bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homologous desensitization of ATP‐stimulated mitogenesis: Mechanism involves desensitization of arachidonic acid release and cAMP elevation but not the activation of protein kinase A
Authors: Huang Ning‐Na , Wang Ding‐Ji , Heller Elizabeth , Heppel Leon A. 
Published: February 2005

AbstractProlonged incubation of quiescent 3T3, 3T6, and A431 cells with the P2Y purinoceptor agonists ATP, ADP, or AMPPNP reduced the mitogenic responses of target cells to a further challenge by these agonists, as measured by [3H]thymidine incorporation. The mitogenic desensitization was agonist‐specific, for no effect was seen on DNA synthesis stimulated by epidermal growth factor, insulin, bombesin, 12‐0‐tetradecanoyl‐phorbol‐12 acetate (TPA), or adenosine. The desensitization was completely reversible, since after a 24 hr incubation in the absence of ATP, the cells responded fully to the mitogenic action of ATP. The presence of a low level of cycloheximide blocked recovery, suggesting that down‐regulation of the P2Y receptor may have occurred during desensitization. In Swiss 3T3 cells, stimulation of DNA synthesis occurs predominantly by activation of arachidonic acid release, followed by its oxidation to prostaglandin E2 and stimulation of adenylyl cyclase. Interestingly, prolonged preincubation with ATP produced a similar degree of desensitization of DNA synthesis and of ATP‐dependent arachidonic acid release and cAMP accumulation. Furthermore, this was true for both wild type cells and mutants with a defective cAMP‐dependent protein kinase (PKA). We conclude that homologous desensitization is likely due to uncoupling of the P2Y purinoceptor from phospholipase A2, and this process does not require activation of protein kinase A. © 1995 Wiley‐Liss Inc.
Constructions of bipartite graphs from finite geometries
Authors: Mellinger Keith E. , Mubayi Dhruv 
Published: February 2005

AbstractWe construct an incidence structure using certain points and lines in finite projective spaces. The structural properties of the associated bipartite incidence graphs are analyzed. These n × n bipartite graphs provide constructions of C6‐free graphs with Ω(n4/3 edges, C10‐free graphs with Ω(n6/5) edges, and Θ(7,7,7)‐free graphs with Ω(n8/7) edges. Each of these bounds is sharp in order of magnitude. © 2005 Wiley Periodicals, Inc. J Graph Theory 49: 1–10, 2005
Characterizing the electrospray ionization mass spectral fragmentation pattern of indole derivatives synthesized from 2‐keto glycosides
Authors: Cao Shuxia , Liu Hongmin , Xu Wen , Liao Xincheng , Zhao Yufen 
Published: February 2005

AbstractFour indole derivatives synthesized from 2‐keto glycosides were analyzed by electrospray ionization tandem mass spectrometry (ESI‐MSn) with low‐energy collision‐induced dissociation to establish a general structural elucidation of indole derivatives. Their fragmentation pathways are proposed on the basis of the MSn studies and deuterium‐labeled experiments. Indole derivatives undergo complicated gas‐phase rearrangements in addition to simple bond cleavages. A rearrangement, which involves a contraction of the six‐membered ring, was observed and a mechanism was proposed. The observations may have some potential applications in the interpretation of the mass spectra of indole derivatives. Copyright © 2005 John Wiley & Sons, Ltd.
Expression of the nm23 homologues nm23‐H4, nm23‐H6, and nm23‐H7 in human gastric and colon cancer
Authors: Seifert M , Welter C , Mehraein Y , Seitz G 
Published: February 2005

