bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specificity of an extracellular proteinase from Conidiobolus coronatus and its inhibition by an inhibitor from insect hemolymph
Authors: Bania Jacek , Samborski Jaroslaw , Bogus Mieczyslawa , Polanowski Antoni 
Published: July 2006

AbstractThe relatively little‐investigated entomopathogen Conidiobolus coronatus secretes several proteinases into culture broth. Using a combination of ion‐exchange and size‐exclusion chromatography, we purified to homogeneity a serine proteinase of Mr 30,000–32,000, as ascertained by SDS‐PAGE. The purified enzyme showed subtilisin‐like activity. It very effectively hydrolyzed N‐Suc‐Ala2‐Pro‐Phe‐pNa with a Km‐1.36 × 10–4 M and Kcat‐24 s–1, and N‐Suc‐Ala2‐Pro‐Leu‐pNa with Km‐6.65 × 10–4 M and Kcat‐11 s–1. The specificity index kcat/Km for the tested substrates was calculated to be 176,340 s–1 M–1 and 17,030 s–1 M–1, respectively. Using oxidized insulin B chain as a substrate, the purified proteinase exhibited specificity to aromatic and hydrophobic amino‐acid residues, such as Phe, Leu, and Gly at the P1 position, splitting primarily the peptide bonds: Phe1‐Val2, Leu15‐Tyr16, and Gly23‐Phe24. The proteinase appeared to be sensitive to the specific synthetic inhibitors of the serine proteinases DFP (diisopropyl flourophosphate) and PMSF (phenyl‐methylsulfonyl fluoride) as well as to some naturally occurring protein inhibitors of chymotrypsin. It is worth noting that the enzyme exhibited the highest sensitivity to inhibition by AMCI‐1 (with an association constant of 3 × 1010 M–1), an inhibitor of cathepsin G/chymotrypsin from the larval hemolymph of Apis mellifera, reinforcing the possibility of involvement of inhibitors from hemolymph in insect innate immunity. The substrate specificity and proteinase inhibitor effects indicate that the purified proteinase from the fermentation broth of Conidiobolus coronatus is a subtilisin‐like serine proteinase. Arch. Insect Biochem. Physiol. 62:186–196, 2006. © 2006 Wiley‐Liss, Inc.
Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus
Authors: Kaufman Kenneth M. , Kelly Jennifer A. , Herring Billy J. , Adler Adam J. , Glenn Stuart B. , Namjou Bahram , Frank Summer G. , Dawson Sarah L. , Bruner Gail R. , James Judith A. , Harley John B. 
Published: July 2006

AbstractObjectiveThe R620W (1858C→T) polymorphism in PTPN22 has been implicated in type 1 diabetes mellitus, rheumatoid arthritis, Graves' disease, Hashimoto thyroiditis, autoimmune thyroid disease, and systemic lupus erythematosus (SLE). The aim of this study was to evaluate this polymorphism in patients with familial SLE and in those with sporadic SLE.MethodsA total of 4,981 DNA samples were genotyped (from 1,680 SLE patients, 1,834 family members, and 1,467 controls). Both population‐based case–control and family‐based association designs were used for the analyses.ResultsIn the European American familial SLE cohort, the minor 1858T allele was more common in randomly selected patients compared with controls (χ2 = 5.61, P = 0.018, odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.07–1.99). The heterozygous C/T genotype was also more common in these European American patients compared with controls (OR 1.63, 95% CI 1.15–2.30). Family‐based association tests showed preferential transmission of the 1858T allele to affected offspring (χ2 = 5.87, P = 0.015). In contrast, the frequency of the 1858T minor allele was not significantly increased in the European American patients with sporadic SLE compared with controls, nor did these patients have preferential transmission of the 1858T allele. Indeed, the difference in the 1858T allele frequency between patients with familial SLE and those with sporadic SLE was measurable (allelic χ2 = 4.22, P = 0.04, OR 1.51, 95% CI 1.02–2.24). Our data also showed that among patients with SLE, the 1858T allele was separately associated with type 1 diabetes mellitus and with autoimmune thyroid disease, confirming the findings of other investigators.ConclusionThe 1858T allele of PTPN22 is associated with familial SLE but not with sporadic SLE in European Americans, thereby potentially explaining previous contradictory reports.
Influence of CTLA4 haplotypes on susceptibility and some extraglandular manifestations in primary Sjögren's syndrome
Authors: Downie‐Doyle Sarah , Bayat Noushin , Rischmueller Maureen , Lester Susan 
Published: July 2006

