bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell cycle checkpoint efficiency and cellular response to paclitaxel in prostate cancer cells
Authors: Lanzi Cinzia , Cassinelli Giuliana , Cuccuru Giuditta , Supino Rosanna , Zuco Valentina , Ferlini Cristiano , Scambia Giovanni , Zunino Franco 
Published: August 2002

AbstractBACKGROUNDDefects in the cell cycle machinery of prostate cancer cells might impair the efficiency of cell cycle checkpoints and affect the cell response to chemotherapeutic drugs. We examined the relationship between the status of microtubule damage‐activated checkpoints and the response of hormone‐refractory prostate cancer cells to paclitaxel.METHODSThe two cell lines DU145 and PC3 harboring defects at proteins involved in the regulation of checkpoints activated by microtubule damage were examined for cell sensitivity, apoptotic response, and efficiency of checkpoints in response to paclitaxel.RESULTSIn spite of a comparable sensitivity to the antiproliferative effects of paclitaxel, DU145 and PC3 cells exhibited different cell cycle control at checkpoints activated by microtubule damage. A transient mitotic arrest was induced by the taxane in both cell lines. However, PC3 cells underwent a rapid mitotic slippage and displayed a defective postmitotic checkpoint as evidenced by the appearance of polyploid cells. In this cell line, paclitaxel‐induced cell death was a slow and delayed event, occurring also after S‐phase re‐entry. The mitotic checkpoint appeared to be more stringent in DU145 cells compared to PC3 cells. Moreover, despite the expression of mutated proteins involved in the prevention of DNA endoreduplication (p53, pRb, and p16INK4A), these cells did not progress into the cell cycle but efficiently underwent apoptosis by 24 hr. Such a response of DU145 cells was associated with phosphorylation of the p21WAF1 protein.CONCLUSIONSThese observations evidence that activation of checkpoints following microtubule damage in prostate cancer may be regulated through complex mechanisms possibly involving p21WAF1. Our findings support that the status of cell cycle checkpoints might affect the modality of cell death. However, the relevance of the mode of cell death for the sensitivity to taxanes remains to be determined. Prostate 48:254–264, 2001. © 2001 Wiley‐Liss, Inc.
Androgen depletion activates telomerase in the prostate of the nonhuman primate, Macaca mulatta
Authors: Ravindranath Neelakanta , Ioffe Sergey L. , Marshall Gary R. , Ramaswamy Suresh , Plant Tony M. , Dym Martin 
Published: August 2002

AbstractBACKGROUNDThe activity of telomerase, an enzyme that synthesizes telomeric repeats at the ends of chromosomes, is not detectable in normal human prostate. However, the majority of human prostate cancers exhibit telomerase activity. Since androgens play a major role in prostate tumorigenesis, we investigated the effect of androgen‐depletion on the expression of telomerase activity in the prostate.METHODSAdult male rhesus monkeys were either bilaterally castrated or subjected to sham surgery (n = 5 each). Approximately 6 weeks later, the animals were killed and the different regions of the prostate gland were removed and frozen immediately. Telomerase activity was assayed using the telomeric repeat amplification protocol.RESULTSAll five regions of the prostate from sham operated control animals failed to exhibit telomerase activity. In the castrated monkey, all regions of the prostate, except for the anterior lobe, expressed high levels of telomerase activity.CONCLUSIONSOur results indicate that in monkeys, androgen‐ablation leads to up‐regulation of telomerase activity. The negative‐regulation of telomerase activity by androgens is probably lost during prostate tumorigenesis. Prostate 49:79–89, 2001. © 2001 Wiley‐Liss, Inc.
Potential of mean force for protein–protein interaction studies
Authors: Jiang Lin , Gao Ying , Mao Fenglou , Liu Zhijie , Lai Luhua 
Published: August 2002

