bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constant‐pH molecular dynamics using continuous titration coordinates
Authors: Lee Michael S. , Salsbury Freddie R. , Brooks Charles L. 
Published: June 2004

AbstractIn this work, we explore the question of whether pKa calculations based on a microscopic description of the protein and a macroscopic description of the solvent can be implemented to examine conformationally dependent proton shifts in proteins. To this end, we introduce a new method for performing constant‐pH molecular dynamics (PHMD) simulations utilizing the generalized Born implicit solvent model. This approach employs an extended Hamiltonian in which continuous titration coordinates propagate simultaneously with the atomic motions of the system. The values adopted by these coordinates are modulated by potentials of mean force of isolated titratable model groups and the pH to control the proton occupation at particular sites in the polypeptide. Our results for four different proteins yield an absolute average error of ∼1.6 pK units, and point to the role that thermally driven relaxation of the protein environment in the vicinity of titrating groups plays in modulating the local pKa, thereby influencing the observed pK1/2 values. While the accuracy of our method is not yet equivalent to methods that obtain pK1/2 values through the ad hoc scaling of electrostatics, the present approach and constant pH methods in general provide a useful framework for studying pH‐dependent phenomena. Further work to improve our model to approach quantitative agreement with experiment is outlined. Proteins 2004. © 2004 Wiley‐Liss, Inc.
The occurrence of CH…O hydrogen bonds in α‐helices and helix termini in globular proteins
Authors: Manikandan K. , Ramakumar S. 
Published: June 2004

AbstractA comprehensive database analysis of CH…O hydrogen bonds in 3124 α‐helices and their corresponding helix termini has been carried out from a nonredundant data set of high‐resolution globular protein structures resolved at better than 2.0 Å in order to investigate their role in the helix, the important protein secondary structural element. The possible occurrence of 5 → 1 CH…O hydrogen bond between the ith residue CH group and (i − 4)th residue CO with C…O ≤ 3.8 Å is studied, considering as potential donors the main‐chain Cα and the side‐chain carbon atoms Cβ, Cγ, Cδ and Cϵ. Similar analysis has been carried out for 4 → 1 CH…O hydrogen bonds, since the CH…O hydrogen bonds found in helices are predominantly of type 5 → 1 or 4 → 1. A total of 17,367 (9310 of type 5 → 1 and 8057 of type 4 → 1) CH…O hydrogen bonds are found to satisfy the selected criteria. The average stereochemical parameters for the data set suggest that the observed CH…O hydrogen bonds are attractive interactions. Our analysis reveals that the Cγ and Cβ hydrogen atom(s) are frequently involved in such hydrogen bonds. A marked preference is noticed for aliphatic β‐branched residue Ile to participate in 5 → 1 CH…O hydrogen bonds involving methylene Cγ 1 atom as donor in α‐helices. This may be an enthalpic compensation for the greater loss of side‐chain conformational entropy for β‐branched amino acids due to the constraint on side‐chain torsion angle, namely, χ1, when they occur in helices. The preference of amino acids for 4 → 1 CH…O hydrogen bonds is found to be more for Asp, Cys, and for aromatic residues Trp, Phe, and His. Interestingly, overall propensity for CH…O hydrogen bonds shows that a majority of the helix favoring residues such as Met, Glu, Arg, Lys, Leu, and Gln, which also have large side‐chains, prefer to be involved in such types of weak attractive interactions in helices. The amino acid side‐chains that participate in CH…O interactions are found to shield the acceptor carbonyl oxygen atom from the solvent. In addition, CH…O hydrogen bonds are present along with helix stabilizing salt bridges. A novel helix terminating interaction motif, X‐Gly with Gly at Ccap position having 5 → 1 CαH…O, and a chain reversal structural motif having 1 → 5 Cα‐H…O have been identified and discussed. Our analysis highlights that a multitude of local CH…O hydrogen bonds formed by a variety of amino acid side‐chains and Cα hydrogen atoms occur in helices and more so at the helix termini. It may be surmised that the main‐chain Cα and the side‐chain CH that participate in CH…O hydrogen bonds collectively augment the cohesive energy and thereby contribute together with the classical NH…O hydrogen bonds and other interactions to the overall stability of helix and therefore of proteins. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Modeling correlated main‐chain motions in proteins for flexible molecular recognition
Authors: Zavodszky Maria I. , Lei Ming , Thorpe M. F. , Day Anthony R. , Kuhn Leslie A. 
Published: June 2004

