bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantum chemical study of leaving group activation in T. vivax nucleoside hydrolase
Authors: Loverix Stefan , Versees Wim , Steyaert Jan , Geerlings Paul 
Published: September 2005

AbstractGeneral acid catalysis is a powerful and widely used strategy in enzymatic nucleophilic displacement reactions. However, in the nucleoside hydrolase of the parasite Trypanosoma vivax, crystallographic and mutagenesis studies failed to identify a general acid. The only groups in the vicinity of the leaving group that contribute to catalysis are (i) the indole side chain of Trp260, and (ii) the 5′‐group of the substrate's ribose moiety. The x‐ray structure of the slow Asp10Ala mutant of nucleoside hydrolase with the substrate inosine bound in the active site displays a face‐to‐face aromatic stacking interaction between Trp260 and the purine base of the substrate, as well as a peculiar C4′‐endo ribose pucker that allows the 5′‐OH group to accept an intramolecular hydrogen bond from the C8 of the purine. The first interaction (aromatic stacking) has been shown to raise the pKa of the leaving purine. Here, we present a DFT study showing that the 5′‐OH group of ribose fulfills a similar role, rather than stabilizing the oxocarbenium‐like transition state. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Water: How to evaluate its contribution in protein–ligand interactions
Authors: Cozzini Pietro , Fornabaio Micaela , Mozzarelli Andrea , Spyrakis Francesca , Kellogg Glen E. , Abraham Donald J. 
Published: September 2005

AbstractWater can be considered the most important molecule in living systems. It can play a variety of roles: (a) the solvent of most biological molecules, (b) substrate and product of enzyme catalysis, (c) a building block of macromolecules, or (d) functioning as a “lubricant” via the formation of networks linking distant residues. In particular, protein–protein, protein–nucleic acid, and protein–ligand recognition are water dependent via both enthalpic and entropic contributions. We present a computational approach based on the natural force field Hydropathic INTeractions (HINT) that incorporates atomic LogPoctanol/water data, to evaluate the strength of the interaction between water molecules and protein, as well as the contribution of water molecules bridging protein and ligand to the free energy of binding. We describe the rules for characterizing the binding/energetic roles of water molecules located at ligand binding sites. As an example, results from a set of 23 HIV‐1 protease ligand complexes are described. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Characterization of gingerol‐related compounds in ginger rhizome (Zingiber officinale Rosc.) by high‐performance liquid chromatography/electrospray ionization mass spectrometry
Authors: Jiang Hongliang , Sólyom Anikó M. , Timmermann Barbara N. , Gang David R. 
Published: September 2005

AbstractThis study sought to determine the utility of liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS) coupled with diode array detection in identifying gingerol‐related compounds from crude extracts of ginger rhizome. The fragmentation behaviors of compounds in both (−)‐ and (+)ESI‐MS/MS were used to infer and confirm the chemical structures of several groups of compounds, including the gingerols, methylgingerols, gingerol acetates, shogaols, paradols, gingerdiols, mono‐ and diacetyl gingerdiols, and dehydrogingerdiones. Diode array detection at different wavelengths was used to confirm MS/MS‐based identification. In total, 31 gingerol‐related compounds were identified from the methanolic crude extracts of fresh ginger rhizome in this study. Three of these compounds were found to be new compounds. This study demonstrated that LC/ESI‐MS/MS is a powerful on‐line tool for identification of gingerol‐related compounds, especially for thermally labile compounds that cannot be readily detected by GC/MS analysis. Copyright © 2005 John Wiley & Sons, Ltd.
Inferences on the mean of zero‐inflated lognormal data: the generalized variable approach
Authors: Tian Lili 
Published: September 2005

AbstractThis paper considers the problems of confidence interval estimation and hypothesis testing for the mean of zero‐inflated lognormal data. We present an unified novel approach based on the concepts of generalized test variables and generalized pivotal quantities. Simulation results demonstrate that the coverage accuracy of proposed confidence intervals and the type I error control of the proposed exact tests are satisfactory. Copyright © 2005 John Wiley & Sons, Ltd.
A new approach to sample size calculation for reference interval studies
Authors: Jennen‐Steinmetz C. , Wellek S. 
Published: September 2005

