bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrostatic rate enhancement and transient complex of protein–protein association
Authors: Alsallaq Ramzi , Zhou Huan‐Xiang
Published: October 2007

The association of two proteins is bounded by the rate at which they, via diffusion, find each other while in appropriate relative orientations. Orientational constraints restrict this rate to ∼105–106 M−1 s−1. Proteins with higher association rates generally have complementary electrostatic surfaces; proteins with lower association rates generally are slowed down by conformational changes upon complex formation. Previous studies (Zhou, Biophys J 1997;73:2441–2445) have shown that electrostatic enhancement of the diffusion‐limited association rate can be accurately modeled by
$k_{\bf D}$
= $k_{D}0\ {exp} ( - \langle U_{el} \rangle^{\star}/k_{B} T),$
where kD and kD0 are the rates in the presence and absence of electrostatic interactions, respectively, 〈Uel〉☆ is the average electrostatic interaction energy in a “transient‐complex” ensemble, and kBT is the thermal energy. The transient‐complex ensemble separates the bound state from the unbound state. Predictions of the transient‐complex theory on four protein complexes were found to agree well with the experiment when the electrostatic interaction energy was calculated with the linearized Poisson–Boltzmann (PB) equation (Alsallaq and Zhou, Structure 2007;15:215–224). Here we show that the agreement is further improved when the nonlinear PB equation is used. These predictions are obtained with the dielectric boundary defined as the protein van der Waals surface. When the dielectric boundary is instead specified as the molecular surface, electrostatic interactions in the transient complex become repulsive and are thus predicted to retard association. Together these results demonstrate that the transient‐complex theory is predictive of electrostatic rate enhancement and can help parameterize PB calculations. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Improved model building and assessment of the Calcium‐sensing receptor transmembrane domain
Authors: Bu Lintao , Michino Mayako , Wolf Romain M. , Brooks Charles L.
Published: October 2007

A three‐dimensional model of the human Calcium‐sensing receptor (CaSR) seven transmembrane domain was built via a novel sequence alignment method based on the conserved contacts in proteins using the crystal structure of bovine rhodopsin as the template. This model was tested by docking NPS 2143, the first identified allosteric antagonist of CaSR. In our model, Glu837 plays a critical role in anchoring the protonated nitrogen atom and hydroxy oxygen atom of NPS 2143. The phenyl moiety of the ligand contacts residues Phe668, Pro672, and Ile841. The naphthalene moiety is surrounded by several hydrophobic residues, including Phe684, Phe688, and Phe821. Our model appears to be consistent with all six residues that have been demonstrated to be critical for NPS 2143 binding, in contrast with existing homology models based on traditional sequence alignment of CaSR to rhodopsin. This provides validation of our sequence alignment method and the use of the rhodopsin backbone as the initial structure in homology modeling of other G protein‐coupled receptors that are not members of the rhodopsin family. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Do collagenases unwind triple‐helical collagen before peptide bond hydrolysis? Reinterpreting experimental observations with mathematical models
Authors: Nerenberg Paul S. , Salsas‐Escat Ramon , Stultz Collin M.
Published: October 2007

It has been postulated that triple‐helical collagen is actively unwound by collagenases before peptide bond hydrolysis—a supposition that explains the small catalytic rate constant associated with collagenolysis. We propose an alternate model of collagen degradation that does not require active unwinding by collagenases, but instead suggests that the regions of collagen near the collagenase cleavage site can adopt either a native triple‐helical or a partially unfolded conformation. In this model, collagenases preferentially bind to and stabilize partially unfolded conformers before cleaving the scissile bond. Existing experimental observations (which were previously taken to support active unwinding models) are reinterpreted using corroborative evidence from numerical simulations and found to be consistent with this framework. These data support the notion that collagen, like all other biological heteropolymers, undergoes thermal fluctuations that cause it to sample distinct structures in the neighborhood of the native state, and collagenolysis occurs when collagenases recognize the appropriate unwound conformers. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Conformation and dynamics of the three‐helix bundle UBA domain of p62 from experiment and simulation
Authors: Evans Clare‐Louise , Long Jed E. , Gallagher Thomas R. A. , Hirst Jonathan D. , Searle Mark S.
Published: October 2007

The ubiquitin associated domain of p62 is a small three‐helix bundle of ∼50 residues that mediates the recognition of polyubiquitin chains and ubiquitylated substrates. The solution structure of a 52 residue construct containing this domain has been characterized using heteronuclear nuclear magnetic resonance (NMR) methods. The resulting ensemble of NMR‐derived structures was used in molecular dynamics (MD) simulations to investigate the equilibrium conformation and dynamics of this domain. NOE and 15N relaxation data have been used to validate the structural ensemble produced by the MD simulations and show a good correlation for residues in regions of secondary structure. A similar approach was taken using an ensemble of structures from the MD simulations to calculate electronic circular dichroism (CD) and IR spectra from first principles with an encouraging correlation with the experimental CD and IR data. Proteins 2008. © 2007 Wiley‐Liss, Inc.
An asymmetric dimer of β‐lactoglobulin in a low humidity crystal form—Structural changes that accompany partial dehydration and protein action
Authors: Vijayalakshmi L. , Krishna R. , Sankaranarayanan R. , Vijayan M.
Published: October 2007

