bluuebunny/crossref_metadata_2025 huggingface dataset:
Metal‐Binding Properties of the Peptide APP170–188: A Model of the ZnII‐Binding Site of Amyloid Precursor Protein (APP)
Authors: Ciuculescu Eliza‐Diana , Mekmouche Yasmina , Faller Peter
Published: December 2004

Amyloid precursor protein (APP) plays a key role in Alzheimer's disease (AD), although the function of this membrane protein is still unclear. Metal ions are implicated in AD and they also interact with APP. APP possesses a strong ZnIIbinding site, which is evolutionary conserved. In this paper a synthetic peptide, APP170–188, with a sequence corresponding to the conserved ZnII‐binding domain of APP, was synthesised and its metal‐binding properties analysed. Titration experiments pointed to the binding of a stoichiometric amount of divalent ions. Further studies indicated that the binding of divalent metals like ZnII, CdIIand CoIIinduces the dimerisation of the peptide. This dimer contains a dinuclear cluster in which the two divalent metals are bridged by two thiolate ligands from cysteine residues. The other two ligands of the tetrahedral coordination sites of each metal ion are terminal thiolate ligands. This structure was supported by the following arguments. The complex formed with CoIIpresents the characteristic features for tetrahedral tetrathiolate coordination in its UV‐visible spectrum. The sequence of APP170–188contains only three cysteine residues, which is incompatible with a monomeric CoII–APP170–188complex. EPR measurements of the complex with one equivalent of CoIIshow almost no signal at 4 K, which is compatible with an antiferromagnetic spin‐coupling of the metal ions in a cluster structure. Size‐exclusion chromatography indicated that the elution time for the complexes with ZnIIand CdIIcorresponds to the expected molecular weight of a dimer. The circular dichroism (CD) spectrum of the complex with one equivalent of CdIIshows a band at 265 nm(+), and an ellipticity similar to those observed for similar CdII–thiolate clusters. Possible biological implications of the ZnIIbinding site and the metal‐induced dimerisation are discussed.
Preparation and Optical Absorption of Zircons, Co‐Doped with Vanadium and Rare Earth Elements.
Authors: Niesert Adelheid , Sieves Rolf , Siggel Alfred , Langer Klaus , Jansen Martin
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Thermal and Photolytic Reactions of Group 12 Metal Atoms in HCl‐Doped Argon Matrices: Formation and Characterization of the Hydride Species HMCl (M: Zn, Cd, or Hg).
Authors: Macrae Victoria A. , Green Jennifer C. , Greene Tim M. , Downs Antony J.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Enantioselective Synthesis of Non‐Natural Amino Acids Using Phenylalanine Dehydrogenases Modified by Site‐Directed Mutagenesis.
Authors: Busca Patricia , Paradisi Francesca , Moynihan Eamonn , Maguire Anita R. , Engel Paul C.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
α‐Addition of Activated Methylenes to Alkynoates. A Straightforward Synthesis of Multifunctional Compounds.
Authors: Hanedanian Mikael , Loreau Olivier , Taran Frederic , Mioskowski Charles
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
The Interaction of Fluorinated 2‐Arylhydrazone‐1,3‐dicarbonyl Compounds with o‐Phenylenediamine.
Authors: Khudina O. G. , Shchegol'kov E. V. , Burgart Ya. V. , Saloutin V. I. , Chupakhin O. N.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
N‐Methylmorpholine N‐Oxide: A Rare Nonmetallic Catalyst for the Most Efficient Silylcyanation of Aldehydes.
Authors: Kim Sung Soo , Rajagopal Gurusamy , Kim Dong Won , Song Dae Ho
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Alkyl (α‐Phenylthioalkenyl) Ketones Containing a (Z)‐Trisubstituted Olefinic Fragment.
Authors: Grigorieva N. Ya. , Tsiklauri P. G.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of C3‐Symmetric Nano‐Sized Polyaromatic Compounds by Trimerization and Suzuki—Miyaura Cross‐Coupling Reactions.
Authors: Kotha Sambasivarao , Kashinath Dhurke , Lahiri Kakali , Sunoj Raghavan B.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
N‐Benzyl‐2‐chloroindole‐3‐carboxylic Acids as Potential Antiinflammatory Agents. Synthesis and Screening for the Effects on Human Neutrophil Functions and on COX1/COX2 Activity.
Authors: Andreani Aldo , Granaiola Massimiliano , Leoni Alberto , Locatelli Alessandra , Morigi Rita , Rambaldi Mirella , Roda Aldo , Guardigli Massimo , Traniello Serena , Spisani Susanna
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Mononuclear Rearrangement of Difurazanyltriazenes.
Authors: Shaposhnikov S. D. , Mel'nikova S. F. , Tselinsky I. V.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Cross‐Condensation of Derivatives of Cyanoacetic Acid and Carbonyl Compounds. Part 2. One‐Pot Synthesis of Substituted 2‐Amino‐7‐methyl‐5‐oxo‐4,5‐dihydropyrano[4,3‐b]pyrans in Ethanol and Ionic Liquid [bmim][PF6].
Authors: Shestopalov A. M. , Zlotin S. G. , Shestopalov A. A. , Mortikov V. Yu. , Rodinovskaya L. A.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis and Fluorescence Properties of 3‐Benzoxa‐ and Thiazol‐2‐ylquinoline‐5 or 7‐maleimides.
Authors: Nair J. S. , Rajasekharan K. N.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Microwave Induced Eco‐Friendly Solvent‐Free Biginelli Reaction Catalyzed by Calcium Chloride.
Authors: Misra Anup Kumar , Agnihotri Geetanjali , Madhusudan Soni Kamlesh
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Novel Pyrrolo[1,2‐a][3.1.6]benzothiadiazocine Ring Synthesis. Unusual Truce—Smiles Type Rearrangement of 1‐{[1‐(2‐Nitrophenyl)‐1H‐pyrrol‐2‐yl]sulfonyl (or sulfinyl)}acetone.
Authors: Kimbaris Athanasios , Cobb Jonathan , Tsakonas Georgios , Varvounis George
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Briaexcavatolides X—Z, Three New Briarane‐Related Derivatives from the Gorgonian Coral Briareum excavatum.
Authors: Sung Ping‐Jyun , Hu Wan‐Ping , Wu Shwu‐Li , Su Jui‐Hsin , Fang Lee‐Shing , Wang Jeh‐Jeng , Sheu Jyh‐Horng
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Simple and Efficient per‐O‐Acetylation of Carbohydrates by Lithium Perchlorate Catalyst.
Authors: Lu Kuo‐Cheng , Hsieh Shu‐Yi , Patkar Laxmikant N. , Chen Chien‐Tien , Lin Chun‐Cheng
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Conversion of N‐Acetylneuraminic Acid Glycosyl Chloride into Dibenzyl Glycosyl Phosphate: O‐Glycosylation in the Absence of a Promoter.
Authors: Shpirt A. M. , Kononov L. O. , Torgov V. I. , Shibaev V. N.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
An Improved Stereocontrolled Route to cis‐Erythrinanes by Combined Intramolecular Strecker and Bruylants Reaction.
Authors: Reimann Eberhard , Ettmayr Christian
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Nankakurine A, a Novel C16N2‐Type Alkaloid from Lycopodium hamiltonii.
Authors: Hirasawa Yusuke , Morita Hiroshi , Kobayashi Jun'ichi
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Neutron Diffraction Studies of Magnetic and Superconducting Compounds
Authors: Yelon W. B. , Cai Q. , James W. J. , Anderson H. U. , Yang J. B. , Zhou X. D. , Blackstead H. A.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
The Noninnocent Nature of 1,3‐Dialkylimidazolium Ionic Liquids
Authors: Dupont Jairton , Spencer John
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Read‐Out of Single Spins by Optical Spectroscopy
Authors: Jelezko F. , Wrachtrup J.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Wettablity of Poly(ethylene terephthalate) Substrates Modified by a Two‐Step Plasma Process: Ultra Water Repellent Surface Fabrication
Authors: Teshima K. , Sugimura H. , Inoue Y. , Takai O. , Takano A.
Published: December 2004