AbstractA new criterion is proposed for determining the sample size required for a study performed for the purpose of establishing reference intervals. The basic idea behind the criterion is to compare the empirical coverage (i.e. the probability content) of the reference region obtained from the sample with its target value (e.g. 95 per cent) and to set suitable limits δ1, δ2 to the difference between both quantities which must not be exceeded with sufficiently large probability β (e.g. β=90 per cent). For the most frequently used parametric and distribution‐free methods of estimating univariate reference limits, implicit formulae are derived relating the sample size to the design parameters δ1, δ2 and β. For symmetric specification of (δ1, δ2), explicit approximation formulae for the computation of n are given. Exact values obtained by means of suitable numerical techniques are presented in a set of tables covering specifications of δ1, δ2 and β which can be recommended for real applications. The tables can be used both for one‐ and two‐sided reference intervals. Copyright © 2005 John Wiley & Sons, Ltd.
The role of dipeptidyl peptidase IV (DP IV, CD26) in T cell activation and multiple sclerosis
Authors: Reinhold Dirk , Kähne Thilo , Steinbrecher Andreas , Gerber Annegret , Preller Vera , Gornickel Bettina , Wrenger Sabine , Ansorge Siegfried , Brocke Stefan 
Published: September 2005

AbstractThe ectoenzyme dipeptidyl peptidase IV (DP IV; E.C. 3.4.14.5; CD26) plays a crucial role in T cell activation, representing a new type of costimulatory T cell structure. Effectors of DP IV‐like activity, including naturally occurring and specific synthetic inhibitors, suppress DNA synthesis as well as cytokine production (IL‐2, IL‐10, IL‐12, IFN‐γ) of stimulated T cells. These effects are in part caused by the immunosuppressive cytokine TGF‐β1, leading to blockade of the cell cycle at the restriction point G1/S via p27kip. At the same time, DP IV inhibitors provoke tyrosine phosphorylation and p38 MAP kinase activation. Elevated numbers of CD26+T cells were observed in patients with autoimmune diseases such as rheumatoid arthritis or multiple sclerosis (MS). The expression of DP IV/CD26 in resting T cell clones derived from patients with MS was found to be 3‐ to 4‐fold higher than on resting peripheral blood T cells from healthy persons. In myelin‐specific T cells from MS patients, DP IV inhibitors suppress DNA synthesis, as well as IFN‐γ, IL‐4 and TNF‐α production. Moreover, in experimental autoimmune encephalomyelitis (EAE), a well characterized CD4+T cell‐mediated autoimmune disease leading to CNS inflammation and demyelinization, administration of a DP IV/CD26 inhibitor prevents clinical and neuropathological signs of EAE and suppresses ongoing disease. This review summarizes evidence for the role of DP IV enzyme activity in regulation of T cell activation, outlines signal transduction mechanisms used or affected by this enzyme and provides support for the concept of a novel peptidase‐based immunosuppressive approach to treat autoimmune diseases like MS.
Are parental health habits transmitted to their children? An eight year longitudinal study of physical activity in adolescents and their parents
Authors: Anderssen Norman , Wold Bente , Torsheim Torbj⊘rn 
Published: September 2005

ABSTRACTParents are believed to play a role in influencing their children's health behaviours. This longitudinal study of two generations (parents and their children) examined associations between parents’ self‐reported leisure‐time physical activity changes and the self‐reported physical activity changes of their offspring in a sample of 557 adolescents over an 8 year period (from 13 to 21 years of age). The results revealed only weak and non‐existent associations between changes in parents’ physical activity and changes in adolescent physical activity from 13 to 21 years of age. The findings did not support the hypothesis that adolescents’ leisure‐time physical activity covaried with their parents’ leisure‐time physical activity over time. This may mean that parental physical activity is not transmitted to their children to the degree that is often believed.
Friendship group identification, multidimensional self‐concept, and experience of developmental tasks in adolescence
Authors: Tarrant Mark , MacKenzie Liam , Hewitt Lisa A 
Published: September 2005

ABSTRACTThis study applied a social identity perspective to the study of adolescent self‐concept and social development. British adolescents aged 14–15 years () completed a questionnaire which asked them to: (i) rate their degree of identification with a school‐based friendship group; (ii) complete a measure of multi‐dimensional self‐concept; and (iii) report their experiences of a variety of personal, relational and socio‐institutional (e.g., achieving economic independence) developmental tasks. Compared to low identifiers, participants who were highly identified with a friendship group reported highest levels of self‐esteem; and these differences were most marked in non‐academic domains of self. High identifiers also displayed higher levels of general self‐esteem and reported more positive experiences of personal and relational developmental tasks. The discussion focuses on the potential benefits to understanding of social developmental processes that can be derived from a consideration of adolescents’ subjective appraisals of their peer relations.
Activation of peroxisome proliferator‐activated receptor‐α and ‐γ in auricular tissue from heart failure patients
Authors: Gómez‐Garre Dulcenombre , Herraíz Marta , González‐Rubio Ma Luisa , Bernal Rosa , Aragoncillo Paloma , Carbonell Amparo , Rufilanchas Juan José , Fernández‐Cruz Arturo 
Published: September 2005

