bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data mining techniques to study the disulfide-bonding state in proteins: signal peptide is a strong descriptor
Authors: Tessier Dominique , Bardiaux Benjamin , Larré Colette , Popineau Yves 
Published: June 2004

Abstract
In the eucaryotic cell, the formation of disulfide bonds takes place in general inside the endoplasmic reticulum which provides a unique folding environment. The DisulfideDB database gathers information about this biological process with structural, evolutionary and neighborhood information on cysteines in proteins. Mining this information with an association rule discovery program permits to extract some strong rules for the prediction of the disulfide-bonding state of cysteines.
Supplementary information: The web supplement to this paper, including the UML diagram of the database and some procedures used with the association rule discovery tool, may be found at http://www.nantes.inra.fr/centre/unites-recherche/urpvi/bioinformatique/publi.html.
Affinity transfer by CDR grafting on a nonimmunoglobulin scaffold
Authors: Nicaise Magali , Valerio‐Lepiniec Marielle , Minard Philippe , Desmadril Michel 
Published: June 2004

AbstractNeocarzinostatin (NCS) is a small “all β” protein displaying the same overall fold as immunoglobulins. This protein possesses a well‐defined hydrophobic core and two loops structurally equivalent to the CDR1 and CDR3 of immunoglobulins. NCS is the most studied member of the enediynechromoprotein family, and is clinically used as an antitumoral agent. NCS has promise as a drug delivery vehicle if new binding specificities could be conferred on its protein scaffold. Previous studies have shown that the binding specificity of the crevasse can be extended to compounds completely unrelated to the natural enediyne chromophore family. We show here that it is possible to introduce new interaction capacities to obtain a protein useful for drug targeting by modifying the immunoglobulin CDR‐like loops. We transferred the CDR3 of the VHH chain of camel antilysozyme immunoglobulin to the equivalent site in the corresponding loop of neocarzinostatin. We then evaluated the stability of the resulting structure and its affinity for lysozyme. The engineered NCS‐CDR3 presents a structure similar to that of the wild‐type NCS, and is stable and efficiently produced. ELISA, ITC, and SPR measurements demonstrated that the new NCS‐CDR3 specifically bound lysozyme.
Crystal structure of rat α‐parvalbumin at 1.05 Å resolution
Authors: Bottoms Christopher A. , Schuermann Jonathan P. , Agah Sayeh , Henzl Michael T. , Tanner John J. 
Published: June 2004

AbstractThe crystal structure of rat α‐parvalbumin has been determined at 1.05 Å resolution, using synchrotron data collected at Advanced Photon Source beamline 19‐ID. After refinement with SHELX, employing anisotropic displacement parameters and riding hydrogen atoms,R= 0.132 andRfree= 0.162. The average coordinate estimated standard deviations are 0.021 Å and 0.038 Å for backbone atoms and side‐chain atoms, respectively. Besides providing a more precise view of the α‐isoform than previously available, these data permit comparison with the 0.91 Å structure determined for pike β‐parvalbumin. Visualization of the anisotropic displacement parameters as thermal ellipsoids yields insight into the atomic motion within the Ca2+‐binding sites. The asymmetric unit includes three parvalbumin (PV) molecules. Interestingly, the EF site in one displays uncharacteristic flexibility. The ellipsoids for Asp‐92 are particularly large and non‐spherical, and the shape of the Ca2+ellipsoid implies significant vibrational motion perpendicular to the plane defined by the fouryandzligands. The relative dearth of crystal‐packing interactions in this site suggests that the heightened flexibility may be the result of diminished intermolecular contacts. The implication is that, by impeding conformational mobility, crystal‐packing forces may cause serious overestimation of EF‐hand rigidity. The high quality of the data permitted 11 residues to be modeled in alternative side‐chain conformations, including the two core residues, Ile‐97 and Leu‐105. The discrete disorder observed for Ile‐97 may have functional ramifications, providing a mechanism for communicating binding status between the CD and EF binding loops and between the PV metal ion‐binding domain and the N‐terminal AB region.
Insulin forms amyloid in a strain‐dependent manner: An FT‐IR spectroscopic study
Authors: Dzwolak Wojciech , Smirnovas Vytautas , Jansen Ralf , Winter Roland 
Published: June 2004

