bluuebunny/crossref_metadata_2025 huggingface dataset:
Osmolyte effect on the stability and folding of a hyperthermophilic protein
Authors: Mukaiyama Atsushi , Koga Yuichi , Takano Kazufumi , Kanaya Shigenori
Published: October 2007

Proteins are known to be stabilized by naturally occurring osmolytes such as amino acids, sugars, and methylamines. Here, we examine the effect of trimethylamine‐N‐oxide (TMAO) on the conformational stability of ribonuclease HII from a hyperthermophile, Thermococcus kodakaraensis (Tk‐RNase HII), which inherently possesses high conformational stability. Heat‐ and guanidine hydrochloride‐induced unfolding experiments demonstrated that the conformational stability of Tk‐RNase HII in the presence of 0.5M TMAO was higher than that in the absence of TMAO at all examined temperatures. TMAO affected the unfolding and refolding kinetics of Tk‐RNase HII to a similar extent. These results indicate that proteins are universally stabilized by osmolytes, regardless of their robustness, and suggest a stabilization mechanism by osmolytes, caused by the unfavorable interaction of osmolytes with protein backbones in the denatured state. Our results also imply that the basic protein folding principle is not dependent on protein stability and evolution. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Large‐scale characteristics of the energy landscape in protein–protein interactions
Authors: O'Toole Nicholas , Vakser Ilya A.
Published: October 2007

Characterization of intermolecular energy landscapes in protein–protein interactions is important for understanding the mechanisms of these interactions as well as for designing better protein docking methods. A simplified representation of the landscape was used for a systematic study of its large‐scale characteristics in a large nonredundant dataset of protein complexes. The focus of the study is on the basic features of the low‐resolution energy basins and their distribution on the landscape. The results clearly show that, in general, the number of such basins is small, these basins are well formed, correlated with actual binding modes, and the pattern of basins distribution depends on the type of the complex. For docking studies, the results suggest that adequate starting points for the structural refinement are detectable by low‐resolution procedures and the number of such starting points is relatively small. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Conformational selection in silico: Loop latching motions and ligand binding in enzymes
Authors: Wong Sergio , Jacobson Matthew P.
Published: October 2007

Ligand binding frequently induces significant conformational changes in a protein receptor. Understanding and predicting such conformational changes represent an important challenge for computational biology, including applications to structure‐based drug design. We describe an approach to this problem based on the assumption that the holo state is at least transiently populated in the absence of a ligand; this hypothesis has been referred to as “conformational selection.” Here, we apply a method that tests this hypothesis on a challenging class of ligand‐induced conformational changes, which we refer to as loop latching: the closing of a loop around an active site that sequesters the ligand from solvent. The method uses a combination of replica exchange molecular dynamics and a loop prediction algorithm to generate low‐energy loop structures, and docking to select the conformation appropriate for binding a particular ligand. On a test set of six proteins, it yields loop structures including hololike conformations, generally below 2 Å RMSD from the liganded structure, for loops that span up to 15 residues. Docking serves as a stringent test of the predictions. In five of the six cases, the predicted loop conformations improve the ranks of cognate ligands relative to using the apo structure, although the results remain, in most cases, significantly worse than using a holo structure. The poses of the cognate ligands are correct in four of the six test cases, while they are correct for five of the six using a holo structure. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Engineering proteins with tunable thermodynamic and kinetic stabilities
Authors: Pey Angel L. , Rodriguez‐Larrea David , Bomke Susanne , Dammers Susanne , Godoy‐Ruiz Raquel , Garcia‐Mira Maria M. , Sanchez‐Ruiz Jose M.
Published: October 2007

It is widely recognized that enhancement of protein stability is an important biotechnological goal. However, some applications at least, could actually benefit from stability being strongly dependent on a suitable environment variable, in such a way that enhanced stability or decreased stability could be realized as required. In therapeutic applications, for instance, a long shelf‐life under storage conditions may be convenient, but a sufficiently fast degradation of the protein after it has performed the planned molecular task in vivo may avoid side effects and toxicity. Undesirable effects associated to high stability are also likely to occur in food‐industry applications. Clearly, one fundamental factor involved here is the kinetic stability of the protein, which relates to the time‐scale of the irreversible denaturation processes and which is determined to some significant extent by the free‐energy barrier for unfolding (the barrier that “separates” the native state from the highly‐susceptible‐to‐irreversible‐alterations nonnative states). With an appropriate experimental model, we show that strong environment‐dependencies of the thermodynamic and kinetic stabilities can be achieved using robust protein engineering. We use sequence‐alignment analysis and simple computational electrostatics to design stabilizing and destabilizing mutations, the latter introducing interactions between like charges which are screened out at high salt. Our design procedures lead naturally to mutating regions which are mostly unstructured in the transition state for unfolding. As a result, the large salt effect on the thermodynamic stability of our consensus plus charge‐reversal variant translates into dramatic changes in the time‐scale associated to the unfolding barrier: from the order of years at high salt to the order of days at low salt. Certainly, large changes in salt concentration are not expected to occur in biological systems in vivo. Hence, proteins with strong salt‐dependencies of the thermodynamic and kinetic stabilities are more likely to be of use in those cases in which high‐stability is required only under storage conditions. A plausible scenario is that inclusion of high salt in liquid formulations will contribute to a long protein shelf‐life, while the lower salt concentration under the conditions of the application will help prevent the side effects associated with high‐stability which may potentially arise in some therapeutic and food‐industry applications. From a more general viewpoint, this work shows that consensus engineering and electrostatic engineering can be readily combined and clarifies relevant aspects of the relation between thermodynamic stability and kinetic stability in proteins. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Prediction of RNA binding sites in a protein using SVM and PSSM profile
Authors: Kumar Manish , Gromiha M. Michael , Raghava G. P. S.
Published: October 2007