AbstractObjective:Peroxisome proliferator‐activated receptors (PPARs), key transcriptional regulators of lipid and energy metabolism in cardiomyocytes, have recently been proposed to modulate cardiovascular pathophysiological responses in experimental models. However, there is little information about the functional activity of PPARs in human heart failure.Aims:To investigate PPAR‐α and ‐γ expression and activity, and the association with ET‐1 production and fibrosis, in cardiac biopsies from patients with end‐stage heart failure due to ischemic cardiomyopathy (ICM) in comparison and from non‐failing donor hearts. All samples were obtained during cardiac transplantation.Methods and results:Morphological analysis (by Masson trichrome and image analysis) did not detect fibrosis in the left atrium from non‐failing donors (NFLA) or from ICM patients (FLA). However, left ventricles from failing hearts (FLV) contained a greater number of fibrotic areas (NFLA: 3.21±1.15, FLA: 1.63±0.83, FLV: 14.5±3.45%; n=9, P<0.05). By RT‐PCR, preproET‐1 expression was similar in the non‐failing and failing atrium but was significantly higher in the ventricles from failing hearts (NFLA: 1.00±0.06, FLA: 1.08±0.11, FLV: 1.74±0.19; n=9, P<0.05). PPAR‐α and PPAP‐γ mRNA (by RT‐PCR) and protein (by Western blot) levels were higher in the ventricles from failing hearts compared with the atrium from failing and non‐failing hearts. Electrophoretic mobility shift assays showed that PPAR‐α and PPAP‐γ were not activated in the ventricles (NFLA: 1.00±0.11, FLA: 1.89±0.24, FLV: 0.95±0.07; n=9, P<0.05).Conclusions:These data suggest that PPAR‐α and PPAP‐γ are selectively activated in the atria from ICM patients and might be functionally important in the maintenance of atrial morphology.
Role of β1‐ and α2c‐adrenergic receptor polymorphisms and their combination in heart failure: A case‐control study
Authors: Metra Marco , Zani Claudia , Covolo Loredana , Nodari Savina , Pezzali Natalia , Gelatti Umberto , Donato Francesco , Nardi Giuseppe , Cas Livio Dei 
Published: September 2005

AbstractBackground:Adrenergic activation has a central role in the development of HF. The function of the β1‐ and the α2C‐adrenergic receptors is influenced by gene polymorphisms: the β1Arg389 variant is associated with increased β1‐receptor sensitivity and the α2C‐receptor Del322–325 variant is associated with decreased α2C receptor function and increased norepinephrine release. We hypothesised that these polymorphisms could influence the prevalence of heart failure.Methods:The role of the β1‐ and α2C‐adrenergic receptor gene polymorphisms as risk factors for heart failure (HF) was assessed in an Italian white Caucasian population using a case‐control study design. Genomic DNA was analysed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RLFP).Results:We compared 260 Caucasian patients with HF and 230 normal subjects. The β1Arg389 allele was frequent both in the patients with HF (69%) and in the normal subjects (73%). The α2CDel322–325 variant was rare in both groups (9% and 8%, respectively). Patients homozygotes for either the β1Arg389 or the α2CDel322–325 alleles had no increased risk of HF (odds ratio [OR], 0.8; 95%CI: 0.5—1.2 and OR, 0.8; 95% CI: 0.4—1.8, respectively). Patients homozygotes for both the β1Arg389 and the α2CDel322–325 alleles had no increased risk of HF as well (OR: 0.6; 95% CI: 0.2—2.1).Conclusions:β1‐ARs and α2C‐ARs polymorphisms are not associated with an increased risk of HF in an Italian white Caucasian population.
Independent and incremental prognostic value of endogenous ouabain in idiopathic dilated cardiomyopathy
Authors: Pitzalis Maria Vittoria , Hamlyn John M. , Messaggio Elisabetta , Iacoviello Massimo , Forleo Cinzia , Romito Roberta , de Tommasi Elisabetta , Rizzon Paolo , Bianchi Giuseppe , Manunta Paolo 
Published: September 2005

