bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐Input/Multi‐Output Molecular Response System Based on the Dynamic Redox Behavior of 3,3,4,4‐Tetraaryldihydro[5]helicene Derivatives: Reversible Formation/Destruction of Chiral Fluorophore and Modulation of Chiroptical Properties by Solvent Polarity
Authors: Suzuki Takanori , Ishigaki Yusuke , Iwai Tomohiro , Kawai Hidetoshi , Fujiwara Kenshu , Ikeda Hiroshi , Kano Yusuke , Mizuno Kazuhiko 
Published: July 2009

Abstract3,3,4,4‐Tetaaryldihydro[5]helicenes (1) and 1,1′‐binaphthyl‐2,2′‐diylbis(diarylcarbenium)s (22+) can be reversibly interconverted upon electron transfer, which is accompanied by a vivid color change (electrochromism) as well as by the formation/cleavage of a CC bond (“dynamic redox behavior”). Because only the neutral donor 1 exhibits strong fluorescence, electrochemical input can further modify the fluorescent properties of the pair. Due to the configurational stability of the helicity in 1 and axial chirality in 22+, the redox reaction of optically pure material proceeds stereospecifically, which induces a chiroptical change such as circular dichroism (CD) as an additional output. The CD spectra of dications 22+ exhibit solvent dependency (chiro‐solvatochromism), which is accompanied by solvatochromic behavior based on the π–π interaction of the two cationic chromophores as well as coordinative interaction of the Lewis basic solvent to the Lewis acidic triarylcarbenium moieties. Thus, the present system is endowed with multi‐input functionality for modifying multiple output signals.
Systematic Extraction of Structure–Activity Relationship Information from Biological Screening Data
Authors: Wawer Mathias , Bajorath Jürgen 
Published: July 2009

AbstractA data mining approach is introduced that automatically extracts SAR information from high‐throughput screening data sets and that helps to select active compounds for chemical exploration and hit‐to‐lead projects. SAR pathways are systematically identified consisting of sequences of similar active compounds with gradual increases in potency. Fully enumerated SAR pathway sets are subjected to pathway scoring, filtering, and mining, and pathways with the most significant SAR information content are prioritized. High‐scoring SAR pathways often reveal activity cliffs contained in screening data. Subsets of SAR pathways are analyzed in SAR trees that make it possible to identify microenvironments of significant SAR discontinuity from which hits are preferentially selected. SAR trees of alternative pathways leading to activity cliffs identify key compounds and help to develop chemically intuitive SAR hypotheses.
Watson's analytical approach for immunofluorescence histogram analysis
Authors: Lampariello Francesco 
Published: July 2009

AbstractIn this short note, the key points of the histogram analysis method proposed by Watson (Cytometry 2001;43:55–68) were examined. The complete relationship among the mean values of the distributions on which that method is based was derived analytically. It was shown that the symmetry assumption is not necessary, and that the assumption of equal variances of the unlabeled and labeled cell distributions cannot be verified a posteriori. Moreover, a possible shift between the unlabeled cell distribution in the test and the negative control may greatly influence the estimation of the labeled cell percentage. Finally, by using an experimental set of histograms, it was shown that the assumptions underlying Watson's analytical method are likely not to be fulfilled in real immunofluorescence data. © 2009 International Society for Advancement of Cytometry
Coxsackievirus B4 and type 1 diabetes pathogenesis: contribution of animal models
Authors: Jaïdane H. , Sané F. , Gharbi J. , Aouni M. , Romond M. B. , Hober D. 
Published: July 2009

AbstractThe role of enteroviruses, in particular type B coxsackieviruses (CV‐B), in type 1 diabetes (T1D) pathogenesis is supported by epidemiological, clinical and experimental observations.The investigation of T1D pathogenesis benefits from the contribution of animal models called spontaneously diabetic. Among these animals the non‐obese diabetic (NOD) mouse and the bio‐breeding diabetes‐prone (BBDP) rat present a genetic susceptibility manifested by the expression of an autoimmune diabetes similar to the pathology observed in human beings. Other models whose genetic predisposition is less known are of considerable contribution as well. Numerous major observations relative to several aspects of T1D pathogenesis in the context of CV‐B infections, such as susceptibility, diabetogenicity, pancreatotropism, mechanisms of β cells destruction and others, have been deduced thanks to investigations with animal models.Despite their limits, these models are necessary in improving our knowledge of the role of enteroviruses, like CV‐B4, in the pathogenesis of T1D, and the recent advances ensuing from their contribution may have important therapeutic and preventive spin‐offs. Copyright © 2009 John Wiley & Sons, Ltd.
Acetyl‐CoA carboxylases 1 and 2 show distinct expression patterns in rats and humans and alterations in obesity and diabetes
Authors: Kreuz Sebastian , Schoelch Corinna , Thomas Leo , Rist Wolfgang , Rippmann Jörg F. , Neubauer Heike 
Published: July 2009