RNA‐binding proteins (RBPs) play key roles in post‐transcriptional control of gene expression, which, along with transcriptional regulation, is a major way to regulate patterns of gene expression during development. Thus, the identification and prediction of RNA binding sites is an important step in comprehensive understanding of how RBPs control organism development. Combining evolutionary information and support vector machine (SVM), we have developed an improved method for predicting RNA binding sites or RNA interacting residues in a protein sequence. The prediction models developed in this study have been trained and tested on 86 RNA binding protein chains and evaluated using fivefold cross validation technique. First, a SVM model was developed that achieved a maximum Matthew's correlation coefficient (MCC) of 0.31. The performance of this SVM model further improved the MCC from 0.31 to 0.45, when multiple sequence alignment in the form of PSSM profiles was used as input to the SVM, which is far better than the maximum MCC achieved by previous methods (0.41) on the same dataset. In addition, SVM models were also developed on an alternative dataset that contained 107 RBP chains. Utilizing PSSM as input information to the SVM, the training/testing on this alternate dataset achieved a maximum MCC of 0.32. Conclusively, the prediction performance of SVM models developed in this study is better than the existing methods on the same datasets. A web server ‘Pprint’ was also developed for predicting RNA binding residues in a protein sequence which is freely available at http://www.imtech.res.in/raghava/pprint/. Proteins 2008. © 2007 Wiley‐Liss, Inc.
The peculiar structural features of kiwi fruit pectin methylesterase: Amino acid sequence, oligosaccharides structure, and modeling of the interaction with its natural proteinaceous inhibitor
Authors: Ciardiello M. Antonietta , D'Avino Rossana , Amoresano Angela , Tuppo Lisa , Carpentieri Andrea , Carratore Vito , Tamburrini Maurizio , Giovane Alfonso , Pucci Piero , Camardella Laura
Published: October 2007

Pectin methylesterase (PME) from kiwi fruit (Actinidia deliciosa) is a glycoprotein, showing an apparent molecular mass of 50 kDa upon size exclusion chromatography and SDS‐PAGE. The primary structure, elucidated by direct sequencing of the protein, comprises 321 amino acid residues providing a molecular mass of 35 kDa. The protein has an acetylated Thr residue at the amino terminus and five N‐glycosylation consensus sequences, four of which are actually glycosylated. A careful investigation of the oligosaccharide structures demonstrated that PME glycans belong to complex type oligosaccharides essentially consisting of xylosylated polyfucosylated biantennary structures. Alignment with known mature plant PME sequences indicates that the postulated active site residues are conserved. Kiwi PME activity is inhibited following the interaction with the proteinaceous inhibitor PMEI, isolated from the same source. Gel‐filtration experiments show that kiwi PME/PMEI complex is stable in a large pH range and dissociates only at pH 10.0. Modeling of the interaction with the inhibitor was performed by using the crystal structure of the complex between kiwi PMEI and tomato PME as a template. The model shows that the binding site is the same reported for tomato PME. However, additional salt link interactions are found to connect the external loops of kiwi PME to PMEI. This finding may explain the higher pH stability of the complex formed by the two kiwi proteins respect to that formed by PMEI and tomato PME. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Altering the laccase functionality by in vivo assembly of mutant libraries with different mutational spectra
Authors: Zumárraga Miren , Camarero Susana , Shleev Sergey , Martínez‐Arias Arturo , Ballesteros Antonio , Plou Francisco J. , Alcalde Miguel
Published: October 2007