AbstractWe describe a new method for modeling protein and ligand main‐chain flexibility, and show its ability to model flexible molecular recognition. The goal is to sample the full conformational space, including large‐scale motions that typically cannot be reached in molecular dynamics simulations due to the computational intensity, as well as conformations that have not been observed yet by crystallography or NMR. A secondary goal is to assess the degree of flexibility consistent with protein–ligand recognition. Flexibility analysis of the target protein is performed using the graph‐theoretic algorithm FIRST, which also identifies coupled networks of covalent and noncovalent bonds within the protein. The available conformations of the flexible regions are then explored with ROCK by random‐walk sampling of the rotatable bonds. ROCK explores correlated motions by only sampling dihedral angles that preserve the coupled bond networks in the protein and generates conformers with good stereochemistry, without using a computationally expensive potential function. A representative set of the conformational ensemble generated this way can be used as targets for docking with SLIDE, which handles the flexibility of protein and ligand side‐chains. The realism of this protein main‐chain conformational sampling is assessed by comparison with time‐resolved NMR studies of cyclophilin A motions. ROCK is also effective for modeling the flexibility of large cyclic and polycyclic ligands, as demonstrated for cyclosporin and zearalenol. The use of this combined approach to perform docking with main‐chain flexibility is illustrated for the cyclophilin A–cyclosporin complex and the estrogen receptor in complex with zearalenol, while addressing the question of how much flexibility is allowed without hindering molecular recognition. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Protein unfolding at interfaces: Slow dynamics of α‐helix to β‐sheet transition
Authors: Sethuraman Ananthakrishnan , Vedantham Ganesh , Imoto Taiji , Przybycien Todd , Belfort Georges 
Published: June 2004

AbstractA two‐phase sequential dynamic change in the secondary structure of hen egg lysozyme (Lys) adsorbed on solid substrates was observed. The first phase involved fast conversion of α‐helix to random/turns (within the first minute or at very low coverage or high substrate wettability) with no perceptible change in β‐sheet content. The second phase (1–1200 min), however, involved a relatively slow conversion from α‐helix to β‐sheet without a noticeable change in random/turns. An important finding of this work is that the concentration of lysozyme in the adsorbed state has a substantial effect on the fractional content of secondary structures. Attenuated total reflection Fourier transform infrared (ATR/FTIR) spectroscopy, along with a newly‐developed optimization algorithm for predicting the content of secondary structure motifs, was used to correlate the secondary structure and the amount of adsorbed lysozyme with the surface wettability of six different flat nanoporous substrates. Although three independent variables, surface wettability, solution concentration and time for adsorption, were used to follow the fractional structural changes of lysozyme, the results were all normalized onto a single plot with the amount adsorbed as the universal independent variable. Consequently, lateral interactions among proteins likely drive the transition process. Direct intermolecular force adhesion measurements between lysozyme and different functionalized self‐assembled alkanethiol monolayers confirm that hydrophobic surfaces interact strongly with proteins. The lysozyme‐unfolding pathway during early adsorption appears to be similar to that predicted by published molecular modeling results. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Structure of an anti‐DNA fab complexed with a non‐DNA ligand provides insights into cross‐reactivity and molecular mimicry
Authors: Schuermann Jonathan P. , Henzl Michael T. , Deutscher Susan L. , Tanner John J. 
Published: June 2004