Dimeric lactoglobulin molecules exist in the open conformation at basic pH, whereas they exist in the closed conformation at acidic pH, after undergoing the Tanford transition around neutral pH. Orthorhombic crystals consisting of molecules in the open conformation, grown close to neutral pH, undergo a water‐mediated transformation when the relative humidity around the crystals is reduced. The two subunits in the dimer are related by a crystallographic twofold axis in the native crystals while the dimer is asymmetric in the low humidity form. Interestingly, one of the subunits in the dimer in the low humidity form is in an open conformation while the other is in a closed conformation. This is the first observation of such an asymmetric dimer. A hydrogen bond between the side chains of Gln35 and Tyr42 exists and the side chain of Glu89 is substantially buried in the closed subunit of the asymmetric unit, as in other structures with molecules in the closed conformation. However, the closure of the EF loop is not complete; its conformation can be described as half‐closed. A comparison of different crystal structures of β‐lactoglobulin indicates that the conformation of the loops in the molecule is substantially influenced by other factors such as crystal packing, the pH, and the composition of the medium, while the change in the conformation of the EF loop follows the Tanford transition. The mutual disposition of the two subunits in the low humidity form is halfway between those in the open and closed structures. The present work further demonstrates that structural changes that occur during partial dehydration could mimic those that occur during the action of proteins. Proteins 2008. © 2007 Wiley‐Liss, Inc.
QMEAN: A comprehensive scoring function for model quality assessment
Authors: Benkert Pascal , Tosatto Silvio C. E. , Schomburg Dietmar
Published: October 2007

In protein structure prediction, a considerable number of alternative models are usually produced from which subsequently the final model has to be selected. Thus, a scoring function for the identification of the best model within an ensemble of alternative models is a key component of most protein structure prediction pipelines. QMEAN, which stands for Qualitative Model Energy ANalysis, is a composite scoring function describing the major geometrical aspects of protein structures. Five different structural descriptors are used. The local geometry is analyzed by a new kind of torsion angle potential over three consecutive amino acids. A secondary structure‐specific distance‐dependent pairwise residue‐level potential is used to assess long‐range interactions. A solvation potential describes the burial status of the residues. Two simple terms describing the agreement of predicted and calculated secondary structure and solvent accessibility, respectively, are also included. A variety of different implementations are investigated and several approaches to combine and optimize them are discussed. QMEAN was tested on several standard decoy sets including a molecular dynamics simulation decoy set as well as on a comprehensive data set of totally 22,420 models from server predictions for the 95 targets of CASP7. In a comparison to five well‐established model quality assessment programs, QMEAN shows a statistically significant improvement over nearly all quality measures describing the ability of the scoring function to identify the native structure and to discriminate good from bad models. The three‐residue torsion angle potential turned out to be very effective in recognizing the native fold. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Local interactions in protein folding determined through an inverse folding model
Authors: Bastolla Ugo , Porto Markus , Ortíz Angel R.
Published: October 2007

We adopt a model of inverse folding in which folding stability results from the combination of the hydrophobic effect with local interactions responsible for secondary structure preferences. Site‐specific amino acid distributions can be calculated analytically for this model. We determine optimal parameters for the local interactions by fitting the complete inverse folding model to the site‐specific amino acid distributions found in the Protein Data Bank. This procedure reduces drastically the influence on the derived parameters of the preference of different secondary structures for buriedness, which affects local interaction parameters determined through the standard approach based on amino acid propensities. The quality of the fit is evaluated through the likelihood of the observed amino acid distributions given the model and the Bayesian Information Criterion, which indicate that the model with optimal local interaction parameters is strongly preferable to the model where local interaction parameters are determined through propensities. The optimal model yields a mean correlation coefficient r = 0.96 between observed and predicted amino acid distributions. The local interaction parameters are then tested in threading experiments, in combination with contact interactions, for their capacity to recognize the native structure and structures similar to the native against unrelated ones. In a challenging test, proteins structurally aligned with the Mammoth algorithm are scored with the effective free energy function. The native structure gets the highest stability score in 100% of the cases, a high recognition rate comparable to that achieved against easier decoys generated by gapless threading. We then examine proteins for which at least one highly similar template exists. In 61% of the cases, the structure with the highest stability score excluding the native belongs to the native fold, compared to 60% if we use local interaction parameters derived from the usual amino acid propensities and 52% if we use only contact interactions. A highly similar structure is present within the five best stability scores in 82%, 81%, and 76% of the cases, for local interactions determined through inverse folding, through propensity, and set to zero, respectively. These results indicate that local interactions improve substantially the performances of contact free energy functions in fold recognition, and that similar structures tend to get high stability scores, although they are often not high enough to discriminate them from unrelated structures. This work highlights the importance to apply more challenging tests, as the recognition of homologous structures, for testing stability scores for protein folding. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Sequence‐based protein domain boundary prediction using BP neural network with various property profiles
Authors: Ye Lei , Liu Ting , Wu Zhaohui , Zhou Ruhong
Published: October 2007

