bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete MALDI-ToF MS analysis of cross-linked peptide–RNA oligonucleotides derived from nonlabeled UV-irradiated ribonucleoprotein particles
Authors: KÜHN-HÖLSKEN EVA , LENZ CHRISTOF , SANDER BJÖRN , LÜHRMANN REINHARD , URLAUB HENNING
Published: November 2005

Protein–RNA cross-linking combined with mass spectrometry is a powerful tool to elucidate hitherto noncharacterized protein–RNA contacts in ribonucleoprotein particles, as, for example, within spliceosomes. Here, we describe an improved methodology for the sequence analysis of purified peptide–RNA oligonucleotide cross-links that is based solely on MALDI-ToF mass spectrometry. The utility of this methodology is demonstrated on cross-links isolated from UV-irradiated spliceosomal particles; these were (1) [15.5K–61K–U4atac] small nuclear ribonucleoprotein (snRNP) particles prepared by reconstitution in vitro, and (2) U1 snRNP particles purified from HeLa cells. We show that the use of 2′,4′,6′-trihydroxyacetophenone (THAP) as MALDI matrix allows analysis of cross-linked peptide–RNA oligonucleotides in the reflectron mode at high resolution, enabling sufficient accuracy to assign unambiguously cross-linked RNA sequences. Most important, post-source decay (PSD) analysis under these conditions was successfully applied to obtain sequence information about the cross-linked peptide and RNA moieties within a single spectrum, including the identification of the actual cross-linking site. Thus, in U4atac snRNA we identified His270 in the spliceosomal U4/U6 snRNP-specific protein 61K (hPrp31p) cross-linked to U44; in the U1 snRNP we show that Leu175 of the U1 snRNP-specific 70K protein is cross-linked to U30 of U1 snRNA. This type of analysis is applicable to any type of RNP complex and may be expected to pave the way for the further analysis of protein–RNA complexes in much lower abundance and/or of cross-links that are obtained in low yield.
A pseudoknot in the 3′ non-core region of the glmS ribozyme enhances self-cleavage activity
Authors: WILKINSON SARA R. , BEEN MICHAEL D.
Published: November 2005

The recently described glmS ribozyme is a self-cleaving RNA sequence found in the 5′ noncoding region of the transcript of the gene for glucosamine-6-phosphate (GlcN6P) synthase in many Gram-positive bacteria. This ribozyme is associated with the GlcN6P riboswitch, and ribozyme activity in response to binding of the metabolite, GlcN6P, is proposed to effect levels of gene expression. The previously defined core sequence of the GlcN6P-dependent ribozyme contained fewer than 80 nt of contiguous sequence, but a sequence containing conserved secondary structural features and encompassing the core was twice as long. Structural elements outside of the ribozyme core could contribute to ribozyme activity or participate in gene regulation as part of the expression platform or both. Here, a 174-nt transcript containing the Bacillus anthracis glmS ribozyme was used to examine the contribution of part of the non-core sequence to in vitro cleavage activity. The loop portion of hairpin loop 3, located just 3′ of the ribozyme core, can potentially pair with a sequence ~80 nt downstream to form a pseudoknot tertiary interaction. Disruptive and compensatory mutations in the two duplex regions of the pseudoknot had effects on in vitro cleavage rates that support a role for the pseudoknot in enhanced ribozyme activity. Cleavage activity became less sensitive to disruptive mutations in the pseudoknot as MgCl2 concentrations were raised from 2.5 to 10 mM, suggesting that one role of the pseudoknot could be to help stabilize the core structure.
The polypyrimidine tract binding protein is a monomer
Authors: MONIE TOM P. , HERNANDEZ HELENA , ROBINSON CAROL V. , SIMPSON PETER , MATTHEWS STEPHEN , CURRY STEPHEN
Published: November 2005

The polypyrimidine tract binding (PTB) protein is a potent regulator of alternative mRNA splicing. It also participates in other essential cellular functions, including translation initiation and polyadenylation. Several published reports have suggested that the protein forms a dimer in solution, a feature that has been widely incorporated into mechanistic models of protein function. However, recent studies have provided indications that full-length PTB is a monomer. Here we present new biophysical and biochemical evidence supporting the monomeric status of the protein. By use of blue-native polyacrylamide gel electrophoresis and size-exclusion chromatography, PTB was observed as a single molecular species under native reducing environments, though in oxidizing conditions, a larger protein species was also detected. Further analyses of wild-type and mutant PTB molecules with SDS-PAGE and time-of-flight electrospray ionization mass spectroscopy confirmed these observations. They also identified the single reduced species as monomeric PTB and the higher-molecular-weight nonreduced species as disulphide-linked PTB dimer mediated by Cys23. Our results indicate that the use of oxidizing environments in previous studies is likely to have contributed to the misassignment of PTB as a dimer. Although purified PTB may form disulphide-linked dimers under these conditions, in the reducing intracellular environment the protein will be monomeric. These findings have implications for the construction of models of PTB function in regulating mRNA metabolism.
MicroRNA function: Multiple mechanisms for a tiny RNA?: FIGURE 1.
Authors: PILLAI RAMESH S.
Published: November 2005