AbstractIncreased circulating levels of endogenous ouabain (EO) have been observed in some heart failure patients, but their long term clinical significance is unknown. This study investigated the prognostic value of EO for worsening heart failure among 140 optimally treated patients (age 50±14 years; 104 male; NYHA class 1.9±0.7) with idiopathic dilated cardiomyopathy. Plasma EO was determined by RIA and by liquid chromatography mass spectrometry, values were linearly correlated (r=0.89) in regression analysis. During follow‐up (13±5 months), heart failure progression was defined as worsening clinical condition leading to one or more of the following: sustained increase in conventional therapies, hospitalization, cardiac transplant, or death. NYHA functional class, age, LVEF, peak VO2and plasma levels of EO were predictive for heart failure progression. Heart failure worsened 1.5 fold (HR: 1.005; 95% CI: 1.001—1.007;p<0.01) for each 100 pmol/L increase in plasma EO. Moreover, those patients with higher plasma EO values had an odds ratio of 5.417 (95% CI: 2.044—14.355;p<0.001) for heart failure progression. Following multivariate analysis, LVEF, NYHA class and plasma EO remained significantly linked with clinical events. This study provides the first evidence that circulating EO is a novel, independent and incremental marker that predicts the progression of heart failure.
Decreased expression of AQP2 and AQP4 water channels and Na, K‐ATPase in kidney collecting duct in AQP3 null mice
Authors: Wan Kim Soo , Gresz Veronika , Rojek Aleksandra , Wang Weidong , Verkman A.S. , Frøkiær Jørgen , Nielsen Søren 
Published: September 2005

Background information. Phenotype analysis has demonstrated that AQP3 (aquaporin 3) null mice are polyuric and manifest a urinary concentration defect. In the present study, we report that deletion of AQP3 is also associated with an increased urinary sodium excretion. To investigate further the mechanism of the decreased urinary concentration and significant natriuresis, we examined the segmental and subcellular localization of collecting duct AQPs [AQP2, p‐AQP2 (phosphorylated AQP2), AQP3 and AQP4], ENaC (epithelial sodium channel) subunits and Na, K‐ATPase by immunoperoxidase and immunofluorescence microscopy in AQP3 null (−/−), heterozygous (+/−) mice, wild‐type and unrelated strain of normal mice.Results. The present study confirms that AQP3 null mice exhibit severe polyuria and polydipsia and demonstrated that they exhibit increased urinary sodium excretion. In AQP3 null mice, there is a marked down‐regulation of AQP2 and p‐AQP2 both in CNT (connecting tubule) and CCD (cortical collecting duct). Moreover, AQP4 is virtually absent from CNT and CCD in AQP3 null mice. Basolateral AQP2 was virtually absent from AQP3 null mice and normal mice in contrast with rat. Thus the above results demonstrate that no basolateral AQPs are expressed in CNT and CCD of AQP3 null mice. However, in the medullary‐collecting ducts, there is no difference in the expression levels and subcellular localization of AQP2, p‐AQP2 and AQP4 between AQP3 +/− and AQP3 null mice. Moreover, a striking decrease in the immunolabelling of the α1 subunit of Na, K‐ATPase was observed in CCD in AQP3 null mice, whereas a medullary‐collecting duct exhibited normal labelling. Immunolabelling of all the ENaC subunits in the collecting duct was comparable between the two groups.Conclusions. The results improve the possibility that the severe urinary concentrating defect in AQP3 null mice may in part be caused by the decreased expression of AQP2, p‐AQP2 and AQP4 in CNT and CCD, whereas the increased urinary sodium excretion may in part be accounted for by Na, K‐ATPase in CCD in AQP3 null mice.
Training and aging modulate the loss‐of‐balance phenotype observed in a new ENU‐induced allele of Otopetrin1
Authors: Besson Vanessa , Nalesso Valérie , Herpin Alexandre , Bizot Jean‐Charles , Messaddeq Nadia , Romand Raymond , Puech Anne , Blanquet Véronique , Hérault Yann 
Published: September 2005

Background information. The sensing of head movement in mammals depends upon the vestibular endorgan of the inner ear, a complex structure made up of the semicircular canals and otoliths. Due to the similarity between the human and mouse vestibular apparatus, the analysis of mutant mouse is a valuable strategy aiming to identify genes involved in the control of balance and movement.Results. In the course of a genome‐wide chemical‐mutagenesis programme, we isolated a recessive mutation, named ied (inner ear defect), which induced a severe loss‐of‐balance. A detailed phenotypic analysis of the mutant mice demonstrates that the balance impairment does not affect the motor activity and can be rescued, in part, by training, despite a complete agenesis of otoconia in the utricule and the saccule of the inner ear. Molecular characterization of the ied mutation revealed a transversion that affects the splicing of the second exon of the Otopetrin1 gene located on mouse chromosome 5. The consequence of such a mutation leads to a disruption of the transcription of the gene.Conclusions. The identification of the ied knock‐down allele strengthens the role of the Otopetrin1 in the sensing of balance. Moreover, the rescue of the ied mutant phenotype in specific behavioural tasks confirmed that other sensory inputs or neural plasticity can compensate, to some extent, for the loss‐of‐balance. In the future, the ied mutant mice might be helpful to study the genetic control of the compensation strategies developed by organisms to counteract balance defects.
Activation of Mrc1, a mediator of the replication checkpoint, by telomere erosion
Authors: Grandin Nathalie , Bailly Aymeric , Charbonneau Michel 
Published: September 2005