AbstractCalculating protein–protein interaction energies is crucial for understanding protein–protein associations. On the basis of the methodology of mean‐field potential, we have developed an empirical approach to estimate binding free energy for protein–protein interactions. This knowledge‐based approach has been used to derive distance‐dependent free energies of protein complexes from a nonredundant training set in the Protein Data Bank (PDB), with a careful treatment of homology. We calculate atom pair potentials for 16 pair interactions, which can reflect the importance of hydrophobic interactions and specific hydrogen‐bonding interactions. The derived potentials for hydrogen‐bonding interactions show a valley of favorable interactions at a distance of ≈3 Å, corresponding to that of an established hydrogen bond. For the test set of 28 protein complexes, the calculated energies have a correlation coefficient of 0.75 compared with experimental binding free energies. The performance of the method in ranking the binding energies of different protein–protein complexes shows that the energy estimation can be applied to value binding free energies for protein–protein associations. Proteins 2002;46:190–196. © 2001 Wiley‐Liss, Inc.
Native and non‐native interactions along protein folding and unfolding pathways
Authors: Paci Emanuele , Vendruscolo Michele , Karplus Martin 
Published: August 2002

AbstractGō‐type models, which include only native contact interactions in the energy function, are being used increasingly to describe the protein folding reaction. To investigate the validity of such models, we determine the role of native and non‐native interactions along folding and unfolding pathways. For this purpose, we use a molecular mechanics energy function with an implicit solvation model (an effective energy function or potential of mean force) that can be expressed in a pairwise decomposable form. We find that for the native state and a wide range of other configurations, the contact energy is an accurate description, in part due to the cancellation of non‐zero contributions from more distant residues. However, significant errors in the energy are introduced for non‐native structures if the energy is calculated from the native contacts alone. Non‐native contacts tend to make a significant contribution, particularly for molten globules and collapsed states along the unfolding pathways. The implication of these results for the use of Gō‐type models in studies of protein folding are discussed. Proteins 2002;47:379–392. © 2002 Wiley‐Liss, Inc.
Increasing the precision of comparative models with YASARA NOVA—a self‐parameterizing force field
Authors: Krieger Elmar , Koraimann Günther , Vriend Gert 
Published: August 2002

AbstractOne of the conclusions drawn at the CASP4 meeting in Asilomar was that applying various force fields during refinement of template‐based models tends to move predictions in the wrong direction, away from the experimentally determined coordinates. We have derived an all‐atom force field aimed at protein and nucleotide optimization in vacuo (NOVA), which has been specifically designed to avoid this problem. NOVA resembles common molecular dynamics force fields but has been automatically parameterized with two major goals: (i) not to make high resolution X‐ray structures worse and (ii) to improve homology models built by WHAT IF. Force‐field parameters were not required to be physically correct; instead, they were optimized with random Monte Carlo moves in force‐field parameter space, each one evaluated by simulated annealing runs of a 50‐protein optimization set. Errors inherent to the approximate force‐field equation could thus be canceled by errors in force‐field parameters. Compared with the optimization set, the force field did equally well on an independent validation set and is shown to move in silico models closer to reality. It can be applied to modeling applications as well as X‐ray and NMR structure refinement. A new method to assign force‐field parameters based on molecular trees is also presented. A NOVA server is freely accessible athttp://www.yasara.com/serversProteins 2002;47:393–402. © 2002 Wiley‐Liss, Inc.
Comparison of different schemes to treat long‐range electrostatic interactions in molecular dynamics simulations of a protein crystal
Authors: Walser Regula , Hünenberger Philippe H. , van Gunsteren Wilfred F. 
Published: August 2002

AbstractEight molecular dynamics simulations of a ubiquitin crystal unit cell were performed to investigate the effect of different schemes to treat the long‐range electrostatic interactions as well as the need to include counter ions. A crystal system was chosen as the test system, because the higher charge density compared with a protein in solution makes it more sensitive to the way of treating the electrostatic interactions. Three different schemes of treating the long‐range interactions were compared: straight cutoff, reaction‐field approximation, and a lattice‐sum method (P3M). For each of these schemes, two simulations were performed, one with and one without the counter ions. Two additional simulations with a reaction‐field force and different initial placements of the counter ions were performed to examine the effect of the initial positions of the ions. The inclusion of long‐range electrostatic interactions using either a reaction‐field or a lattice‐sum method proved to be necessary for the simulation of crystals. These two schemes did not differ much in their ability to reproduce the crystallographic structure. The inclusion of counter ions, on the other hand, seems not necessary for obtaining a stable simulation. The initial positions of the ions have a visible but small effect on the simulation. Proteins 2001;44:509–519. © 2001 Wiley‐Liss, Inc.
A new method to model membrane protein structure based on silent amino acid substitutions
Authors: Briggs John A.G. , Torres Jaume , Arkin Isaiah T. 
Published: August 2002