Given the rapid growth in the number of sequences without known structures, it is becoming increasingly important to not only accurately define protein structural domains but also predict domain boundaries from the amino‐acid sequence alone. In this article, we present a Back‐Propagation (BP) neural network method using 9 different sequence profiles, based on chemical, physical, and statistical properties, to predict the domain boundary of two‐domain proteins from one dimensional sequences. We have achieved an accuracy of 69% with a 10‐fold cross validation on a 238 nonredundant two‐domain protein dataset that we built based on a common set from both SCOP and CATH classifications. The method has also been applied to a larger third‐party dataset with 522 proteins; and an accuracy of 62% has been achieved. Our prediction results on both datasets are found to be significantly better than those from some other methods, such as DomCut and DGS on the same datasets, and also comparable to that from the PPRODO method, upon which the larger dataset was based. Our cross validation results are also noticeably better than previous ones from other BP neural network methods, probably because we have used more property descriptors with significantly more training nodes in our neural network. The integration with PPRODO method also indicates that the information obtained from our current approach is complementary to that available through multiple sequence alignments. Moreover, the relative importance of each property profile has been analyzed in detail. Proteins 2008. © 2007 Wiley‐Liss, Inc.
MALIDUP: A database of manually constructed structure alignments for duplicated domain pairs
Authors: Cheng Hua , Kim Bong‐Hyun , Grishin Nick V.
Published: October 2007

We describe MALIDUP (manual alignments of duplicated domains), a database of 241 pairwise structure alignments for homologous domains originated by internal duplication within the same polypeptide chain. Since duplicated domains within a protein frequently diverge in function and thus in sequence, this would be the first database of structurally similar homologs that is not strongly biased by sequence or functional similarity. Our manual alignments in most cases agree with the automatic structural alignments generated by several commonly used programs. This carefully constructed database could be used in studies on protein evolution and as a reference for testing structure alignment programs. The database is available at http://prodata.swmed.edu/malidup. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Self‐assembly of the octapeptide lanreotide and lanreotide‐based derivatives: the role of the aromatic residues
Authors: Pandit Anjali , Fay Nicolas , Bordes Luc , Valéry Céline , Cherif‐Cheikh Roland , Robert Bruno , Artzner Franck , Paternostre MaÏté
Published: October 2007

We investigated the spectroscopic properties of the aromatic residues in a set of octapeptides with various self‐assembly properties. These octapeptides are based on lanreotide, a cyclic peptide analogue of somatostatin‐14 that spontaneously self‐assembles into very long and monodisperse hollow nanotubes. A previous study on these lanreotide‐based derivatives has shown that the disulfide bridge, the peptide hairpin conformation and the aromatic residues are involved in the self‐assembly process and that modification of these properties either decreases the self‐assembly propensity or modifies the molecular packing resulting in different self‐assembled architectures. In this study we probed the local environment of the aromatic residues, naphthyl‐alanine, tryptophan and tyrosine, by Raman and fluorescence spectroscopy, comparing nonassembled peptides at low concentrations with the self‐assembled ones at high concentrations. As expected, the spectroscopic characteristics of the aromatic residues were found to be sensitive to the peptide–peptide interactions. Among the most remarkable features we could record a very unusual Raman spectrum for the tyrosine of lanreotide in relation to its propensity to form H‐bonds within the assemblies. In Lanreotide nanotubes, and also in the supramolecular architectures formed by its derivatives, the tryptophan side chain is water‐exposed. Finally, the low fluorescence polarization of the peptide aggregates suggests that fluorescence energy transfer occurs within the nanotubes. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Thermoelectric effect in laser annealed printed nanocrystalline silicon layers
Authors: Lechner Robert , Wiggers Hartmut , Ebbers André , Steiger Jürgen , Brandt Martin S. , Stutzmann Martin
Published: October 2007

Nanocrystalline boron and phosphorus doped silicon particles were produced in a microwave reactor, collected, and dispersed in ethanol. Pulsed laser annealing of spin‐coated films of these particles resulted in p‐ and n‐type conductive layers on flexible substrates if a threshold laser energy density of 60 mJ/cm2 was exceeded. The thermopower of the laser sintered layers exhibits a distinct maximum at a doping concen‐ tration around 1019 cm–3 for both boron and phosphorus doping with an absolute value of the Seebeck coefficient of about 300 µV/K. Since the thermal conductivity of the layers is reduced by nearly the same factor compared to bulk crystalline silicon as the electrical conductivity, these results are promising for the application of such nanocrystalline layers in thin film thermoelectric devices. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Role of diet in the prevention of common kidney stones
Authors: Finch William J.G. , Irving Stuart O.
Published: October 2007

