bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvements in retention rates and changes in client group with methadone maintenance streaming
Authors: WHITE JASON M. , RYAN CHRISTINA F. , ALI ROBERT L.
Published: October 2005

This study evaluated changes in client population and in retention rates following the introduction of a system of methadone maintenance streaming. A low intervention and low supervision stream was combined with two abstinence‐orientated streams. Privileges of take‐home doses and local pharmacy dose collection were contingent on successful participation in the abstinence‐orientated streams. The clinic also modified policy to allow clients greater control over dose levels. The case notes of the first 100 clients entering the programme in the year prior to the changes (1991) and in the year following the changes (1993) were compared. The results showed a significant increase in retention rates. The demographic and heroin using histories did not change, but the newer programme attracted a greater proportion of clients with no previous history of methadone maintenance treatment. Mean clinic dose increased from 45 mg to 63 mg when clients were allowed to exert control over dose. These findings reveal improved outcomes in a public methadone maintenance programme as a result of policy changes designed to give clients greater control of their treatment.
SEMINAR IN PRACTICAL MANAGEMENT: Dissemination of research findings to alcohol and other drug practitioners
Authors: SHANLEY CHRIS , LODGE MIKE , MATTICK RICHARD P.
Published: October 2005

This article provides an overview of the literature in the area of research dissemination, and suggests ways of increasing communication between researchers and clinicians. It then describes a dissemination project based at the Centre for Education and Information on Drugs and Alcohol (CEIDA) which was designed to convey the results of a major research project in the alcohol and other drug area to practitioners in New South Wales. The article includes the development, implementation and evaluation of the project. The format employed—an intensive workshop conducted in different locations—was found to be a useful strategy, particularly when used to promote a large research project of clinical significance and when used in conjunction with other dissemination strategies.
Knowledge and use of alcohol and other drugs among Vietnamese‐speaking migrants
Authors: BERTRAM SUSAN , FLAHERTY BRUCE , EVERINGHAM SAM
Published: October 2005

A survey of the Vietnamese community in Sydney was conducted in 1992 to determine whether it was at a higher or lower risk of drug‐related harm than the general community. Data was collected on knowledge, attitudes and behaviour associated with alcohol and other drug use and compared with overall NSW figures. The sample of 341 Vietnamese‐speakers aged 15–65 years was obtained by face‐to‐face interviews conducted in private households using a cluster sampling technique. Of the sample, 72% indicated they did not speak English well or at all. Recognition of tobacco and alcohol as drugs and the specific health and social problems associated with use was much lower among the Vietnamese‐speakers than the general community. Compared with the general community (1991 NCADA Household Survey), reported use of tobacco on the day of the survey among Vietnamese‐speakers was higher among men (37% versus 26%) but much lower among women (4% versus 22%). Reported use of other drugs such as alcohol, analgesics, minor tranquillizers and illicit drugs was lower than in the general community. It is recommended that the low level of knowledge of the health and social problems associated with tobacco and alcohol in particular should be addressed by community‐based education programmes.
The case for liver transplantation in end‐stage alcoholic liver disease
Authors: BATEY ROBERT G.
Published: October 2005

Liver transplantation is now a routine procedure and is seen as a valid treatment option for end‐stage liver disease. Alcoholism has been regarded as a relative or absolute contraindication to liver transplantation in many transplant units. Recent data document a success rate for transplantation in alcoholic patients that equals that in other patient groups. Issues relating to the ethical and scientific arguments surrounding this complex area of treatment are discussed. It is concluded that individual patients should be assessed in their own right for this treatment option. It is argued that patient groups should not be denied access to specific life‐saving treatments.
Quantitative measure of muscle strength and size in chronic alcoholism: an early indication of tissue damage
Authors: FREILICH RONNIE , KIRSNER RICHARD , WHELAN GREG , CHMIEL RUDOLPH , BYRNE EDWARD
Published: October 2005