AbstractBackgroundAcetyl‐CoA carboxylases (ACC) 1 and 2 are central enzymes in lipid metabolism. To further investigate their relevance for the development of obesity and type 2 diabetes, expression of both ACC isoforms was analyzed in obese fa/fa Zucker fatty and Zucker diabetic fatty rats at different ages in comparison to Zucker lean controls.MethodsACC1 and ACC2 transcript levels were measured by quantitative real‐time polymerase chain reaction in metabolically relevant tissues of Zucker fatty, Zucker diabetic fatty and Zucker lean control animals. Quantitative real‐time polymerase chain reaction was also applied to measure ACC tissue distribution in human tissues. For confirmation on a protein level, quantitative mass spectrometry was used.ResultsDisease‐related transcriptional changes of both ACC isoforms were observed in various tissues of Zucker fatty and Zucker diabetic fatty rats including liver, pancreas and muscle. Changes were most prominent in oxidative tissues of diabetic rats, where ACC2 was significantly increased and ACC1 was reduced compared with Zucker lean control animals. A comparison of the overall tissue distribution of both ACC isoforms in humans and rats surprisingly revealed strong differences. While in rats ACC1 was mainly expressed in lipogenic and ACC2 in oxidative tissues, ACC2 was predominant in oxidative and lipogenic tissues in humans.ConclusionOur data support a potential role for both ACC isoforms in the development of obesity and diabetes in rats. However, the finding of fundamental species differences in ACC1 and ACC2 tissue expression might be indicative for different functions of both isoforms in humans and rats and raises the question to which degree these models are predictive for the physiology and pathophysiology of lipid metabolism in humans. Copyright © 2009 John Wiley & Sons, Ltd.
Tuning Electronic Properties of Biomimetic [2Fe‐2S] Clusters by Ligand Variations (Eur. J. Inorg. Chem. 22/2009)
Authors: Ballmann Joachim , Dechert Sebastian , Demeshko Serhiy , Meyer Franc 
Published: July 2009

AbstractThe cover picture shows the molecular structures of three novel 2,2′‐dithiobiphenyl‐ligated [2Fe‐2S] clusters together with some of their characteristic spectroscopic data. Specifically tailored capping ligands with different substituents in the 3,3′,5,5″positions (tBu, H, Cl) have been applied in order to examine the influence of the ligands on the electronic structures of the [2Fe‐2S] cluster cores. The article by F. Meyer et al. on p. 3219 ff demonstrates that the ligand modifications impose significant changes to the fundamental properties of the clusters, e.g. to their redox potentials. Electrochemical and spectroscopic data in solution and in the solid state (including X‐ray structures) are discussed in detail in this contribution.
Confirmation of immuno‐reactivity of the recombinant major birch pollen allergen Bet v 1a by affinity‐CIEF
Authors: Dullnig Verena , Weiss Richard , Amon Sabine , Rizzi Andreas , Stutz Hanno 
Published: July 2009