AbstractThe presence of 20% (v/v) ethanol triggers growth of insulin amyloid with distinct infrared spectroscopic features, compared with the fibrils obtained under ambient conditions. Here we report that the two insulin amyloid types behave in the prion strain‐like manner regarding seeding specificity and ability of the self‐propagating conformational template to overrule unfavorable environmental factors and maintain the initial folding pattern. The type of the original seed has been shown to prevail over cosolvent effects and determines spectral position and width of the amide I′ infrared band of the heterogeneously seeded amyloid. These findings imply that “strains” may be a common generic trait of amyloids.
The C‐terminal domain of full‐length E. coli SSB is disordered even when bound to DNA
Authors: Savvides Savvas N. , Raghunathan Srinivasan , Fütterer Klaus , Kozlov Alex G. , Lohman Timothy M. , Waksman Gabriel 
Published: June 2004

AbstractThe crystal structure of full‐length homotetrameric single‐stranded DNA (ssDNA)‐binding protein from Escherichia coli (SSB) has been determined to 3.3 Å resolution and reveals that the entire C‐terminal domain is disordered even in the presence of ssDNA. To our knowledge, this is the first experimental evidence that the C‐terminal domain of SSB may be inherently disordered. The N‐terminal DNA‐binding domain of the protein is well ordered and is virtually indistinguishable from the previously determined structure of the chymotryptic fragment of SSB (SSBc) in complex with ssDNA. The absence of observable interactions with the core protein and the crystal packing of SSB together suggest that the disordered C‐terminal domains likely extend laterally away from the DNA‐ binding domains, which may facilitate interactions with components of the replication machinery in vivo. The structure also reveals the conservation of molecular contacts between successive tetramers mediated by the L45 loops as seen in two other crystal forms of SSBc, suggesting a possible functional relevance of this interaction.
The role of aromaticity, exposed surface, and dipole moment in determining protein aggregation rates
Authors: Tartaglia Gian Gaetano , Cavalli Andrea , Pellarin Riccardo , Caflisch Amedeo 
Published: June 2004

AbstractThe mechanisms by which peptides and proteins form ordered aggregates are not well understood. Here we focus on the physicochemical properties of amino acids that favor ordered aggregation and suggest a parameter‐free model that is able to predict the change of aggregation rates over a large set of natural sequences. Furthermore, the results of the parameter‐free model correlate well with the aggregation propensities of a set of peptides designed by computer simulations.
Facile chemical synthesis and equilibrium unfolding properties of CopG
Authors: Wales Thomas E. , Richardson Jane S. , Fitzgerald Michael C. 
Published: June 2004

AbstractThe 45‐amino acid polypeptide chain of the homodimeric transcriptional repressor, CopG, was chemically synthesized by stepwise solid phase peptide synthesis (SPPS) using a protocol based on Boc‐chemistry. The product obtained from the synthesis was readily purified by reversed‐phase HPLC to give a good overall yield (21% by weight). Moreover, the synthetic CopG constructs prepared in this work folded into three‐dimensional structures similar to the wild‐type protein prepared using conventional recombinant methods as judged by far UV‐CD spectroscopy. A fluorescent CopG analog, (Y39W)CopG, was also designed and chemically synthesized to facilitate biophysical studies of CopG's protein folding and assembly reaction. The guanidinium chloride‐induced equilibrium unfolding properties of the wild‐type CopG and (Y39W)CopG constructs in this work were characterized and used to develop a model for CopG's equilibrium unfolding reaction. Our results indicate that CopG's folding and assembly reaction is well modeled by a two‐state process involving folded dimer and unfolded monomer. Using this model, ΔGf and m‐values of −13.42 ± 0.04 kcal/mole dimer and 1.92 ± 0.01 kcal/(mole M) were calculated for CopG.
Zinc‐dependent dimerization of the folding catalyst, protein disulfide isomerase
Authors: Solovyov Anton , Gilbert Hiram F. 
Published: June 2004