We measured quadriceps strength and thickness in 101 male alcoholic patients and in 58 controls in order to investigate the force‐size relationships of skeletal muscle in an alcoholic population. The relationship of these parameters with the duration of alcoholism, nutritional status and biochemical and haematological markers of heavy chronic alcohol use was investigated. Alcohol consumption of more than 42 standard drinks (420 g alcohol) per week for at least 5 years is associated with muscle weakness and wasting. There was no evidence of under‐nutrition in these alcoholic subjects and muscle wasting occurred independently of peripheral neuropathy, a history of muscle pain, abnormalities of liver enzymes and elevation of mean red cell corpuscular volume. Quantitation of muscle size and strength in heavy drinkers may provide a useful early indicator of health impairment in alcoholics.
Training primary health care workers about drugs: a national survey of UK trainers' perceptions towards training
Authors: ALBERY IAN P. , HEUSTON JOAN , DURAND MARY ALISON , GROVES PARAMABANDHU , GOSSOP MICHAEL , STRANG JOHN
Published: October 2005

Reports have consistently shown that non‐specialist drug workers (whose working role is not specifically concentrated on dealing with drug‐related issues) are reluctant to work with drug users. A number of explanations have been offered to account for this unwillingness including attitudinal factors, occupational constraints and a lack of motivation to learn about drug‐related issues. Previously, it has been shown that training affects commitment to working with substance misusers, although failure to attract particular professional groups (e.g. general practitioners) into training courses has also been reported. No previous research has examined the views of trainers about training primary health care and health‐related workers. This study of a (non‐probability) sample of UK drug trainers (n = 145) assessed training activity for different health care workers, and trainers' differential perceptions of training needs and methods. GPs were the group least likely to become trained about drug issues. Training in attitudes towards drug using individuals was perceived to be more important than either skills or knowledge training for GPs, practice nurses, other nurses and probation officers. Experiential training methods were perceived to be more important than a didactic approach for training all health groups except GPs for whom lecture type instruction was believed to be equally appropriate. Seventy‐nine percent of subjects reported providing training across drugs and alcohol or drugs, alcohol and tobacco. Most trainers who stated that certain professions required independent training believed that GPs should be trained separately from other groups.
Predictors of smoking in pregnancy and attitudes and knowledge of risks of pregnant smokers
Authors: WALSH RAOUL A. , REDMAN SELINA , BRINSMEAD MAXWELL W. , FRYER JAYNE L.
Published: October 2005

This study examined the prevalence and predictors of smoking by pregnant women attending a public antenatal clinic. The prevalence of smoking in this population (n= 2577) was found to be 38.0% (95% CI 36.1–39.9%). A review of previous research investigating variables associated with smoking in pregnancy indicated that only three of 42 studies had used multivariate analysis. Using step‐wise logistic regression analysis, five variables were found to be independent predictors of smoking in pregnancy: education (having 4 years or less high school), marital status (being unmarried), gravidity (being multigravida), age (being under 25 years) and language spoken at home (speaking English). The model correctly predicted 63.7% of cases. The knowledge and attitudes of pregnant smokers were also investigated using data from a sub‐sample of consenting subjects. Three‐quarters of the women claimed that they had reduced their smoking since discovering they were pregnant. However, their mean intake of 13.7 cigarettes daily remained at a hazardous level. Approximately half (51%) these smokers claimed to have tried to quit smoking in the current pregnancy. Most (61%) women said they believed smoking was definitely harmful to the unborn child. However, awareness and acceptance of specific risks were inadequate. Of the women in a current relationship, 72% said their partner was a regular smoker. Less than half (45%) the continuing smokers who had seen a doctor about their current pregnancy could recall being advised to stop smoking. There is a need for health care providers to adopt a more systematic and tailored approach to smoking cessation counselling. Efforts to convert quit attempts in pregnancy into sustained cessation represent a priority area of programme development and evaluation.
Deliberate self‐harm in alcohol and drug misusers: patient characteristics and patterns of clinical care
Authors: HAWTON KEITH , SIMKIN SUE , FAGG JOAN
Published: October 2005

The aims of this study were to describe the characteristics of alcohol and drug misusers presenting to a general hospital following suicide attempts and to investigate the patterns of clinical care they received before and after the attempts. The Oxford Monitoring System for Attempted Suicide and patient case‐notes were used to obtain information on alcohol and drug misusers assessed by the general hospital psychiatric services after deliberate self‐harm in 1992. Of 724 patients, 200 (28%) were substance misusers (36% of males, 23% of females). Both alcoholics and drug misusers were more likely than other attempters to be male, have histories of personality disorder and criminal offences and to make repeat attempts, and the drug misusers were more likely to be living alone and unemployed. These are characteristics associated with particularly high risk of suicide. A large proportion of the substance misusers had received specific treatment for their misuse before their attempts and the majority were offered this afterwards. Over a quarter did not accept the care they were offered. The general hospital management of attempted suicide patients must include systematic assessment for evidence of alcohol and drug misuse and maintain close links with substance misuse services. Patients identified as having problems in the use of alcohol without having developed dependence and/or physical symptoms are a group that warrants specific attention. Audits should be conducted in general hospitals to ensure that sufficient attention is being paid to the detection and management of suicide attempters with substance misuse.
The definition of harm reduction
Authors: LENTON SIMON , SINGLE ERIC
Published: October 2005