The fabrication of ultra‐water‐repellent poly(ethylene terephthalate) substrates has been achieved by a two‐step plasma process. First, appropriate nanotextures are prepared on the substrate through an oxygen plasma treatment, and then a hydrophobic layer is coated on the nanotextured surfaces with plasma‐enhanced CVD using tetramethylsilane. The resulting modified substrates show ultra‐water‐repellent characteristics with a water contact angle greater than 150° (Figure).
Modified predictor–corrector numerical scheme for real‐time pseudo dynamic tests using state‐space formulation
Authors: Zhang Yunfeng , Sause Richard , Ricles James M. , Naito Clay J.
Published: December 2004

This paper deals with an explicit numerical integration method for real‐time pseudo dynamic tests. The proposed method, termed the MPC‐SSP method, is suited to use in real‐time pseudo dynamic tests as no iteration steps are involved in each step of computation. A procedure for implementing the proposed method in real‐time pseudo dynamic tests is described in the paper. A state‐space approach is employed in this study to formulate the equations of motion of the system, which is advantageous in real‐time pseudo dynamic testing of structures with active control devices since most structural control problems are formulated in state space. A stability and accuracy analysis of the proposed method was performed based on linear elastic systems. Owing to an extrapolation scheme employed to predict the system's future response, the MPC‐SSP method is conditionally stable. To demonstrate the effectiveness of the MPC‐SSP method, a series of numerical simulations were performed and the performance of the MPC‐SSP method was compared with other pseudo dynamic testing methods including Explicit Newmark, Central Difference, Operator Splitting, and OS‐SSP methods based on both linear and non‐linear single‐degree‐of‐freedom systems. Copyright © 2004 John Wiley & Sons, Ltd.
Big decisions and their consequences
Authors: Shaw John C. (Jack)
Published: December 2004

Success comes as a result of a relatively few “Big Decisions” carried out by boards and executive management.
How leaders gain (and lose) confidence
Authors: Kanter Rosabeth Moss
Published: December 2004

Confidence is the bridge connecting expectations and performance, investment and results.
The role of sensation seeking and need for cognition on Web‐site evaluations: A resource‐matching perspective
Authors: Martin Brett A. S. , Sherrard Michael J. , Wentzel Daniel
Published: December 2004

The Internet theoretically enables marketers to personalize a Web site to an individual consumer. This article examines optimal Website design from the perspective of personality trait theory and resource‐matching theory. The influence of two traits relevant to Internet Web‐site processing—sensation seeking and need for cognition —were studied in the context of resource matching and different levels of Web‐site complexity. Data were collected at two points of time: personality‐trait data and a laboratory experiment using constructed Web sites. Results reveal that (a) subjects prefer Web sites of a medium level of complexity, rather than high or low complexity; (b) high sensation seekers prefer complex visual designs, and low sensation seekers simple visual designs, both in Web sites of medium complexity; and (c) high need‐for‐cognition subjects evaluated Web sites with high verbal and low visual complexity more favorably. © 2005 Wiley Periodicals, Inc.
An experimental study of credibility in e‐negotiations
Authors: Citera Maryalice , Beauregard Russell , Mitsuya Takashi
Published: December 2004