AbstractAntibodies that recognize DNA (anti‐DNA) are part of the autoimmune response underlying systemic lupus erythematosus. To better understand molecular recognition by anti‐DNA antibodies, crystallographic studies have been performed using an anti‐ssDNA antigen‐binding fragment (Fab) known as DNA‐1. The previously determined structure of a DNA‐1/dT5 complex revealed that thymine bases insert into a narrow groove, and that ligand recognition primarily involves the bases of DNA. We now report the 1.75‐Å resolution structure of DNA‐1 complexed with the biological buffer HEPES (4‐(2‐Hydroxyethyl)piperazine‐1‐ethanesulfonic acid). All three light chain complementarity‐determining regions (CDRs) and HCDR3 contribute to binding. The HEPES sulfonate hydrogen bonds to His L91, Asn L50, and to the backbone of Tyr H100 and Tyr H100A. The Tyr side‐chains of L32, L92, H100, and H100A form nonpolar contacts with the HEPES ethylene and piperazine groups. Comparison to the DNA‐1/dT5 structure reveals that the dual recognition of dT5 and HEPES requires a 13‐Å movement of HCDR3. This dramatic structural change converts the combining site from a narrow groove, appropriate for the edge‐on insertion of thymine bases, to one sufficiently wide to accommodate the HEPES sulfonate and piperazine. Isothermal titration calorimetry verified the association of HEPES with DNA‐1 under conditions similar those used for crystallization (2 M ammonium sulfate). Interestingly, the presence of 2 M ammonium sulfate increases the affinities of DNA‐1 for both HEPES and dT5, suggesting that non‐polar Fab–ligand interactions are important for molecular recognition in highly ionic solvent conditions. The structural and thermodynamic data suggest a molecular mimicry mechanism based on structural plasticity and hydrophobic interactions. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Nuclear moments and electron density matrices in atoms
Authors: Pavlov R. L. , Raychev P. P. , Garistov V. P. , Dimitrova‐Ivanovich M. , Maruani J. 
Published: June 2004

AbstractAn electron density matrix approach for the determination of nuclear multipole moments is presented. The electronic matrix elements entering the expressions of the experimentally observed hyperfine coupling constants of atoms are expressed as functionals of the electron charge or spin density matrices. In principle, the calculation of these functionals could be made using any (relativistic or not) molecular orbital (MO) or DFT method. The electronic matrix elements for all possible hyperfine interaction operators, including the yet unobserved magnetic octupole couplings, are considered. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Robust absolute stability of a class of s.i.s.o. control systems
Authors: O. Guardabassi Guido 
Published: June 2004

AbstractA class of s.i.s.o. nonlinear systems rigorously linearizable by output feedback is dealt with in this paper. Any system of such a class can easily be controlled by the tandem connection of a linear controller and a linearizing compensator. The question addressed in the present paper is the robustness of such a control system against mismatched (nonlinear) compensation and linear uncertainty. Copyright © 2004 John Wiley & Sons, Ltd.
Multivariable override control for systems with output and state constraints
Authors: Turner Matthew C. , Postlethwaite Ian 
Published: June 2004

AbstractAn override control strategy for systems having limits on their outputs, states or linear combinations of the two, is discussed. The technique described is applicable to all nonlinear system‐controller combinations which can be written in a certain linear closed‐loop form. The discussion is first confined to the synthesis of a compensator where the limited states/outputs are perfectly known, and is then broadened to include an observer‐based compensator for the case when these measurements are not directly available. It is shown that, although a form of ‘separation principle’ indeed holds for the observer‐based problem, the type of solution available for this form of override control is not quite as strong as that available when an observer is not required. The results are illustrated using a simple multivariable example. Copyright © 2004 John Wiley & Sons, Ltd.
Immunohistochemical and electron‐microscopic identification of neuroendocrine cells in the stomach of uremic rats
Authors: Kasacka Irena 
Published: June 2004

AbstractMany disturbances in electrolyte and hormonal balance in the body induced by functional impairment of renal parenchyma may affect the activity of amine precursor uptake and decarboxylation (APUD) cells, which constitute a very important link in the regulation of homeostasis. The aim of the present study was the morphological, immunohistochemical and ultrastructural estimation of enteroendocrine cells in the stomach of uremic rats. Fragments of gastric pylorus were collected 1, 2 and 4 weeks after nephrectomy. Paraffin embedded sections were stained with H + E and by silver impregnation. For identification of neuroendocrine cells, immunohistochemical reactions were performed using specific antibodies against somatostatin, synaptophysin, neuron‐specific enolase and anti‐calcitonin gene related peptide. The analysis showed an increased number of APUD cells in the stomach of uremic rats compared to control rats, which may be a morphological expression of their hyperfunction in the functional impairment of renal parenchyma. These results suggest that chronic renal failure can modulate the secretory processes of APUD cells.
Macrophage‐associated erythropoiesis and lymphocytopoiesis in mouse fetal liver: ultrastructural and ISH analysis
Authors: Li Dong , Wang Guo‐Yun , Liu Zhao‐Fen , Shi Yong‐Xiang , Zhang Hui , Bai Zeng‐Liang 
Published: June 2004