AbstractEight members of the nm23‐gene family have been described. The involvement of nm23‐H1 and nm23‐H2 in tumour progression and metastasis, as well as in gene regulation and apoptosis, has been shown in numerous studies. Whether nm23‐H4, ‐H6, and ‐H7 play a role in tumours is, however, largely unknown. This study describes data on the expression of these three nm23 homologues in human colon and gastric cancer by real‐time RT‐PCR and immunohistochemistry. Increased expression of these genes, most strikingly nm23‐H4 and ‐H7, was observed in the majority of tumours analysed. No correlation with tumour stage according to the TNM classification was found. In contrast, by immunohistochemical analysis, nm23‐H4 and ‐H6 overexpression correlated with the intestinal tumour type in gastric cancer tissues, whereas no increased immunoreactivity for the three nm23 proteins was noted in the diffuse type tumour specimens. These findings indicate that nm23‐H6, and particularly nm23‐H4 and ‐H7, may be involved in the development of colon and gastric carcinoma, the latter possibly in a type‐specific manner. A contribution to tumour progression or metastasis could not, however, be proven. Elucidation of the specific mechanisms by which the nm23 homologues nm23‐H4, ‐H6, and ‐H7 are involved in tumour development requires further studies. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Analysis of GTPases carrying hydrophobic amino acid substitutions in lieu of the catalytic glutamine: Implications for GTP hydrolysis
Authors: Mishra Rajeev , Gara Sudheer Kumar , Mishra Shambhavi , Prakash Balaji 
Published: February 2005

AbstractRas superfamily GTP‐binding proteins regulate important signaling events in the cell. Ras, which often serves as a prototype, efficiently hydrolyzes GTP in conjunction with its regulator GAP. A conserved glutamine plays a vital role in GTP hydrolysis in most GTP‐binding proteins. Mutating this glutamine in Ras has oncogenic effects, since it disrupts GTP hydrolysis. The analysis presented here is of GTP‐binding proteins that are a paradox to oncogenic Ras, since they have the catalytic glutamine (Glncat) substituted by a hydrophobic amino acid, yet can hydrolyze GTP efficiently. We term these proteins HAS‐GTPases. Analysis of the amino acid sequences of HAS‐GTPases reveals prominent presence of insertions around the GTP‐binding pocket. Homology modeling studies suggest an interesting means to achieve catalysis despite the drastic hydrophobic substitution replacing the key Glncat of Ras‐like GTPases. The substituted hydrophobic residue adopts a “retracted conformation,” where it is positioned away from the GTP, as its role in catalysis would be unproductive. This conformation is further stabilized by interactions with hydrophobic residues in its vicinity. These interacting residues are strongly conserved and hydrophobic in all HAS‐GTPases, and correspond to residues Asp92 and Tyr96 of Ras. An experimental support for the “retracted conformation” of Switch II arises from the crystal structures of Ylqf and hGBP1. This conformation allows us to hypothesize that, unlike in classical GTPases, catalytic residues could be supplied by regions other than the Switch II (i.e., either the insertions or a neighboring domain). Proteins 2005. © 2005 Wiley‐Liss, Inc.
Cation–π interactions in protein–protein interfaces
Authors: Crowley Peter B. , Golovin Adel 
Published: February 2005

AbstractArginine is an abundant residue in protein–protein interfaces. The importance of this residue relates to the versatility of its side chain in intermolecular interactions. Different classes of protein–protein interfaces were surveyed for cation–π interactions. Approximately half of the protein complexes and one‐third of the homodimers analyzed were found to contain at least one intermolecular cation–π pair. Interactions between arginine and tyrosine were found to be the most abundant. The electrostatic interaction energy was calculated to be ∼3 kcal/mol, on average. A distance‐based search of guanidinium:aromatic interactions was also performed using the Macromolecular Structure Database (MSD). This search revealed that half of the guanidinium:aromatic pairs pack in a coplanar manner. Furthermore, it was found that the cationic group of the cation–π pair is frequently involved in intermolecular hydrogen bonds. In this manner the arginine side chain can participate in multiple interactions, providing a mechanism for inter‐protein specificity. Thus, the cation–π interaction is established as an important contributor to protein–protein interfaces. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Solution structure of APETx1 from the sea anemone Anthopleura elegantissima: A new fold for an HERG toxin
Authors: Chagot Benjamin , Diochot Sylvie , Pimentel Cyril , Lazdunski Michel , Darbon Hervé 
Published: February 2005

