bluuebunny/crossref_metadata_2025_split huggingface dataset:
A statistical approach using network structure in the prediction of protein characteristics
Authors: Chen Pao-Yang , Deane Charlotte M. , Reinert Gesine 
Published: June 2007

AbstractMotivation: The Majority Vote approach has demonstrated that protein–protein interactions can be used to predict the structure or function of a protein. In this article we propose a novel method for the prediction of such protein characteristics based on frequencies of pairwise interactions. In addition, we study a second new approach using the pattern frequencies of triplets of proteins, thus for the first time taking network structure explicitly into account. Both these methods are extended to jointly consider multiple organisms and multiple characteristics.Results: Compared to the standard non-network-based method, namely the Majority Vote method, in large networks our predictions tend to be more accurate. For structure prediction, the Frequency-based method reaches up to 71% accuracy, and the Triplet-based method reaches up to 72% accuracy, whereas for function prediction, both the Triplet-based method and the Frequency-based method reach up to 90% accuracy. Function prediction on proteins without homologues showed slightly less but comparable accuracies. Including partially annotated proteins substantially increases the number of proteins for which our methods predict their characteristics with reasonable accuracy. We find that the enhanced Triplet-based method does not currently yield significantly better results than the enhanced Frequency-based method, suggesting that triplets of interactions do not contain substantially more information about protein characteristics than interaction pairs. Our methods offer two main improvements over current approaches—first, multiple protein characteristics are considered simultaneously, and second, data is integrated from multiple species. In addition, the Triplet-based method includes network structure more explicitly than the Majority Vote and the Frequency-based method.Availability: The program is available upon request.Contact: pchen@stats.ox.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.
Specific reactions ofS‐nitrosothiols with cysteine hydrolases: A comparative study between dimethylargininase‐1 and CTP synthetase
Authors: Braun Oliver , Knipp Markus , Chesnov Serge , Vašák Milan 
Published: June 2007

AbstractS‐Transnitrosation is an important bioregulatory process whereby NO+equivalents are transferred betweenS‐nitrosothiols and Cys of target proteins. This reaction proceeds through a common intermediate R–S–N(O−)–S–R′ and it has been proposed that products different fromS‐nitrosothiols may be formed in protein cavities. Recently, we have reported on the formation of such a product, anN‐thiosulfoximide, at the active site of the Cys hydrolase dimethylargininase‐1 (DDAH‐1) upon reaction withS‐nitroso‐l‐homocysteine (HcyNO). Here we have addressed the question of whether this novel product can also be formed with the endogenously occurringS‐nitrosothiolsS‐nitroso‐l‐cysteine (CysNO) andS‐nitrosoglutathione (GSNO). Further, to explore the reason responsible for the unique formation of anN‐thiosulfoximide in DDAH‐1 we have expanded these studies to cytidine triphosphate synthetase (CTPS), which shows a similar active site architecture. ESI‐MS and activity measurements showed that the bulky GSNO does not react with both enzymes. In contrast, S‐nitrosylation of the active site Cys occurred in DDAH‐1 with CysNO and in CTPS with CysNO and HcyNO. Although kinetic analysis indicated that these compounds act as specific irreversible inhibitors, noN‐thiosulfoximide was formed. The reasons likely responsible for the absence of theN‐thiosulfoximide formation are discussed using molecular models of DDAH‐1 and CTPS. In tissue extracts DDAH was inhibited only by HcyNO, with an IC50value similar to that of the isolated protein. Biological implications of these studies for the function of both enzymes are discussed.
Cleavage of recombinant proteins at poly‐His sequences by Co(II) and Cu(II)
Authors: Andberg Martina , Jäntti Jussi , Heilimo Sara , Pihkala Päivi , Paananen Arja , Koskinen Ari M.P. , Söderlund Hans , Linder Markus B. 
Published: June 2007