AbstractProtein disulfide isomerase (PDI), an essential folding catalyst and chaperone of the endoplasmic reticulum (ER), has four structural domains (a‐b‐b′‐a′‐) of approximately equal size. Each domain has sequence or structural homology with thioredoxin. Sedimentation equilibrium and velocity experiments show that PDI is an elongated monomer (axial ratio 5.7), suggesting that the four thioredoxin domains are extended. In the presence of physiological levels (<1 mM) of Zn2+ and other thiophilic divalent cations such as Cd2+ and Hg2+, PDI forms a stable dimer that aggregates into much larger oligomeric forms with time. The dimer is also elongated (axial ratio 7.1). Oligomerization involves the interaction of Zn2+ with the cysteines of PDI. PDI has active sites in the N‐terminal (a) and C‐terminal (a′)thioredoxin domains, each with two cysteines (CGHC). Two other cysteines are found in one of the internal domains (b′). Cysteine to serine mutations show that Zn2+‐dependent dimerization occurs predominantly by bridging an active site cysteine from either one of the active sites with one of the cysteines in the internal domain (b′). The dimer incorporates two atoms of Zn2+ and exhibits 50% of the isomerase activity of PDI. At longer times and higher PDI concentrations, the dimer forms oligomers and aggregates of high molecular weight (>600 kDa). Because of a very high concentration of PDI in the ER, its interaction with divalent ions could play a role in regulating the effective concentration of these metal ions, protecting against metal toxicity, or affecting the activity of other (ER) proteins that use Zn2+ as a cofactor.
Identification of active site residues in mevalonate diphosphate decarboxylase: Implications for a family of phosphotransferases
Authors: Krepkiy Dmitriy , Miziorko Henry M. 
Published: June 2004

AbstractA combination of sequence homology analyses of mevalonate diphosphate decarboxylase (MDD) proteins and structural information for MDD leads to the hypothesis that Asp 302 and Lys 18 are active site residues in MDD. These residues were mutated to replace acidic/basic side chains and the mutant proteins were isolated and characterized. Binding and competitive displacement studies using trinitrophenyl‐ATP, a fluorescent analog of substrate ATP, indicate that these mutant enzymes (D302A, D302N, K18M) retain the ability to stoichiometrically bind nucleotide triphosphates at the active site. These observations suggest the structural integrity of the mutant MDD proteins. The functional importance of mutated residues was evaluated by kinetic analysis. The 103 and 105‐fold decreases in kcat observed for the Asp 302 mutants (D302N and D302A, respectively) support assignment of a crucial catalytic role to Asp 302. A 30‐fold decrease in activity and a 16‐fold inflation of the Km for ATP is documented for the K18M mutant, indicating that Lys 18 influences the active site but is not crucial for reaction chemistry. Demonstration of the influence of conserved aspartate 302 appears to represent the first documentation of the functional importance of a residue in the MDD catalytic site and affords insight into phosphotransferase reactions catalyzed by a variety of enzymes in the galactokinase, homoserine kinase, mevalonate kinase, phosphom‐evalonate kinase (GHMP kinase) family.
Transporting the American Peace Movement to British Palestine: Judah L. Magnes, American Pacifist and Zionist
Authors: Kotzin Daniel P. 
Published: June 2004

During the First World War, the American Reform rabbi Judah L. Magnes was a leading member of the People's Council of America for Democracy and Peace. He was also a Zionist. After the First World War, he moved to Mandatory Palestine and became a founder and first chancellor of the Hebrew University in Jerusalem. It was in this arena that he emerged as the leading advocate for the establishment of a bi‐national state in Palestine where Jews and Arabs would share power equally.Magnes’ Zionism was shaped by both the ideas of the People's Council and his experience as a pacifist in America. Taking a transnational perspective, this article explores the ways in which, during the time he resided in Jerusalem (1923–1948), Magnes retained his identity as an American pacifist while actively involving himself in political, social, and cultural issues relating to the relationship between Jews and Arabs in Mandatory Palestine. A central argument is that Magnes’ activities in Mandatory Palestine were shaped by American pacifist ideas and his experience as a pacifist in America. His ultimate failure illustrates the difficulty he had as an American adapting American ideals to the Arab‐Jewish conflict in British Palestine. Magnes’ experiences as a pacifist in the United States and Palestine also provide a larger understanding of the relationship between democracy and nationalism across national boundaries.
Lipid raft‐enriched stem cell‐like keratinocytes in the epidermis, hair follicles and sinus tracts in hidradenitis suppurativa
Authors: Gniadecki Robert , Jemec Gregor B. E. 
Published: June 2004