MicroRNAs are sequence-specific regulators of post-transcriptional gene expression in many eukaryotes. They are believed to control the expression of thousands of target mRNAs, with each mRNA believed to be targeted by multiple microRNAs. Recent studies have uncovered various mechanisms by which microRNAs down-regulate their target mRNAs and have linked a well-known subcellular structure, the cytoplasmic processing bodies (PBs) to the microRNA pathway. The finding that microRNAs are misexpressed in cancers has reinforced the idea that their regulatory roles are very important.
Evidence for an RNA chaperone function of polypyrimidine tract-binding protein in picornavirus translation
Authors: SONG YUTONG , TZIMA ELENI , OCHS KERSTIN , BASSILI GERGIS , TRUSHEIM HEIDI , LINDER MONICA , PREISSNER KLAUS T. , NIEPMANN MICHAEL
Published: November 2005

The cellular polypyrimidine tract-binding protein (PTB) is recruited by the genomic RNAs of picornaviruses to stimulate translation initiation at their internal ribosome entry site (IRES) elements. We investigated the contribution of the individual RNA recognition motif (RRM) domains of PTB to its interaction with the IRES of foot-and-mouth disease virus (FMDV). Using a native gel system, we found that PTB is a monomer, confirming recent reports that challenged the previous view that PTB is a dimer. Mapping the spatial orientation of PTB relative to the bound IRES RNA, we found that the two C-terminal RRM domains III and IV of PTB bind in an oriented way to the IRES. Domain III contacts the IRES stem-loop 2, while domain IV contacts the separate IRES 3′ region. PTB domain I appears not to be involved directly in RNA binding, but domain II stabilizes the RNA binding conferred by domains III and IV. A PTB protein containing only these two C-terminal PTB domains is sufficient to enhance the entry of initiation factor eIF4G to the IRES and stimulate IRES activity, and the long-lived PTB–IRES interaction stabilized by domain II is not a prerequisite for this function. Thus, PTB most likely acts as an RNA chaperone to stabilize IRES structure and, in that way, augment IRES activity.
Kinetics of electrophile-nucleophile combinations: A general approach to polar organic reactivity
Authors: Mayr Herbert , Ofial Armin R.
Published: November 2005

Benzhydrylium ions (Ar2CH+) and structurally related quinone methides are employed as reference electrophiles for comparing the nucleophilicities of a large variety of compounds, e.g., alkenes, arenes, alkynes, allylsilanes, allylstannanes, enol ethers, enamines, diazo compounds, carbanions, transition-metal π-complexes, hydride donors, phosphanes, amines, alkoxides, etc., using the correlation equation log k (20 °C) = s(N + E), where s and N are nucleophile-dependent parameters and E is an electrophilicity parameter. The same equation was employed to derive the electrophilicity parameter E for different types of carbocations, cationic transition-metal π-complexes, typical Michael acceptors, and electron-deficient arenes. The E, N, and s parameters thus obtained can be used for predicting rates and selectivities of polar organic reactions.
Is the single transition-state model appropriate for the fundamental reactions of organic chemistry?
Authors: Parker Vernon D.
Published: November 2005

In recent years, we have reported that a number of organic reactions generally believed to follow simple second-order kinetics actually follow a more complex mechanism. This mechanism, the reversible consecutive second-order mechanism, involves the reversible formation of a kinetically significant reactant complex intermediate followed by irreversible product formation. The mechanism is illustrated for the general reaction between reactant and excess reagent under pseudo-first-order conditions in eq. i where k
f' is the pseudo-first-order rate constant equal to k
f[Excess Reagent].

Reactant + Excess reagent = Reactant complex = Products (i)

The mechanisms are determined for the various systems, and the kinetics of the complex mechanisms are resolved by our "non-steady-state kinetic data analysis". The basis for the non-steady-state kinetic method will be presented along with examples. The problems encountered in attempting to identify intermediates formed in low concentration will be discussed.
Cycloproparenyl anions: From models to real systems
Authors: Eckert-Maksic Mirjana , Glasovac Zoran
Published: November 2005

An overview of our recent work on cycloproparenyl anions is given. Preparation, the electronic structure, and the properties of the progenitor of the series, cyclopropabenzenyl anion, are discussed. It is shown that the cyclopropabenzenyl anion is by ca. 145 kJ mol-1 more stable than the parent cyclopropenyl anion according to results of the MP2/6-31+G(d) calculations. This finding was attributed to a delicate balance of two opposing effects: (a) propensity of the aromatic ring to alleviate unfavorable 4π electron interaction within the three-membered ring by the anionic resonance effect and (b) a pyramidalization of the anionic center, which tends to maximize the s-character of the lone pair. We have also shown that stability of the cyclopropabenzenyl anion could be considerably enhanced by substitution of the aromatic ring with fluorine and cyano groups, as well as by a linear extension of the aromatic backbone. Finally, the impact of the fusion of additional cyclopropenyl ring to the benzene moiety to acidity of the benzylic position in cyclopropabenzene is discussed.
Advanced opto-electronics materials by fullerene and acetylene scaffolding
Authors: Diederich François
Published: November 2005