AbstractImproved ways to cleave peptide chains at engineered sites easily and specifically would form useful tools for biochemical research. Uses of such methods include the activation or inactivation of enzymes or the removal of tags for enhancement of recombinant protein expression or tags used for purification of recombinant proteins. In this work we show by gel electrophoresis and mass spectroscopy that salts of Co(II) and Cu(II) can be used to cleave fusion proteins specifically at sites where sequences of His residues have been introduced by protein engineering. The His residues could be either consecutive or spaced with other amino acids in between. The cleavage reaction required the presence of low concentrations of ascorbate and in the case of Cu(II) also hydrogen peroxide. The amount of metal ions required for cleavage was very low; in the case of Cu(II) only one to two molar equivalents of Cu(II) to protein was required. In the case of Co(II), 10 molar equivalents gave optimal cleavage. The reaction occurred within minutes, at a wide pH range, and efficiently at temperatures ranging from 0°C to 70°C. The work described here can also have implications for understanding protein stability in vitro and in vivo.
Local quality assessment in homology models using statistical potentials and support vector machines
Authors: Fasnacht Marc , Zhu Jiang , Honig Barry 
Published: June 2007

AbstractIn this study, we address the problem of local quality assessment in homology models. As a prerequisite for the evaluation of methods for predicting local model quality, we first examine the problem of measuring local structural similarities between a model and the corresponding native structure. Several local geometric similarity measures are evaluated. Two methods based on structural superposition are found to best reproduce local model quality assessments by human experts. We then examine the performance of state‐of‐the‐art statistical potentials in predicting local model quality on three qualitatively distinct data sets. The best statistical potential, DFIRE, is shown to perform on par with the best current structure‐based method in the literature, ProQres. A combination of different statistical potentials and structural features using support vector machines is shown to provide somewhat improved performance over published methods.
DosT and DevS are oxygen‐switched kinases in Mycobacterium tuberculosis
Authors: Sousa Eduardo Henrique Silva , Tuckerman Jason Robert , Gonzalez Gonzalo , Gilles‐Gonzalez Marie‐Alda 
Published: June 2007

AbstractExposure of Mycobacterium tuberculosis to hypoxia is known to alter the expression of many genes, including ones thought to be involved in latency, via the transcription factor DevR (also called DosR). Two sensory kinases, DosT and DevS (also called DosS), control the activity of DevR. We show that, like DevS, DosT contains a heme cofactor within an N‐terminal GAF domain. For full‐length DosT and DevS, we determined the ligand‐binding parameters and the rates of ATP reaction with the liganded and unliganded states. In both proteins, the heme state was coupled to the kinase such that the unliganded, CO‐bound, and NO‐bound forms were active, but the O2‐bound form was inactive. Oxygen‐bound DosT was unusually inert to oxidation to the ferric state (half life in air >60 h). Though the kinase activity of DosT was unaffected by NO, this ligand bound 5000 times more avidly than O2 to DosT (Kd [NO] ∼5 nM versus Kd [O2] = 26 μM). These results demonstrate direct and specific O2 sensing by proteins in M. tuberculosis and identify for the first time a signal ligand for a sensory kinase from this organism. They also explain why exposure of M. tuberculosis to NO donors under aerobic conditions can give results identical to hypoxia, i.e., NO saturates DosT, preventing O2 binding and yielding an active kinase.
A single mutation in the active site swaps the substrate specificity of N‐acetyl‐L‐ornithine transcarbamylase and N‐succinyl‐L‐ornithine transcarbamylase
Authors: Shi Dashuang , Yu Xiaolin , Cabrera‐Luque Juan , Chen Tony Y. , Roth Lauren , Morizono Hiroki , Allewell Norma M. , Tuchman Mendel 
Published: June 2007