Background information. In budding yeast, the loss of either telomere sequences (in telomerase‐negative cells) or telomere capping (in mutants of two telomere end‐protection proteins, Cdc13 and Yku) lead, by distinct pathways, to telomeric senescence. After DNA damage, activation of Rad53, which together with Chk1 represents a protein kinase central to all checkpoint pathways, normally requires Rad9, a checkpoint adaptor.Results. We report that in telomerase‐negative (tlc1Δ) cells, activation of Rad53, although diminished, could still take place in the absence of Rad9. In contrast, Rad9 was essential for Rad53 activation in cells that entered senescence in the presence of functional telomerase, namely in senescent cells bearing mutations in telomere end‐protection proteins (cdc13‐1 yku70Δ). In telomerase‐negative cells deleted for RAD9, Mrc1, another checkpoint adaptor previously implicated in the DNA replication checkpoint, mediated Rad53 activation. Rad9 and Rad53, as well as other DNA damage checkpoint proteins (Mec1, Mec3, Chk1 and Dun1), were required for complete DNA‐damage‐induced cell‐cycle arrest after loss of telomerase function. However, unexpectedly, given the formation of an active Rad53–Mrc1 complex in tlc1Δ rad9Δ cells, Mrc1 did not mediate the cell‐cycle arrest elicited by telomerase loss. Finally, we report that Rad9, Mrc1, Dun1 and Chk1 are activated by phosphorylation after telomerase inactivation.Conclusions. These results indicate that loss of telomere capping and loss of telomere sequences, both of which provoke telomeric senescence, are perceived as two distinct types of damages. In contrast with the Rad53–Rad9‐mediated cell‐cycle arrest that functions in a similar way in both types of telomeric senescence, activation of Rad53–Mrc1 might represent a specific response to telomerase inactivation and/or telomere shortening, the functional significance of which has yet to be uncovered.
Oxidation of heparan sulphate by hypochlorite: role of N-chloro derivatives and dichloramine-dependent fragmentation
Authors: Rees Martin D. , Pattison David I. , Davies Michael J. 
Published: September 2005

Activated phagocytes release the haem enzyme MPO (myeloperoxidase) and produce superoxide radicals and H2O2 via an oxidative burst. MPO uses H2O2 and Cl− to form HOCl, the physiological mixture of hypochlorous acid and its anion present at pH 7.4. As MPO binds to glycosaminoglycans, oxidation of extracellular matrix and cell surfaces by HOCl may be localized to these materials. However, the reactions of HOCl with glycosaminoglycans are poorly characterized. The GlcNAc (N-acetylglucosamine), GlcNSO3 (glucosamine-N-sulphate) and GlcNH2 [(N-unsubstituted) glucosamine] residues of heparan sulphate are potential targets for HOCl. It is shown here that HOCl reacts with each of these residues to generate N-chloro derivatives, and the absolute rate constants for these reactions have been determined. Reaction at GlcNH2 residues yields chloramines and, subsequently, dichloramines with markedly slower rates, k2∼3.1×105 and 9 M−1·s−1 (at 37 °C) respectively. Reaction at GlcNSO3 and GlcNAc residues yields N-chlorosulphonamides and chloramides with k2∼0.05 and 0.01 M−1·s−1 (at 37 °C) respectively. The corresponding monosaccharides display a similar pattern of reactivity. Decay of the polymer-derived chloramines, N-chlorosulphonamides and chloramides is slow at 37 °C and does not result in major structural changes. In contrast, dichloramine decay is rapid at 37 °C and results in fragmentation of the polymer backbone. Computational modelling of the reaction of HOCl with heparan sulphate proteoglycans (glypican-1 and perlecan) predicts that the GlcNH2 residues of heparan sulphate are major sites of attack. These results suggest that HOCl may be an important mediator of damage to glycosaminoglycans and proteoglycans at inflammatory foci.