E‐negotiators' credibility was compared to that of face‐to‐face (FTF) negotiators in an integrative bargaining task. Dyads were randomly assigned to negotiate either on the computer or FTF. E‐negotiators perceived their opponents to be less credible and reported less selfcredibility than FTF negotiators. Although lying did not vary significantly from FTF to e‐negotiations, self‐credibility and lying were negatively correlated. E‐negotiators were also more likely to advocate using dishonesty in the future. Consistent with psychological distance theory, skepticism regarding the credibility of e‐negotiators appears warranted. © 2005 Wiley Periodicals, Inc.
Mass spectrometric analysis of the glycosphingolipid‐enriched microdomains of rat natural killer cells
Authors: Man Petr , Novák Petr , Cebecauer Marek , Horváth Ondrej , Fišerová Anna , Havlíček Vladimír , Bezouška Karel
Published: December 2004

Glycosphingolipid‐enriched microdomains (GEM) are membrane entities that concentrate glycosylphosphatiolylinositol(GPI)‐anchored, acylated and membrane proteins important for immune receptor signaling. Using rat leukemic cell line RNK‐16 we have initiated proteomic studies of microdomains in natural killer (NK) cells. Isolated plasma membranes were treated with Brij 58, or Nonidet‐P40, or sodium carbonate. Extracts were separated by sucrose density gradient centrifugation into very light membrane, medium light membrane and heavy fractions, and a complete protein profile was analyzed by tandem mass spectrometry. Up to 250 proteins were unambiguously identified in each analyzed fraction. The first study of the proteome of NK cell GEM revealed several new aspects including identification of molecules not expected to be expressed in rat NK cells (e.g., NAP‐22) or associated with GEM (e.g., NKR‐P1, CD45, CD2). Moreover, it provided clear data consolidating controversial views concerning the occurrence of major histcompatibility complex glycoproteins and RT6.1/CD73/CD38 complex in NK cells. Our results also identified a large number of receptors as candidates for future functional studies.
A modified tandem affinity purification tag technique for the purification of protein complexes in mammalian cells
Authors: Drakas Robert , Prisco Marco , Baserga Renato
Published: December 2004

The tandem affinity purification (TAP) tag technique has been used with success to identify under nondenaturing conditions protein complexes in yeast. The technique can be used in mammalian cells, but we found that the original technique does not yield enough recovery for the identification of proteins when mammalian cells growing in monolayer have to be used. We present here a modified TAP tag technique that allows sufficient recovery of proteins from mouse fibroblasts growing in monolayer cultures. The recovery allows protein identification by mass spectrometry.
Proteomic analysis of the proliferative and secretory phases of the human endometrium: Protein identification and differential protein expression
Authors: DeSouza Leroi , Diehl Georg , Yang Eric C.C. , Guo Jingzhong , Rodrigues Mary Joe , Romaschin Alexander D. , Colgan Terence J. , Siu K.W. Michael
Published: December 2004

Proteomic analyses of the proliferative and secretory phases of the human endometrium were carried out to identify proteins and discover differentially expressed proteins using isotope‐coded affinity tags, three stages of chromatographic separation and online tandem mass spectrometry (MS/MS). From an initial list of 346 proteins identified by ProICAT, manual inspection of MS/MS spectra and confirmatory searches pared the list down to 119 positively identified proteins. Only five of the proteins showed consistent differential expression. The utility of some of these proteins as indicators of true differential expression in the endometrium is open to discussion. The two proteins with unquestionable differential expressions in the secretory endometrium are: glutamate NMDA receptor subunit zeta 1 precursor and FRAT1. Some of the proteins that show no differential expression have previously been examined in gene‐expression studies with similar conclusions.
Preparation and characterization of biotinylated and enzyme‐immobilized heterobifunctional latex particles as nanobio devices
Authors: Du Yong‐Zhong , Kodaka Masato
Published: December 2004

A novel biotinylated and enzyme‐immobilized nanobio device was prepared with heterobifunctional composite latex particles. Hemispherical poly(glycidyl methacrylate‐co‐divinylbenzene)/polystyrene [P(GMA‐DVB)/PSt] particles with epoxy and hydroxyl groups were prepared by soap‐free seeded emulsion polymerization with P(GMA‐DVB) seed particles. Hydroxyl groups were introduced to PSt chain terminals in the seeded stage by adding 2‐mercaptoethanol as a chain‐transfer agent. To obtain the desired hemispherical structure particles, we studied the effects of the preswelling process, the type and amount of solvents added in the seeded polymerization step, the weight ratio of the secondary monomer (styrene) to the seed particle (M/P), and the type of initiators. Under suitable conditions, heterobifunctional P(GMA‐DVB)/PSt was obtained, which was confirmed by observing the binding of streptavidin–colloidal gold with transmission electron microscopy (TEM). To obtain biotinylated and enzyme‐immobilized particles, 5‐(N‐succinimidyloxycarbonyl)pentyl D‐biotinamide was first reacted with the hydroxyl group on the PSt domain of the particle. Pyruvate kinase (PK) was then directly immobilized to the biotinylated particles through a reaction with the epoxy group in the PGMA domain. The monolayer of PK on the latex particle surface was considered to be formed by covalent binding. The activity of immobilized PK was almost conserved, even after being stored at 4 °C for 48 days. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 562–574, 2005
A system for wind power estimation in mountainous terrain. Prediction of Askervein hill data
Authors: Eidsvik Karl J.
Published: December 2004