Functional π-systems with unusual opto-electronic properties are intensively investigated from both fundamental research and technological application viewpoints. This article reports on novel π-conjugated systems obtained by acetylenic and fullerene scaffolding. Linearly conjugated acetylenic nanorods, consisting of monodisperse poly(triacetylene) (PTA) oligomers and extending up to 18 nm length, were prepared to investigate the limits of effective conjugation and to explore at which length a monodisperse oligomer reaches the properties of an infinite polydisperse polymer. With the cyanoethynylethenes (CEEs), a powerful new class of electron acceptors is introduced that undergo intense intramolecular charge-transfer (CT) interactions with appended donors. Macrocyclic scaffolds with unusual opto-electronic properties are perethynylated dehydroannulenes, expanded radialenes, and radiaannulenes bearing peripheral dialkylanilino donor groups. Extended porphyrin-fullerene conjugates are investigated for their novel photophysical and efficient multicharge storage properties. Self-assembly of fullerenes and porphyrins, governed by weak interactions between the two components, leads to unprecedented nanopatterned surfaces that are investigated by scanning tunneling microscopy (STM).
Cyclodextrin-based catalysts and molecular reactors
Authors: Easton Christopher J.
Published: November 2005

The naturally occurring cyclodextrins and their derivatives have been developed as miniature reaction vessels, to manipulate the outcomes of chemical transformations at the molecular level. In this manner, the rate of hydrolysis of a phosphate triester has been enhanced by almost five orders of magnitude, and the ratios of products obtained from electrophilic aromatic substitution reactions, from competing reactions to give indigoid dyes, and from nitrile oxide cycloadditions have all been changed, by factors of up to 3500 times.
An alternative view of enzyme catalysis
Authors: Menger Fredric M.
Published: November 2005

This paper begins with a brief review of theories and concepts that have influenced today's view of enzyme catalysis: transition-state stabilization, entropy, orbital steering, proximity, and intramolecularity. The discussion then launches into the "spatiotemporal" model of enzyme catalysis in which fast intramolecular and enzymatic rates are ascribed to short distances that are imposed rigidly upon the reacting entities. An equation relating rate and distance is set forth, as are experimental and computational data supporting this relationship. Finally, enzyme systems themselves are analyzed in terms of the distance parameter and the so-called "split-site" model in which ground-state geometries play a crucial role. Among the many surprising conclusions is a transition-state stabilization by noncovalent forces (e.g., hydrogen-bonding) that are positioned far away from the actual transition-state chemistry. The model also confronts and dismisses the claim in classical enzymology that the ubiquitous enzyme-substrate complex is either inconsequential or inhibitory to the overall reaction rate.
Bioantioxidants: From chemistry to biology
Authors: Zhou Bo , Liu Zhong-Li
Published: November 2005

Bioantioxidants, or dietary antioxidants, are dietary substances in food that significantly decrease the adverse effects of reactive oxygen species (ROS) on normal physiological functions in humans. Inhibition of ROS-induced oxidative damages by supplementation of bioantioxidants, the so-called "antioxidant therapy", has become an attractive therapeutic strategy to reduce the risk of ROS-related diseases and has led to flourishing research in the past decade. However, many questions dealing with the correlation between chemical and biological activities, the bioavailability and "non-antioxidant" effects of bioantioxidants are still under debate.

This article outlines our current kinetic and mechanistic studies on naturally occurring antioxidants, including vitamin E, green tea polyphenols (GOHs), and resveratrol, as well as their synthetic analogs in micelles, in red blood cells, in low-density lipoprotein (LDL) and in microsomes. The cytotoxicity and apoptosis-inducing activity of these antioxidants against cancer cells were also studied. It was found that there was significant correlation between the chemical and biological antioxidant activities, as well as between the antioxidant activity and the cytotoxic and apoptosis-inducing activities.
Stability in chemistry and biology: Life as a kinetic state of matter
Authors: Pross Addy
Published: November 2005

Despite the considerable advances in our understanding of biological processes, the physicochemical relationship between living and nonliving systems remains uncertain and a continuing source of controversy. In this review, we describe a kinetic model based on the concept of dynamic kinetic stability that attempts to incorporate living systems within a conventional physicochemical framework. Its essence: all replicating systems, both animate and inanimate, represent elements of a replicator space. However, in contrast to the world of nonreplicating systems (all inanimate), where selection is fundamentally thermodynamic, selection within replicator space is effectively kinetic. As a consequence, the nature of stability within the two spaces is of a distinctly different kind, which, in turn, leads to different physicochemical patterns of aggregation. Our kinetic approach suggests: (a) that all living systems may be thought of as manifesting a kinetic state of matter (as apposed to the traditional thermodynamic states associated with inanimate systems), and (b) that key Darwinian concepts, such as fitness and natural selection, are particular expressions of more fundamental physicochemical concepts, such as kinetic stability and kinetic
selection. The approach appears to provide an improved basis for understanding the physicochemical process of complexification by which life on earth emerged, as well as a means of relating life's defining characteristics - its extraordinary complexity, its far-from-equilibrium character, and its purposeful (teleonomic) nature - to the nature of that process of complexification.
International collaboration in drug discovery and development from natural sources
Authors: Cragg Gordon M. , Newman David J.
Published: November 2005

