bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecology and subsistence strategies in the eastern Italian Alps during the Middle Palaeolithic
Authors: Fiore Ivana , Gala Monica , Tagliacozzo Antonio 
Published: June 2004

AbstractItaly is very rich in Middle Palaeolithic sites, and the Veneto region ranges among those with the best archaeozoological information. Most of the Middle Palaeolithic sites are located in caves and rock shelters situated at the mouths of the Alpine valleys, in the piedmont slopes. The two sites that offer the best archaeozoological data are Grotta di Fumane and Grotta S. Bernardino. Grotta S. Bernardino was occupied alternately by humans and carnivores, in particular bear. The fauna is largely dominated by ungulate remains, with red and roe deer prevalent over chamois and ibex; elk and giant deer are also present. Among the carnivores, the most frequent species is cave bear followed by lynx and leopard. Furthermore, hare, beaver and marmot are present together with remains of both fish and birds. It is possible that bears or birds of prey introduced the rare fish remains. In the Mousterian levels, hunting of the most common species was mainly directed towards young adult and adult individuals, suggesting the possibility of selective hunting. Marmot, beaver and probably bear, together with some species of birds (ducks, geese and Galliformes) were also hunted. At Grotta Fumane, Mousterian and Aurignacian levels reveal evidence of human activity related to carcass processing and bone exploitation. The most frequent ungulates are red deer, followed by roe deer and ibex; less frequent are chamois, bovids and giant deer (Megaloceros giganteus). Among the carnivores, bears (both Ursus arctos and Ursus spelaeus) are present, as are wolf, red fox and hyena (Crocuta crocuta). Hare and marmot are also present together with abundant bird remains. The most common species of bird are: Tetrao tetrix, Crex crex and Pyrrhocorax graculus. Mortality data for ungulates suggest that young adults and adults were preferentially selected. The faunal assemblage indicates that economic, ecological and climatic changes took place between the Mousterian and the Aurignacian levels. Copyright © 2004 John Wiley & Sons, Ltd.
Gasoline prices and motor vehicle fatalities
Authors: Grabowski David C. , Morrisey Michael A. 
Published: June 2004

AbstractFatal motor vehicle crashes per capita remained relatively stable over the 1990s, in spite of new traffic safety laws and vehicle innovations. One explanation for this stability is that the price of gasoline declined, which resulted in more vehicle miles traveled and potentially more fatalities. By using 1983–2000 monthly gasoline price and fatality panel data and fixed effects specifications, this study exploits within‐state variation over time in gasoline prices and found that a 10‐cent decrease in gasoline prices increased motor vehicle fatalities by 2.3 percent over a 2‐year period. The effect on higher‐risk younger adults is more than twice as large. The secular decline in real gasoline prices over the 1990s may partially explain why motor vehicle fatalities per capita have not decreased even with the adoption of more stringent state policies. © 2004 by the Association for Public Policy Analysis and Management.
Atomic force microscopy revelation of molecular complexes in the multiprotein cytochrome P450 2B4‐containing system
Authors: Kuznetsov Vadim Yu. , Ivanov Yuri D. , Archakov Alexander I. 
Published: June 2004

AbstractThe application of atomic force microscopy (AFM) to the identification and visualization of individual molecules and their complexes in a reconstituted monooxygenase P450 2B4 system without the phospholipid was demonstrated. The method employed in this study distinguishes the monomeric proteins from their binary complexes and, also, the binary from the ternary complexes. The AFM images of the full‐length P450 2B4 system's constituent components – cytochrome P450 2B4 (2B4), NADPH‐cytochrome P450 reductase and cytochrome b5 (b5), were obtained on highly‐oriented pyrolitic graphite. The typical heights of the d‐2B4, d‐flavoprotein (Fp) and d‐b5 molecules were measured and found to be 2.2 ± 0.2, 2.3 ± 0.2 and 1.8 ± 0.1 nm, respectively. The measured heights of the binary d‐Fp/d‐2B4 and d‐2B4/d‐b5 complexes were estimated to be 3.4 ± 0.2 and 2.8 ± 0.2 nm, respectively. No formation of d‐Fp/d‐b5 complexes was registered. The ternary d‐Fp/d‐2B4/d‐b5 complexes were visualized and their heights were found to be roughly equal to 4.3 ± 0.3 nm and 6.2 ± 0.3 nm.
Identification of proteins in activated human neutrophils susceptible to tyrosyl radical attack. A proteomic study using a tyrosylating fluorophore
Authors: Avram Diana , Romijn Edwin P. , Pap Everard H. W. , Heck Albert J. R. , Wirtz Karel W. A. 
Published: June 2004