In mountainous terrain, where the wind power potential is largest, the estimation of the local wind power can be done rationally by means of available information about the large‐scale flow and the detailed terrain and numerical flow models for downscaling, provided that the numerical model estimates can be assigned sufficient confidence. In this study the confidence of a local model in such an estimation system is discussed. The model is based upon the Reynolds‐averaged Navier–Stokes equations with (K, ϵ) turbulence closure and integrated with finite element numerical techniques. The model has previously been validated relative to complicated laboratory‐scale flows and appears to predict some full‐scale geophysical flows plausibly. Here its predictions are compared quantitatively with the full‐scale Askervein hill experimental data. The model estimates the data to within the experimental uncertainty, which we judge to be comparable to 10%, as other comparable models also do. This contributes to assign confidence to the downscaling estimation system mentioned. Copyright © 2004 John Wiley & Sons, Ltd.
The role of tRNA as a molecular spring in decoding, accommodation, and peptidyl transfer
Authors: Frank Joachim , Sengupta Jayati , Gao Haixiao , Li Wen , Valle Mikel , Zavialov Andrey , Ehrenberg Måns
Published: December 2004

Translation is the process by which the genetic information contained in mRNA is used to link amino acids in a predetermined sequential order into a polypeptide chain, which then folds into a protein. Transfer RNAs (tRNAs) are the adapter molecules designed to provide the “lookup” from codons to amino acids. Cryo‐EM has provided evidence that the ribosome, as a molecular machine, undergoes many structural changes during translation. Recent findings show that the tRNA structure itself undergoes large conformational changes as well, and that the decoding process must be seen as a complex dynamic interplay between tRNA and the ribosome.
Replication of damaged DNA by translesion synthesis in human cells
Authors: Lehmann Alan R.
Published: December 2004

Most types of DNA damage block the passage of the replication machinery. In order to bypass these blocks, cells employ special translesion synthesis (TLS) DNA polymerases, which have lower stringency than replicative polymerases. DNA polymerase η is the major polymerase responsible for bypassing UV lesions in DNA and its absence results in the variant form of the genetic disorder, xeroderma pigmentosum. Other TLS polymerases have specificities for different types of damage, but their precise roles inside the cell have not yet been established. These polymerases are located in replication factories during DNA replication and the polymerase sliding clamp PCNA plays an important role in mediating switching between different polymerases.
Structure and dynamic properties of nucleosome core particles
Authors: Chakravarthy Srinivas , Park Young-Jun , Chodaparambil Jayanth , Edayathumangalam Rajeswari S. , Luger Karolin
Published: December 2004

It is now widely recognized that the packaging of genomic DNA, together with core histones, linker histones, and other functional proteins into chromatin profoundly influences nuclear processes such as transcription, replication, DNA repair, and recombination. Whereas earlier structural studies portrayed nucleosomes (the basic repeating unit of chromatin) as monolithic and static macromolecular assemblies, we now know that they are highly dynamic and capable of extensive crosstalk with the cellular machinery. Histone variants have evolved to locally alter chromatin structure, whereas histone chaperones and other cellular factors promote histone exchange and chromatin fluidity. Both of these phenomena likely facilitate interconversion between different chromatin states that show varying degrees of transcriptional activity.
A novel β1,3‐N‐acetylglucosaminyltransferase (β3Gn‐T8), which synthesizes poly‐N‐acetyllactosamine, is dramatically upregulated in colon cancer
Authors: Ishida Hiroyasu , Togayachi Akira , Sakai Tokiko , Iwai Toshie , Hiruma Toru , Sato Takashi , Okubo Reiko , Inaba Niro , Kudo Takashi , Gotoh Masanori , Shoda Junichi , Tanaka Naomi , Narimatsu Hisashi
Published: December 2004

A new member of the UDP‐N‐acetylglucosamine: β‐galactose β1,3‐N‐acetylglucosaminyltransferase (β3Gn‐T) family having the β3‐glycosyltransferase motifs was identified using an in silico method. This novel β3Gn‐T was cloned from a human colon cancer cell line and named β3Gn‐T8 based on its position in a phylogenetic tree and enzymatic activity. β3Gn‐T8 transfers GlcNAc to the non‐reducing terminus of the Galβ1–4GlcNAc of tetraantennary N‐glycan in vitro. HCT15 cells transfected with β3Gn‐T8 cDNA showed an increase in reactivity to both LEA and PHA‐L4 in a flow cytometric analysis. These results indicated that β3Gn‐T8 is involved in the biosynthesis of poly‐N‐acetyllactosamine chains on tetraantennary (β1,6‐branched) N‐glycan. In most of the colorectal cancer tissues examined, the level of β3Gn‐T8 transcript was significantly higher than in normal tissue. β3Gn‐T8 could be an enzyme involved in the synthesis of poly‐N‐acetyllactosamine on β1–6 branched N‐glycans in colon cancer.
Possible role for avPGC‐1α in the control of expression of fiber type, along with avUCP and avANT mRNAs in the skeletal muscles of cold‐exposed chickens
Authors: Ueda Masatoshi , Watanabe Kouichi , Sato Kan , Akiba Yukio , Toyomizu Masaaki
Published: December 2004

Peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α), a transcriptional coactivator, plays a role in mitochondrial biogenesis, muscle fiber specialization, and adaptive thermogenesis. Because of an absence of brown adipose tissue, the skeletal muscle tissue in chickens serves as an important source of thermogenesis to counter the cold. The present experiments were conducted (i) to clone the cDNA of PGC‐1α homologs from chicken skeletal muscle and to examine alterations to PGC‐1α mRNA expression in the skeletal muscles of cold‐exposed chickens, (ii) to study the effect of cold‐acclimation on the metabolic fiber phenotype of typically fast‐glycolytic (type IIB) pectoralis muscles, and (iii) to compare avANT and avUCP mRNA expression in control and cold‐exposed chickens. Results show that the cloned avPGC‐1α cDNA encodes a 796 amino‐acid protein (GenBank Accession No. AB170013) showing 84% identity with rodent PGC‐1α cDNA. Exposure of chickens to a cold environment resulted in the prompt upregulation of avPGC‐1α expression, which preceded increments in avUCP and avANT expression in skeletal muscle mitochondria. Consistent with the morphological appearance of muscles, an increase in the number of fast‐oxidative‐glycolytic (type IIA) fibers in the pectoralis muscle, which contains exclusively type IIB fibers in control chickens, was observed in cold‐acclimated chickens. These findings provide novel information about possible regulatory pathways in avian skeletal muscle during thermogenesis.
Mapping the interaction of bradykinin 1–5 with the exodomain of human protease activated receptor 4
Authors: Nieman Marvin T. , Pagan-Ramos Eileen , Warnock Mark , Krijanovski Yelena , Hasan Ahmed A.K. , Schmaier Alvin H.
Published: December 2004

The angiotensin converting enzyme breakdown product of bradykinin, bradykinin 1–5 (RPPGF), inhibits thrombin‐induced human or mouse platelet aggregation. RPPGF binds to the exodomain of human protease‐activated receptor 1 (PAR1). Studies determined if RPPGF also binds to the exodomain of human PAR4. RPPGF binds to a peptide of the thrombin cleavage site on PAR4. Recombinant wild‐type and mutated exodomain of human PAR4 was prepared. The N‐terminal arginine on RPPGF binds to the P2 position or proline46 on PAR4 to block thrombin cleavage. These data indicate that RPPGF influences thrombin activity by binding to the thrombin cleavage site on both PAR4 and PAR1.
Recognition and selection of tRNA in translation
Authors: Rodnina Marina V. , Gromadski Kirill B. , Kothe Ute , Wieden Hans-Joachim
Published: December 2004

Aminoacyl‐tRNA (aa‐tRNA) is delivered to the ribosome in a ternary complex with elongation factor Tu (EF‐Tu) and GTP. The stepwise movement of aa‐tRNA from EF‐Tu into the ribosomal A site entails a number of intermediates. The ribosome recognizes aa‐tRNA through shape discrimination of the codon–anticodon duplex and regulates the rates of GTP hydrolysis by EF‐Tu and aa‐tRNA accommodation in the A site by an induced fit mechanism. Recent results of kinetic measurements, ribosome crystallography, single molecule FRET measurements, and cryo‐electron microscopy suggest the mechanism of tRNA recognition and selection.
Co‐translational protein targeting by the signal recognition particle
Authors: Shan Shu-ou , Walter Peter
Published: December 2004

The signal recognition particle (SRP) mediates the co‐translational targeting of nascent proteins to the eukaryotic endoplasmic reticulum membrane, or the bacterial plasma membrane. During this process, two GTPases, one in the SRP and one in the SRP receptor (SR), form a complex in which both proteins reciprocally activate the GTPase reaction of one another. The recent crystal structures of the T. aquaticus SRP · SR complex show that the two GTPases associate via an unusually extensive and highly cooperative interaction surface, and form a composite active site at the interface. GTPase activation proceeds through a unique mechanism, stimulated by both interactions between the twinned GTP molecules across the dimer interface and by conformational rearrangements that position catalytic residues in each active site with respect to the bound substrates. Distinct classes of mutations have been isolated that inhibit specific stages during SRP–SR complex formation and activation, suggesting discrete conformational stages during formation of the active SRP · SR complex. Each stage provides a potential control point in the targeting reaction at which regulation by additional components can be exerted, thus ensuring the binding and release of cargo at the appropriate time.
Distinct roles of the ERK pathway in modulating apoptosis of Ras‐transformed and non‐transformed cells induced by anticancer agent FR901228
Authors: Song Ping , Wei Jinxiong , Robert Wang Hwa-Chain
Published: December 2004

Ectopic expression of oncogenic H‐Ras in cells results in increases of cell susceptibility to the anticancer agent FR901228. Investigating the roles of Ras‐induced pathways in FR901228‐induced apoptosis, we have found that the phosphatidylinositol 3‐kinase pathway plays an anti‐apoptotic role, whereas the stress‐activated protein kinase p38 pathway plays a pro‐apoptotic role in FR901228‐induced apoptosis. Interestingly, the extracellular signal‐regulated kinase (ERK) pathway plays an anti‐apoptotic role in non‐transformed cells; however, it plays a pro‐apoptotic role in Ras‐transformed cells in response to FR901228 treatment. An essential role of the ERK pathway in regulating caspase‐3 contents may contribute to its pro‐apoptotic role in Ras‐transformed cells.
On the structural basis of peptide‐bond formation and antibiotic resistance from atomic structures of the large ribosomal subunit
Authors: Steitz Thomas A.
Published: December 2004

The atomic structures of the large ribosomal subunit from Haloarcula marismortui and its complexes with substrates and antibiotics have provided insights into the way the 3000 nucleotide 23S rRNA folds into a compact, specific structure and interacts with 27 ribosomal proteins as well as the structural basis of the peptidyl transferase reaction and its inhibition by antibiotics. The structure shows that the ribosome is indeed a ribozyme.
Overexpression of a family of RPEL proteins modifies cell shape
Authors: Favot Laure , Gillingwater Marc , Scott Caroline , Kemp Paul R.
Published: December 2004