Welcome to the Harm Reduction Digest, where in each regular edition of Thug and Alcohol Review invited co‐authors will contribute to pieces on the theory and practice of harm reduction. While the focus of subsequent HR Digests will be accounts of the practice of harm reduction interventions, programmes and policies from around the world, it was decided that the first Digest ought to address the definition of Harm Reduction. Consequently the style of this digest is probably more formal than most that will follow it. Many of you will have read DAR's special issue on harm reduction (1995, 14(3)) where Alex Wodak, Bill Saunders, Patricia Erickson, Eric Single and Nick Heather all addressed the issue of definition in their respective contributions. Since this there have been a handful of papers and reports which have also grappled with the issue of definition. Co‐author of this piece is Professor Eric Single, from the Department of Public Health Sciences at the University of Toronto. Eric addressed issues around the definition of harm reduction in the 1996 Dorothy Black lecture in London and, with Professor Timothy Rohl, as independent evaluators of Australia's National Drug Strategy, wrote on the topic in their report ‘Mapping the Future’.
Alcohol and drug disorders in the International Classification of Diseases: a shifting kaleidoscope
Authors: ROOM ROBIN
Published: October 2005

This paper considers the development of the alcohol and drug categories in the mental disorders section of successive editions of the International Classifications of Diseases, and the current definitions of the key categories. With respect to “dependence”, it is argued that the concept was originally defined with respect to culturally close societies, but even between those societies there remain differences in nuance; that in current definitions dependence is not unitary; that there are difficulties in applying the concept across drugs; that technical definitions have drifted far from lay concepts; and that there are substantial questions about its cross‐cultural applicability. As practitioners struggle to keep up with the shifts in nosological terminology and definitions over the last 30 years, the terms and criteria may well be quite vague in application despite their concreteness in appearance.
Wine in moderation: how could and should recent in vitro and in vivo data be interpreted?
Authors: STOCKLEY CREINA S.
Published: October 2005

In Australia, death from cardiovascular diseases accounts for approximately 25% of all deaths. Epidemiological data suggest that the moderate consumption of alcoholic beverages may significantly reduce the risk of death from cardiovascular disease and indeed from all causes. Data also suggest that the ethanol component common to all alcoholic beverages confers primarily this protection and other data suggests that the wine‐specific polyphenolic compounds confer additional protective effects. Is the amount and pattern of consumption really relevant? In vitro and in vivo studies have been undertaken recently, the results of which have both weakened and strengthened the traditional arguments cited on the type, amount and pattern of the consumption of alcoholic beverages. For example, the components of wine may act in concert rather than individually for cancer and cardioprotection, and more rather than less may be required for activity. This paper reviews relevant studies and evaluates critically their results, putting them in context with actual dietary practices rather than guidelines and policies.
Therapeutic use of cannabis: clarifying the debate
Authors: GOWING LINDA R. , ALI ROBERT L. , CHRISTIE PAUL , WHITE JASON M.
Published: October 2005

The debate regarding therapeutic use of cannabis is being confused by a lack of distinction between therapeutic and social use of cannabis. Separate consideration of therapeutic and social use would enable strategies to minimise any negative social impact of therapeutic use. For therapeutic use of cannabis to be considered on its own merits, greater emphasis needs to be placed on scientific evidence of therapeutic efficacy. At present the evidence is limited, it mostly relates to the use of synthetic cannabinoids, and much of it fails to compare cannabis with the best therapies available for the conditions of interest. Claims of therapeutic efficacy tend to be based on opinion and anecdote rather than the results of controlled studies. Further research is needed to clarify the potential therapeutic benefits, to enable claims of therapeutic use to be objectively assessed and to enable informed decisions to be made about the relative risks and benefits for any individual using cannabis for therapeutic purposes. Further research is required to clarify the efficacy of pure, synthetic cannabinoids compared to cannabis, the most effective route of administration, and the importance of delivering a known dose. The most likely value of cannabis is as an adjunct, rather than a replacement for, current medical approaches. The potential therapeutic benefits of cannabis will be greatest for those conditions where long‐term cannabis use, with its attendant health risks, is not an issue and where the patient has the capacity to titrate dose against symptoms. There is sufficient evidence of potential therapeutic benefit to justify the facilitation of further research.
Polydrug use at raves by a Western Australian sample
Authors: BOYS ANNABEL , LENTON SIMON , NORCROSS KATH
Published: October 2005