AbstractObjectiveCytotoxic T lymphocyte–associated antigen 4 (CTLA‐4) is a key negative regulator of the T cell immune response, and the CTLA4 gene is highly polymorphic. Many positive associations between CTLA4 single‐nucleotide polymorphisms (SNPs) and various autoimmune diseases have been identified. Two CTLA4 SNPs that are important relative to genetic susceptibility in human autoimmune diseases are the +49GA polymorphism in exon 1 and the CT60A/G polymorphism in the 3′‐untranslated region. Using these 2 polymorphisms as markers, we investigated possible genetic associations of CTLA4 in Australian patients with primary Sjögren's syndrome.MethodsOne hundred eleven Australian Caucasian patients with primary SS and 156 population‐based controls were genotyped for CTLA4 by polymerase chain reaction–restriction fragment length polymorphism methods, using the restriction enzymes BseXI (+49G/A) and HpyCh4 IV (CT60).ResultsThe CT60 and +49G/A SNPs were in strong linkage disequilibrium, and only 3 haplotypes were observed. Significant differences in the haplotype frequencies between patients with primary SS and controls (P = 0.032) were observed, with susceptibility to primary SS associated with both the +49A;CT60A haplotype and the +49A;CT60G haplotype, whereas the +49G;CT60G haplotype was protective against primary SS. The +49A;CT60G haplotype association was predominantly with Ro/La autoantibody–positive primary SS, and the dose of this haplotype influenced the severity of daytime sleepiness (P = 0.036). The +49A;CT60A haplotype appeared to be protective against the development of Raynaud's phenomenon in patients with primary SS (odds ratio 0.49, 95% confidence interval 0.27–0.91).ConclusionThe CTLA4 +49G/A and CT60 haplotypes are associated with susceptibility to primary SS and with some extraglandular manifestations of the disease.
Association of α‐actinin–binding anti–double‐stranded DNA antibodies with lupus nephritis
Authors: Renaudineau Yves , Croquefer Sabine , Jousse Sandrine , Renaudineau Eric , Devauchelle Valérie , Guéguen Paul , Hanrotel Catherine , Gilburd Boris , Saraux Alain , Shoenfeld Yehuda , Putterman Chaim , Youinou Pierre 
Published: July 2006

AbstractObjectiveAnti–double‐stranded DNA (anti‐dsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross‐reacting with α‐actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity.MethodsOne hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti‐DNA component). Anti‐dsDNA antibodies were detected by conventional enzyme‐linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti–α‐actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity‐purified for cross‐reactivity studies and measurement of antibody avidity.ResultsSera from 62 of the SLE patients had anti‐dsDNA antibodies; 21 of these sera also had anti–α‐actinin antibodies, as compared with 1 of the 38 sera without anti‐dsDNA antibodies. Of the 22 patients with anti–α‐actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti–α‐actinin antibodies (P< 0.01). In patients with GN, anti–α‐actinin, but not anti‐dsDNA, antibodies correlated with the SLEDAI score (minus the anti‐DNA component) and with treatment. The fraction of serum anti‐dsDNA antibodies that cross‐reacted with α‐actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high‐avidity anti‐dsDNA antibodies and an in‐house conventional ELISA.ConclusionThe α‐actinin–binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.
Phosphocitrate blocks calcification‐induced articular joint degeneration in a guinea pig model
Authors: Cheung Herman S. , Sallis John D. , Demadis Konstantino D. , Wierzbicki Andrzej 
Published: July 2006