Proteins containing RPEL motifs (e.g., MAL) are important in the regulation of gene expression by the actin cytoskeleton. Screening the ENSEMBL database for RPEL proteins identified four additional proteins that contain RPEL motifs and nuclear localisation sequences, three of which (RPEL‐A, RPEL‐B and RPEL‐C) are expressed in adult mouse tissues with different expression profiles. The mRNAs encoding RPEL‐B and RPEL‐C were subject to alternative splicing. Expression of these genes in cells indicated that they had a marked effect on cell shape. Furthermore, when expressed with a nuclear localised actin all of the different forms became restricted to the nucleus.
Up‐regulation of 94‐kDa glucose‐regulated protein by hypoxia‐inducible factor‐1 in human endothelial cells in response to hypoxia
Authors: Paris Sébastien , Denis Hélène , Delaive Edouard , Dieu Marc , Dumont Valéry , Ninane Noëlle , Raes Martine , Michiels Carine
Published: December 2004

Hypoxic environment in solid tumor is known to favor cell survival and to initiate the formation of new capillaries. In this work, we identified by 2D gel analysis 94‐kDa glucose‐regulated protein (GRP94) as being upregulated in human endothelial cells in response to hypoxia. Three putative hypoxia responsive elements (HRE) were found in the GRP94 promoter. Competition experiments of HIF‐1 DNA binding using specific probes containing each HRE sequence of the GRP94 promoter clearly evidenced that HIF‐1 binds these sequences with high affinity. The human GRP94 promoter was then cloned upstream of the luciferase gene and showed enhanced activity in hypoxic conditions. Mutation of two of the three HREs present in this promoter completely inhibited the hypoxia‐induced increase in luciferase activity.
Ionizing radiation‐induced damage on developing cerebellar granule cells cultures can be prevented by an early amifostine post‐treatment
Authors: Guelman Laura Ruth , Cabana Javier Ignacio , Pagotto Romina María del Luján , Zieher Luis María
Published: December 2004

Developing central nervous system (CNS) is highly sensitive to ionizing radiation due, in part, to reactive oxygen species (ROS) damage.

A variety of compounds able to protect brain cells essentially by decreasing ROS production have been widely used to confirm ROS participation in different mechanisms of brain injury, as well as to evaluate them as therapeutic tools.

To test if ionizing radiation‐induced damage on immature cerebellar granule cells is mainly mediated by ROS accumulation, a free radical scavenger –amifostine (amf) – was used in an in vitro model. Moreover, the amf therapeutic effect was investigated.

Results show that only an early (20–30 min) post‐treatment with amf, acting through an antioxidant mechanism, has been effective in preventing cerebellar granule cell loss observed after ionizing radiation exposure in vitro.

These data suggest that immature cerebellar granule cells grown in vitro are highly vulnerable to ROS damage and that a therapeutic intervention could be effective in a narrow temporal window. Moreover, radiation‐induced cell death can be partially prevented by a complete limitation of ROS generation, suggesting that other mechanisms besides oxidative stress would also be responsible for the cellular damage found in this model.
Limitations of the pelvic examination for evaluation of the female pelvic organs
Authors: Padilla L.A. , Radosevich D.M. , Milad M.P.
Published: December 2004

Objective

To assess factors influencing an accurate pelvic examination under the best possible circumstances.

Methods

Before undergoing laparoscopy or laparotomy, 84 women under general anesthesia underwent pelvic examinations by an attending gynecologist, a gynecology resident, and a medical student blinded to the indication for surgery. Surgical findings were compared with the examiners' findings. Dependent variables (uterine size, uterine contour, and presence of adnexal masses) and effect modifiers (examiner experience and body mass index) were analyzed.

Results

The overall pelvic examination was accurate 70.2% of the time for attending gynecologists, 64.0% for residents, and 57.3% for medical students. The sensitivity to detect adnexal masses was much lower than the sensitivity to assess uterine size or uterine contour. Obesity noticeably reduced detection of adnexal masses.

Conclusion

The bimanual examination appears to be a limited screening test for the female upper genital tract even under the best possible circumstances. Uterine assessment appears to be more accurate than adnexal assessment.
Visual inspection of the cervix with acetic acid for cervical intraepithelial lesions
Authors: Goel A. , Gandhi G. , Batra S. , Bhambhani S. , Zutshi V. , Sachdeva P.
Published: December 2004

Objective: Evaluation of visual inspection of the cervix with acetic acid (VIA) for screening cervical intraepithelial neoplasia. Methods: In this prospective study, 400 women were screened using the Papanicolaou (PAP) smear, VIA and colposcopy. Those who had positive results with any of the screening methods underwent large loop excision of the transformation zone (LLETZ). The sensitivity and specificity of each of the screening methods was analyzed. Results: The sensitivity of VIA (96.7%) was much higher than that of the Pap smear (50%), and almost as high as that of colposcopy (100%). The specificity of VIA (36.4%) was lower than that of the Pap smear (97%) and colposcopy (96.9%), resulting in high false‐positive rates for VIA. Two cases of endocervical lesions were missed with VIA. Conclusion: Visual inspection of the cervix with acetic acid is very sensitive for ectocervical lesions. The advantages of the VIA method are its low cost and ease of use (it can be used by paramedical workers), its high sensitivity and its immediate results (it is possible to “see and treat” at the first visit). Its main limitation is a high rate of false‐positive results, which may lead to overtreatment if a “see and treat” policy is applied.
TQM across multiple countries:Convergence HypothesisversusNational Specificityarguments
Authors: Rungtusanatham M. , Forza C. , Koka B.R. , Salvador F. , Nie W.
Published: December 2004