The generation of diversity for directed protein evolution experiments shows an important bottleneck in the in vitro random mutagenesis protocols. Most of them are biased towards specific changes that eventually confer a predicted and conservative mutational spectrum, limiting the exploration of the vast protein space. The current work describes a simple methodology to in vivo recombine mutant libraries with different nucleotide bias created by in vitro methods. This in vivo assembly was based on the accurate physiology of Saccharomyces cerevisiae, which as host, provided its high homologous recombination frequency to shuffle the libraries in a nonmutagenic way. The fungal thermophilic laccase from Myceliophthora thermophila expressed in S. cerevisiae was submitted to this protocol under the selective pressure of high concentrations of organic solvents. Mutant 2E9 with ∼3‐fold better kinetics than parent type showed two consecutive amino acid changes (G614D ‐GGC/GAC‐ and E615K ‐GAG/AAG‐) because of the in vivo shuffling of the mutant libraries. Both mutations are located in the C‐terminal tail that is specifically processed at the Golgi during the maturation of the protein by the Kex2 protease. Notoriously, the oxygen consumption at the T2/T3 trinuclear copper cluster was altered and the catalytic copper at the T1 site was perturbed showing differences in its redox potential and geometry. The change in the isoelectric point of C‐terminal extension upon mutations seems to affect the folding of the protein at the posttranslational processing steps providing new insights in the significance of the C‐terminal tail for the functionality of the ascomycete laccases. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Design and analysis of structure–activity relationship of novel antimicrobial peptides derived from the conserved sequence of cecropin
Authors: Hao Gang , Shi Yong‐Hui , Han Jing‐Hui , Li Qi‐Hui , Tang Ya‐Li , Le Guo‐Wei
Published: October 2007

We have de novo designed four antimicrobial peptides AMP‐A/B/C/D, the 51‐residues peptides, which are based on the conserved sequence of cecropin. In the present study, the four peptides were chemically synthesized and their activities assayed. Their secondary structure, amphipathic property, electric field distribution and transmembrane domain were subsequently predicted by bioinformatics tools. Finally, the structure–activity relationship was analyzed from the results of activity experiments and prediction. The results of activity experiments indicated that AMP‐B/C/D clearly possessed excellent broad‐spectrum activity against bacteria, whereas AMP‐A was almost inactive against most of the bacterial strains tested. AMP‐B/C/D showed more potent activity against Gram‐positive bacteria than against Gram‐negative bacteria. By utilizing bioinformatics analysis tools, we found that the secondary structure of the four cation peptides was mainly α‐helix, and the result of CD spectrum also displayed that all the peptides had considerable α‐helix in the presence of either 50% TFE or SDS micelles. AMP‐C showed much better activity than other peptides against most of the bacteria tested, owing to its remarkable cation property and the amphipathic character of its N‐terminal. The study of structure–activity relationship of the designed peptides confirmed that amphipathic structure and high net positive charge were prerequisites for maintaining their activities. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Synthesis and ex vivo profiling of chemically modified cytomegalovirus CMVpp65 epitopes
Authors: Jones Matthew A. , Notta Jatinder K. , Cobbold Mark , Palendira Mainthan , Hislop Andrew D. , Wilkie John , Snaith John S.
Published: October 2007

The effect of substituting unnatural hydrophobic amino acids into the critical MHC binding residues of an HLA‐A*0201‐restricted cytomegalovirus CMVpp65 epitope, NLVPMVATV, has been investigated. A new set of peptides containing the amino acids tert‐butyl glycine (Tgl), cyclohexyl glycine (Chg), neo‐pentyl glycine (Npg), cyclohexyl alanine (Cha) and cyclo leucine (Cyl), at either position 2, to mimic Leu, or position 9, to mimic Val, have been synthesised. Immunological profiling using class I MHC stabilisation assays to assess MHC binding affinity, and enzyme‐linked immunospot (ELISPOT) assays to assess the ability of the modified peptides to re‐stimulate a specific cytotoxic T‐lymphocyte (CTL) response, compared to the native epitope, have been performed. It was found that the majority of the unnatural substitutions resulted in a decrease in either HLA‐A*0201 binding affinity or cytotoxic T‐cell activity. However, the HLA‐A*0201 binding affinity was unrelated to the ability to re‐stimulate a T‐cell response. Minimisation and molecular dynamics studies proved helpful in dissecting the ELISPOT responses. Two principal peptide binding modes were found by minimisation, designated kinked and straight. Peptides that bound in a kinked conformation were poor at re‐stimulating a T‐cell response. Of the peptides that bound in a straight conformation, molecular dynamics (MD) simulations revealed that those capable of re‐stimulating the strongest responses had the greatest degree of flexibility (as determined by RMSD values across the MD simulation) around the P6 residue, one of the residues important for T‐cell receptor recognition. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Structure–activity relationships for the cardiotropic action of the Led‐NPF‐I peptide in the beetles Tenebrio molitor and Zophobas atratus
Authors: Marciniak Paweł , Grodecki Sebastian , Konopińska Danuta , Rosiński Grzegorz
Published: October 2007