AbstractTo elucidate the process of fetal liver hematopoiesis, the relationships between stroma and hematopoietic cells involved in maturation were investigated. Cultured mouse fetal liver explants were established for morphological analysis of the interactions between fetal liver stroma and hematopoietic cells ex vivo. Fetal liver stroma comprised epithelial cells and macrophages, which occupied most of the culture surface. Macrophages proliferated extensively in primary culture, but almost disappeared after 3 passages. Close morphological and functional relationships were established between macrophages and hemopoietic cells, whereas epithelial cells did not interact with blood cells. Scanning electron microscopy revealed that macrophages were in close contact with erythroblasts and formed a three‐dimensional network. In each erythroblastic island, 2–3 lymphocytes were also in contact with the macrophages; erythroblasts, lymphocytes and macrophages formed close, firm associations through their cytoplasmic membranes. This cell orientation was confirmed by transmission electron microscopy of fetal liver in vivo. In situ hybridization revealed that the macrophages expressed jagged‐1, an important ligand of the Notch signaling system in hematopoiesis.
Suppressing effects of bisphenol A on the secretory function of ovine anterior pituitary cells
Authors: Katoh K. , Matsuda A , Ishigami A , Yonekura S , Ishiwata H , Chen C , Obara Y 
Published: June 2004

AbstractWe investigated the action of bisphenol A (BPA) on cellular GH release and content, cell number, GHmRNA expression, and concentrations of cellular cyclic AMP ([cAMP]c) and calcium ion ([Ca2+]c) in primary cultured ovine anterior pituitary cells. The following results were found: (1) BPA as well as nonylphenol (NP) at 10−6 to 10−3 M significantly and concentration‐dependently suppressed basal and GHRH‐stimulated GH release, and the cellular GH content, (2) BPA suppressed the cell number in a time‐ and concentration‐dependent manner, (3) 10−4 M BPA suppressed GHmRNA expression to 68% of control (BPA‐free), and abolished GHRH (10−8 M)‐induced increases in [cAMP]c and [Ca2+]c. From these findings we conclude that BPA possesses a suppressing action on GH synthesis and release, and this suppressing action is probably related to impairment of cellular signal transduction systems in ovine anterior pituitary cells.
Marginal blebbing during the early stages of TNF‐induced apoptosis indicates alteration in actomyosin contractility
Authors: Domnina L.V. , Ivanova O.Y. , Pletjushkina O.Y. , Fetisova E.K. , Chernyak B.V. , Skulachev V.P. , Vasiliev J.M. 
Published: June 2004

AbstractDynamics of alterations of cell surface topography during TNF‐induced apoptosis of HeLa cells was examined by phase‐contrast videomicroscopy and immunomorphological analysis. The final stage of apoptosis accompanied by cell rounding and general blebbing of the cell surface became after 4–6 h of incubation but much earlier, after 1.5–3 h, essentially flattened lamellipodia at the active edges transformed into the small blebs that were continuously extended and retracted during the next 1–2 h. This phenomenon was called “marginal blebbing”. It took place before the cytochrome c release from mitochondria to cytosol. Marginal blebbing was inhibited by drugs that depolymerized actin microfilaments (cytochalasin, latrunculin) or decreased Rho‐kinase‐dependent contractility of actin—myosin cortex (H7, HA‐1077, Y27632). A pancaspase inhibitor, zVAD‐fmk, completely prevented marginal and general blebbing, and TNF‐induced apoptosis. DEVD‐fmk, a specific inhibitor of caspase‐3, inhibited both marginal and general blebbing but not cell rounding and death. Thus, marginal blebbing is an early microfilament‐dependent apoptotic event. It is suggested that it is initiated by minimal activation of caspase‐3 and the following local Rho‐kinase‐dependent stimulation of actin—myosin cortex contractility. Localization of marginal blebs at the active edge may be associated with special organization of cortex in that zone.
Estimating migration rates from two tag–release/one recovery experiments
Authors: Shirakihara Kunio , Kitada Shuichi 
Published: June 2004