AbstractTyrosyl radicals cross‐linked to protein tyrosine residues (tyrosylated proteins) represent hallmarks of neutrophil‐mediated injury at the inflammatory locus. Yet the proteins targeted by tyrosyl radicals in an intact cellular system remain to be elucidated. Here, we show that tyrosyl radicals generated by human neutrophils after activation by phorbol 12‐myristate 13‐acetate (PMA), interferon‐γ (IFN‐γ) or TNF‐α could act in an autocrine manner by cross‐linking to endogenous proteins. We have identified the tyrosylated proteins by using a membrane‐impermeable tyrosine analogue, tyramine coupled to fluorescein (TyrFluo), in combination with proteomics techniques. Confocal microscopy images indicated that initially the tyrosylated proteins were localized in patches at the cell surface to become internalized subsequently. In the neutrophil membrane‐associated proteome, lactoferrin was the prime target of tyrosylation. Out of three isoforms identified, an 80 kDa neutral isoform was tyrosylated more extensively than the 85 kD basic isoform, particularly after PMA activation. Although all three stimuli induced tyrosylation of the filamentous component vimentin, additional tyrosylated vimentin fragments were detected after IFN‐γ‐ and TNF‐α‐stimulation. Moreover, upon activation the bulk of vimentin behaved as a dimer (Mr 120 kDa) being slightly tyrosylated, yet phosphorylated at Thr‐425 possibly as a requirement for its externalization. Unexpectedly, bovine catalase added to end tyrosyl radicals formation was detected as a highly tyrosylated neutrophil‐associated protein. A moderate stimulus‐dependent tyrosylation of ATP synthase‐β, α‐enolase, glyceraldehyde 3‐phosphate dehydrogenase, cytokeratin‐10, filamin‐A, and annexin‐I was also observed. When the membrane‐permeable probe (acetylTyrFluo) was used, protein tyrosylation was not observed indicating that the intracellular proteins were well protected against oxidative attack. This study shows that human neutrophils can modulate their proteome via a tyrosine oxidation pathway induced by pro‐inflammatory mediators.
Heterochain model for simultaneous long‐chain branching and crosslinking. I. Matrix formula for the weight‐average molecular weights
Authors: Tobita Hidetaka 
Published: June 2004

AbstractThe hetrochain model was applied to develop a matrix formula describing the weight‐average molecular weights for a reaction system that involves simultaneous long‐chain branching and crosslinking. The heterochain model describes the molecular architecture formed through the primary chain connection that follows the Markovian statistics; therefore, this matrix formula is valid regardless of the chemical and reactor systems used, as long as the Markovian nature is preserved for the chain‐connection statistics. Application to free‐radical (co)polymerization systems is described in subsequent research. The gel point is simply described as a point at which the largest eigenvalue of the matrix M, which defines the chain‐connection statistics, reaches unity. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2780–2790, 2004
Evaluation of the relative stability of liganded versus ligand‐free protein conformations using Simplicial Neighborhood Analysis of Protein Packing (SNAPP) method
Authors: Sherman Douglas B. , Zhang Shuxing , Pitner J. Bruce , Tropsha Alexander 
Published: June 2004