AbstractTranscarbamylases catalyze the transfer of the carbamyl group from carbamyl phosphate (CP) to an amino group of a second substrate such as aspartate, ornithine, or putrescine. Previously, structural determination of a transcarbamylase from Xanthomonas campestris led to the discovery of a novel N‐acetylornithine transcarbamylase (AOTCase) that catalyzes the carbamylation of N‐acetylornithine. Recently, a novel N‐succinylornithine transcarbamylase (SOTCase) from Bacteroides fragilis was identified. Structural comparisons of AOTCase from X. campestris and SOTCase from B. fragilis revealed that residue Glu92 (X. campestris numbering) plays a critical role in distinguishing AOTCase from SOTCase. Enzymatic assays of E92P, E92S, E92V, and E92A mutants of AOTCase demonstrate that each of these mutations converts the AOTCase to an SOTCase. Similarly, the P90E mutation in B. fragilis SOTCase (equivalent to E92 in X. campestris AOTCase) converts the SOTCase to AOTCase. Hence, a single amino acid substitution is sufficient to swap the substrate specificities of AOTCase and SOTCase. X‐ray crystal structures of these mutants in complexes with CP and N‐acetyl‐L‐norvaline (an analog of N‐acetyl‐L‐ornithine) or N‐succinyl‐L‐norvaline (an analog of N‐succinyl‐L‐ornithine) substantiate this conversion. In addition to Glu92 (X. campestris numbering), other residues such as Asn185 and Lys30 in AOTCase, which are involved in binding substrates through bridging water molecules, help to define the substrate specificity of AOTCase. These results provide the correct annotation (AOTCase or SOTCase) for a set of the transcarbamylase‐like proteins that have been erroneously annotated as ornithine transcarbamylase (OTCase, EC 2.1.3.3).
FR258900, a potential anti‐hyperglycemic drug, binds at the allosteric site of glycogen phosphorylase
Authors: Tiraidis Costas , Alexacou Kyra‐Melinda , Zographos Spyros E. , Leonidas Demetres D. , Gimisis Thanasis , Oikonomakos Nikos G. 
Published: June 2007

AbstractFR258900 has been discovered as a novel inhibitor of human liver glycogen phosphorylase a and proved to suppress hepatic glycogen breakdown and reduce plasma glucose concentrations in diabetic mice models. To elucidate the mechanism of inhibition, we have determined the crystal structure of the cocrystallized rabbit muscle glycogen phosphorylase b–FR258900 complex and refined it to 2.2 Å resolution. The structure demonstrates that the inhibitor binds at the allosteric activator site, where the physiological activator AMP binds. The contacts from FR258900 to glycogen phosphorylase are dominated by nonpolar van der Waals interactions with Gln71, Gln72, Phe196, and Val45′ (from the symmetry‐related subunit), and also by ionic interactions from the carboxylate groups to the three arginine residues (Arg242, Arg309, and Arg310) that form the allosteric phosphate‐recognition subsite. The binding of FR258900 to the protein promotes conformational changes that stabilize an inactive T‐state quaternary conformation of the enzyme. The ligand‐binding mode is different from those of the potent phenoxy‐phthalate and acyl urea inhibitors, previously described, illustrating the broad specificity of the allosteric site.
Impact of 21st century climate change on the Baltic Sea fish community and fisheries
Authors: MACKENZIE BRIAN R. , GISLASON HENRIK , MÖLLMANN CHRISTIAN , KÖSTER FRIEDRICH W. 
Published: June 2007