We provide conceptual clarity and new empirical findings for the question of whether or not TQM is universal in its applicability. At the conceptual level, we reposition and reframe the “universality of TQM” question in light of two conflicting theoretical perspectives in the international business literature – one that supports the universal applicability of TQM (i.e., theConvergence Hypothesisargument) and another that questions the universal applicability of TQM (i.e., theNational Specificityargument). We do so to provide a stronger theoretical basis for the “universality of TQM” question and to motivate and initiate a “strong inference” epistemological approach [Platt, J.R., 1964. Strong inference. Science 146 (364), 347–353] to examine, at the empirical level, the applicability of TQM across multiple countries. For this empirical assessment, we compare both the adoption levels of the Deming‐based TQM constructs and the patterns of Deming‐based TQM relationships among German, Italian, Japanese, and USA plants, using secondary data from 143 plants in Round Two of the World‐Class Manufacturing project. After assessing measurement quality (i.e., reliability and validity) and measurement equivalence (i.e., translation, calibration, and metric), MANOVA analysis and regression analysis were deployed to derive relevant empirical results – empirical results that have implications not only for the question of whether or not TQM is universal in its applicability but also for the theoretical tension between theConvergence Hypothesisargument and theNational Specificityargument.
Molecular chain stretch is a multiaxial failure criterion for conventional and highly crosslinked UHMWPE
Authors: Bergström J. S. , Rimnac C. M. , Kurtz S. M.
Published: December 2004

The development of accurate theoretical failure, fatigue, and wear models for ultra‐high molecular weight polyethylene (UHMWPE) is an important step towards better understanding the micromechanisms of the surface damage that occur in load bearing orthopaedic components and improving the lifetime of joint arthoplasties. Previous attempts to analytically predict the clinically observed damage, wear, and fatigue failure modes have met with limited success due to the complicated interaction between microstructural deformations and continuum level stresses. In this work, we examined monotonic uniaxial and multiaxial loading to failure of UHMWPE using eight failure criteria (maximum principal stress, Mises stress, Tresca stress, hydrostatic stress, Coulomb stress, maximum principal strain, Mises strain, and chain stretch). The quality of the predictions of the different models was assessed by comparing uniaxial tension and small punch test data at different rates with the failure model predictions. The experimental data were obtained for two conventional (unirradiated and gamma radiation sterilized in nitrogen) and two highly crosslinked (150 kGy, remelted and annealed) UHMWPE materials. Of the different failures models examined, the chain stretch failure model was found to capture uniaxial and multiaxial failure data most accurately for all of the UHMWPE materials. In addition, the chain stretch failure criterion can readily be calculated for contemporary UHMWPE materials based on available uniaxial tension data. These results lay the foundation for future developments of damage and wear models capable of predicting multiaxial failure under cyclic loading conditions. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Contact pressures in the flexed hip joint during lateral trochanteric loading
Authors: Sparks Damon R. , Beason David P. , Etheridge Brandon S. , Alonso Jorge E. , Eberhardt Alan W.
Published: December 2004

Acetabular fractures are an especially problematic outcome of motor vehicle side impacts. While fracture type has been correlated with impact direction and femoral orientation, actual contact pressures in the hip joint have not been quantified for lateral loading conditions. In the present study, we used pressure sensitive film to measure contact areas and pressures in seven hip joints from four cadavers under quasi‐static lateral loading through the greater trochanter. The aim was to quantify the interactions of the femoral head with the acetabulum associated with variations in femoral orientation. Three angles of hip flexion (80°, 90°, 100°) and hip abduction (−10°, 0°, 10°) were tested, producing nine test orientations for each joint. We observed that contact areas, pressures, and forces varied significantly with femoral orientation for the adducted hip. The principal locations of load transmission were in the anterior and posterior regions of the acetabulum. For the abducted femur, contact pressures were concentrated anteriorly, and with increased adduction, anterior contact pressures diminished while posterior and superior pressures increased. The movement of pressure sites was consistent with mechanisms of acetabular fractures described by Letournel and Judet and provides new data for validation of finite element models of the pelvis in side impact. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Growth and integration of neocartilage with native cartilage in vitro
Authors: Zhang Zijun , McCaffery J. Michael , Spencer Richard G. S. , Francomano Clair A.
Published: December 2004

Poor integration of neocartilage with recipient has been a major obstacle to articular cartilage restoration. An in vitro study was designed to provide insights regarding the integration process. Cartilage explants and chondrocytes were harvested from the distal sternum of 16‐day‐old chick embryos. Four million chondrocytes and one 1 mm3 explant were centrifuged together in a 0.75 ml tube. In the constructs, consisting of cartilage explant and chondrocyte pellet, isolated chondrocytes attached to the surface of the explant at the beginning of the culture, followed by significant chondrocyte death at the interface between chondrocyte pellet and explant. Chondrocyte apoptosis was seen almost exclusively at this interface. Meanwhile, the interface was a zone with active extracellular matrix deposition as demonstrated by immunohistochemistry. By two weeks, the junction of neocartilage and native cartilage explant had formed an acellular zone with collagen fibrils orientated parallel with the surface of the cartilage explant. In conclusion, chondrocyte death leads to acellularity and fibril network reorganization at the neocartilage/explant interface, and impacts the quality of cartilage repair as abnormal matrix remodeling implies. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Early growth of the last Cordilleran ice sheet deduced from glacio-isostatic depression in southwest British Columbia, Canada
Authors: Clague John J. , Froese Duane , Hutchinson Ian , James Thomas S. , Simon Karen M.
Published: December 2004