AbstractAPETx1 is a 42‐amino acid toxin purified from the venom of the sea anemone Anthopleura elegantissima. This cysteine‐rich peptide possesses three disulfide bridges (C4–C37, C6–C30, and C20–C38). Its pharmacological target is the Ether‐a‐gogo potassium channel. We herein determine the solution structure of APETx1 by use of conventional two‐dimensional 1H‐NMR techniques followed by torsion angle dynamics and refinement protocols. The calculated structure of APETx1 belongs to the disulfide‐rich all‐beta structural family, in which a three‐stranded anti‐parallel β‐sheet is the only secondary structure. APETx1 is the first Ether‐a‐gogo effector discovered to fold in this way. We therefore compare the structure of APETx1 to those of the two other known effectors of the Ether‐a‐gogo potassium channel, CnErg1 and BeKm‐1, and analyze the topological disposition of key functional residues proposed by analysis of the electrostatic anisotropy. The interacting surface is made of a patch of aromatic residues (Y5, Y32, and F33) together with two basic residues (K8 and K18) at the periphery of the surface. We pinpoint the absence of the central lysine present in the functional surface of the two other Ether‐a‐gogo effectors. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Flexibility of metal binding sites in proteins on a database scale
Authors: Babor Mariana , Greenblatt Harry M. , Edelman Marvin , Sobolev Vladimir 
Published: February 2005

AbstractProtein metal binding sites in the pre‐bound (apo) state, and their rearrangements upon metal binding were not analyzed previously at a database scale. Such a study may provide valuable information for metal binding site prediction and design. A high resolution, nonredundant dataset of 210 metal binding sites was created, containing all available representatives of apo–holo pairs for the most populated metals in the PDB. More than 40% of the sites underwent rearrangements upon metal binding. In 30 cases rearrangements involved the backbone. The tendency for side‐chain rearrangement inversely correlates with the number of first‐shell residues. Analysis of side‐chain reorientations as a result of metal binding showed that in 95% of the rigid‐backbone binding sites at most one side chain moved. Thus, in general, part of the first coordination shell is already in place in the pre‐bound form. The frequencies of side‐chain reorientation directly correlated with metal ligand flexibility and solvent accessibility in the apo state. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Metal–insulator transition in manganese‐doped InSb crystals
Authors: Obukhov S. A. 
Published: February 2005

AbstractTransport properties of manganese‐doped InSb crystals with hole concentration close to the critical concentration Ncr of the metal–insulator transition (MIT) in p‐InSb(Mn) was found to be different from MIT in semiconductors doped with non‐magnetic impurities such as p‐Ge(Ga), p‐Si(P) and p‐InSb(Ge). On the insulator side of the transition (NMn ≤ Ncr = 2 × 1017 cm–3) in the range of hole concentration p = 1–2 × 1017 cm–3 an activation type of conductivity with energy gap Δ = 7 × 10–6–10–3 eV was observed. Thus, the usually observed variable range hopping conductivity in crystal semiconductors doped with non‐magnetic impurities at low and super‐low temperatures was not revealed in p‐InSb(Mn) at p ≤ Ncr. An external magnetic field decreased Δ and caused a giant decrease of specific resistivity (ρ0/ρB ∼ 104 at T ≤ 0.3 K and B ≥ 3 T). On cooling to temperatures below T = 1.5 K the Hall constant changed sign at B < 3 T. The change of Hall constant sign with decrease of temperature means that conductivity of p‐InSb(Mn) and crystals compensated with Te – p‐InSb(Mn, Te) – at low temperatures was caused by electrons. The proposed model associated an activation energy Δ at p ∼ Ncr with the energy gap between sub‐bands formed in the impurity band. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Binding of singlet oxygen with a stacked guanine dimer
Authors: Kushwaha P. S. , Mishra P. C. 
Published: February 2005

AbstractGeometry optimization calculations were performed using the B3LYP/6‐31+G* method on the complexes of 1O2 and 3O2 molecules with a stacked dimer of planar guanine, varying the distance (D) between the planes of the guanine molecules. In this process, geometries of the guanine molecules were held fixed, D was fixed at different values, while the bond lengths of 1O2 and 3O2 as well as their orientations with respect to the guanine molecules were optimized for each value of D. The complexes in their most stable geometries were solvated in water using the integral equation formalism of the polarized continuum model of the self‐consistent reaction field theory. In gas phase, the most stable complex between 1O2 and the guanine dimer (2G.1O2) is formed when D is about 6 Å, while the most stable complex between 3O2 and the guanine dimer (2G.3O2) is formed when D is about 3.75 Å. In the minimum total energy geometry of 2G.1O2, 1O2 is located between the guanine molecules, above the imidazole ring of one of them. However, in the minimum total energy geometry of 2G.3O2, 3O2 is located outside the stack of guanine molecules, near the amino group of one of them. The solvation calculations showed that in aqueous media, 1O2 would bind with the stacked guanine dimer more strongly than in gas phase, while 3O2 would not bind with the same. The mode of binding of 1O2 with the stacked guanine dimer is such that it seems that 1O2 would replace one basepair in DNA, as happens in the intercalative mode of binding of drugs and other molecules, and it can lead to the formation of 8‐oxoguanine that has a mutagenic nature. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Statistical thermodynamics of binary systems with variable valent states of one of the components
Authors: Zakharov A. Yu. , Zakharov M. A. , Udovsky A. L. , Oonk H. A. J. 
Published: February 2005