AbstractObjectiveCalcium deposition occurs frequently in osteoarthritic (OA) joints. However, evidence for a causal role of calcification in cartilage degeneration is inferential. The present study was undertaken to examine the role of calcification in OA disease progression and to evaluate a formulation of phosphocitrate (PC) as a potential therapeutic agent.MethodsWe have identified a guinea pig OA model in which meniscal calcification appears to correlate with aging and disease progression. We synthesized a new formulation of PC, [CaNa(PC)2(H2O)]n (CaNaPC), which is a potent antimineralization agent and a specific inhibitor of crystal‐induced biologic effects. After weekly treatment of guinea pigs with experimental OA with CaNaPC for 3 months, we examined calcification in menisci and cartilage degeneration. As a control, we examined whether similar CaNaPC treatment had any therapeutic effect in a hemi‐meniscectomy model in which there is no known crystal involvement.ResultsMeniscal calcification correlated with cartilage degeneration in this animal model. PC treatment led to significant reduction of calcium deposits and arrested OA disease progression. Similar treatment had no effect in the hemi‐meniscectomy model.ConclusionCaNaPC diminishes mineralization in a cutaneous calcergy model and a model of OA in which intraarticular mineralization is a prominent feature. In the OA guinea pig model, inhibition of calcification is accompanied by diminished cartilage degeneration. CaNaPC has no therapeutic effect in the hemi‐meniscectomy model. We conclude that pathologic calcification may initiate or amplify processes leading to cartilage degeneration and that CaNaPC may interrupt such a pathway.
An Adaptive Two‐stage Design with Treatment Selection Using the Conditional Error Function Approach
Authors: Wang Jixian 
Published: July 2006

AbstractAs an approach to combining the phase II dose finding trial and phase III pivotal trials, we propose a two‐stage adaptive design that selects the best among several treatments in the first stage and tests significance of the selected treatment in the second stage. The approach controls the type I error defined as the probability of selecting a treatment and claiming its significance when the selected treatment is indifferent from placebo, as considered in Bischoff and Miller (2005). Our approach uses the conditional error function and allows determining the conditional type I error function for the second stage based on information observed at the first stage in a similar way to that for an ordinary adaptive design without treatment selection. We examine properties such as expected sample size and stage‐2 power of this design with a given type I error and a maximum stage‐2 sample size under different hypothesis configurations. We also propose a method to find the optimal conditional error function of a simple parametric form to improve the performance of the design and have derived optimal designs under some hypothesis configurations. Application of this approach is illustrated by a hypothetical example. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effects of mixing intensity on cell seeding and proliferation in three‐dimensional fibrous matrices
Authors: Ouyang Anli , Yang Shang‐Tian 
Published: July 2006

AbstractNonwoven fibrous matrices have been widely used in cell and tissue cultures because their three‐dimensional (3‐D) structures with large surface areas and pore spaces can support high‐density cell growth. Although cell adherence and growth on 2‐D surfaces have been thoroughly investigated, very little is known for cells cultured in 3‐D matrices. The effects of mixing intensity on cell seeding, adherence, and growth in fibrous matrices were thus investigated. Chinese Hamster Ovary and osteosarcoma cells were inoculated into nonwoven polyethylene terephthalate matrices by dynamic and static seeding methods, of which the former was found to be superior in seeding efficiency and cell distribution in the matrices. Dynamic seeding increased seeding efficiency from ∼40% to more than 90%. When higher mixing intensities were applied, both cell attachment and detachment rates increased. Cell attachment was transport limited, as indicated by the increased attachment rate with increasing the mass transfer coefficient of the cells. Meanwhile, cell detachment from the 3‐D matrix can be described by the Bell model. The effects of matrix pore size on cell adherence and proliferation were also investigated. In general, the smaller pore size is favorable to cell attachment and proliferation. Further analysis revealed that the interaction between mixing intensity and pore size played a vital role in hydrodynamic damage to cells, which was found to be significant when the Kolomogorov eddy size was smaller than the matrix pores. Increasing mixing intensity also increased oxygen transfer, decreased the lactate yield from glucose, and improved cell growth. Biotechnol. Bioeng. 2007;96: 371–380. © 2006 Wiley Periodicals, Inc.
MRP1/GS‐X pump ATPase expression: is this the explanation for the cytoprotection of the heart against oxidative stress‐induced redox imbalance in comparison to skeletal muscle cells?
Authors: Krause Maurício S. , Oliveira Lino P. , Silveira Elza M. S. , Vianna Damiana R. , Rossato Juliane S. , Almeida Bibiana S. , Rodrigues Mariana F. , Fernandes Augustus J. M. , Costa João A. Bonatto , Curi Rui , de Bittencourt Paulo I. Homem 
Published: July 2006