AbstractThe importance of accurately modeling membrane proteins cannot be overstated, in lieu of the difficulties in solving their structures experimentally. Often, however, modeling procedures (e.g., global searching molecular dynamics) generate several possible candidates rather then pointing to a single model. Herein we present a new approach to select among candidate models based on the general hypothesis that silent amino acid substitutions, present in variants identified from evolutionary conservation data or mutagenesis analysis, do not affect the stability of a native structure but may destabilize the non‐native structures also found. The proof of this hypothesis has been tested on the α‐helical transmembrane domains of two homodimers, human glycophorin A and human CD3‐ζ, a component of the T‐cell receptor. For both proteins, only one structure was identified using all the variants. For glycophorin A, this structure is virtually identical to the structure determined experimentally by NMR. We present a model for the transmembrane domain of CD3‐ζ that is consistent with predictions based on mutagenesis, homology modeling, and the presence of a disulfide bond. Our experiments suggest that this method allows the prediction of transmembrane domain structure based only on widely available evolutionary conservation data. Proteins 2001;44:370–375. © 2001 Wiley‐Liss, Inc.
Lactones: Part 11. Feeding‐deterrent activity of some bi‐ and tricyclic terpenoid lactones
Authors: Paruch Edyta , Nawrot Jan , Wawrzeńczyk Czeslaw 
Published: August 2002

AbstractThe feeding‐deterrent activities of thirteen synthetic terpenoid lactones, including isomeric bicyclic γ‐spirolactones with the limonene system and tricyclic γ‐lactones with the pinane system, were determined towards three storage pest insects: the adults of Sitophilus granarius, the adults and larvae of Tribolium confusum and the larvae of Trogoderma granarium. The configuration of chiral centres, as well as the presence of additional functional groups (double bond, iodine and hydroxy group) are important for antifeeding activity.© 2001 Society of Chemical Industry
Effect of temperature, organic amendment rate and moisture content on the degradation of 1,3‐dichloropropene in soil
Authors: Dungan Robert S , Gan Jianying , Yates Scott R 
Published: August 2002

Abstract1,3‐Dichloropropene (1,3‐D), which consists of two isomers, (Z)‐ and (E)‐1,3‐D, is considered to be a viable alternative to methyl bromide, but atmospheric emission of 1,3‐D is often associated with deterioration of air quality. To minimize environmental impacts of 1,3‐D, emission control strategies are in need of investigation. One approach to reduce 1,3‐D emissions is to accelerate its degradation by incorporating organic amendments into the soil surface. In this study, we investigated the ability of four organic amendments to enhance the rate of degradation of (Z)‐ and (E)‐1,3‐D in a sandy loam soil. Degradation of (Z)‐ and (E)‐1,3‐D was well described by first‐order kinetics, and rates of degradation for the two isomers were similar. Composted steer manure (SM) was the most reactive of the organic amendments tested. The half‐life of both the (Z)‐ and (E)‐isomers in unamended soil at 20 °C was 6.3 days; those in 5% SM‐amended soil were 1.8 and 1.9 days, respectively. At 40 °C, the half‐life of both isomers in 5% SM‐amended soil was 0.5 day. Activation energy values for amended soil at 2, 5 and 10% SM were 56.5, 53.4 and 64.5 kJ mol−1, respectively. At 20 °C, the contribution of degradation from biological mechanisms was largest in soil amended with SM, but chemical mechanisms still accounted for more than 58% of the (Z)‐ and (E)‐1,3‐D degradation. The effect of temperature and amendment rate upon degradation should be considered when describing the fate and transport of 1,3‐D isomers in soil. Use of organic soil amendments appears to be a promising method to enhance fumigant degradation and reduce volatile emissions.Published in 2001 for SCI by John Wiley & Sons, Ltd
Solid phase synthesis of hydrophobic difficult sequence peptides on BDDMA‐PS support
Authors: Ajikumar P. K. , Devaky K. S. 
Published: August 2002