AbstractThis report contains a generalization of the usual lattice model of multicomponent systems. The generalization allows us to take into account the following factors: (i) the short‐range parts of interatomic repulsions; which are not identical for different pairs of atoms (therefore, it is impossible to take into account the repulsions by means of usual ideal lattice introduction); (ii) the long‐range interatomic potentials are taken into account by means of effective fields approximation; (iii) the existence of the vacancies as one of the components in the system; (iv) the existence of comparatively stable multi‐atomic complexes; and (v) some other factors due to specifics of constituents and their interactions, such as variable valence states and chemical reactions. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Collectivity, shell openness indices, and complexity measures of multiconfigurational states: Computations within full CI scheme
Authors: Luzanov A. V. , Zhikol O. A. 
Published: February 2005

AbstractIt is shown that the multiconfigurational character of the N‐electron wave function can be treated by a new quantitative index, N, computed as a special matrix invariant of the full wave function. Along with N, a simpler index N is given due to the Kutzelnigg and Smith open‐shell theory. The indices are compared with an effective number of unpaired electrons introduced by Takatsuki, Fueno, and Yamaguchi. Full configuration interaction (FCI) computations on such quantities realized in the present work for atoms and dissociation reactions lead to the conclusion that all indices give a qualitatively similar picture. It is stressed that N as a more complicated quantity reflects a global complexity of the electronic state, while other indices represent the electron structure peculiarities only at the one‐electron level. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Effects of thermal modulation on tunneling through a fluctuating barrier in presence of bichromatic electromagnetic field
Authors: Saha Aparna , Sarkar Pranab 
Published: February 2005

AbstractThe effects of thermal modulation on the tunneling dynamics of a particle moving in a bistable potential with a fluctuating barrier in the presence of bichromatic electromagnetic field are examined. This study brings to light various interesting features. While rate constant increases steadily with increasing fluctuation strength, a stochastic resonance‐like behavior is exhibited when tunneling rate is plotted as a function of barrier fluctuation frequency. The tunneling rate constant decreases with the increase in the differences of the strength of the two electric fields; on the other hand, it displays a maxima when plotted as a function of the ratio of the frequencies of the two fields. When the rate constant is plotted as a function of temperature, it increases and eventually settles down to a saturation value. We have also studied the effect of the phase difference between the two electric fields on the tunneling behavior in the presence of thermal modulation. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Theoretical evaluation of the nanocarrier properties of two families of functionalized dendrimers
Authors: Evangelista‐Lara Aurelio , Guadarrama Patricia 
Published: February 2005

AbstractTwo families of dendrimers, denamide (oxy‐amide) and denurea (oxy‐urea), of second and third generation were designed as possible nanocarriers for high‐spectral parasiticide drugs of the family of macrocyclic lactones. Their geometric description was carried out by Connolly's algorithm, obtaining molecular volumes and sizes of cavities. According to these calculations, about 50% of the total dendrimeric molecular volume in both families corresponds to cavities that are able to shelter guest drugs, forming complexes in ratios higher than 1:1. The molecular shape suffers more notorious changes, going through higher dendrimeric generations; therefore, third‐generation dendrimers with two carbon atoms in their fractal patterns are more spherical than second‐generation dendrimers with six carbon atoms in their fractal patterns. The experimentally studied host–guest system formed by PAMAM and ibuprofen (analgesic drug) was taken as a reference in the present study. Molecular dynamics and mechanics calculations were able to reproduce some experimental observations. Nevertheless, the interaction energies of some of the 1:1 complexes were calculated at the density functional theory (DFT) level. Comparing the fractal patterns of the denamide and denurea families with polyamidoamine dendrimers (PAMAM), the observed order of efficiency, in terms of favorable interactions with guest molecules, is as follows: denamide > PAMAM > denurea. The differences in functionalization are responsible for such behavior. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Potential of laser ablation and laser desorption mass spectrometry to characterize organic and inorganic environmental pollutants on dust particles
Authors: Carré Vincent , Aubriet Frédéric , Scheepers Paul T. , Krier Gabriel , Muller Jean‐François 
Published: February 2005