AbstractThe Baltic Sea is a large brackish semienclosed sea whose species‐poor fish community supports important commercial and recreational fisheries. Both the fish species and the fisheries are strongly affected by climate variations. These climatic effects and the underlying mechanisms are briefly reviewed. We then use recent regional – scale climate – ocean modelling results to consider how climate change during this century will affect the fish community of the Baltic and fisheries management. Expected climate changes in northern Europe will likely affect both the temperature and salinity of the Baltic, causing it to become warmer and fresher. As an estuarine ecosystem with large horizontal and vertical salinity gradients, biodiversity will be particularly sensitive to changes in salinity which can be expected as a consequence of altered precipitation patterns. Marine‐tolerant species will be disadvantaged and their distributions will partially contract from the Baltic Sea; habitats of freshwater species will likely expand. Although some new species can be expected to immigrate because of an expected increase in sea temperature, only a few of these species will be able to successfully colonize the Baltic because of its low salinity. Fishing fleets which presently target marine species (e.g. cod, herring, sprat, plaice, sole) in the Baltic will likely have to relocate to more marine areas or switch to other species which tolerate decreasing salinities. Fishery management thresholds that trigger reductions in fishing quotas or fishery closures to conserve local populations (e.g. cod, salmon) will have to be reassessed as the ecological basis on which existing thresholds have been established changes, and new thresholds will have to be developed for immigrant species. The Baltic situation illustrates some of the uncertainties and complexities associated with forecasting how fish populations, communities and industries dependent on an estuarine ecosystem might respond to future climate change.
Electron transfer of dissolved organic matter and its potential significance for anaerobic respiration in a northern bog
Authors: HEITMANN TOBIAS , GOLDHAMMER TOBIAS , BEER JULIA , BLODAU CHRISTIAN 
Published: June 2007

AbstractWe investigated electron transfer processes of dissolved organic matter (DOM) and their potential importance for anaerobic heterotrophic respiration in a northern peatland. Electron accepting and donating capacities (EAC, EDC) of DOM were quantified using dissolved H2S and ferric iron as reactants. Carbon turnover rates were obtained from porewater profiles (CO2, CH4) and inverse modeling. Carbon dioxide was released at rates of 0.2–5.9 mmol m−2 day−1 below the water table. Methane (CH4) formation contributed <10%, and oxygen consumption 2% to 40%, leaving a major fraction of CO2 production unexplained. DOM oxidized H2S to thiosulfate and was reduced by dissolved ferric iron. Reduction with H2S increased the subsequently determined EDC compared to untreated controls, indicating a reversibility of the electron transfer. In situ redox capacities of DOM ranged from 0.2 to 6.1 mEq g−1 C (EAC) and from 0.0 to 1.4 mEq g−1 C (EDC), respectively. EAC generally decreased with depth and changed after a water table drawdown and rebound by 20 and −45 mEq m−2, respectively. The change in EAC during the water table fluctuation was similar to CH4 formation rates. In peatlands, electron transfer of DOM may thus significantly contribute to the oxidation of reduced organic substrates by anaerobic heterotrophic respiration, or by maintaining the respiratory activity of sulfate reducers via provision of thiosulfate. Part of the anaerobic electron flow in peat soils is thus potentially diverted from methanogenesis, decreasing its contribution to the total carbon emitted to the atmosphere.
Bird densities are associated with household densities
Authors: TRATALOS JAMIE , FULLER RICHARD A. , EVANS KARL L. , DAVIES RICHARD G. , NEWSON STUART E. , GREENWOOD JEREMY J. D. , GASTON KEVIN J. 
Published: June 2007

AbstractIncreasing housing density is an important component of global land transformation, with major impacts on patterns of biodiversity. However, while there have been many studies of the changes in biodiversity across rural–urban gradients, which are influenced in large part by housing densities, how biodiversity changes across the full range of regional variation in housing density remains poorly understood. Here, we explore these relationships for the richness and abundance of breeding birds across Britain. Total richness, and that of 27 urban indicator species, increased from low to moderate household densities and then declined at greater household densities. The richness of all species increased initially faster with household density than did that of the urban indicator species, but nonurban indicator species richness declined consistently after peaking at a very low housing density. Avian abundance showed a rather different pattern. Total abundance and that summed across all urban indicator species increased over a wide range of household densities, and declined only at the highest household densities. The abundance of individual urban indicator species generally exhibited a hump‐shaped relationship with housing density. While there was marked intraspecific variation in the form of such relationships, almost invariably avian abundance declined at housing densities below that at which the UK government requires new developments to be built. Our data highlight the difficulties of maintaining biodiversity while minimising land take for new development. High‐density housing developments are associated with declines in many of those species otherwise best able to exploit urban environments, and those components of native biodiversity with which human populations are often most familiar.
Long‐term survival of HIV‐infected patients with haemophilia
Authors: Stieltjes N. , Sultan Y. , Rothschild C. , Torchet M. F. , Laurian Y. , Navarro R. , Fressinaud E. , Gernez A. Parquet , Fonlupt J. , Berthier A. M. 
Published: June 2007