This study aimed to quantify the patterns of drug use among a group of participants in the rave scene in Perth, Western Australia. Interviews were conducted with 83 people who had recently been to a ‘rave’. The study incorporated a semi‐structured qualitative interview and a structured quantitative questionnaire. This paper reports on the quantitative data collected concerning patterns of drug use in association with the last rave attended. Use of ‘dance drugs’ (ecstasy, amphetamines or LSD) was reported by 86.8% of the 76 respondents who had used at least one drug in association with their last rave. Nearly 80% of these had also used at least one other drug on this occasion (mean number used = 2.4). Cannabis and inhalants were the drugs most commonly combined with the ‘dance drugs’, several respondents used more than one ‘dance drug’ concurrently and 16.7% had used alcohol. It seems that a significant proportion of those using ‘dance drugs’ in association with raves and dance parties are mixing these drugs with other substances despite harm reduction advice to the contrary. The need for more research in this area is discussed.
Comparison of unsafe drinking between a rural and metropolitan area
Authors: PEACH HEDLEY G. , BATH NICOLE E. , FARISH STEPHEN J.
Published: October 2005

Factors associated with unsafe drinking in a rural area were identified and the prevalence of unsafe drinking and alcohol related mortality compared with a metropolitan area. Alcohol consumption data were collected from a random sample of adults in Greater Ballarat. Odds ratios of demographic factors associated with unsafe drinking were estimated by logistic regression. Compared with males and 20–29‐year‐olds, females and 30–59‐year‐olds had a significantly lower prevalence of ‘intermediate’ or higher risk drinking and binge‐only drinking. Rural‐metropolitan ratios for the prevalence of unsafe drinking and alcohol related mortality were also greatest in young adults. Young adults must adopt safer drinking habits if the rural excess in mortality is to be reduced.
Determining the Need for Gender‐Specific Chemical Dependence Treatment: Assessment of Treatment Variables
Authors: Cook Linda S. , Epperson Louise , Gariti Peter
Published: October 2005

The effects of gender on selected treatment variables of substance‐abusing persons were investigated with the long‐term goal of designing gender‐appropriate programs for the treatment of addiction. A population of 120 male and female substance abusers was drawn from two urban outpatient drug treatment centers and one HIV outpatient counseling center. Participants were given questionnaires to measure the following variables: trait anxiety, depression, coping style, and level of differentiation of self. Results demonstrated significant gender differences in differentiation of self (p <.005) and coping styles (p < .02) but no significant differences in anxiety or depression.
Socioeconomic inequities in invasive cardiac procedures among patients with incident angina pectoris or myocardial infarction
Authors: Hetemaa Tiina , Manderbacka Kristiina , Reunanen Antti , Koskinen Seppo , Keskimäki Ilmo
Published: October 2005

Aims: In many countries, systematic socioeconomic disparities have emerged in the use of invasive cardiac procedures among myocardial infarction patients and hospitalized coronary patients. This study prospectively examined socioeconomic differences in the use of cardiac procedures in a national cohort of incident coronary patients. Methods: The data were based on individual register linkages among 49,846 patients with incident angina pectoris (AP) or myocardial infarction (MI) during one-year follow-up in 1995—98 in Finland. Socioeconomic differences in invasive coronary procedures were examined using proportional hazard models. Results: The analyses showed that women, AP patients, and persons with lower socioeconomic status received fewer procedures during the one-year follow-up than men, MI patients, and those with higher socioeconomic status. Socioeconomic differences in the utilization of cardiac procedures were similar in both AP and MI groups, among both men and women, and by all socioeconomic indicators: social class, education, and income. Disparities were already emerging after the 28-day follow-up among men and women in both patient groups, and they persisted throughout the study period. Controlling for disease severity, comorbidity, and hospital district did not modify the results. Conclusions: Socioeconomic disparities in receiving invasive coronary procedures among AP patients without MI were similar to those in MI patients.
Promoting sexual and reproductive health in early adolescence in South Africa and Tanzania: Development of a theory- and evidence-based intervention programme
Authors: Aarø Leif Edvard , Flisher Alan J. , Kaaya Sylvia , Onya Hans , Fuglesang Minou , Klepp Knut-Inge , Schaalma Herman
Published: October 2005