AbstractStriated muscle activity is always accompanied by oxidative stress (OxStress): the more intense muscle work and/or its duration, the more a redox imbalance may be attained. In spite of cardiac muscle functioning continuously, it is well known that the heart does not suffer from OxStress‐induced damage over a broad physiological range. Although the expression of antioxidant enzymes may be of importance in defending heart muscle against OxStress, a series of combined antioxidant therapeutic approaches have proved to be mostly ineffective in avoiding cellular injury. Hence, additional mechanisms may be involved in heart cytoprotection other than antioxidant enzyme activities. The strong cardiotoxic effect of doxorubicin‐induced cancer chemotherapy shed light on the possible role for multidrug resistance‐associated proteins (MRP) in this context. Muscle activity‐induced ‘physiological’ OxStress enhances the production of glutathione disulfide (GSSG) thus increasing the ratio of GSSG to glutathione (GSH) content inside the cells, which, in turn, leads to redox imbalance. Since MRP1 gene product (a GS‐X pump ATPase) is a physiological GSSG transporter, adult Wistar rats were tested for MRP1 expression and activity in the heart and skeletal muscle (gastrocnemius), in as much as the latter is known to be extremely sensitive to muscle activity‐induced OxS. MRP1 expression was completely absent in skeletal muscle. In contrast, the heart showed an exercise training‐dependent induction of MRP1 protein expression which was further augmented (2.4‐fold) as trained rats were challenged with a session of acute exercise. On the other hand, inducible expression of the 70‐kDa heat shock protein (HSP70), a universal marker of cellular stress, was completely absent in the heart of sedentary and acutely exercised rats, whereas skeletal muscle showed a conspicuous exercise‐dependent HSP70 expression, which decreased by 45% with exercise training. This effect was paralleled by a 58% decrease in GSH content in skeletal muscle which was even higher (an 80%‐fall) after training thus leading to a marked redox imbalance ([GSSG]/[GSH] raised up to 38‐fold). In the heart, GSH contents and [GSSG]/[GSH] ratio remained virtually unchanged even after exercise challenges, while GS‐X pump activity was found to be 20% higher in the heart related to skeletal muscle. These findings suggest that an intrinsic higher capacity to express the MRP1/GS‐X pump may dictate the redox status in the heart muscle thus protecting myocardium by preventing GSSG accumulation in cardiomyocytes as compared to skeletal muscle fibres. Copyright © 2006 John Wiley & Sons, Ltd.
Viscoelastic Properties of Single Poly(ethylene glycol) Molecules
Authors: Kawakami Masaru , Byrne Katherine , Khatri Bhavin S. , McLeish Tom C. B. , Smith D. Alastair 
Published: July 2006

AbstractThe viscoelastic properties of single poly(ethylene glycol) (PEG) molecules were measured by analysis of thermally and magnetically driven oscillations of an atomic force microscope (AFM) cantilever/molecule system. The molecular and monomer stiffness and friction of the PEG polymer were derived using a simple harmonic oscillator (SHO) model. Excellent agreement between the values of these two parameters obtained by the two approaches indicates the validity of the SHO model under the experimental regimes and the excellent reproducibility of the techniques. A sharp minimum in the monomeric friction is seen at around 180 pN applied force which we propose is due to a force induced change in the shape of the energy landscape describing the conformational transition of PEG from a helical to a planar state, which in turn affects the timescale of the transition and therefore modifies the measured internal friction. A knowledge of the viscoelastic response of PEG monomers is particularly important since PEG is widely used as a linker molecule for tethering groups of interest to the AFM tip in force spectroscopy experiments, and we show here that care must be exercised because of the force‐dependent viscoelastic properties of these linkers.
Supramolecular Silanol Chemistry: Inclusion Complexes of 1,3,5‐Tris(diisopropylhydroxysilyl)benzene and 4,4′‐Bis(pyridines)
Authors: Beckmann Jens , Jänicke Sanna L. 
Published: July 2006