Nature has been a source of medicinal agents for thousands of years, and an impressive number of modern drugs have been isolated from natural sources, particularly plants, with many based on their use in traditional medicine. The past century, however, has seen an increasing role played by microorganisms in the production of the antibiotics and other drugs for the treatment of serious diseases, and more recently, marine organisms have proved to be a rich source of novel bioactive agents. Natural products will continue to play a crucial role in meeting this demand through the expanded investigation of the world's biodiversity, much of which remains unexplored. By using medicinal chemistry, and combinatorial chemical and biosynthetic technology, novel natural product leads will be optimized on the basis of their biological activities to yield effective chemotherapeutic and other bioactive agents. With much of the biological diversity found in tropical and subtropical regions, the investigation of these resources requires multidisciplinary international collaboration in the discovery and development process. Such collaboration can result in substantial short-term benefits accruing to source countries, with the potential for the generation of significant longer-term benefits in the select cases of those agents that proceed into advanced development, and possible commercialization.
Unusual metabolites from some Tanzanian indigenous plant species
Authors: Nkunya Mayunga H. H.
Published: November 2005

In this paper, the chemistry of some unusual natural products that were isolated from various Tanzanian indigenous plant species during the past 20 years is reviewed. Among the compounds covered in this review are cyclohexane epoxides; heptane derivatives; oxygenated pyrenes; phenanthrene derivatives; flavonoids with uncommon structural frameworks; mono-, bis-, and dimeric prenylated indoles; and variously substituted mono-, sesqui-, and diterpenoids.
Protein profiling as a diagnostic tool in clinical chemistry: a review
Authors: Bons Judith A. P. , Wodzig Will K. W. H. , van Dieijen-Visser Marja P.
Published: November 2005

Serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) appears to be an important diagnostic tool for a whole range of diseases. Sensitivities and specificities obtained with this new technology often seem superior to those obtained with current biomarkers. However, reproducibility and standardization are still problematic. The present review gives an overview of the diagnostic value of protein profiles obtained with SELDI in studies on prostate and ovarian cancer. To identify aspects important for protein profiling, we compare and discuss differences in pre- and post-analytical conditions presented in the literature supplemented with some of our own data. Further progress in protein profiling as a diagnostic tool requires a more comprehensive description of technical details in all future studies.
Protein biochip systems for the clinical laboratory
Authors: Marie Dupuy Anne , Lehmann Sylvain , Paul Cristol Jean
Published: November 2005

Classical methods of protein analysis such as electrophoresis, ELISA and liquid chromatography are generally time-consuming, labor-intensive and lack high-throughput capacity. In addition, all existing methods used to measure proteins necessitate multiple division of the original sample and individual tests carried out for each substance, with an associated cost for each test. The chip system allows several tests to be performed simultaneously without dividing the original patient sample. This system facilitates the development of multiplexed assays that simultaneously measure many different analytes in a small sample volume. These emerging technologies fall into two categories: 1) spotted array-based tools, and 2) microfluidic-based tools. Miniaturized and multiplexed immunoassays allow a great deal of information to be obtained from a single sample. These analytical systems are referred to as “lab-on-a-chip” devices. This article presents current trends and advances in miniaturized multiplexed immunoassay technologies, reviewing different systems from research to point-of-care assays. We focus on a subset of chip-based assays that may be used in a clinical laboratory and are directly applicable for biomedical diagnosis. Recent advances in biochip assays combine the power of miniaturization, microfluidics, micro- to nanoparticles, and quantification. A number of applications are just beginning to be explored. The power of biochip assays offers great promise for point-of-care clinical testing and monitoring of many important analytes.
Automation of biochip array technology for quality results
Authors: Molloy Roisin M. , Mc Connell Robert I. , Lamont John V. , FitzGerald Stephen P.
Published: November 2005

Background: Proteomics' requirement for simultaneous measurement of multiple markers is now possible with biochip array technology. Many laboratories utilise in-house, manual procedures for biochip fabrication and sample testing. Reproducibility and standardisation of biochip processes is vital to ensure quality of results and offer the best tool for elucidation of complex relationships between multiple proteins in diseased conditions.

Methods: Various novel control checks have been implemented in biochip fabrication, reagent manufacture, automation and imaging processes for the Evidence analyser. Reference spots enable location of discrete test regions on the surface of the biochip and simultaneous quantification of multiple markers. Performance and standardisation methods are presented.

Results: Formulation of dispense solution for discrete test regions had a direct effect on their shape, stability and integrity on the biochip surface. Assays for fertility hormones and drugs of abuse demonstrated excellent precision, stability and comparison with other commercial methods.