We have examined the effects of the Led‐NPF‐I peptide (Ala‐Arg‐Gly‐Pro‐Gln‐Leu‐Arg‐Leu‐Arg‐Phe‐amide) and a series of ten analogues on the heart contractile activity of Tenebrio molitor and Zophobas atratus, and the structure–activity relationships for cardioactive action of Led‐NPF‐I were established. A video microscopy technique and computer‐based method of data acquisition and analysis were used to study the action of the peptides on continuously perfused heart preparations. Cardiac activity was progressively inhibited by Led‐NPF‐I when the peptide concentrations were increased from 10−9 to 10−5 M. Substitution of the L‐proline residue at position 4 of the native peptide with hydroxyproline, valine or D‐proline caused a loss of cardioinhibitory activity. Also, replacement of arginine residues at all three positions 2, 7 and 9 with another basic amino acid histidine, reduces cardioinhibitory action of Led‐NPF‐I. Some modifications of the C‐terminal residues, as the Phe(4‐NO2)‐, Phe(4‐NH2)‐ and Phe(4‐NMe2)‐analogues, resulted in agonistic peptides with biological activity similar to that of the native peptide. However, three other C‐terminal analogues tested [Tyr10]‐, [D‐Phe10]‐Led‐NPF‐I, and Ala‐Arg‐Gly‐Pro‐Gln‐Leu‐Arg‐Leu‐Arg‐Phe‐OH were inactive in the heart bioassay, which suggests that this end of the amino acid chain may play an important role in bioactivity and interaction of the native peptide with its receptor on the myocardium. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
A Mini Review of Mammalian Toxicity (Q)SAR Models
Authors: Tsakovska Ivanka , Lessigiarska Iglika , Netzeva Tatiana , Worth Andrew P.
Published: October 2007

This paper is based on an in‐depth review performed by the European Chemicals Bureau of the European Commission's Joint Research Centre in support of the development of technical guidance for the implementation of the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) legislation, and is one of a series of minireviews in this journal. Compared with the QSAR modelling of ecotoxicity, the modelling of mammalian toxicity is more complicated. This is reflected by the relatively small number of QSAR studies on mammalian toxicity published in the literature. The main problem is related to wide variations in the accuracy of the in vivo data, in the organisms used, and also in the complexity and poor understanding of the mechanisms involved, especially for long‐term effects. Nevertheless, the efforts already made to develop QSAR models for mammalian toxicity demonstrate the usefulness of the approach not only for predictive purposes but also for a better understanding of the multiple mechanisms involved in the toxicity. However, there is a need to better characterise existing models in accordance with the OECD QSAR validation principles, to develop new models, and to investigate the applicabilities of individual models in the regulatory context, such as for the purposes of the REACH legislation.
Analysis of longitudinal laboratory data in the presence of common selection mechanisms: A view toward greater emphasis on pre‐marketing pharmaceutical safety
Authors: Schildcrout Jonathan S. , Jenkins Cathy A. , Ostroff Jack H. , Gillen Daniel L. , Harrell Frank E. , Trost Donald C.
Published: October 2007

Pharmaceutical safety has received substantial attention in the recent past; however, longitudinal clinical laboratory data routinely collected during clinical trials to derive safety profiles are often used ineffectively. For example, these data are frequently summarized by comparing proportions (between treatment arms) of participants who cross pre‐specified threshold values at some time during follow‐up. This research is intended, in part, to encourage more effective utilization of these data by avoiding unnecessary dichotomization of continuous data, acknowledging and making use of the longitudinal follow‐up, and combining data from multiple clinical trials. However, appropriate analyses require careful consideration of a number of challenges (e.g. selection, comparability of study populations, etc.). We discuss estimation strategies based on estimating equations and maximum likelihood for analyses in the presence of three response history‐dependent selection mechanisms: dropout, follow‐up frequency, and treatment discontinuation. In addition, because clinical trials' participants usually represent non‐random samples from target populations, we describe two sensitivity analysis approaches. All discussions are motivated by an analysis that aims to characterize the dynamic relationship between concentrations of a liver enzyme (alanine aminotransferase) and three distinct doses (no drug, low dose, and high dose) of an nk‐1 antagonist across four Phase II clinical trials. Copyright © 2007 John Wiley & Sons, Ltd.
Penile fracture: diagnosis and management
Authors: Masarani M. , Dinneen M.
Published: October 2007

Penile fracture is an uncommon urological emergency that can have significant complications. Patients usually present to the accident and emergency department, but may seek advice from GPs. Immediate surgical repair is the treatment of choice, with fewer complications, shorter hospital stays, better outcome and increased patient satisfaction compared with conservative therapy. Copyright © 2007 Wiley Interface Ltd
Genetic improvement of the Kenya Dual Purpose Goat: Influence of economic values and prospects for a practical breeding programme
Authors: Bett RC , Kosgey IS , Bebe BO , Kahi AK
Published: October 2007

This study determined the influence of economic values on genetic gain and explored the prospects for a practical breeding programme for the Kenya Dual Purpose Goat. The economic values for production traits (live weight (direct), live eight (maternal), milk yield and consumable meat) and functional traits (doe weight, number of kids weaned, kidding frequency and rate, doe weaning and survival rate, pre‐ and post‐weaning survival rate, and residual feed intake for yearlings and does) in the breeding goal addressed the smallholder production system. There was a potential for genetic progress in the breeding‐goal traits even by using simple selection criteria. In the breeding programme, the predicted genetic gains per year for milk yield were 0.737 and 0.047 kg for the sires of sires and dams of dams pathways, respectively. The required population size of 2500 does in the nucleus would be attained within ten years after the start of the breeding programme. The availability of a simple breeding programme for the Kenya Dual Purpose Goat offers enormous opportunities for private large‐scale flocks or for flocks owned by parastatal or research organisations to exploit genetic and economic benefits from the breeding programme. Copyright © 2007 John Wiley & Sons, Ltd
Development and Risk Behavior Among African American, Caucasian, and Mixed‐race Adolescents Living in High Poverty Inner‐city Neighborhoods
Authors: Bolland John M. , Bryant Chalandra M. , Lian Bradley E. , McCallum Debra M. , Vazsonyi Alexander T. , Barth Joan M.
Published: October 2007