Abstract:  Hidradenitis suppurativa (HS) is a disease, that causes considerable morbidity in patients. A histological hallmark of the disorder is the formation of sinus tracts in the dermis and the subcutis. Biologically, they represent a poorly understood phenomenon involving the infiltrative growth of proliferating non‐malignant keratinocytes. Lipid domains in plasma membranes (lipid rafts) play a role in the function of growth factors and are suspected of having a pathogenic role in cell migration and invasive growth.Using HS as a model, the presence of lipid rafts was studied using cholera toxin conjugated with FITC (CTx‐FITC) and antiβ1 integrin (CD29)‐CyChrome conjugate fluorescence staining of unfixed and acetone‐fixed cryostat sections of lesional and paralesional skin samples. The double‐labeled skin samples were observed in the confocal laser‐scanning fluorescence microscope. Samples were obtained from five patients with HS. The lesional epidermis of HS contained three populations of keratinocytes: CD29brightCTxdim, CD29dimCTxbright and a third hitherto unseen population containing double‐positive CD29brightCTxbright cells. The CD29brightCTxdim population resembles the earlier described epidermal stem‐like cells, while the CD29dimCTxbright basal keratinocytes overlap with the transit‐amplifying cell pool.The new population of double‐positive CD29brightCTxbright cells was localized on the slopes of the papillas, focally in the suprabasal epidermal layers, in some hair follicles and in the majority of sinus tracts. Such double‐positive cells have not previously been encountered by us in normal epidermis and hair follicles.Using HS as a model, it is suggested that the keratinocytes involved in sinus tract formation are CD29brightCTxbright cells. Owing to the physical proximity of the cells, it is hypothesised that the described CD29brightCTxbright cells result from an increased expression of CD29 on the CTxbright cells. It is likely that the double‐positive CD29brightCTxbright cells emerge due to the influence of local inflammatory cytokines.Sinus tract formation may represent an aberrant epidermal repair response executed by the activated CD29brightCTxbright keratinocytes capable of non‐malignant infiltrative growth in the dermis and subcutis.
Transfusion‐related acute lung injury caused by two donors with anti‐human leucocyte antigen class II antibodies: a look‐back investigation
Authors: Nicolle A. L. , Chapman C. E. , Carter V. , Wallis J. P. 
Published: June 2004

Summary.  Transfusion‐related acute lung injury (TRALI) is considered as one of the most important complications of blood transfusion. Previous look‐back investigations have revealed unrecognized cases.We report two cases of TRALI in brief and the outcomes of transfusion in the recipients of previous components from the implicated donors. This look‐back investigation was a retrospective case‐note study assessing whether there were any untoward events associated with the previous transfusions.18 patients were identified as having received a blood component transfusion from one of the two donors with anti‐human leucocyte antigen (HLA) antibodies to antigens occurring frequently in the local population. One of the five patients receiving a unit of fresh frozen plasma had an evidence of TRALI, which was not diagnosed at the time. A second patient, who had been HLA typed and who carried a full match of antigens for the antibody specificities of the plasma received, had no evidence of a reaction. There were no documented reactions in 13 recipients of red cells in optimal additive (OA) solution.Cases of TRALI may go unrecognized. Not all patients with antibody/antigen concordance will develop clinical signs. Red cells in OA solution from donors with anti‐HLA antibodies appear to have a low risk of causing clinically evident lung damage.
Why Study Large Projects? An Introduction to Research on Project Finance
Authors: Esty Benjamin C. 
Published: June 2004

Abstract Despite the fact that more than $200 billion of capital investment was financed through project companies in 2001, an amount that grew at a compound annual rate of almost 20% during the 1990s, there has been very little academic research on project finance. The purpose of this article is to explain why project finance in general and why large projects in particular merit separate academic research and instruction. In short, there are significant opportunities to study the relationship among structural attributes (i.e., high leverage, contractual details, and concentrated equity ownership), managerial incentives, and asset values, as well as improve current practice in this rapidly growing field of finance.
Keeping Up with the Joneses and the Home Bias
Authors: Lauterbach Beni , Reisman Haim 
Published: June 2004