SummaryIn France, patients with haemophilia were infected by HIV up until October 1985, with a maximum of seroconversion between 1983 and 1985. There was a progressive development of AIDS in the 1158 infected patients as reported by Health Authorities. By the end of 1992, 32% of the haemophilia population had developed AIDS and 38 had developed clinical or biological symptoms of immunodeficiency. However, 27% had no clinical symptoms and no severe disorder of the immune system. The present study was established to determine factors common to patients with prolonged survival.
Results in three Australian haemophilia B patients with high‐responding inhibitors treated with the Malmö model
Authors: NILSSON INGA MARIE , BERNTORP ERIK , RICKARD KEVIN A. 
Published: June 2007

SummaryDevelopment of inhibitors to factor IX (F IX) is a serious complication of the treatment of patients with severe haemophilia B. Three Australian haemophilia B patients, a 22‐year‐old man and two 5‐year‐old identical twins, with high‐responding inhibitors and resistant to treatment, were admitted to the centre in Malmö, Sweden, for tolerance induction according to the Malmö treatment model. This tratment consists of a combination of cyclophosphamide, F VIII of F IX, and high‐dose intravenous IgG.Extracorporeal adsorption to protein A in columns, which is included in the protocol when the inhibitor titre is high at the start of treatment, had to be perforemed in the case of the twin brothers. High‐purity F IX concentrates were used. The tolerance inductin was successful in the 22‐year‐old man and in one of the twins; they been toleant for 4 and 2 years, respectively, and are now on a home‐treatment programme taking 30–40 IU F IX/kg twice weekly. These patients have no demonstrable coagulation inhibitory antibodies and in vivo reovery and half‐life of infused F IX are normal. In the other twin it has not been possible to induce tolerance, though after removal of the antibodies by protein A adsorpation it is possible to achieve significant circulalting levels of F IX for 8–10 days.
The knowledge and perception of factor concentrate in persons with haemophilia A
Authors: BOLIVAR EDNA P. , SHOPNICK RINAH I. , MANNUCCI PIER M. , GRINGERI ALESSANDRO , BRETTLER DOREEN B. 
Published: June 2007

Summary.
Objectiues. To evaluate haemophilia patients' knowledge and understanding of factor concentrate products and to assess their feelings regarding purity and viral safety of these products. Methods. Sixty questionnaires were distributed and completed by patients or parents of patients with severe/ moderate haemophilia A at two large comprehensive haemophilia centres in the USA and Italy. Results. Most patients knew what brand of factor concentrate they used, but less than half were aware of how their concentrate was virally inactivated. The majority of responders perceived recombinant factor VlII as being the concentrate with the highest degree of purity. The majority felt the decision of which concentrate to use should be the care‐givers not the patients. Conclusions. It appears that patients need more education concerning the concentrate they are using, and its method of viral inactivation and purity.
Ipsilateral total shoulder and elbow prosthetic replacement in a patient with severe haemophilia B
Authors: PHILLIPS A. M. , RIBBANS W. J. , GODDARD N. J. 
Published: June 2007

SummarySince factor replacement concentrates became widely available in the 1970s, total prosthetic replacement of joints in haemophilic patients has become increasingly common, with success particularly in the knee and hip. However, there has been no published series of elbow or shoulder replacements large enough to draw conclusions about the advisability of these procedures in this group of patients.We report a case of prosthetic replacement of the shoulder in a 58‐year‐old man with haemophilia B, and replacement of the elbow joint of the same limb 21 months later. The results are initially very encouraging, with no pain in either joint since the early post‐operative period. There have been no bleeds into either joint since surgery. Ranges of movement are satisfactory. Follow‐up is now 37 months for the shoulder and 16 months for the elbow.