AbstractThe trisilanol 1,3,5‐(HOiPr2Si)3C6H3 (5), a novel building block for applications in supramolecular chemistry, has been prepared via the intermediates 1,3,5‐(HiPr2Si)3C6H3 (6) and (CliPr2Si)3C6H3 (7). The inclusion complexes 5·0.5H2O, 5·bpy·0.5H2O, 5·bpe, 5·azpy and 5·bpa have been investigated by X‐ray crystallography [bpy = 4,4′‐bipyridine, bpe = (E)‐bis(4‐pyridyl)ethylene, azpy = 4,4′‐azopyridine, bpa = bis(4‐pyridyl)aceylene]. The ratio between donor and acceptor molecules is always 1:1 and the crude supramolecular motifs are very similar for 5·bpy·0.5H2O, 5·bpe, 5·azpy and 5·bpa. The trisilanol molecules form 1D chains, which are connected by nearly perpendicular 4,4′‐bis(pyridine) molecules to give rise to formation of 2D grid networks featuring O–H···O(H)Si and O–H···N hydrogen bonds. Differences are observed in the shape and size of the voids defined by the 2D grids. The smaller voids are blocked by trisilanol molecules of adjacent 2D networks in case of 5·bpy·0.5H2O and 5·bpe. In case of 5·azpy, the larger voids are filled by interpenetration of the same 2D networks. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Designed Assembly and Structures and Photoluminescence of a New Class of Discrete ZnII Complexes of 1H‐1,10‐Phenanthroline‐2‐one
Authors: Zhang Jie‐Peng , Lin Yan‐Yong , Huang Xiao‐Chun , Chen Xiao‐Ming 
Published: July 2006

AbstractThe hydrothermal reaction of 1H‐1,10‐phenanthroline‐2‐one (Hophen), zinc acetate, benzoic acid (Hba), and triethylamine (3.0 mL) yields the tetranuclear complex [Zn4(μ3‐OH)2(ophen)4(ba)2] (2), which features a chair‐like Zn4(μ3‐OH)2 cluster with two ba ligands centrosymmetrically oriented. [(OAc){Zn3(μ3‐OH)(ophen)3}(ox){Zn3(μ3‐OH)(ophen)3}(OAc)] (3; ox = oxalate) was isolated when less triethylamine (1.0 mL) was used. Two Zn3(μ3‐OH)(ophen)3 clusters in 3 are linked together by an oxalate to form a dumbbell‐like structure in which the acetate and oxalate ligands point outward from the Zn3(μ3‐OH)(ophen)3 cluster with an acute bending angle. A geometric analysis reveals that Zn3(μ3‐OH)(ophen)3 and dicarboxylate with an obtuse bending angle cannot form an infinite zigzag chain, whereas the ring isomer can. With isophthalate (ipa), thiophene‐2,5‐dicarboxylate (tda), and 4,4′‐oxybis(benzoate) (oba) instead of the acetate of 3 three new complexes, namely [{Zn3(μ3‐OH)(ophen)3}(ipa)2{Zn3(μ3‐OH)(ophen)3}]·0.5H2O (4), [{Zn3(μ3‐OH)(ophen)3}(tda)2{Zn3(μ3‐OH)(ophen)3}] (5), and [{Zn3(μ3‐OH)(ophen)3}(oba)2{Zn3(μ3‐OH)(ophen)3}] (6), were obtained in which two Zn3(μ3‐OH)(ophen)3 clusters are linked by a pair of ipa, tda, or oba ligands to form isostructural, cluster‐based 2:2 metallomacrocycles. Photoluminescence studies of 2–6 revealed that their luminescent properties are derived from ophen‐based π‐π* excited states. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Zinc(II) Complexation Behaviour of Sulfonamide‐Based Enzyme Inhibitors
Authors: Chaves Sílvia , Marques Sérgio M. , Cachudo Anabela , Esteves M. Alexandra , Santos M. Amélia 
Published: July 2006

AbstractSulfonamide derivatives containing extrafunctional groups, such as hydroxamic acids, hydroxypyrimidinones and carboxylic acids, have been recently identified as inhibitors towards several zinc‐containing enzymes, such as the matrix metalloproteinases (MMPs) and/or carbonic anhydrases (CAs). Since these inhibitors are supposed to bind the zinc ion at the active site, it was decided to study the zinc(II) complexation with a set of representative compounds in order to identify the most probable coordination modes and to find eventual relationships with the inhibitory properties. These studies were performed in aqueous solution, by potentiometry and 1H NMR spectroscopy, and in the solid phase, by infrared spectroscopy. The solution equilibrium studies indicate that these compounds present similar affinity for zinc (pZn ≈ 6). Under stoichiometric conditions, the formation of 1:1 metal complex species involves a preferential (O,O) coordination via the hydroxamic or hydroxypyrimidinone moieties, while the coordination via the sulfonamide groups could mainly be achieved under zinc excess conditions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)