AbstractWe propose a method for estimating migration (movement) rates from two tag–release/one recovery experiments, regardless of tag-shedding or incomplete tag-reporting which are major problems when tag–recovery techniques are applied to commercially exploitable populations. The entire survey area is divided into multiple strata in advance. The first release is limited to one stratum; then, the second release occurs in every stratum. Recoveries from both releases occur in every stratum. The migration rate between the time of the first and second release is estimated together with its variance. To check the applicability of our method, we applied it to tag–recovery data for skipjack tuna from various places at different times and unequal time intervals. The precision of the estimates was low and the coefficient of variation was 22.6–42.1% because of the small number of recoveries. The experimental design necessary to improve precision is discussed.
Estimation of birthdates and catch-at-age using length frequency analysis (LFA), with application for skipjack tuna (Katsuwonus pelamis) caught in the Southwest Atlantic
Authors: Andrade Humber A. , Kinas Paul G. 
Published: June 2004

AbstractConverting length frequencies into age frequencies is an important component of a fisheries assessment. In this paper we use a length frequency analysis (LFA) to estimate birthdates after converting length data into catch-at-age, and use simulation studies to compare model-selection criteria and to examine the reliability of the resulting estimates. Deviance and an adaptation of the Akaike Information Criterion performed best. LFA results in useful estimates of birthdates and of catch-at-age if reliable length frequency data and estimates of growth parameters are available. The analysis is applied to skipjack tuna (Katsuwonus pelamis) caught in the Southwest Atlantic Ocean. Although spawning is reported to be seasonal in subtropical waters, the birthdates of the fish caught there were spread uniformly across the year. Young skipjack become vulnerable to fishing mainly in the first quarter of each year. Recruitment of strong year classes did not affect fishery yields equally in the Southwest Atlantic and the Caribbean Sea, so the assumption of a unit western stock for management purposes and the stock structure of skipjack in the Atlantic need further evaluation.
A quantitative study of the neuronal nitric oxide synthase expression in the superficial layers of the adult rat superior colliculus after perinatal enucleation
Authors: de Bittencourt‐Navarrete Ruben Ernesto , Giraldi‐Guimarães Arthur , Mendez‐Otero Rosalia 
Published: June 2004

AbstractThe level of expression of the neuronal nitric oxide synthase (nNOS) in the retinorecipient layers of rat superior colliculus (SC) was investigated in adult rats after neonatal enucleation using two biochemical methods: (1) measurement of the in vitro specific‐activity of NOS by the conversion of [3H]‐arginine to [3H]‐citrulline and (2) immunochemical analysis by western blotting and densitometry of immunoreactive bands using antibodies that recognise the three prominent isoforms of nNOS, α, β and γ. A total of 20 Lister rats were used in this study. We have shown that the deprivation of the retinocollicular projections at early postnatal ages induces no significant change in the specific‐activity of nNOS. We also have shown that the deafferentation does not significantly influence either the total amount of nNOS in the SC superficial layers or the relative contribution ratio of nNOS isoforms. In conclusion, the expression and activity of nNOS in the SC retinorecipient layers was shown not to be dependent on the presence of retinal afferents during development.
Overstretching of sarcomeres may not cause cerebral palsy muscle contracture
Authors: Smeulders Mark J. C. , Kreulen Michiel , Hage J. Joris , Huijing Peter A. , van der Horst Chantal M. A. M. 
Published: June 2004

AbstractTo answer the question whether the muscle contracture in patients with cerebral palsy is caused by overstretching of in‐series sarcomeres we studied the active and passive force–length relationship of the flexor carpi ulnaris muscle (FCU) in relation to its operating length range in 14 such patients with a flexion deformity of the wrist.Force–length relationship was measured intra‐operatively using electrical stimulation, a force transducer, and a data‐acquisition system. Muscle length was measured in maximally flexed and maximally extended position of the wrist.The spastic FCU was found to exert over 80% of its maximum active force at maximal extension of the wrist and this indicates abundant overlap of the sarcomeres. At maximal wrist extension, FCU passive force corresponded with only 0.7–18% of maximum active force. Both findings imply that the FCU sarcomeres are not overstretched when the wrist is extended. We conclude that the overstretching of in‐series sarcomeres appears not to be the cause of contracture of the spastic FCU. © 2004 Orthopaedic Research Society. Published y Elsevier Ltd. All rights reserved.