Conclusion: Control processes employed in the manufacture and analysis of Evidence components ensure reproducibility of assays for a range of routine and novel markers.
Protein microarrays for the diagnosis of allergic diseases: state-of-the-art and future development
Authors: Harwanegg Christian , Hiller Reinhard
Published: November 2005

In the emerging field of
Separation of human serum proteins using the Beckman-Coulter PF2D™ system: analysis of ion exchange-based first dimension chromatography
Authors: Levreri Isabella , Musante Luca , Petretto Andrea , Bruschi Maurizio , Candiano Giovanni , Melioli Giovanni
Published: November 2005

The ProteomeLab™ PF2D protein fractionation system is a rapid, semi-automated, 2 D-HPLC instrument that uses two different methods to separate plasma serum proteins: ion-exchange chromatography using a wide pH range in the first dimension, and non-porous reverse-phase chromatography in the second dimension. Because this methodology has only very recently been introduced in proteomic laboratories, little is known about the characteristics of PF2D fractionation of human serum proteins. To evaluate the system's application in a clinical laboratory setting, the characteristics of the ion-exchange chromatography-based separation were analyzed. Following fractionation of human serum proteins on a linear pH gradient (ranging from 8.0 to 4.0), each fraction was collected in a cool module of the instrument. Different fractions obtained from the first dimension were then pooled together and loaded on classic 2D gel electrophoresis instrumentation. The different spots obtained were then checked against the Swiss-Prot Data-base. A total of 36 human serum proteins were identified in different PF2D-generated fractions. Some important features of the separation system were observed. Different eluted fractions contained different proteins, thus demonstrating the reliability of the fractionation system. The proteins were also fractionated according to the theoretical isoelectric point (pI). This was consistent with the evidence that the vast majority of immunoglobulins, characterized by an alkaline pI, were not retained by the column and were eluted in the unbound fraction. This outcome also underlines a practical advantage: fractions eluted from pH8 to pH4 contained virtually immunoglobulin-depleted serum proteins. This finding supports an immediate use of the PF2D system in a clinical setting, where abundant proteins should be clearly identified to enable evaluation of other less abundant, but potentially relevant, species.
Rapid, accurate genotyping of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 based on the use of denaturing HPLC
Authors: Li Liang , Mo Qiu-Hua , Xu Xiang-Min
Published: November 2005

The genotypes of alcohol dehydrogenase-1B (
APOA1 polymorphisms are associated with variations in serum triglyceride concentrations in hypercholesterolemic individuals
Authors: Sorkin Simone C. , Forestiero Francisco J. , Hirata Mario H. , Guzmán Elizabeth C. R. , Cavalli Selma A. , Bertolami Marcelo C. , Salazar Luis A. , Hirata Rosario D. C.
Published: November 2005

Background: Apolipoprotein A-I gene (

Methods:

Results: G–75A polymorphism was associated with differences in serum concentrations of triglyceride and very low-density lipoprotein (VLDL)-cholesterol (p=0.026) in HC men. After atorvastatin treatment, women carrying the

Conclusion: Our data suggest that
Simple PCR heteroduplex, SSCP mutation screening methods for the detection of novel catalase mutations in Hungarian patients with type 2 diabetes mellitus
Authors: Vitai Márta , Fátrai Szabolcs , Rass Péter , Csordás Melinda , Tarnai Ildikó
Published: November 2005

Background: The enzyme catalase is the main regulator of hydrogen peroxide metabolism. Deficiency of catalase may cause high concentrations of hydrogen peroxide and increase the risk of the development of pathologies for which oxidative stress is a contributing factor, for example, type 2 diabetes mellitus. Catalase deficiency has been reported to be associated with increased frequency of diabetes mellitus in a cohort of patients in Hungary. In this cohort, the majority of mutations in the catalase gene occur in exon 2.

Methods: Type 2 diabetic patients (n=308) were evaluated for mutations in intron 1 (81bp), exon 2 (172bp) and intron 2 (13bp) of the catalase gene. Screening for mutations utilized PCR single-strand conformational polymorphism (SSCP) and PCR heteroduplex methods. Verification of detected mutations was by nucleotide sequence analysis.

Results: A total of 11 catalase gene mutations were detected in the 308 subjects (3.57%, p<0.001). Five of the 11 were at two previously reported mutation sites: exon 2 (79) G insertion and (138) GA insertion. Six of the 11 were at five previously unreported catalase mutation sites: intron 1 (60) G→T; intron 2 (7) G→A and (5) G→C; exon 2 (96) T→A; and exon 2 (135) T→A. The novel missense mutations on exon 2 (96 and 135) are associated with 59% and 48% decreased catalase activity, respectively; the novel G→C mutation on intron 2 (5) is associated with a 62% decrease in catalase activity. Mutations detected on intron 1 (60) and intron 2 (7) showed no change in catalase activity. The G→C mutation on intron 2 (5) might be a splicing mutation. The two missense mutations on exon 2 (96) and (135) cause substitutions of amino acids 53 (Asp→Glu) and 66 (Glu→Cys) of the catalase protein. These are close to amino acids that are important for the binding of heme to catalase, 44 (Val) and 72–75 (Arg, Val, Val, His). Changes in heme binding may be responsible for the activity losses.