The authors discuss the evidence for the prevention of calcium stones through dietary intervention, and look at some of the emerging options. Copyright © 2007 Wiley Interface Ltd
Management of nocturnal enuresis
Authors: Smith G.
Published: October 2007

Nocturnal enuresis is a common problem that can have a significant impact on the child and family. Various medical and psychological treatment options are available, but it is important to assess the underlying cause when planning management. Copyright © 2007 Wiley Interface Ltd
9. Sorting out pelvic inflammatory disease
Authors: von Knorring N. , Wilson Janet
Published: October 2007

Pelvic inflammatory disease is a major threat to the reproductive health of young women and has a large impact on healthcare resources. Immediate treatment is necessary to prevent long‐term complications such as tubal factor infertility and ectopic pregnancy. The authors emphasise the importance of a pragmatic approach to management. Copyright © 2007 Wiley Interface Ltd
Decomposition and nitrogen release from the foliage litter of fir (Abies sachalinensis) and oak (Quercus crispula) under different forest canopies in Hokkaido, Japan
Authors: Miyamoto Toshizumi , Hiura Tsutom
Published: October 2007

When two tree species co‐occur, decomposition and nitrogen (N) release from the foliage litter depend on two factors: the forest floor conditions under each canopy type and the species composition of the litter. We conducted an experiment using fir and oak to answer several questions regarding decomposition beneath canopies of the two species and the effects of litter species composition on decomposition. We compared the rates of decomposition and N release from three different litters (fir needle, oak leaf, and a mixture of the two) in 1‐mm‐mesh litterbags on the forest floor under three different canopies (a 40‐year‐old fir plantation, large oak trees, and mixed fir and oak trees) in Hokkaido, Japan, over a 2‐year period. Beneath each of these canopy types, the litter decomposition rate and percentage of N remaining in the litterbags containing a mixture of fir and oak litter were not significantly different from the expected values calculated for litterbags containing litter from a single tree species. Oak leaf litter decomposed significantly faster than fir needle litter beneath each canopy type. The litter decomposition rate was significantly higher beneath the fir canopy than under the oak canopy, and was intermediate under the mixed canopy of fir and oak. No net N release, that is, a decrease in the total N compared to the original amount, was detected from fir litter under each canopy type or from oak leaf litter beneath the oak canopy. N increased over the original amount in the fir litter beneath the oak canopy and the mixed canopy of fir and oak, but N was released from the oak litter under the fir canopy and the mixed canopy of fir and oak. These results suggest that oak leaf litter blown onto fir forest floor enhances nutrient cycling, and this might be a positive effect of a mixed stand of conifer and broad‐leaved trees.
Adsorption of Anionic–Cationic Surfactant Mixtures on Metal oxide Surfaces
Authors: Upadhyaya A. , Acosta E. J. , Scamehorn J. F. , Sabatini D. A.
Published: October 2007

This research evaluates the adsorption of anionic and cationic surfactant mixtures on charged metal oxide surfaces (i.e., alumina and silica). For an anionic‐rich surfactant mixture below the CMC, the adsorption of anionic surfactant was found to substantially increase with the addition of low mole fractions of cationic surfactant. Two anionic surfactants (sodium dodecyl sulfate and sodium dihexyl sulfosuccinate) and two cationic surfactants (dodecyl pyridinium chloride and benzethonium chloride) were studied to evaluate the effect of surfactant tail branching. While cationic surfactants were observed to co‐adsorb with anionic surfactants onto positively charged surfaces, the plateau level of anionic surfactant adsorption (i.e., at or above the CMC) did not change significantly for anionic–cationic surfactant mixtures. At the same time, the adsorption of anionic surfactants onto alumina was dramatically reduced when present in cationic‐rich micelles and the adsorption of cationic surfactants on silica was substantially reduced in the presence of anionic‐rich micelles. This demonstrates that mixed micelle formation can effectively reduce the activity of the highly adsorbing surfactant and thus inhibit the adsorption of the surfactant, especially when the highly adsorbing surfactant is present at a low mole fraction in the mixed surfactant system. Thus surfactant adsorption can be either enhanced or inhibited using mixed anionic–cationic surfactant systems by varying the concentration and composition.
Why Work in Perioperative Nursing? Baby Boomers and Generation Xers Tell All
Authors: Thompson Julia A.
Published: October 2007

THIS QUANTITATIVE AND QUALITATIVE study explored factors that influence nurses of different age groups to choose to work in and remain in the specialty of OR nursing, including the effect of work environment perceptions.

BABY BOOMER NURSES (n = 130) and Generation X nurses (n = 117) were surveyed, and seven RNs from each group also participated in semistructured interviews.