Youths growing up in low‐income inner‐city neighborhoods are at substantial risk for initiating substance use, violent behavior, and sexual intercourse at early ages; these risk behaviors continue at comparatively high rates through adolescence. Hopelessness has been implicated as a risk factor for these behaviors. In this paper, we consider how race influences this process. African Americans form a demographic minority within the United States, but they are often the majority within inner‐city neighborhoods. For Caucasians, the opposite typically holds. Mixed‐race populations form a minority within both contexts. Using longitudinal data, we examine the relationship between race and risk behaviors in several impoverished inner‐city neighborhoods where African Americans form the distinct majority and Caucasians and people of mixed racial heritage form a small minority. We also consider how race moderates the relationship between hopelessness and risk behavior. Our findings show that compared to Caucasian or mixed‐race adolescents, African American adolescents are less likely to engage in risk behaviors, and that hopelessness has a less important impact on their behaviors.
Density effects on organs in self‐thinning Pinus densiflora Sieb. et Zucc. stands
Authors: Xue Li , Hagihara Akio
Published: October 2007

Although much research on the density effect in nonself‐thinning populations has been conducted, there has been very little research on density effects in self‐thinning populations. Furthermore, the density effect of plant organs in self‐thinning populations is little reported. The present study analyzed the yield–density (Y–D) effects on organs, such as stem, branch and leaf, together with that on stands of self‐thinning Pinus densiflora Sieb. et Zucc.. The stand yield‐ and organ Y–D effects were well described by reciprocal and parabolic equations, respectively, throughout the experiment. The value of coefficient B in the reciprocal equation decreased monotonically with increasing stand age and became significantly closer to zero at the end of experiment (33‐year‐old stand), indicating that the constant final stand yield was established regardless of the density realized. The value of the relative growth coefficient h in the allometric equation between mean organ weight and mean aboveground weight was significantly smaller than 1.0 for stem, indicating that stem yield increases monotonically with increasing realized density. The h‐value was significantly larger than 1.0 for branch throughout the experiment, and for leaf except at 33 years old, indicating that optimum densities exist. The h‐value for leaf was not significantly different from 1.0 at 33 years old, indicating that the leaf yield reached a constant level regardless of realized density. The constant final leaf yield was established at almost the same growth stage as the establishment of constant final stand yield.
Direct Method of Preparation of Dodecanesulfonamide Derivatives and Some Surface Properties
Authors: Mousli R. , Tazerouti Amel
Published: October 2007

Alkanesulfonamide compounds are known as surfactants because of the presence of –SO2NH– function in their molecule. Thus, they are used in many formulations in the chemical and textile industries and also as inhibitors of corrosion. Generally, sulfonamide derivatives are prepared using sulfonyl chlorides as the raw material. The methods often described in the literature involve the use of ammonia gas and pressure. A simple and direct method to prepare pure alkanesulfonamide derivatives possessing good surface properties is presented in this work. Thus, n‐dodecanesulfonyl chlorides obtained by photochemical sulfochlorination of n‐dodecane under visible light using sulfuryl chloride were separated from the reaction mixture. These sulfonyl chlorides, a mixture of primary and secondary isomers, were transformed in one step into N‐ethyldodecanesulfonamides, N‐ethanoldodecanesulfonamides and the salts of dodecanesulfonamidoacetic acid. After purification on chromatographic column, the six position isomers of these sulphonamide derivatives were analysed and well separated by gas phase chromatography using a nonpolar column. Then, gas phase chromatography analysis coupled to mass spectrometry using electronic impact (GC/MS/IE) was performed to identify the different position isomers. The primary isomers of sulphonamide derivatives were identified by crossed injection of the compounds obtained by synthesis from the 1‐chlorododecane using the Grignard reagent, and identified by IR,1H‐ and 13C‐RMN, elementary analysis and GC/MS/IE. Some physico‐chemical properties of these sulphonamide derivatives were examined. The variation of surface tension versus the concentration of both primary and secondary sulphonamide derivatives were studied, and the critical micellar concentration was determined for the compounds showing surface activity. The foaming power was also determined by the Bartsch method, and the results obtained were compared to those of a commercial surfactant, the linear alkylbenzenesulfonate. The stability of the foam formed was also evaluated.
Preoperative Fasting: Knowledge and Perceptions
Authors: Baril Patrice , Portman Harriet
Published: October 2007

PREOPERATIVE PATIENT FASTING is an essential element of the patient preparation process, but patients may be fasting for excessive lengths of time.

INVESTIGATORS AT ONE FACILITY used semi‐structured interviews to explore the knowledge and beliefs of patients, nurses, and anesthesia care providers regarding the practice of preoperative patient fasting.