Conclusion: Mutations that cause decreased catalase activity may contribute to susceptibility to inherited type 2 diabetes mellitus. Exon 2 and neighboring introns of the catalase gene may be minor hot spots for type 2 diabetes mellitus susceptibility mutations.
Alteration in serum leptin correlates with alterations in serum N-telopeptide of collagen type I and serum osteocalcin during the progression of osteoporosis in ovariectomized rats
Authors: Stavropoulou Anastasia , Christopoulou Gina E. , Anastassopoulos George , Panteliou Sofia D. , Lyritis George P. , Spiliotis Bessie E. , Karamanos Nikos K. , Panagiotopoulos Elias , Lambiris Elias
Published: November 2005

The role of leptin during the progression of osteoporosis was investigated in ovariectomized rats by correlation of serum leptin levels with N-telopeptide of collagen type I (NTx) and osteocalcin levels before ovariectomy and 20, 40 and 60days after the operation. Furthermore, peripheral quantitative computed tomography was used to confirm the development of severe osteoporosis in rats on day 60. The levels of NTx and osteocalcin were significantly increased on day 20 [61.9±5.4nM BCE (bone collagen equivalents) and 215.6±53.3ng/mL, respectively] in comparison to those before ovariectomy (41.3±1.7nM BCE and 60.4±10.9ng/mL). Accordingly, leptin was significantly elevated on day 20 (3033±661 vs. 606±346 pg/mL before ovariectomy). Bone markers and leptin levels remained constant up to day 40, while a slight, but not statistically significant, decrease was noted for osteocalcin and leptin on day 60. Although leptin and bone markers did not correlate before ovariectomy (r=0.09 for NTx and r=−0.05 for osteocalcin), strong correlation was observed at all time points after ovariectomy. The data obtained suggest that the alterations in serum leptin levels during the progression of osteoporosis in ovariectomized rats follow the alterations in bone markers.
Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells
Authors: Schroecksnadel Katharina , Frick Barbara , Winkler Christiana , Wirleitner Barbara , Weiss Günter , Fuchs Dietmar
Published: November 2005

Hyperhomocysteinemia is regarded as an independent risk factor for vascular diseases, and homocysteine is supposed to contribute to oxidative stress and endothelial damage. Statin therapy is an established intervention to reduce the risk of acute events in patients suffering from cardiovascular diseases. Apart from their lipid-lowering capacity, statins also exert anti-inflammatory and antioxidant effects. As cellular immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular diseases, the anti-inflammatory capacity of statins could partly be responsible for the beneficial effects observed in patients. Earlier we reported that stimulated peripheral blood mononuclear cells (PBMCs) release homocysteine. Here we studied the influence of atorvastatin on homocysteine production in stimulated PBMCs and compared changes in cysteine concentrations and in neopterin production, which is a sensitive indicator of cellular immune activation. Stimulation of human PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significant homocysteine and neopterin production compared to unstimulated cells, whereas cysteine concentrations remained unchanged. Treatment of PBMCs with increasing doses of atorvastatin (10–100μM) suppressed both biochemical pathways in a dose-dependent manner, and cell proliferation was inhibited in parallel. Again, cysteine levels were not influenced by any treatment. The down-regulating effect of atorvastatin on homocysteine formation in vitro indicates that statins may prevent homocysteine accumulation in the blood via immunosuppression.
Buprenorphine detection in biological samples
Authors: De Giovanni Nadia , Fucci Nadia , Scarlata Salvatore , Donzelli Giovanni
Published: November 2005

Buprenorphine is a narcotic analgesic used in the treatment of moderate-to-severe pain. In Italy, buprenorphine is now being used as an alternative in the therapeutic treatment of heroin abusers. Even if confirmation methods are needed for identification and quantitation, a rapid and sensitive test, such as an immunoassay, is essential for screening. We evaluated the Buprenorphine One-step ELISA test (designed for serum specimens) for the qualitative determination of buprenorphine in other matrices, such as urine, saliva and hair.
High-affinity antibodies in a new immunoassay for plasma tissue factor: reduction in apparent intra-individual variation
Authors: van der Putten Roy F. M. , te Velthuis Henk , Aarden Lucien A. , ten Cate Hugo , Glatz Jan F. C. , Hermens Wim Th.
Published: November 2005

Tissue factor, the main initiator of blood coagulation, is shed into plasma by blood cells and endothelium. While studying such circulating plasma tissue factor with a commercially available immunoassay, we found unsatisfactory results and therefore developed a new and highly sensitive enzyme-linked immunosorbent assay (ELISA). High-affinity monoclonal antibodies raised against recombinant soluble tissue factor were used and the new assay had a detection limit of 40fmol/L, approximately six-fold lower than existing assays. Normal ranges in 20 healthy donors were established in serum and in citrated EDTA and heparinized plasma. Tissue factor was also measured in three successive plasma samples from 43 patients with type 2 diabetes mellitus. In citrated plasma from healthy donors, tissue factor concentrations were 2.5 (1.0–9.3) pmol/L (median with range) and were not significantly different in diabetics. With a commercially available immunoassay, seven plasma samples were below the detection limit. Use of the new assay reduced intra-individual variation in diabetics from 49% to 14% and we conclude that high-affinity antibodies may markedly improve immunoassay performance.
Physiological matrix metalloproteinase concentrations in serum during childhood and adolescence, using Luminex® Multiplex technology
Authors: Thrailkill Kathryn M. , Moreau Cindy S. , Cockrell Gael , Simpson Pippa , Goel Rajiv , North Paula , Fowlkes John L. , Bunn Robert C.
Published: November 2005