AbstractAffinity‐CIEF has been applied to characterize a recombinant product of the major birch pollen allergen Betula verrucosa isoform 1a (Bet v 1a) immuno‐chemically. For this purpose mAbs of the IgG‐type have been produced in‐lab from two murine hybridoma lines, specified as clones 2 and 5.1. Both IgG clones were characterized by SDS‐PAGE, MALDI‐TOF‐MS and CIEF. The purified IgG solutions had to be dialysed against 10 mmol/L phosphate (pH 7.4) to prevent IgG precipitation and to ensure appropriate CIEF separation. Both tested monoclonal IgGs (mIgGs) comprised four constituents covering pI ranges of 6.98–7.09 and 6.78–7.03 for clones 2 and 5.1 with major peaks at pI 7.09 and 7.03, respectively. When increasing amounts of Bet v 1a (pI 4.95) were incubated with 2.0 μmol/L mIgG, novel peaks were progressively induced in a pI range slightly more acidic than the focusing region of mIgGs. These peaks grew on the expense of original mIgG peaks. All pI values were calculated using two pI marker compounds with a repeatability of better than 0.03 units. New peaks represent complexes between Bet v 1a and mIgG either of 1:1 or of 2:1 binding stoichiometry. At a molar ratio of 2:1, saturation of both IgG paratopes with allergen (Ag) molecules was achieved as indicated by unbound Bet v 1a. The current CIEF approach addresses the proof of single epitope integrity in the course of immuno‐chemical characterization of Bet v 1a. Contrary to traditional immunoassays, affinity CIEF allows for a distinction and relative quantification of mAbs, Ag–antibody complexes and Ag variants coexisting in one sample.
Protein nitration during defense response in Arabidopsis thaliana
Authors: Cecconi Daniela , Orzetti Stefano , Vandelle Elodie , Rinalducci Sara , Zolla Lello , Delledonne Massimo 
Published: July 2009

AbstractNitric oxide and reactive oxygen species play a key role in the plant hypersensitive disease resistance response, and protein tyrosine nitration is emerging as an important mechanism of their co‐operative interaction. Up to now, the proteins targeted by this post‐translational modification in plants are still totally unknown. In this study, we analyzed for the first time proteins undergoing nitration during the hypersensitive response by analyzing via 1D‐ and 2D‐western blot the protein extracts from Arabidopsis thaliana plants challenged with an avirulent bacterial pathogen (Pseudomonas syringae pv. Tomato). We show that the plant disease resistance response is correlated with a modulation of nitration of proteins involved in important cellular process, such as photosynthesis, glycolysis and nitrate assimilation. These findings shed new light on the signaling functions of nitric oxide and reactive oxygen species, paving the way on studies on the role of this post‐translational modification in plants.
Determination of liposome–buffer distribution coefficients of charged drugs by capillary electrophoresis frontal analysis
Authors: Franzen Ulrik , Jorgensen Lene , Larsen Claus , Heegaard Niels H. H. , Østergaard Jesper 
Published: July 2009

AbstractThe potential of using CE frontal analysis (CE‐FA) to study the interactions between a range of charged low molecular weight drug substances and liposomes was evaluated. The liposomes used were net negatively charged and consisted of 2‐oleoyl‐1‐palmitoyl‐sn‐glycero‐3‐phosphocholine and 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphate monosodium salt in a ratio of 80/20 mol%. Apparent distribution coefficients (Dmem), defined as the molar concentration of drug substance in the membrane phase divided by the molar concentration of drug substance in the aqueous phase, were successfully determined for six positively and eight negatively charged drug substances with log Dmem ranging from 1.35 to 3.63. The extent of liposome–buffer distribution was found to be dependent on the drug concentration. The results obtained with the developed CE‐FA method were in good agreement with results obtained by equilibrium dialysis. Furthermore, the CE‐FA method was faster, less labor intensive and required smaller sample volumes (∼50 μL) compared with equilibrium dialysis. Thus, CE‐FA is an efficient and useful tool for the characterization of interactions between liposomes and low molecular weight drug substances.
Extracting long‐term patterns of population changes from sporadic counts of migrant birds
Authors: Flemming Joanna Mills , Cantoni Eva , Field Christopher , McLaren Ian 
Published: July 2009

AbstractDeclines of many North American birds are of conservation concern. For almost 40 years, experienced birders have kept daily counts of migrant landbirds during visits to Seal and Brier Islands, both of which are off Nova Scotia's southern tip. Here we assess the utility of Generalized Additive Models (GAMs) to extract patterns of population change of a common migrant to Seal Island, the Ruby‐crowned Kinglet, while controlling for other influences including season, weather and effort. We also demonstrate, using counts of the Kinglet from Brier Island as well as counts of another common migrant, the Yellow‐rumped Warbler, how our GAM methods can combine data from different geographic areas or distinct species. Most existing analyses of similar long‐term data sets have used linear models to estimate trends. Our results and comparisons suggest that GAMs are a powerful way of extracting more information from such data. Copyright © 2009 John Wiley & Sons, Ltd.
Hybrid testing and modeling of a suspended zipper steel frame
Authors: Stavridis Andreas , Shing P. B. 
Published: July 2009