RESULTS SHOWED THAT NURSES of both age groups were more alike than different in the factors that influence them to choose and remain in OR nursing and in their perceptions of their work environment. Baby Boomers indicated a higher level of commitment to their jobs than did Generation Xers.
Verbal Medication Orders in the OR
Authors: Hendrickson Thomas
Published: October 2007

MEDICATION ERRORS are the fourth most commonly reported sentinel event, and changes in practice are needed to provide a safe environment for patients in the OR.

EXISTING MEASURES for preventing medication errors in the OR have focused on labeling medication containers on and off the sterile field. Very little attention, however, has been given to the potential for errors caused by verbal orders in the OR or to developing processes to prevent such errors.

SIMPLE SOLUTIONS for improving the safety of verbal medication orders include instituting a read‐back system in which verbal orders are written on a dry‐erase board and verified by the ordering physician, requesting clarification of questionable orders, and reducing distractions in the OR.
On Call: Alert or Unsafe? A Report of the AORN On‐Call Electronic Task Force
Authors: Kenyon Trudy A.G. , Gluesing Rebecca E. , White Karen Y. , Dunkel Wanda L. , Burlingame Byron L.
Published: October 2007

RESEARCH HAS LINKED health care providers' long work hours with patient care errors. Perioperative staff members often work extended hours because of long shifts and being on call.

AORN's ON‐CALL ELECTRONIC TASK FORCE conducted a survey of nurses to determine their work load, call scheduling, and experiences related to fatigue. Of the 1,013 respondents, 67.7% said they had experienced effects of sleep deprivation.

A FOLLOW‐UP SURVEY revealed that few call programs are in compliance with AORN's recommended practices. Compliant call programs are detailed for adaptation in other perioperative settings.
Translating Research on Venous Thromboembolism into Practice
Authors: Cantrell Shirley W. , Ward Karen S. , Van Wicklin Sharon A.
Published: October 2007

EVIDENCE‐BASED NURSING PRACTICE incorporates the best research available with clinical expertise. It can be difficult, however, for nurses to integrate use of evidence into their everyday work.

THIS ARTICLE PROVIDES an example of using research findings to implement best nursing practice for patients at risk for venous thromboembolism (VTE). Remaining current on methods to prevent and treat VTE is essential for nurses throughout the hospital but is especially important in the perioperative environment.

NURSES CAN USE THIS EXAMPLE as a basis for establishing evidence‐based practice in other patient care situations.
Knee Joint Preservation With Autologous Cartilage Implantation
Authors: Nagle Judith A.
Published: October 2007

DAMAGE TO THE BODY'S JOINT CARTILAGE is becoming a disabling problem for Americans as they live longer and remain active.

TRADITIONALLY, ARTICULAR DAMAGE has been treated with arthroscopic debridement and microfracture, abrasion arthroplasty, and osteochondral autograft. Orthopedic surgeons now can offer patients a new option: autologous cartilage implantation (ACI), in which cultured autologous cartilage cells are used to repair and promote growth in cartilage defects.

USE OF ACI PRESERVES the articular surfaces of the knee in patients with early onset osteoarthritis, decreases pain, maintains patients' quality of life, and delays possible total joint replacement.
Antecedents and consequences of social capital on buyer performance improvement
Authors: Lawson Benn , Tyler Beverly B. , Cousins Paul D.
Published: October 2007

The ability to leverage social capital within strategic buyer–supplier relationships is increasingly cited as a key driver of value creation. Despite the importance of strategic partnerships, the process by which social capital accumulates within buyer–supplier relationships and contributes to buyer performance improvements is not well understood. Drawing on social capital theory, we develop a model linking positive relational capital, and its antecedents, supplier integration and supplier closeness, to buyer performance improvements. Further, we hypothesize that structural capital, as reflected in managerial communication and technical exchanges, is also positively related to buyer performance improvements. Using data provided by 111 procurement executives from the United Kingdom, we find support for our hypotheses. The study extends the supply chain management and social capital literature and suggests important implications for both research and practice.
Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase
Authors: Dell'Agli Mario , Maschi Omar , Galli Germana V. , Fagnani Rossana , Dal Cero Esther , Caruso Donatella , Bosisio Enrica
Published: October 2007