Relative sea level at Vancouver, British Columbia rose from below the present datum about 30,000 cal yr B.P. to at least 18 m above sea level 28,000 cal yr B.P. In contrast, eustatic sea level in this interval was at least 85 m lower than at present. The difference in the local and eustatic sea-level positions is attributed to glacio-isostatic depression of the crust in the expanding forefield of the Cordilleran ice sheet during the initial phase of the Fraser Glaciation. Our findings suggest that about 1 km of ice was present in the northern Strait of Georgia 28,000 cal yr B.P., early during the Fraser Glaciation.
Environmental significance of 13C/12C and 18O/16O ratios of modern land-snail shells from the southern great plains of North America
Authors: Balakrishnan Meena , Yapp Crayton J. , Theler James L. , Carter Brian J. , Wyckoff Don G.
Published: December 2004

13C/12C and 18O/16O ratios of aragonite shells of modern land snails from the southern Great Plains of North America were measured for samples from twelve localities in a narrow east–west corridor that extended from the Flint Hills in North Central Oklahoma to the foothills of the Sangre de Cristo Mountains in Northern New Mexico, USA. Across the study area, shell δ18O values (PDB scale) ranged from −4.1‰ to 1.2‰, while δ13C values ranged from −13.2‰ to 0.0‰. δ18O values of the shell aragonite were predicted with a published, steady state, evaporative flux balance model. The predicted values differed (with one exception) by less than 1‰ from locality averages of measured δ18O values. This similarity suggests that relative humidity at the time of snail activity is an important control on the δ18O values of the aragonite and emphasizes the seasonal nature of the climatic information preserved in the shells. Correlated δ13C values of coexisting Vallonia and Gastrocopta suggest similar feeding habits and imply that these genera can provide information on variations in southern Great Plains plant ecology. Although there is considerable scatter, multispecies, transect average δ13C values of the modern aragonite shells are related to variations in the type of photosynthesis (i.e., C3, C4) in the local plant communities. The results of this study emphasize the desirability of obtaining isotope ratios representing averages of many shells in a locale to reduce possible biases associated with local variations among individuals, species, etc., and thus better represent the “neighborhood” scale temporal and/or spatial environmental variations of interest in studies of modern and ancient systems.
Protein interaction quantified in vivo by spectrally resolved fluorescence resonance energy transfer
Authors: RAICU Valerică , JANSMA David B. , MILLER R. J. Dwayne , FRIESEN James D.
Published: December 2004

We describe a fluorescence resonance energy transfer (FRET)-based method for finding in living cells the fraction of a protein population (αT) forming complexes, and the average number (n) of those protein molecules in each complex. The method relies both on sensitized acceptor emission and on donor de-quenching (by photobleaching of the acceptor molecules), coupled with full spectral analysis of the differential fluorescence signature, in order to quantify the donor/acceptor energy transfer. The approach and sensitivity limits are well suited for in vivo microscopic investigations. This is demonstrated using a scanning laser confocal microscope to study complex formation of the sterile 2 α-factor receptor protein (Ste2p), labelled with green, cyan, and yellow fluorescent proteins (GFP, CFP, and YFP respectively), in budding yeast Saccharomyces cerevisiae. A theoretical model is presented that relates the efficiency of energy transfer in protein populations (the apparent FRET efficiency, Eapp) to the energy transferred in a single donor/acceptor pair (E, the true FRET efficiency). We determined E by using a new method that relies on Eapp measurements for two donor/acceptor pairs, Ste2p–CFP/Ste2p–YFP and Ste2p–GFP/Ste2p–YFP. From Eapp and E we determined αT≈1 and n≈2 for Ste2 proteins. Since the Ste2p complexes are formed in the absence of the ligand in our experiments, we conclude that the α-factor pheromone is not necessary for dimerization.
Regulation of the cell-cycle-dependent internal ribosome entry site of the PITSLRE protein kinase: roles of Unr (upstream of N-ras) protein and phosphorylated translation initiation factor eIF-2α
Authors: TINTON Sandrine A. , SCHEPENS Bert , BRUYNOOGHE Yanik , BEYAERT Rudi , CORNELIS Sigrid
Published: December 2004

The PITSLRE kinases belong to the large family of cyclin-dependent protein kinases. Their function has been related to cell-cycle regulation, splicing and apoptosis. We have previously shown that the open reading frame of the p110PITSLRE transcript contains an IRES (internal ribosome entry site) that allows the expression of a smaller p58PITSLRE isoform during the G2/M stage of the cell cycle. In the present study we investigated further the role of cis- and trans-acting factors in the regulation of the PITSLRE IRES. Progressive deletion analysis showed that both a purine-rich sequence and a Unr (upstream of N-ras) consensus binding site are essential for PITSLRE IRES activity. In line with these observations, we demonstrate that the PITSLRE IRES interacts with the Unr protein, which is more prominently expressed at the G2/M stage of the cell cycle. We also show that phosphorylation of the α-subunit of the canonical initiation factor eIF-2 is increased at G2/M. Interestingly, phosphorylation of eIF-2α has a permissive effect on the efficiency of both the PITSLRE IRES and the ornithine decarboxylase IRES, two cell cycle-dependent IRESs, in mediating internal initiation of translation, whereas this was not observed with the viral EMCV (encephalomyocarditis virus) and HRV (human rhinovirus) IRESs.