AbstractThis article illustrates the successful and efficient solid phase assembly of hydrophobic difficult sequence peptides following both t‐Boc and Fmoc chemistry. The peptides were synthesized on an optimized 1,4‐butanediol dimethacrylate‐crosslinked polystyrene support (BDDMA‐PS). Four difficult sequence test peptides, VAVAG, VIVIG, QVGQVELG and VQAAIDYING, were synthesized in relatively good yield and purity without any aggregation problems. The peptides were assembled on chloromethylated and 4‐hydroxymethylphenoxymethyl (HMP) BDDMA‐PS resins. The peptides were fabricated using Boc amino acid 1‐hydroxybenzotriazolyl and Fmoc amino acid pentafluorophenyl active esters in coupling reactions. The peptides after synthesis were cleaved from the polymeric support by exposing the peptidyl resin to 90% trifluroacetic acid/5% thioanisole/5% EDT mixture. The HPLC and MALDI TOF MS studies of the peptides revealed the high homogeneity of the synthesized peptides. Chloromethylated resin having a functional group loading of 1.14 mmol Cl/g was used for the synthesis. The yield and homogeneity of these peptides synthesized using the new support were high when compared with the conventional DVB‐PS resin. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.
Identification of single amino acid residues essential for the binding of lipopolysaccharide (LPS) to LPS binding protein (LBP) residues 86–99 by using an Ala‐scanning library
Authors: Reyes O. , Vallespi M. G. , Garay H. E. , Cruz L. J. , González L. J. , Chinea G. , Buurman W. , Araña M. J. 
Published: August 2002

AbstractLipopolysaccharide binding protein (LBP) is a 60 kDa acute phase glycoprotein capable of binding to LPS of Gram‐negative bacteria and facilitating its interaction with cellular receptors. This process is thought to be of great importance in systemic inflammatory reactions such as septic shock. A peptide corresponding to residues 86–99 of human LBP (LBP86–99) has been reported to bind specifically with high affinity the lipid A moiety of LPS and to inhibit the interaction of LPS with LBP. We identified essential amino acids in LBP86–99 for binding to LPS by using a peptide library corresponding to the Ala‐scanning of human LBP residues 86–99. Amino acids Trp91 and Lys92 were indispensable for peptide–LPS interaction and inhibition of LBP–LPS binding. In addition, several alanine‐substituted synthetic LBP‐derived peptides inhibited LPS–LBP interaction. Substitution of amino acids Arg94, Lys95 and Phe98 by Ala increased the inhibitory effect. The mutant Lys95 was the most active in blocking LPS binding to LBP. These findings emphasize the importance of single amino acids in the LPS binding capacity of small peptides and may contribute to the development of new drugs for use in the treatment of Gram‐negative bacterial sepsis. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.
A comparison of three‐ and four‐helix bundle TASP molecules
Authors: Causton Ashley S. , Sherman John C. 
Published: August 2002

AbstractWe have designed, synthesized and characterized three‐ and four‐helix bundle template‐assembled synthetic proteins (TASPs). The TASPs were synthesized using disulphide bonds between the peptides and either the cyclotribenzylene (CTB) template, or the cavitand (BOWL) template, to form the three‐ and four helix bundles, respectively. The TASPs were constructed using peptides that were linked via their N‐termini (peptide CGGGEELLKKXEELLKKG, where X = L, I, Nle or V), or via their C‐termini (peptide GEELLKKLEELLKKGGGC). Each TASP was assayed for its structure, stability, ‘native‐like’ characteristics and whether it was a monomer in solution. All TASPs were found to be highly helical, and highly resistant to chemical denaturation using guanidine hydrochloride (GnHCl). Analysis of the GnHCl‐induced unfolding curves of the different TASPs demonstrated stability differences based on the number of helices in the bundle, the end of the helix that was attached to the template, and the identity of the core amino acid. The TASPs all had molten‐globule structure, which is (generally) consistent with a degenerate sequence in the core. The four‐helix bundle TASPs appeared to be monomers in solution, whereas there is some evidence that the three‐helix bundle TASPs are weakly self‐associating. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.
Peptoid residues and β‐turn formation
Authors: Rainaldi Mario , Moretto Vittorio , Crisma Marco , Peggion Evaristo , Mammi Stefano , Toniolo Claudio , Cavicchioni Giorgio 
Published: August 2002