The aim of the present study was to confirm that olive oil phenols reduce human platelet aggregability and to verify the hypothesis that cAMP- and cGMP- phosphodiesterases (PDE) could be one of the targets of the biological effect. Four extracts from oils characterized by a high phenol content (HPE), and low phenol levels (LPE) were prepared and analyzed quali- and quantitatively by HPLC-UV and electrospray ionization–MS/MS. Human washed platelets stimulated with thrombin were used for the aggregation assay. Human platelet cAMP-PDE and recombinant PDE5A1 were used as enzyme source. Platelet aggregation and enzyme activity were assayed in the presence of HPE, LPE and individual phenols. The phenol content of HPE ranged between 250 and 500 mg/kg, whereas the LPE content was 46 mg/kg. The compounds identified were hydroxytyrosol (HT), tyrosol (TY), oleuropein aglycone (OleA) and the flavonoids quercetin (QU), luteolin (LU) and apigenin (AP). OleA was the most abundant phenol (range 23·3 to 37·7 %) and LU was the most abundant flavonoid in the extracts. Oil extracts inhibited platelet aggregation with an 50% inhibitory concentration interval of 1·23–11·2 μg/ml. The inhibitory effect of individual compounds (10 μm) including homovanillyl alcohol (HVA) followed this order: OleA>LU>HT = TY = QU = HVA, while AP was inactive. All the extracts inhibited cAMP-PDE, while no significant inhibition of PDE5A1 (50μg/ml) was observed. All the flavonoids and OleA inhibited cAMP-PDE, whereas HT, TY, HVA (100 μm) were inactive. Olive oil extracts and part of its phenolic constituents inhibit platelet aggregation; cAMP-PDE inhibition is one mechanism through which olive oil phenols inhibit platelet aggregation.
Natural history of suicidal behaviors in a population-based sample of young adults
Authors: BREZO JELENA , PARIS JOEL , BARKER EDWARD DYLAN , TREMBLAY RICHARD , VITARO FRANK , ZOCCOLILLO MARK , HÉBERT MARTINE , TURECKI GUSTAVO
Published: October 2007

Background

Suicidal behaviors in young individuals represent an important public health problem. Understanding their natural history and relationships would therefore be of clinical and research value. In this study, we examined the natural histories of several suicidal behaviors and investigated two conceptual models of suicidality (dimensional and categorical) in the context of adolescent and adult-onset suicide attempts.

Method

Participants were members of a prospectively studied, representative, population-based school cohort followed since age 6 (n=3017) through mid-adolescence (n=1715) to their early twenties (n=1684). Outcome measures included suicidal ideation, attempts and completions.

Results

Approximately one in 500 individuals died by suicide. About 33% had suicidal ideas and 9·3% made at least one suicide attempt. Over half (4·9%) of the self-reported attempters made their first attempt before age 18. With the exception of current suicidal ideas, non-fatal suicidal behaviors were more prevalent in females. In general, parental and cross-sectional self-reports underestimated suicidality rates. Aikaike (AIC) and Bayesian (BIC) information criteria suggested the ordinal model, and dimensional conceptualization of suicide attempts of different onset age, to be more optimal than its multinomial/categorical counterpart (ordinal: AIC 567.55, BIC 635.67; multinomial: AIC 616.59, BIC 723.83). Both models, nevertheless, identified five common factors of relevance to suicidal diathesis: gender, disruptive disorders, childhood anxiousness and abuse, and suicidal thoughts.

Conclusions

Non-fatal suicidal behaviors in adolescents and young adults are more common than suggested by cross-sectional studies and parental reports. The dimensional model may be more useful in explaining the relationship of suicide attempts of different age of onset.
The contribution of gene–environment interaction to psychopathology
Authors: Thapar Anita , Harold Gordon , Rice Frances , Langley Kate , O'Donovan Michael
Published: October 2007

The study of gene–environment interaction (G × E) constitutes an area of significant social and clinical significance. Different types of research study designs are being used to investigate the contribution of G × E to psychopathology, although the term G × E has also been used and interpreted in different ways. Despite mixed evidence that G × E contributes to psychopathology, some promising and consistent findings are emerging. Evidence is reviewed in relation to depression, antisocial behavior, schizophrenia, and attention-deficit/hyperactivity disorder. Although findings from various research designs have different meaning, interestingly much of the evidence with regard to the contribution of G × E that has arisen from twin and adoption studies has been for antisocial behavior and depression. It is for these same forms of psychopathology that molecular genetic evidence of G × E has also been most convincing. Finally, current and anticipated methodological challenges and implications for future research in this area are considered.
Genetic expression outside the skin: Clues to mechanisms of Genotype × Environment interaction
Authors: Reiss David , Leve Leslie D.
Published: October 2007

The rapidly moving study of Gene × Environment interaction (G × E) needs interim conceptual tools to track progress, integrate findings, and apply this knowledge to preventive intervention. We define two closely related concepts: the social mediation of the expression of genetic influences and the interaction between the entire genotype and the social environment (G × E). G × E, the primary focus of this report, assesses individual differences in the full genotype using twin, sibling, and adoption designs and, for the most part, employs fine-grained analyses of relational processes in the social environment. In comparison, studies of Allele × Environment interaction assess the influence on development of one or more measured polymorphisms as modified by environmental factors. G × E studies build on work showing how the social environment responds to genetic influences and how genetic influences shape the social environment. Recent G × E research has yielded new insight into variations in the sensitivity of the social environment to genotypic influences and provides clues to the specificity and timing of these environmental responses that can be leveraged to inform preventive interventions aimed at reducing genetic risk for problem behavior.
Gene × Environment interactions in speech sound disorder predict language and preliteracy outcomes
Authors: McGrath Lauren M. , Pennington Bruce F. , Willcutt Erik G. , Boada Richard , Shriberg Lawrence D. , Smith Shelley D.
Published: October 2007