Matrix metalloproteinases are a family of zinc-dependent proteinases which are involved in the breakdown and remodeling of extracellular matrix. As children grow and adolescents reach pubescence, their bodies undergo changes that require age-related morphogenesis of the extracellular matrix, possibly requiring unique patterns of matrix metalloproteinase (MMP) expression during periods of rapid tissue growth (i.e., childhood) or accelerated tissue remodeling and expansion (i.e., adolescence). Therefore, we have characterized age-specific and gender-specific differences in circulating concentrations of MMPs (specifically MMP-1, -2, -3, -8 and -9) in 189 serum samples obtained from healthy subjects, aged 2–18 years. MMP concentrations were measured using Fluorokine
Partner Notification Methods for African American Men Being Treated for Trichomoniasis: A Consideration of Main Men, Second Hitters, and Third Players
Authors: Lichtenstein Bronwen , Schwebke Jane R.
Published: November 2005

This pilot study sought information on African American men's preferences for partner notification methods for a common sexually transmitted infection called trichomoniasis. Two focus groups of African American men were convened at a public STI clinic where they were being treated for trichomoniasis. The groups identified a sexual hierarchy in men's preferences for methods of partner notification. The hierarchy consisted of main men (Cake Daddies), second men (Second Hitters), and third or fourth men (Third Players), with placement depending on age, income, and social status. Health department employees affirmed the existence of a sexual hierarchy in a separate focus group. Sexual and economic bartering formed the basis of the hierarchy, and the secrecy involved in such arrangements presented a considerable challenge for STI control. Disease intervention specialists who were responsible for contact tracing spoke of cat‐and‐mouse methods in contacting the men without understanding fully exactly how the hierarchy influenced men's responses to partner notification. The findings suggest that STI control efforts must take the sexual hierarchy and its privacy implications into account if partner notification methods are to be acceptable to African American men.
“Taming Tradition”: Medicalized Female Genital Practices in Western Kenya
Authors: Christoffersen‐Deb Astrid
Published: November 2005

This article considers the question of female genital practices at the hands of health workers in western Kenya. Recent articles inMedical Anthropology Quarterlyhave critically engaged with the biomedical arguments condemning such practices. This article studies the case of medicalized circumcision in which biomedical concerns over health risks have become incorporated in their vernacular practice. Although some suggest that medicalization may provide a harm‐reduction strategy to the abandonment of the practice, research in one region challenges this suggestion. It argues that changing and conflicting ideologies of gender and sexuality have led young women to seek their own meaning through medicalized practice. Moreover, attributing this practice to financial motivations of health workers overlooks the way in which these “moral agents” must be situated within their social and cultural universe. Together, these insights challenge the view that medicine can remain neutral in the mediation of tradition.
A Room for Reflection: Self‐Observation and Transformation in Participatory HIV Prevention Work
Authors: Middelthon Anne‐Lise
Published: November 2005

This article looks at HIV prevention projects in which established stigmatized and stigmatizing roles were actively reversed and manipulated in pursuit of HIV harm reduction. In two Norwegian projects, sex workers and drug users carried out harm‐reduction activities with other drug users and sex workers. Although HIV‐related harm reduction was the aim of the projects, termination or reduction of drug use or sex work was not. Such changes nevertheless occurred among the sex workers and drug users who took active part in the project. The article considers these changes in order to reflect on the meanings and roles of participation in HIV prevention work. In particular, the discussion theorizes on possible ways in which alteration of roles and subject positions may produce self‐reflective effects with transformative potentials.
Trends in Religious Healing and the Integration of Biomedicine and Complementary and Alternative Medicine in the United States and Around the Globe: A Review
Authors: Baer Hans A.
Published: November 2005

Religion and Healing in America. Linda L. Barnes and Susan S. Sered, eds. New York: Oxford University Press, 2005 (cloth and paper). xvi + 535 pp.

Complementary and Alternative Medicine in the United States
Institute of Medicine. Washington, DC: National Academies Press, 2005 (cloth). xx + 337 pp.

Consciousness and Healing: Integral Approaches to Mind‐Body Medicine. Marilyn Schlitz and Tina Amorok with Marc S. Micozzi, eds. St. Louis: Elsevier Churchill Livingstone, 2005 (cloth and paper). lx + 583 pp.

Negotiating the Holistic Turn: The Domestication of Alternative Medicine. Judith Fadlon. Albany: State University of New York Press, 2005. x + 157 pp.
Medical Pluralism in the Andes
Authors: Joralemon Donald
Published: November 2005

Medical Pluralism in the Andes. Joan D. Koss‐Chioino, Thomas Leatherman, and Christine Greenway. New York: Routledge, 2003. xix + 256 pp.
Nursing Against the Odds
Authors: Shelton Deborah
Published: November 2005

Nursing Against the Odds. Suzanne Gordon. Ithaca and London: Cornell University Press, 2005. ix + 489 pp.
Effects of a Long-Term Volunteer Surgical Program in a Developing Country: The Case in Vietnam from 1993 to 2003
Authors: Uetani Miyuki , Jimba Masamine , Niimi Teruyuki , Natsume Nagato , Katsuki Takeshi , Xuan Le Thi Thanh , Wakai Susumu
Published: November 2005

Objective:

This study evaluates the activities of the Japanese Cleft Palate Foundation from 1993 to 2003 in southern Vietnam.