AbstractStainless steel factories are known to release particles into the atmosphere. Such particulate matter contains significant amounts of heavy metals or toxic inorganic compounds and organic pollutants such as, for example, Cr(VI) and polycyclic aromatic hydrocarbons (PAHs). The investigation of Cr(VI) and PAHs is often complicated by the associated matrix. Organic and inorganic pollutants present in stainless steel dust particles have been investigated with the same laser microprobe mass spectrometer according to two original methodologies. These analytical methods do not require time‐consuming pretreatment (extraction, solubilization) or preconcentration steps. More specifically, experiments are conducted with a Fourier transform ion cyclotron resonance mass spectrometer coupled to an ArF (193 nm) or a tripled frequency Nd‐YAG (355 nm) laser. Experiments at 355 nm allow the nature of the most frequently occurring Cr(III)/Cr(VI) compounds in dust particles to be identified. Examination of PAHs at 193 nm is assisted by the formation of π‐complexes with 7,7′,8,8′‐tetracyanoquinodimethane to prevent their evaporation in the mass spectrometer during analysis and to ensure an increase in sensitivity. Copyright © 2005 John Wiley & Sons, Ltd.
A new method to analyze matrix‐assisted laser desorption/ionization time‐of‐flight peptide profiling mass spectra
Authors: Dekker Lennard J. , Dalebout Johannes C. , Siccama Ivar , Jenster Guido , Sillevis Smitt Peter A. , Luider Theo M. 
Published: February 2005

AbstractIn protein and peptide mass spectrometry in which profiling of peaks is involved, their masses and intensities are important characteristics. Because of the relative low reproducibility of peak intensities associated with complex samples in matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS), it is difficult to accurately assess the number of peaks and their intensities. In this study we evaluate these two characteristics for tryptic digests of cerebro‐spinal fluid. We observed that the reproducibility of peak intensities was relatively poor (CV = 42%) and that additional normalization or spiking did not lead to a large improvement (CV = 30%). Moreover, at least seven mass spectra per sample were required to obtain a reliable peak list. An improvement of the sensitivity (i.e., eventually more peaks are detected) is observed if more replicates per sample are measured. We conclude that the reproducibility and sensitivity of peptide profiling can be significantly improved by a combination of measuring at least seven spectra per sample with a dichotomous scoring of the intensities. This approach will aid the analysis of large numbers of mass spectra of patient samples in a reproducible way for the detection and validation of candidate biomarkers. Copyright © 2005 John Wiley & Sons, Ltd.
Generating survival times to simulate Cox proportional hazards models
Authors: Bender Ralf , Augustin Thomas , Blettner Maria 
Published: February 2005

AbstractSimulation studies present an important statistical tool to investigate the performance, properties and adequacy of statistical models in pre‐specified situations. One of the most important statistical models in medical research is the proportional hazards model of Cox. In this paper, techniques to generate survival times for simulation studies regarding Cox proportional hazards models are presented. A general formula describing the relation between the hazard and the corresponding survival time of the Cox model is derived, which is useful in simulation studies. It is shown how the exponential, the Weibull and the Gompertz distribution can be applied to generate appropriate survival times for simulation studies. Additionally, the general relation between hazard and survival time can be used to develop own distributions for special situations and to handle flexibly parameterized proportional hazards models. The use of distributions other than the exponential distribution is indispensable to investigate the characteristics of the Cox proportional hazards model, especially in non‐standard situations, where the partial likelihood depends on the baseline hazard. A simulation study investigating the effect of measurement errors in the German Uranium Miners Cohort Study is considered to illustrate the proposed simulation techniques and to emphasize the importance of a careful modelling of the baseline hazard in Cox models. Copyright © 2005 John Wiley & Sons, Ltd.