Few studies have investigated the role of gene × environment interactions (G × E) in speech, language, and literacy disorders. Currently, there are two theoretical models, thediathesis–stress modeland thebioecological model, that make opposite predictions about the expected direction of G × E, because environmental risk factors may either strengthen or weaken the effect of genes on phenotypes. The purpose of the current study was to test for G × E at two speech sound disorder and reading disability linkage peaks using a sib-pair linkage design and continuous measures of socioeconomic status, home language/literacy environment, and number of ear infections. The interactions were tested using composite speech, language, and preliteracy phenotypes and previously identified linkage peaks on 6p22 and 15q21. Results showed five G × E at both the 6p22 and 15q21 locations across several phenotypes and environmental measures. Four of the five interactions were consistent with the bioecological model of G × E. Each of these four interactions involved environmental measures of the home language/literacy environment. The only interaction that was consistent with the diathesis–stress model was one involving the number of ear infections as the environmental risk variable. The direction of these interactions and possible interpretations are explored in the discussion.
Exploring interactive effects of genes and environments in etiology of individual differences in reading comprehension
Authors: Grigorenko Elena L. , Deyoung Colin G. , Getchell Marya , Haeffel Gerald J. , Klinteberg Britt A.F. , Koposov Roman A. , Oreland Lars , Pakstis Andrew J. , Ruchkin Vladislav V. , Yrigollen Carolyn M.
Published: October 2007

It is established that reading and reading-related processes are heritable; genes thus play an important role in the foundation of individual differences in reading. In this article, we focus on one facet of reading–comprehension. Comprehension is a higher order cognitive skill that requires many other cognitive processes for it to unfold completely and successfully. One such process is executive functioning, which has been associated with genetic variation in the catechol-O-methyltransferase (COMT) gene. Genotypes and haplotypes of four single nucleotide polymorphisms in COMT were investigated in 179 incarcerated adolescent delinquents. Four hierarchical logistic regression models predicting the presence/absence of comprehension difficulties were fitted to the data; genetic variation in COMT and the presence/absence of maternal rejection were investigated as main effects and as effects acting interactively. Three out of four interaction terms were found to be important predictors of individual differences in comprehension. These findings were supported by the results of the haplotype analyses, in which the four investigated polymorphisms were considered simultaneously.
Evidence for a gene–gene interaction in predicting children's behavior problems: Association of serotonin transporter short and dopamine receptor D4 long genotypes with internalizing and externalizing behaviors in typically developing 7-year-olds
Authors: Schmidt Louis A. , Fox Nathan A. , Hamer Dean H.
Published: October 2007

Recent work on the molecular genetics of complex traits in typical and atypical human development has focused primarilyon associations of single genes with behavior. Disparate literature suggests that the presence of one or two copies of the short allele of the serotonin transporter (5-HTT) gene and the long allele (7-repeat allele) version of the dopamine receptor D4 (DRD4) gene predicts internalizing- and externalizing-related behaviors, respectively. Apparently for the first time in the extant literature, we report a gene–gene statistical interaction on behavior problems in a group of typically developing children at age 7. DNA was extracted from buccal cells collected from 108 children and genotyped for short and long alleles of the5-HTTgene and the short (2–5 repeats) versus long (6–8 repeats) allele of theDRD4gene. Mothers completed the Child Behavior Checklist. As predicted, children with one or two copies of the short allele of the5-HTTgeneandthe long allele version of theDRD4gene exhibited significantly more internalizing and externalizing behaviors at age 7 than children with other combinations of the5-HTTandDRD4short and long genotypes. As well, children with the5-HTTlongand DRD4long genotypes had the lowest reported scores on internalizing and externalizing behaviors at age 7, suggesting that the presence of the5-HTTlong genotype may serve as a protective factor against these behaviors in children with the longDRD4genotype. Implications of these findings for understanding cumulative biological risk and protective factors in childhood behavior problems and psychopathology are discussed.
Assessing gene–environment interactions on anxiety symptom subtypes across childhood and adolescence
Authors: Lau Jennifer Y. F. , Gregory Alice M. , Goldwin Michelle A. , Pine Daniel S. , Eley Thalia C.
Published: October 2007

Consistent evidence shows both genetic and stress-related risks on child and adolescent anxiety, yet few studies have considered the degree to which genetic effects are moderated by stress (gene–environment interaction). We used longitudinal data from both a child and adolescent sample of twins to examine three novel issues on the presence of gene–environment interaction on anxiety symptoms. First, we assessed moderation of genetic risks on anxiety symptoms by negative life events in each age group. Second, by distinguishing between “stable” and “age-specific” genetic factors, we explored the continuity of gene–environment interaction across time and/or its emergence at specific ages. Third, we compared the presence of gene–environment interaction across different symptom types (general, panic, social, and separation). Genetic effects on separation anxiety symptoms in childhood (mean age = 8 years, 6 months) and panic anxiety symptoms in adolescence (mean age = 15 years) increased across independent negative life events. Shared environmental effects on separation anxiety symptoms and nonshared environmental effects on general anxiety symptoms in adolescence were also moderated by negative life events. We interpret these preliminary findings tentatively in the context of gene–environment interaction on anxiety in general, and on early separation and later panic anxiety in particular.
Interactions of child maltreatment and serotonin transporter and monoamine oxidase A polymorphisms: Depressive symptomatology among adolescents from low socioeconomic status backgrounds
Authors: Cicchetti Dante , Rogosch Fred A. , Sturge-Apple Melissa L.
Published: October 2007