AbstractMany proteins change their conformation upon ligand binding. For instance, bacterial periplasmic binding proteins (bPBPs), which transport nutrients into the cytoplasm, generally consist of two globular domains connected by strands, forming a hinge. During ligand binding, hinge motion changes the conformation from the open to the closed form. Both forms can be crystallized without a ligand, suggesting that the energy difference between them is small. We applied Simplicial Neighborhood Analysis of Protein Packing (SNAPP) as a method to evaluate the relative stability of open and closed forms in bPBPs. Using united residue representation of amino acids, SNAPP performs Delaunay tessellation of the protein, producing an aggregate of space‐filling, irregular tetrahedra with nearest neighbor residues at the vertices. The SNAPP statistical scoring function is derived from log‐likelihood scores for all possible quadruplet compositions of amino acids found in a representative subset of the Protein Data Bank, and the sum of the scores for a given protein provides the total SNAPP score. Results of scoring for bPBPs suggest that in most cases, the unliganded form is more stable than the liganded form, and this conclusion is corroborated by similar observations of other proteins undergoing conformation changes upon binding their ligands. The results of these studies suggest that the SNAPP method can be used to predict the relative stability of accessible protein conformations. Furthermore, the SNAPP method allows delineation of the role of individual residues in protein stabilization, thereby providing new testable hypotheses for rational site‐directed mutagenesis in the context of protein engineering. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Combining evolutionary and structural information for local protein structure prediction
Authors: Pei Jimin , Grishin Nick V. 
Published: June 2004

AbstractWe study the effects of various factors in representing and combining evolutionary and structural information for local protein structural prediction based on fragment selection. We prepare databases of fragments from a set of non‐redundant protein domains. For each fragment, evolutionary information is derived from homologous sequences and represented as estimated effective counts and frequencies of amino acids (evolutionary frequencies) at each position. Position‐specific amino acid preferences called structural frequencies are derived from statistical analysis of discrete local structural environments in database structures. Our method for local structure prediction is based on ranking and selecting database fragments that are most similar to a target fragment. Using secondary structure type as a local structural property, we test our method in a number of settings. The major findings are: (1) the COMPASS‐type scoring function for fragment similarity comparison gives better prediction accuracy than three other tested scoring functions for profile–profile comparison. We show that the COMPASS‐type scoring function can be derived both in the probabilistic framework and in the framework of statistical potentials. (2) Using the evolutionary frequencies of database fragments gives better prediction accuracy than using structural frequencies. (3) Finer definition of local environments, such as including more side‐chain solvent accessibility classes and considering the backbone conformations of neighboring residues, gives increasingly better prediction accuracy using structural frequencies. (4) Combining evolutionary and structural frequencies of database fragments, either in a linear fashion or using a pseudocount mixture formula, results in improvement of prediction accuracy. Combination at the log‐odds score level is not as effective as combination at the frequency level. This suggests that there might be better ways of combining sequence and structural information than the commonly used linear combination of log‐odds scores. Our method of fragment selection and frequency combination gives reasonable results of secondary structure prediction tested on 56 CASP5 targets (average SOV score 0.77), suggesting that it is a valid method for local protein structure prediction. Mixture of predicted structural frequencies and evolutionary frequencies improve the quality of local profile‐to‐profile alignment by COMPASS. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Structural components of SCAN‐domain dimerizations
Authors: Nam Kiyean , Honer Christian , Schumacher Christoph 
Published: June 2004

AbstractThe SCAN or leucine‐rich domain has been characterized as a highly conserved sequence in zinc finger transcription factors that mediates selective dimer formation between SCAN‐domain‐containing proteins. In order to accommodate various SCAN‐domain sequence features, a minimal functional folding unit was defined on the premise of proper structural folding and biochemical binding. The 58‐amino acid minimal functional units derived from each of four SCAN‐domain protein families were subjected to a three‐dimensional position‐specific scoring matrix (3D‐PSSM) and ungapped threading analysis. The resulting fold prediction represented the SCAN‐domain's minimal functional unit as a bundle of three alpha helices folded to a core structure. In addition, the minimal functional folding unit biochemically retained the selective dimerization properties of the native proteins. In order to elucidate the structural components within the SCAN‐domain that engage in binding interactions, we attempted to correlate the physicochemical helix properties, as represented by a hydropathy profile, with the experimental dimerization selectivities. The amino‐terminal helix revealed the highest diversity measure among the three helices of the minimal functional unit and is therefore likely to offer critical surface‐exposed binding residues. Indeed, by interchanging the amino‐terminal helix between SCAN‐domains without alteration of their structural frames consisting of conserved hydrophobic residues, a modulation of binding preferences was demonstrated. The minimal functional folding unit of SCAN‐domains may therefore contain within the amino‐terminal alpha helix structural components that determine selective dimerization patterns and combinatorial control of transcription factors. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Transition states for folding of circular‐permuted proteins
Authors: Chen Jie , Wang Jun , Wang Wei 
Published: June 2004