FINDINGS INDICATE that some patients had excessive fasting times, and practitioners had erroneous perceptions about patient knowledge regarding the rationale for fasting and compliance with instructions. Clinicians expressed concern about the effects of excessive fasting but were reluctant to relax the policy.
Reviews
Authors: Van Wicklin Sharon Ann , Austin Elizabeth A. , Strebeck Jamie , Pelletier Lori A.
Published: October 2007

Daily Miracles: Stories and Practices of Humanity and Excellence in Health CareAlan Briskin and Jan Boller 2006, 66 pages $13.95 softcover

Women's Health Concerns Sourcebook second edition, Amy L. Sutton, Ed, 2004, 746 pages $78 hardcover

Acute & Chronic Wounds: Current Management Concepts third edition, Ruth A. Bryant and Denise P. Nix, 2007, 704 pages $59.95 hardcover

Getting Your Way Every Day: Mastering the Lost Art of Pure Persuasion Alan Axelrod, 2006, 304 pages, $17.95 softcover
Biometric and developmental gene–environment interactions: Looking back, moving forward
Authors: Tabery James
Published: October 2007

A history of research on gene–environment interaction (G × E) is provided in this article, revealing the fact that there have actually been two distinct concepts of G × E since the very origins of this research. R. A. Fisher introduced what I call thebiometricconcept of G × E (G × EB), whereas Lancelot Hogben introduced what I call thedevelopmentalconcept of G × E (G × ED). Much of the subsequent history of research on G × E has largely consisted of the separate legacies of these separate concepts, along with the (sometimes acrimonious) disputes that have arisen time and again when employers of each have argued over the appropriate way to conceptualize the phenomenon. With this history in place, more recent attempts to distinguish between different concepts of G × E are considered, paying particular attention to the commonly made distinction between “statistical interaction” and “interactionism,” and Michael Rutter's distinction between statistical interaction and “the biological concept of interaction.” I argue that the history of the separate legacies of G × EBand G × EDbetter supports Rutter's analysis of the situation and that this analysis best paves the way for an integrative relationship between the various scientists investigating the place of G × E in the etiology of complex traits.
Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm
Authors: Spinelli Simona , Schwandt Melanie L. , Lindell Stephen G. , Newman Timothy K. , Heilig Markus , Suomi Stephen J. , Higley J. Dee , Goldman David , Barr Christina S.
Published: October 2007

Human studies have suggested an association between a variable length polymorphism in the serotonin transporter gene promoter region and vulnerability to anxiety and depression. Relative to the long (l) allele, the short (s) allele increases the risk of developing depression in individuals exposed to stressful life events. An orthologue of the human variant is present in rhesus macaques and allows for studies in animals exposed to stress. Here, we used an established model of early life stress exposure, in which rhesus macaques are raised without adults in a group of peers (peer-only reared [PR]), or with their mothers. At 6 months of age, animals were subjected to 4-day long social separations for 4 consecutive weeks, with 3 days of reunion in between. Data were collected during both the acute (Day 1) and chronic phases (Days 2–4) of separation. Behavioral factors were separately extracted for each phase of separation. For acute separation, the behavioral factors generated were despair and behavioral pathology and, for the chronic phase despair, agitation, and behavioral pathology. During both phases of social separation, PR l/s animals were more likely to exhibit pathological behaviors, whereas PR l/l monkeys show higher levels of despair compared to the other three groups. These findings indicate that early stress affects the behavioral response to separation differently as a function of recombinant human serotonin transporter linked polymorphic repeat genotype and suggest that carriers of the s allele are not only more anxious but may also be more vulnerable to developing behavioral pathology in the face of chronic adversity.
Meta-analysis of gene–environment interactions in developmental psychopathology
Authors: Taylor Alan , Kim-Cohen Julia
Published: October 2007

As studies of measured gene–environment interactions (G × E) in developmental psychopathology gain momentum, methods for systematically and quantitatively summarizing effects across multiple studies are urgently needed. Meta-analyses of G × E findings are critical for evaluating the overall statistical and theoretical significance of any given G × E based on cumulative and systematically combined knowledge. Although meta-analytic methods for the combination of study findings based on single effect measures such as odds ratios and mean differences are well established, equivalent methods for the meta-analysis of studies investigating interactions are not well developed. This article describes one simple approach to the meta-analysis of G × E effects using, as a contemporaneous example, the interaction of the monoamine oxidase A (MAOA) gene and the impact of childhood maltreatment on risk for developing antisocial behavior.
Parenting quality interacts with genetic variation in dopamine receptor D4 to influence temperament in early childhood
Authors: Sheese Brad E. , Voelker Pascale M. , Rothbart Mary K. , Posner Michael I.
Published: October 2007