Design:

We assessed trends associated with patient age at first operation for primary lip repair and palate repair by using medical records of the patients.

Participants:

This study consisted of 790 patients with nonsyndromic cleft lip and/or palate (CL/P).

Results:

The median patient age for lip repair was reduced from 14.0 years in 1993 to 1.3 years by 2003. For palate repair, the median age was reduced from 13.5 years in 1993 to 5.0 years in 1999 through 2003. The age distributions of both lip and palate repair in the later years became smaller than the age distributions in 1993. The number of adult patients declined throughout the period.

Conclusions:

The Japanese Cleft Palate Foundation contributed to lowering the age at first operation for CL/P and to reducing the number of adult patients in Ben Tre province, southern Vietnam. However, appropriate supports will be necessary to maintain CL/P treatment and to improve locally supported health care for patients with CL/P.
Shifts in the landscape of learning: New challenges, new opportunities
Authors: Eisen Mary‐Jane
Published: November 2005

The rapid growth in the number of older adult learners presents new challenges and opportunities for adult educators. These include facilitating the development of individuals as they make the transition to their later years and of American society as it struggles to reenvision aging.
Life journeys: Awakenings and learning experiences
Authors: Luckie Jo Ann C.
Published: November 2005

This chapter examines spiritual awakenings and creative expression that influence changes in the life course. In what ways can learning environments foster growth and integration of the whole person?
Environments for development
Authors: Grabinski C. Joanne
Published: November 2005

This chapter considers Robert Kegan's concept of holding environments, as well as six steps necessary for creation of new or adaptation of existing learning environments that facilitate adult development across the life course.
Applications of Phase‐sensitive X‐Ray Imaging to the Structural Analysis of Composite Laminate High‐performance Sail Fabrics
Authors: Tesei L. , Tesei G. , Mancini L. , Tromba G. , Zanini F.
Published: November 2005

High‐performance sail fabrics cannot be studied with conventional X‐ray imaging set‐ups because of their low absorption, while other techniques do not give a full insight of the inner structure of the material. We show preliminary results of the application of phase‐contrast X‐ray imaging to the study of modern laminate sailcloth.
Biomimetic Bonelike Composites and Novel Bioactive Glass Coatings
Authors: Tomsia A. P. , Saiz E. , Song J. , Bertozzi C. R.
Published: November 2005

Metallic orthopaedic implants have been successfully used for decades but they have serious shortcomings related to their osseointegration and the fact that their mechanical properties do not match those of bone. This paper reviews recent advances in the fabrication of novel coatings to improve implant osseointegration and in the development of a new generation of hybrid organic‐inorganic implant materials specifically designed for orthopaedic applications.
Cover Picture: Recent Developments in Nanostructured Materials (Adv. Eng. Mater. 11/2005)
Authors: Suryanarayana C.
Published: November 2005

The cover shows transmission electron micrographs of typical microstructures in as‐deposited copper samples. More about recent developments in nanostructured materials research can be found in the review paper by C. Suryanarayana on page 983.

Nanostructured materials with extremely fine grain sizes, typically less than 100 nm, have been shown to exhibit extremely high strength and hardness, increased diffusivity, useful sintering characteristics, and other unusual properties. Significant developments have taken place in recent years in trying to achieve high strength and ductility at the same time. New and potential applications are also being sought after. Several commercial ventures have also started (estimated to be around 1000 in different parts of the world). This overview will present the recent developments in our understanding of the mechanical behavior and molecular dynamics simulation studies, highlight the present unresolved issues, and discuss some of the promising applications for these novel and exciting materials.
Alzheimer's patients engage an alternative network during a memory task
Authors: Pariente Jérémie , Cole Susanna , Henson Richard , Clare Linda , Kennedy Angus , Rossor Martin , Cipoloti Lisa , Puel Michèle , Demonet Jean Francois , Chollet Francois , Frackowiak Richard S. J.
Published: November 2005

We conducted an event‐related functional magnetic resonance imaging experiment to better understand the potentially compensatory alternative brain networks activated by a clinically relevant face‐name association task in Alzheimer's disease (AD) patients and matched control subjects. We recruited 17 healthy subjects and 12 AD patients at an early stage of the disease. They underwent functional magnetic resonance imaging scanning in four sessions. Each of the sessions combined a “study” phase and a “test” phase. Face/name pairs were presented in each study phase, and subjects were asked to associate faces with names. In the test phase, a recognition task, faces seen in the study phase were presented each with four different names. The task required selection of appropriate previously associated names from the study phase. Responses were recorded for post hoc classification into those successfully or unsuccessfully encoded. There were significant differences between the groups in accuracy and reaction time. Comparison of correctly versus incorrectly encoded and recognized pairs in the two groups indicated bilateral hippocampal hypoactivation both when encoding and recognizing in the AD group. Moreover, patients showed bilateral hyperactivation of parts of the parietal and frontal lobes. We discuss whether hyperactivation of a frontoparietal network reflects compensatory strategies for failing associative memory in AD patients. Ann Neurol 2005;58:870–879