Child maltreatment and polymorphisms of the serotonin transporter (5-HTT) and monoamine oxidase A (MAOA) genes were examined in relation to depressive symptomatology. Adolescents (Mage = 16.7 years) from low socioeconomic backgrounds with a history of child maltreatment (n= 207) or no such history (n= 132) were interviewed and provided buccal cells for genetic analysis. Gene × environment interactions were observed. Heightened depressive symptoms were found only among extensively maltreated youth with lowMAOAactivity. Among comparably maltreated youth with highMAOAactivity, self-coping strategies related to lower symptoms. Sexual abuse and the5-HTT short/shortgenotype predicted higher depression, anxiety, and somatic symptoms. This Gene × Environment interaction was further moderated byMAOAactivity level. The results highlight the protective functions of genetic polymorphisms and coping strategies in high risk youth and offer direction for understanding resilience and its promotion from a multiple levels of analysis perspective.
Mendelian randomization: A novel test of the gateway hypothesis and models of gene–environment interplay
Authors: Irons Daniel E. , McGue Matt , Iacono William G. , Oetting William S.
Published: October 2007

To determine if drinking behavior in adolescence provides a “gateway” leading to the misuse of other psychoactive substances and antisocial behavior, we genotyped 180 Asian adolescent adoptees to determine if they inherited the deficient from of the aldehyde dehydrogenase 2 (ALDH2) enzyme that is important in the metabolism of alcohol. Based on the gateway model, we hypothesized that those with normal enzyme activity (70% of the sample) who began to misuse alcohol would also misuse other drugs and display antisocial tendencies. Those with the enzyme deficiency (30%), because they experience unpleasant side effects associated with drinking, were expected to show less evidence of alcohol misuse and thus be less likely to progress to the misuse of other substances or engage in antisocial acts. Consistent with previous research, we found that ALDH2 deficiency was significantly associated with lower rates of drinking and getting drunk but not with ever having tried alcohol. Contrary to the gateway model, we found no evidence that ALDH2 deficiency was associated with lower rates of nonalcohol substance use or antisociality. Finally, in an examination of factors that may moderate the impact of the metabolic protection because of ALDH2 deficiency, we identified siblings rather than parents as the major source of familial environmental effect on adolescent drinking.
Working towards ‘An Unforeseen Miracle’ Redux: Latvian Refugees in Vladivostok, 1918–1920, and in Latvia, 1943–1944
Authors: PURS ALDIS
Published: October 2007

During the First World War the survival of hundreds of thousands of Latvian refugees, dispersed across the Russian Empire, overlapped with issues of identity. Latvians in Siberia and the Far East created a refugee organisation complete with military, diplomatic and cultural programmes for themselves and their homeland. The key players attempted to recreate the same organisational trajectories and outcomes during the Second World War, under very different geopolitical conditions. This article presents new archival research and suggests new interpretations of the dynamic nature of political organisation, refugee experience and identity in Latvia through the first half of the twentieth century.
The Perils of Displacement: The Soviet Evacuee between Refugee and Deportee
Authors: MANLEY REBECCA
Published: October 2007

In the wake of the German invasion of June 1941, sixteen and a half million Soviet citizens were evacuated to the country's interior. Unlike the archetypal European refugee, the Soviet evacuee was displaced but not stateless. This article, based on previously unexamined sources from archives in Russia and Uzbekistan, examines the status of the displaced in a state in which rights were grounded in territory and the lack of fixed residence could have dire implications. More specifically, it focuses on the way in which the evacuee was conceived in relation to the ‘refugee’ and the ‘deportee’.
Displacing and Re-placing Population in the Two World Wars: Armenia and Poland Compared
Authors: GATRELL PETER
Published: October 2007

During the twentieth century Armenia and Poland alike were sites of widespread population displacement, which brought into sharp focus arguments about national ‘survival’ advanced by patriotic leaders who found in refugees the embodiment of recurrent national suffering. Population displacement also attracted external support from sympathetic foreigners and from the Armenian and Polish diaspora, who regarded it as an affront to civilisation. Among Armenians a groundswell of support for repatriation gathered momentum after both world wars, because Soviet ‘protection’ offered the most realistic chance for national survival. In contrast many Poles opted not to return to Poland after 1945, regarding the communist takeover as a betrayal of Poland's struggle for independence.