AbstractAn analytical and experimental study has been conducted to evaluate the seismic performance of a three‐story suspended zipper steel frame. The frame was concentrically braced and had zipper struts to transfer the unbalanced forces induced on the beams due to the buckling of the lower‐story braces. The experimental study was conducted with the hybrid test technique, in which only the bottom‐story braces of the three‐story frame were physically tested, while the behavior of the rest of the frame was modeled using a general structural analysis software. The paper discusses issues pertinent to the calibration of the computer model for the analytical substructure as well as for the entire frame, including the selection of an appropriate damping matrix, and the modeling of the buckling behavior of the braces and bracing connections. The analytical model of the entire frame was validated with the hybrid tests and was able to accurately capture the material and geometric nonlinearities that developed when the braces yielded and buckled. This study has demonstrated the usefulness of hybrid testing in improving analytical models and modeling assumptions and providing information that cannot be obtained from an analytical study alone. The results have shown that the suspended zipper frame can distribute the brace nonlinearity over the first two stories as intended in the design and will not have catastrophic failure under the design‐level earthquakes considered in this study, despite the significant inelastic deformations. Copyright © 2009 John Wiley & Sons, Ltd.
Calpain activation by hepatitis C virus proteins inhibits the extrinsic apoptotic signaling pathway #
Authors: Simonin Yannick , Disson Olivier , Lerat Hervé , Antoine Etienne , Binamé Fabien , Rosenberg Arielle R. , Desagher Solange , Lassus Patrice , Bioulac-Sage Paulette , Hibner Urszula 
Published: July 2009

Abstract
An unresolved question regarding the physiopathology of hepatitis C virus (HCV) infection is the remarkable efficiency with which host defenses are neutralized to establish chronic infection. Modulation of an apoptotic response is one strategy used by viruses to escape immune surveillance. We previously showed that HCV proteins down-regulate expression of BH3-only Bcl2 interacting domain (Bid) in hepatocytes of HCV transgenic mice. As a consequence, cells acquire resistance to Fas-mediated apoptosis, which in turn leads to increased persistence of experimental viral infections in vivo. This mechanism might participate in the establishment of chronic infections and the resulting pathologies, including hepatocellular carcinoma. We now report that Bid is also down-regulated in patients in the context of noncirrhotic HCV-linked tumorigenesis and in the HCV RNA replicon system. We show that the nonstructural HCV viral protein NS5A is sufficient to activate a calpain cysteine protease, leading to degradation of Bid. Moreover, pharmacological inhibitors of calpains restore both the physiological levels of Bid and the sensitivity of cells toward a death receptor–mediated apoptotic signal. Finally, human HCV-related tumors and hepatocytes from HCV transgenic mice that display low Bid expression contain activated calpains. Conclusion: Calpains activated by HCV proteins degrade Bid and thus dampen apoptotic signaling. These results suggest that inhibiting calpains could lead to an improved efficiency of immune-mediated elimination of HCV-infected cells. (Hepatology 2009.)
Modulation of glycosphingolipid metabolism significantly improves hepatic insulin sensitivity and reverses hepatic steatosis in mice #
Authors: Bijl Nora , Sokolović Milka , Vrins Carlos , Langeveld Mirjam , Moerland Perry D. , Ottenhoff Roelof , van Roomen Cindy P. A. A. , Claessen Nike , Boot Rolf G. , Aten Jan , Groen Albert K. , Aerts Johannes M. F. G. , van Eijk Marco 
Published: July 2009

Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. The hyperinsulinemia that occurs as a consequence of insulin resistance is thought to be an important contributor to the development of fatty liver. We have shown that the iminosugar N-(5′-adamantane-1′-yl-methoxy)-pentyl-1-deoxynojirimycin (AMP-DNM), an inhibitor of the enzyme glucosylceramide synthase, is a potent enhancer of insulin signaling in rodent models for insulin resistance and type 2 diabetes. The present study was designed to assess the impact of AMP-DNM on insulin levels, liver triglyceride synthesis, and gene expression profile. Treatment of ob/ob mice with AMP-DNM restored insulin signaling in the liver, corrected blood glucose values to levels found in lean mice, and decreased insulin concentration. The expression of sterol regulatory element-binding protein 1c target genes involved in fatty acid synthesis normalized. AMP-DNM treatment significantly reduced liver to body weight ratio and reversed hepatic steatosis, comprising fat as well as inflammatory markers. In addition, AMP-DNM treatment corrected to a large extent the gene expression profile of ob/ob mice livers toward the profile of lean mice. Conclusion: Pharmacological lowering of glycosphingolipids with the iminosugar AMP-DNM is a promising approach to restore insulin signaling and improve glucose homeostasis as well as hepatic steatosis. (Hepatology 2009.)
Farnesyltransferase inhibitors reduce ras activation and ameliorate acetaminophen-induced liver injury in mice #
Authors: Saha Banishree , Nandi Dipankar 
Published: July 2009