AbstractTo explore the role of entropy and chain connectivity in protein folding, a particularly interesting scheme, namely, the circular permutation, has been used. Recently, experimental observations showed that there are large differences in the folding mechanisms between the wild‐type proteins and their circular permutants. These differences are strongly related to the change in the intrachain connectivity. Some results obtained by molecular dynamics simulations also showed a good agreement with the experimental findings. Here, we use a topology‐based free‐energy functional method to study the role of the chain connectivity in folding by comparing features of transition states of the wild‐type proteins with those of their circular permutants. We concentrate our study on 3 small globular proteins, namely, the α‐spectrin SH3 domain (SH3), the chymotrypsin inhibitor 2 (CI2), and the ribosomal protein S6, and obtain exciting results that are consistent with the available experimental and simulation results. A heterogeneity of the interaction energies between contacts for protein CI2 and for protein S6 is also introduced, which characterizes the strong interactions between contacts with long loops, as speculated from experiments for protein S6. The comparison between the folding nucleus of the wild‐type proteins and those of their circular permutants indicates that chain connectivity affects remarkably the shapes of the energy profiles and thus the folding mechanism. Further comparisons between our theoretical calculated ϕth values and the experimental observed ϕexp values for the 3 proteins and their permutants show that our results are in good agreement with experimental ones and that correlations between them are high. These indicate that the free‐energy functional method really provides a way to analyze the folding behavior of the circular‐permuted proteins and therefore the folding mechanism of the wild‐type proteins. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Fast and accurate computation of the 13C chemical shifts for an alanine‐rich peptide
Authors: Vila Jorge A. , Baldoni Héctor A. , Ripoll Daniel R. , Scheraga Harold A. 
Published: June 2004

AbstractThe purpose of this work is, first, to present a fast and accurate technique to compute Boltzmann‐averaged values of the quantum‐chemical 13C chemical shifts for each amino acid in oligopeptides, demonstrated here by an application to the peptide Ac‐XXAAAAAAAOO‐NH2 (where X denotes diaminobutyric acid, A is alanine, and O is ornithine) [XAO] and, second, to discuss the capability of the 13Cα and 13Cβ chemical shifts to distinguish the PPII conformation from the α‐helix and statistical‐coil conformations. Use is made of a combination of approaches, summarized as follows: (1) derivation of an ensemble of conformations by using a molecular mechanics technique; (2) use of a clustering procedure to form families and build a reduced set of conformations consisting of the lowest‐energy conformations of each family, and (3) computation of the 13C chemical shifts for the lowest‐energy conformations of each family, using a quantum‐chemical approach that treats a selected residue, or group of residues, with a 6‐311+G(2d,p) locally‐dense basis set, while the remaining residues in the sequence are treated with a 3‐21G basis set. The whole procedure is quite accurate and speeds up the computation of the Boltzmann‐averaged values of the 13C‐chemical shifts by several orders of magnitude. The present application sheds some light on the conformational preference for alanine and non‐alanine residues to occupy the PPII helical region of the Ramachandran map. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Gibbs adsorption isotherm combined with Monte Carlo sampling to see action of cosolutes on protein folding
Authors: Harries Daniel , Parsegian V. Adrian 
Published: June 2004

AbstractDriven by conditions set by smaller solutes, proteins fold and unfold. Experimentally, these conditions are stated as intensive variables ‐ pH and other chemical potentials ‐ as though small solutes were infinite resources that come at an externally varied free energy cost. Computationally, the finite spaces of simulation allow only fixed numbers of these solutes. By combining the analytic Gibbs adsorption isotherm with the computational Monte Carlo sampling of polymer configurations, we have been able to overcome an inherent limitation of computer simulation. The idea is to compute analytically the free energy changes wrought by solutes on each particular configuration. Then numerical computation is needed only to sample the set of configurations as efficiently as when no bathing solute is present. For illustration, the procedure is applied to an idealized two‐dimensional heteropolymer to yield lessons about the effect of cosolutes on protein stability. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Efficiency of a second‐generation HIV‐1 protease inhibitor studied by molecular dynamics and absolute binding free energy calculations
Authors: Lepšík M. , Kříž Z. , Havlas Z. 
Published: June 2004

