its phosphorylated form bound to the Egr‐1 gene. Expression of a dominant‐negative mutant of CREB reduced GnRH receptor‐induced upregulation of Egr‐1 expression, indicating that CREB plays a role in the signaling pathway that regulates Egr‐1 expression in gonadotrophs. We further identified the genes encoding basic fibroblast growth factor, tumor necrosis factor α, and transforming growth factor β as bona fide target genes of Egr‐1 in gonadotrophs. The analysis of gonadotroph cells that express—in addition to GnRH receptors—muscarinic M3 acetylcholine receptors revealed that the nuclear events connecting GnRH receptors and muscarinic M3 acetylcholine receptors with the Egr‐1 gene are indistinguishable. J. Cell. Biochem. 105: 1267–1278, 2008. © 2008 Wiley‐Liss, Inc.
Modulation of mouse RANKL gene expression by Runx2 and vitamin D3
Authors: Kitazawa Riko , Mori Kiyoshi , Yamaguchi Akira , Kondo Takeshi , Kitazawa Sohei 
Published: September 2008

AbstractThe expression of receptor activator of nuclear factor‐κB ligand (RANKL) is regulated by bone‐seeking hormones such as PTH and 1α,25‐dihydroxyvitamin D3 (1,25(OH)2D3). Runx2, a master gene for osteoblastic differentiation, also modulates osteoclastogenesis by regulating the RANKL gene. To elucidate the mechanism whereby runx2 and 1,25(OH)2D3 regulate RANKL expression, we studied the function of runx2 on the chromatin structure and on the proximal binding sites using osteoblastic cell lines derived from normal (ST2) and runx2‐deficient mice (RD‐C6). Although the expression of RANKL in the steady‐state was higher in RD‐C6 than in ST2, 1,25(OH)2D3‐treatment of the cells increased it 20‐fold in ST2 but only 1.8‐fold in RD‐C6. Transient transfection studies with proximal RANKL 2kb promoter, runx2 knock‐down in ST2, and forced expression of runx2 in RD‐C6 all confirmed that runx2 set the steady‐state expression of the RANKL gene at a low level, but exerted a positive effect on enhanced transcriptional activity in response to 1,25(OH)2D3. Also, assessment of the acetylation status of the area spanning 40 kb upstream of the basic promoter in ST2 and RD‐C6 by ChIP assay revealed that whereas H3 and H4 histone acetylation was detected even in the steady‐state in RD‐C6, it was detected only with 1,25(OH)2D3 in ST2. In the steady‐state, runx2 may suppress RANKL gene by condensing the chromatin structure; however, it exerts a positive effect on 1,25(OH)2D3‐induced RANKL transcription when the proximal runx2 sites are accessible. Thus, RANKL expression in stromal/osteoblastic cells is keenly regulated by 1,25(OH)2D3 which transactivates the gene at two different levels. J. Cell. Biochem. 105: 1289–1297, 2008. © 2008 Wiley‐Liss, Inc.
Lanthanum enhances in vitro osteoblast differentiation via pertussis toxin‐sensitive gi protein and ERK signaling pathway
Authors: Wang Xi , Yuan Lan , Huang Jian , Zhang Tian‐Lan , Wang Kui 
Published: September 2008

AbstractConverging lines of evidence suggest that lanthanum tends to deposit in bone. The influence of lanthanum ion (La3+) on osteoblast differentiation and the related mechanism are essential to understanding its effect on bone metabolism. In this study, La3+ treatment enhanced in vitro osteoblast differentiation as evidenced by promoting alkaline phosphatase (ALP) activity, osteocalcin (OC) secretion, and matrix mineralization. The expressions of osteoblast‐specific genes of Cbfa‐1, osteopontin (OPN), and bone sialoprotein (BSP) were all increased in the presence of La3+, but no change was observed in that of type I collagen (COL‐I). Further studies demonstrated that La3+ treatment enhanced phosphorylation of extracellular signal‐regulated kinase (ERK). Inhibition of ERK activation by U0126 suppressed the effects of La3+ on osteoblast activity. Moreover, pretreatment of the cells with pertussis toxin (PTx), a Gi protein inhibitor, suppressed the La3+‐enhanced ERK phosphorylation and osteoblast differentiation. These findings suggest that La3+ exposure enhances in vitro osteoblast differentiation and the effect depends on ERK phosphorylation via PTx‐sensitive Gi protein signaling. J. Cell. Biochem. 105: 1307–1315, 2008. © 2008 Wiley‐Liss, Inc.
Cross‐regulation between distinct natural killer T cell subsets influences immune response to self and foreign antigens
Authors: Arrenberg Philomena , Halder Ramesh , Kumar Vipin 
Published: September 2008

AbstractNatural killer T (NKT) cells generally recognize lipid‐antigens presented in the context of the MHC class I‐like molecule CD1d. CD1d‐restricted NKT cells consist of two broad subsets: Type I, which express an invariant T cell receptor (TCR) and type II, which utilize diverse TCR gene segments. A major type II NKT subset has been shown to recognize a self‐glycolipid, sulfatide. Both subsets play important roles in autoimmune diseases, tumor surveillance, and infectious diseases. While type I NKT cells protect from tumor growth by enhancing tumor surveillance, type II NKT cells may suppress anti‐tumor immune responses. In a murine autoimmune hepatitis model, type I NKT cells contribute to pathogenesis, whereas activation of sulfatide‐reactive type II NKT cells protects from disease. Sulfatide‐mediated activation of type II NKT cells results in modification of dendritic cells and induction of anergy in type I NKT cells. Elucidation of this novel pathway of cross‐regulation among NKT cell subsets will provide tools for intervention in autoimmune diseases and for designing strategies for effective anti‐tumor immunity. J. Cell. Physiol. 218: 246–250, 2009. © 2008 Wiley‐Liss, Inc.