Abstract We argue that when individuals care about their consumption relative to that of their neighbours, a home bias emerges, that is investors overweight domestic stocks in their portfolios. Domestic stocks are preferred because they also serve the objective of mimicking the economic fortunes and welfare of the investor's neighbours, countrymen, and social reference group. We also demonstrate that globalization mitigates the home bias, and derive a modified international CAPM.
Investor Sentiment and the Closed‐end Fund Puzzle: Out‐of‐sample Evidence
Authors: Doukas John A. , Milonas Nikolaos T. 
Published: June 2004

AbstractIn this paper we examine the proposition that small investor sentiment, measured by the change in the discount/premium on closed‐end funds, is an important factor in stock returns. We conduct an out‐of‐sample test of the investor sentiment hypothesis in a market environment that is more likely to be prone to investor sentiment than the USA. We fail to provide supporting evidence for the claim of Lee et al. (1991) that investor sentiment affects the risk of common stocks. Consistent with Elton et al. (1998), who show that investor sentiment does not enter the return generating process, our tests do not detect investor sentiment in a capital market that is more susceptible to small investor sentiment. Our results provide additional support against the claim that investor sentiment represents an independent and systematic asset pricing risk.
Corporate Governance and Expected Stock Returns: Evidence from Germany
Authors: Drobetz Wolfgang , Schillhofer Andreas , Zimmermann Heinz 
Published: June 2004

Abstract Recent empirical work shows evidence for higher valuation of firms in countries with a better legal environment. We investigate whether differences in the quality of firm‐level corporate governance also help to explain firm performance in a cross‐section of companies within a single jurisdiction. Constructing a broad corporate governance rating (CGR) for German public firms, we document a positive relationship between governance practices and firm valuation. There is also evidence that expected stock returns are negatively correlated with firm‐level corporate governance, if dividend yields are used as proxies for the cost of capital. An investment strategy that bought high‐CGR firms and shorted low‐CGR firms earned abnormal returns of around 12% on an annual basis during the sample period.
Why Do Firms Hold Cash? Evidence from EMU Countries
Authors: Ferreira Miguel A. , Vilela Antonio S. 
Published: June 2004

Abstract This paper investigates the determinants of corporate cash holdings in EMU countries. Our results suggest that cash holdings are positively affected by the investment opportunity set and cash flows and negatively affected by asset's liquidity, leverage and size. Bank debt and cash holdings are negatively related, which supports that a close relationship with banks allows the firm to hold less cash for precautionary reasons. Firms in countries with superior investor protection and concentrated ownership hold less cash, supporting the role of managerial discretion agency costs in explaining cash levels. Capital markets development has a negative impact on cash levels, contrary to the agency view.
Implied Foreign Exchange Risk Premia
Authors: Panigirtzoglou Nikolaos 
Published: June 2004

Abstract This paper uses implied volatilities from foreign exchange option prices and the results of no‐arbitrage theory to estimate foreign exchange risk premia. In particular, under the assumption of no‐arbitrage, the foreign exchange risk premium is driven by the difference between investors’ market prices of risk in the two currencies. In an international economy with three currencies, sterling, US dollar and Deutschemark, we can use the information on implied volatilities of the three cross rates to derive estimates of implied or ex ante market prices of risk and of foreign exchange risk premia. The foreign exchange risk premia estimates are then compared to survey‐based risk premia.
Why Do European Firms Issue Convertible Debt?
Authors: Bancel Franck , Mittoo Usha R. 
Published: June 2004

Abstract We survey European managers to gain some insights into motivations of convertible issuance. Our analysis shows that a majority of firms issue convertibles as ‘delayed equity’ and as ‘debt sweetener’. Managers also use convertibles to avoid short‐term equity dilution and to signal firm's future growth opportunities. We document a large cross‐sectional variation across firms in rationales for issuing convertibles and find mixed support for most theoretical models. Our evidence suggests that the popularity of convertibles is driven primarily by their versatility in adjusting their design to fit the financing needs of individual firms, and by their increased demand among institutional investors.