We examined the influence of a common allelic variation in the dopamine receptor D4 (DRD4) gene and caregiver quality on temperament in early childhood. Children 18–21 months of age were genotyped for the DRD4 48 base pair tandem repeat polymorphism, which has been implicated in the development of attention, sensation seeking, and attention-deficit/hyperactivity disorder. The children also interacted with their caregiver for 10 min in a laboratory setting, and these videotaped interactions were coded for parenting quality using an observational rating procedure. The presence of the DRD4 7-repeat allele was associated with differences in the influence of parenting on a measure of temperamental sensation seeking constructed from caregiver reports on children's activity level, impulsivity, and high-intensity pleasure. Children with the 7-repeat allele were influenced by parenting quality, with lower quality parenting associated with higher levels of sensation seeking; children without the 7-repeat allele were uninfluenced by parenting quality. Differences between alleles were not related to the child's self-regulation as assessed by the effortful control measure. Previous studies have indicated that the 7-repeat allele is under positive selective pressure, and our results are consistent with the hypothesis that the DRD4 7-repeat allele increased children's sensitivity to environmental factors such as parenting. This study shows that genes influence the relation between parenting and temperament in ways that are important to normal development and psychopathology.
Bidirectional genetic and environmental influences on mother and child behavior: The family system as the unit of analyses
Authors: Mills-Koonce W. Roger , Propper Cathi B. , Gariepy Jean-Louis , Blair Clancy , Garrett-Peters Patricia , Cox Martha J.
Published: October 2007

Family systems theory proposes that an individual's functioning depends on interactive processes within the self and within the context of dyadic family subsystems. Previous research on these processes has focused largely on behavioral, cognitive, and psychophysiological properties of the individual and the dyad. The goals of this study were to explore genetic and environmental interactions within the family system by examining how the dopamine receptor D2 gene (DRD2) A1+ polymorphism in mothers and children relates to maternal sensitivity, how maternal and child characteristics might mediate those effects, and whether maternal sensitivity moderates the association between DRD2 A1+ and child affective problems. Evidence is found for an evocative effect of child polymorphism on parenting behavior, and for a moderating effect of child polymorphism on the association between maternal sensitivity and later child affective problems. Findings are discussed from a family systems perspective, highlighting the role of the family as a context for gene expression in both mothers and children.
Gene–environment interactions reexamined: Does mother's marital stability interact with the dopamine receptor D2 gene in the etiology of childhood attention-deficit/hyperactivity disorder?
Authors: Waldman Irwin D.
Published: October 2007

Potential candidate Gene × Environment interactions in the etiology of childhood attention-deficit/hyperactivity disorder (ADHD) are examined between the dopamine receptor D2 gene (DRD2) and putative family environmental risk factors that reflect mothers' marital stability. Specifically, interactions were tested between DRD2 and mothers' marital status, number of marriages or cohabiting relationships, and age at first marriage. Moderate relations were found among the marital stability measures, and mother's marital status and number of marriages or cohabiting relationships (but not age at first marriage) were risk factors for their children's ADHD. All three mother's marital stability variables were associated with either the child's or mother's DRD2 genotypes. Gene × Environment interactions were found for children's ADHD diagnoses between children's DRD2 genotypes and mother's marital status and number of marriages or cohabiting relationships. It is of interest that these interactions were strengthened with the progressive addition of sets of covariates intended to control for alternative causal pathways that represent background genetic and environmental context confounds. The present findings highlight the importance of considering both the nexus of putative environmental risk factors and whether their etiology and effects are truly environmental in future Gene × Environment interaction research.
Socioeconomic status mediates the genetic contribution of the dopamine receptor D4 and serotonin transporter linked promoter region repeat polymorphisms to externalization in preadolescence
Authors: Nobile Maria , Giorda Roberto , Marino Cecilia , Carlet Ombretta , Pastore Valentina , Vanzin Laura , Bellina Monica , Molteni Massimo , Battaglia Marco
Published: October 2007

The impact of socioeconomic status (SES) and genetic polymorphisms on individual differences for externalized behaviors have often been investigated separately in studies of children and adults. In a general population sample of 607 Italian preadolescents, we examined the independent and joint effects of SES and the dopamine receptor D4 (DRD4) and serotonin transporter linked promoter region (5-HTTLPR) polymorphisms upon rule-breaking and aggressive behaviors measured with the Child Behavior CheckList/6–18. We found evidence, which was based on both one locus and two-loci genotype analyses, that low SES andDRD4long and5-HTTLPRlong alleles, both alone and in interaction, are associated with higher aggressive behavior scores. The effects were similar but more modest and limited to one locus genotype analyses for rule-breaking behavior. Consistent with studies that showed the effects of societal moderators on the heritability of externalized behaviors across different segments of the population, we suggest that diminished social constraints associated with low parental SES may act as enhancers of the genetic influence of specificDRD4and5-HTTLPRalleles over aggressive behaviors in preadolescence.
Introduction: World Wars and Population Displacement in Europe in the Twentieth Century
Authors: GATRELL PETER
Published: October 2007

This special issue ofContemporary European Historyis devoted to the impact of the two world wars on civilian population displacement in Europe. Each contributor has brought fresh material to bear on specific instances of involuntary migration that are either unfamiliar or poorly understood. The contributors seek to establish the origins of population displacement and the assistance provided by governments, non-government organisations and individuals and, where possible, also to reflect on the ways in which displacement was understood both at the time and subsequently.
‘A Wave on to Our Shores’: The Exile and Resettlement of Refugees from the Western Front, 1914–1918
Authors: PURSEIGLE PIERRE
Published: October 2007