Abstract
Hepatotoxicity due to overdose of the analgesic and antipyretic acetaminophen (APAP) is a major cause of liver failure in adults. To better understand the contributions of different signaling pathways, the expression and role of Ras activation was evaluated after oral dosing of mice with APAP (400–500 mg/kg). Ras–guanosine triphosphate (GTP) is induced early and in an oxidative stress-dependent manner. The functional role of Ras activation was studied by a single intraperitoneal injection of the neutral sphingomyelinase and farnesyltransferase inhibitor (FTI) manumycin A (1 mg/kg), which lowers induction of Ras-GTP and serum amounts of alanine aminotransferase (ALT). APAP dosing decreases hepatic glutathione amounts, which are not affected by manumycin A treatment. However, APAP-induced activation of c-Jun N-terminal kinase, which plays an important role, is reduced by manumycin A. Also, APAP-induced mitochondrial reactive oxygen species are reduced by manumycin A at a later time point during liver injury. Importantly, the induction of genes involved in the inflammatory response (including iNos, gp91phox, and Fasl) and serum amounts of proinflammatory cytokines interferon-γ (IFNγ) and tumor necrosis factor α, which increase greatly with APAP challenge, are suppressed with manumycin A. The FTI activity of manumycin A is most likely involved in reducing APAP-induced liver injury, because a specific neutral sphingomyelinase inhibitor, GW4869 (1 mg/kg), did not show any hepatoprotective effect. Notably, a structurally distinct FTI, gliotoxin (1 mg/kg), also inhibits Ras activation and reduces serum amounts of ALT and IFN-γ after APAP dosing. Finally, histological analysis confirmed the hepatoprotective effect of manumycin A and gliotoxin during APAP-induced liver damage. Conclusion: This study identifies a key role for Ras activation and demonstrates the therapeutic efficacy of FTIs during APAP-induced liver injury. (Hepatology 2009.)
Long-term exclusive zinc monotherapy in symptomatic Wilson disease: Experience in 17 patients #
Authors: Linn Francisca H. H. , Houwen Roderick H. J. , van Hattum Jan , van der Kleij Stefan , van Erpecum Karel J. 
Published: July 2009

Abstract
Exclusive monotherapy with zinc in symptomatic Wilson disease is controversial. Seventeen symptomatic patients with Wilson disease were treated with zinc only. The mean age at diagnosis and start of treatment was 18 years (range 13–26) with approximately half presenting as adolescents. Presentation was exclusively hepatic, exclusively neurologic, and combined in seven, five, and five patients, respectively. The median follow-up was 14 years (range 2–30). At baseline, two of the 12 patients with hepatic disease exhibited decompensated cirrhosis, five exhibited compensated cirrhosis, and five had less severe disease. Both patients with decompensated cirrhosis improved to a compensated state after initiation of therapy. Two of the five patients with initial compensated cirrhosis progressed to decompensated state, and three remain stable. Three of the five patients with moderate or mild liver disease remain stable and two improved. Apart from decreasing bilirubin levels, no significant changes occurred in the liver biochemistry or function during long-term follow-up. Nine of 10 neurologic patients improved markedly and one deteriorated. Two patients with exclusively neurologic presentation developed liver disease during zinc treatment. Two patients with exclusively hepatic presentation developed mild neurologic symptoms. According to 24-hour urinary copper excretions (213 ± 38 versus 91 ± 23 μg: P = 0.01) and serum non–ceruloplasmin-bound copper concentrations (11 ± 2 versus 7 ± 1 μg/dL: P = 0.1) at the end of follow-up, the efficacy of decoppering was less in the exclusively hepatic than in the neurologic group. The prescribed zinc dose and 24-hour urinary zinc excretions tended to be less in the exclusively hepatic group. Conclusion: The outcome of exclusive zinc therapy is generally good in cases of neurologic disease. A less satisfactory outcome in hepatic disease may relate to less efficient decoppering. (Hepatology 2009.)