AbstractA subnanomolar inhibitor of human immunodeficiency virus type 1 (HIV‐1) protease, designated QF34, potently inhibits the wild‐type and drug‐resistant enzyme. To explain its broad activity, the binding of QF34 to the wild‐type HIV‐1 protease is investigated by molecular dynamics simulations and compared to the binding of two inhibitors that are used clinically, saquinavir (SQV) and indinavir (IDV). Analysis of the flexibility of protease residues and inhibitor segments in the complex reveals that segments of QF34 were more mobile during the dynamics studies than the segments of SQV and IDV. The dynamics of hydrogen bonding show that QF34 forms a larger number of stable hydrogen bonds than the two inhibitors that are used clinically. Absolute binding free energies were calculated with molecular mechanics–generalized Born surface area (MM–GBSA) methodology using three protocols. The most consistent results were obtained using the single‐trajectory approach, due to cancellation of errors and inadequate sampling in the separate‐trajectory protocols. For all three inhibitors, energy components in favor of binding include van der Waals and electrostatic terms, whereas polar solvation and entropy terms oppose binding. Decomposition of binding energies reveals that more protease residues contribute significantly to the binding of QF34 than to the binding of SQV and IDV. Moreover, contributions from protease main chains and side chains are balanced in the case of QF34 (52:48 ratio, respectively), whereas side chain contributions prevail in both SQV and IDV (main‐chain:side‐chain ratios of 41:59 and 45:55, respectively). The presented results help explain the ability of QF34 to inhibit multiple resistant mutants and should be considered in the design of broad‐specificity second‐generation HIV‐1 protease inhibitors. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Domain swapping of CD4 upon dimerization
Authors: Sanejouand Yves‐Henri 
Published: June 2004

AbstractIt has recently been shown that disulfide bond Cys130—Cys159 in domain 2 of monomeric CD4 is involved in the formation of CD4 disulfide‐bonded dimers on cell surfaces and that it can influence the permissiveness of cells to HIV infection. Because this disulfide bond is buried in the monomer, a large conformational change must take place in order to allow for such disulfide exchange. Using standard optimization techniques, whose efficiency was first checked in the well‐documented CD2 case, we have shown that 3D domain swapping is a likely candidate for the conformational change, the hinge loop, or linker, being loop E—F. Indeed, as a consequence of domain swapping, because Cys130 and Cys159 belong to β‐strands C and F, respectively, two disulfide bonds become established between Cys130 in one monomer and Cys159 in the other one. Such a disulfide exchange has already been observed when the nuclear magnetic resonance (NMR) structure of the prion protein was compared to the crystallographic, dimeric one. In both cases, domain swapping implies disulfide exchange because the linker is located in the sequence between two disulfide‐bonded cysteines. As in the CD2 case, the proposed configuration of the CD4 dimer is found as a pair of neighboring monomers in the crystallographic unit cell. Moreover, because in this configuration the epitope of monoclonal antibody MT151, which does not compete with Gp120 for CD4 binding, is in the cleft between the pair of CD4 monomers, it is suggested that MT151 achieves its HIV‐blocking activity by interfering with the formation of CD4 domain‐swapped dimers on cell surface. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Toward an atomistic model for predicting transcription‐factor binding sites
Authors: Endres Robert G. , Schulthess Thomas C. , Wingreen Ned S. 
Published: June 2004

AbstractIdentifying the specific DNA‐binding sites of transcription‐factor proteins is essential to understanding the regulation of gene expression in the cell. Bioinformatics approaches are fast compared to experiments, but require prior knowledge of multiple binding sites for each protein. Here, we present an atomistic force‐field method to predict binding sites based only on the X‐ray structure of a related bound complex. Specific flexible contacts between the protein and DNA are modeled by a library of amino acid side‐chain rotamers. Using the example of the mouse transcription factor, Zif268, a well‐studied zinc‐finger protein, we show that the protein sequence alone, without the detailed experimental structure, gives a strong bias toward the consensus binding site. Proteins 2004. © 2004 Wiley‐Liss, Inc.