In the wake of the German invasion of Belgium and France in August 1914, four million persons went into exile. While such a displacement of population testified to a dramatic change in the character of war in western Europe, historiography and collective memory alike have so far concurred in marginalising the experience of refugees during the First World War. This article examines their unprecedented encounter with host communities in France and Great Britain. It demonstrates that the refugees' plight reveals the strengths as well as the tensions inherent in the process of social mobilisation that was inseparable from the First World War.
Assistance and Surveillance: War Refugees in Italy, 1914–1918
Authors: ERMACORA MATTEO
Published: October 2007

This article deals with the forms of assistance given to refugees in Italy during the First World War. The entire subject has been neglected because of the dominant myth of a victorious nation. The Italian situation was peculiar because of the high level of migration and the multi-ethnic origin of people in the border areas. By pinpointing the pattern of relocation in Italy during the war this article seeks to explain the policies pursued by the state and by aid agencies, the rationale behind that aid and the continuities and discontinuities in the assistance given to the refugees. Significant political, juridical and social issues evolved around the image of the refugee, including the protection that the state owed to its citizens.
War, Ethnic Conflict and the Refugee Crisis in Lithuania, 1939–1940
Authors: BALKELIS TOMAS
Published: October 2007

After the destruction of the Polish state by the invading Nazi and Soviet armies in the autumn of 1939, about 30,000 Polish nationals fled to eastern Lithuania. This article examines the relationship between population displacement and ethnic rivalry in Lithuania at the onset of the Second World War. As ‘war victims’ in need of help and protection, over time these Polish refugees became increasingly ‘ethnicised’, socially differentiated and isolated from Lithuanian society, and vilified as a potential political threat. Furthermore, the official decision to create a legal category of so-called ‘newcomers’ deprived those Poles who had settled in Vilnius between the wars of citizenship and residence rights in Lithuania. This policy inflated the number of ‘refugees’ to more than 100,000. Various other official measures, such as the creation of camps, forced labour schemes, deportations and repatriations, show how the government manipulated the refugee crisis for its own political purposes.
Landscape regulation of bacterial growth efficiency in boreal freshwaters
Authors: Berggren Martin , Laudon Hjalmar , Jansson Mats
Published: October 2007

Allochthonous organic carbon in aquatic systems is metabolized by heterotrophic bacteria, with significant consequences for the biostructure and energy pathways of freshwater ecosystems. The degree to which allochthonous substrates support growth of bacteria is largely dependent on bacterial growth efficiency (BGE), i.e., bacterial production (BP) per unit of assimilated carbon. Here we show how the spatial variability of BGE in the boreal region can be mediated by the distribution of the two dominating landscape elements forest and mires. Using an 11 days bioassay approach, the production and respiration of bacteria were measured in water samples from nine small Swedish streams (64°N 19°E), representing a gradient ranging from organic carbon supplied mainly from peat mires to carbon supplied mainly from coniferous forests. BP was positively correlated to forest coverage (%) of the catchment, while bacterial respiration was similar in all streams. Consequently, BGE showed a strong positive correlation with forest coverage. Partial least square regression showed that BGE was chiefly regulated by qualitative properties of the organic material, indicated by the absorbance ratio a254/a365 plus C/N and C/P ratios. The data suggest that a share of the organic carbon pool, drained mainly from forest soils, had a potential of being incorporated into bacterial biomass with great efficiency. Its potential for supporting growth was probably nutrient regulated as indicated by inorganic nutrient enrichment experiments.
Variation in methane production pathways associated with permafrost decomposition in collapse scar bogs of Alberta, Canada
Authors: Prater James L. , Chanton Jeffrey P. , Whiting Gary J.
Published: October 2007

Stable isotope analysis was used to determine the distribution of methanogenic pathways at permafrost collapse scar bogs to test the hypothesis that microbial respiration and methane production are stimulated by the input of organic matter associated with permafrost degradation and collapse. An alternative hypothesis is that recently assimilated carbon produced by the fen‐like vegetation (Carex, Eriophorum) growing in open water moats formed by the collapsing edge of these features stimulates microbial respiration. We found that CO2 reduction was the dominant pathway for methanogenesis within the Sphagnum areas that dominate the surface cover of these features, but relatively more acetate fermentation occurred near collapse scar moats. Methane emission and net CO2 uptake were correlated. Both were elevated in collapse scar moats and then decreased along a transect from the moats toward the center Sphagnum‐dominated areas. There also appeared to be a shift toward relatively more acetate fermentation in deeper samples associated with increasing cation (calcium and magnesium) concentrations. Our results indicate that organic inputs from permafrost degradation alone do not appear to stimulate acetate fermentation. Permafrost decomposition provides conditions along the collapsing edge that are conducive to colonization by fen‐like vegetation that stimulates acetate fermentation and increases methane production and emission rates.