AbstractA set of terminally protected tripeptoids containing a residue of either N‐methylglycine or N‐isobutylglycine in position i + 1/i + 2 were synthesized and tested for intramolecularly H‐bonded β‐turn formation. By exploiting FT‐IR absorption and 1H NMR techniques, their folding tendencies were compared with those of a variety of reference peptides. The amount of β‐turn induction and the relative extent of the various types of intramolecularly H‐bonded β‐turn conformers were determined in chloroform solution. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.
Antiinflammatory and antioxidant property of saponins of tea [Camellia sinensis (L) O. Kuntze] root extract
Authors: Sur P. , Chaudhuri T. , Vedasiromoni J. R. , Gomes A. , Ganguly D. K. 
Published: August 2002

AbstractTwo groups of saponins, TS‐1 and TS‐2, isolated from tea root extract (TRE) were tested for antiinflammatory and in vitro antioxidant activity. Both TS‐1 and TS‐2 inhibited carrageenan‐induced paw oedema in rats. The antioxidant activity of these compounds was evaluated using the xanthine–xanthine oxidase system. The study indicated that the previously observed antitumour activity of TRE might be mediated through scavenging of free radicals by saponins and their antiinflammatory activity. Copyright © 2001 John Wiley & Sons, Ltd.
In vitro antileishmanial activity of three saponins isolated from ivy, α‐hederin, β‐hederin and hederacolchiside A1, in association with pentamidine and amphotericin B
Authors: Ridoux O. , Di Giorgio C. , Delmas F. , Elias R. , Mshvildadze V. , Dekanosidze G. , Kemertelidze E. , Balansard G. , Timon‐David P. 
Published: August 2002

AbstractThe in vitro antileishmanial activity of three saponins isolated from ivy, α‐hederin, β‐hederin and hederacolchiside A1, was investigated on parasites of the species Leishmania mexicana, in their promastigote and amastigote forms compared with their toxicity versus human monocytes. The results showed that saponins exhibited a strong antiproliferative activity on all stages of development of the parasite but demonstrated a strong toxicity versus human cells. Association of subtoxic concentrations of saponins with antileishmanial drugs such as pentamidine and amphotericin B demonstrated that saponins could enhance the efficiency of conventional drugs on both the promastigote and the amastigote stages of development of the parasite. The results demonstrated moreover that the action of saponins on promastigote membrane was cumulative with those of amphotericin B. Copyright © 2001 John Wiley & Sons, Ltd.
Spasmolytic activity of Toddalia asiatica var. Floribunda
Authors: Lakshmi V. , Kapoor S. , Pandey K. , Patnaik (Late) G. K. 
Published: August 2002

AbstractThe spasmolytic activity of the aerial parts of Toddalia asiatica var. floribunda (family Rutaceae) was evaluated. The ethanol extract exhibited significant spasmolytic activity and was then partitioned into five fractions. The activity was found to be concentrated only in the hexane and chloroform fractions. This activity was shown not to be due to the coumarins, toddalolactone and toddanone, as was previously thought. Copyright © 2002 John Wiley & Sons, Ltd.
Cytochrome P450nor: A nitric oxide reductase—Structure, spectra, and mechanism
Authors: Harris Danni L. 
Published: August 2002

AbstractThe present study characterizes key proposed intermediates and reaction pathway steps in the enzymatic cycle of cytochrome P450nor, a nitric oxide reductase. This unusual P450, with reductase rather than monoxygenase function, catalyzes the conversion of •NO to N2O, an important detoxification step in the global nitrogen cycle. Density functional theoretical (DFT) and semiempirical INDO/ROHF/CI quantum chemical characterization of the putative species in the enzymatic cycle have been made and direct comparisons made with published experimental spectral and structural data. The computed INDO/ROHF‐CIS spectra of the NO bound heme species indicate a previously reported experimental transient electronic spectrum to be due the NO bound reduced ferrous heme species. The identity of the active heme species in the P450nor mechanism is unknown and may be either a nitrogen (FeN) N‐ferryl analogue of the oxyferryl/compound I P450 species or the NO bound reduced ferrous heme species. Formation of products from either requires the addition of two protons and a second •NO to the NO bound reduced ferrous heme form to form N2O, water, and resting state heme products. The mechanism of proton transfer to the NO bound reduced ferrous NO species is assessed and contrasted with that discovered for the reduced oxyferrous heme species of cytochrome P450 monoxygenases. DFT reaction pathways studies are reported for the addition of •NO to the N‐ferryl species and indicate it to be a competent active species forming N2O via an exothermic, barrierless process. © 2002 John Wiley & Sons, Inc. Int J Quantum Chem, 2002