Aims: Action to prevent the spread of HIV among young people in Sub-Saharan Africa is needed urgently. In order to be effective, such action should be theory and evidence based and carefully adapted to local cultures and contexts. The present article describes the organization, theoretical basis, and methodological approach of a project that aims at developing and evaluating school-based interventions targeting adolescents aged 12—14 years. Methods: Researchers from European and African universities have developed interventions that were conducted in three sites: Cape Town and Polokwane (South Africa) and Dar es Salaam (Tanzania). In each site the interventions were evaluated through large-scale field experiments with intervention schools and delayed intervention schools and with baseline and two follow-up data collections. Mimimum sample sizes were estimated for each site based on local data and taking into acount that the unit of allocation was schools and not individual students (the design effect). During the formative phase as well as within the field experiments, qualitative studies were also conducted. Discussion: The interventions were developed consistent with the Intervention Mapping approach, and the theoretical framework was based on a modified version of the Theory of Planned Behaviour. The limitations of Western social cognition models were recognized, and the theoretical framework has therefore been expanded in two directions: towards integrating cultural processes and towards taking societal factors and constraints into account. Conclusion: The project will throw light on the application of social cognition models as well as the usefulness of the Intervention Mapping approach to intervention development in sub-Saharan Africa.
Vulnerable but strong: Deaf people challenge established understandings of deafness
Authors: Breivik Jan-Kåre
Published: October 2005

Background: In the last 35 years, hearing majorities have, in variable degree, gradually recognized that deaf people can be strong and able and a common knowledge of deaf people as linguistic minorities is partly embraced in public life. This is by and large a result of a long-time deaf struggle for the recognition of sign language and against paternalistic policies of pity. Aim: This article aims at showing how contemporary deaf identities are crafted by balancing vulnerability and empowering forces. Methods: In the presentation of life narratives from one deaf Norwegian and one deaf American, different aspects of being deaf are explored. These two stories have emerged from two related deaf research projects. They are deliberately chosen because they illustrate central insights gained within this research. Results: The empowering aspects of being sign language users are in focus, as well as the joys of being connected to a global deaf movement. Difficulties and hardship are also part and parcel of the deaf lives displayed, and strong arguments are put forward against the medical model of deafness in particular. Conclusion: One conclusion is that deaf identities are vulnerable but at the same time can be strongly rewarding.
Predictors of smoking cessation in patients admitted for acute coronary heart disease
Authors: Quist-Paulsen Petter , Bakke Per S. , Gallefoss Frode
Published: October 2005

Background

Smoking cessation is probably the most important single action after a coronary event. In order to increase the effectiveness of smoking cessation programs, it is important to have knowledge of the predictors of smoking cessation. Further, it is unknown whether smoking cessation programs have impact on these predictors.

Methods

Data were obtained from a randomized controlled trial of smoking cessation intervention in 240 smokers aged less than 76 years admitted for myocardial infarction, unstable angina, or cardiac bypass surgery. Baseline characteristics were prospectively recorded. Smoking cessation was determined by self report and biochemical verification at 12 months follow-up.

Results

In multivariate logistic regression analysis, a high level of nicotine addiction, low level of self-confidence in quitting and having previous coronary heart disease were significant negative predictors of smoking cessation at 12 months follow-up. Having previous coronary heart disease and a diagnosis other than acute myocardial infarction as a reason for admission were important negative predictors of abstinence in the usual care group, in contrast to the intervention group, although this did not reach a level of significance in the subgroup interaction analyses. A high level of nicotine addiction was a strong negative predictor in both groups.

Conclusion

A high level of nicotine addiction is an important negative predictor of smoking cessation, even within an individualized smoking cessation program. Smoking cessation intervention seems to be especially effective in patients with previous coronary heart disease and in patients with unstable angina or coronary artery bypass surgery, compared to usual care.
Modelling of orbital deformation using finite-element analysis
Authors: Al-Sukhun Jehad , Lindqvist Christian , Kontio Risto
Published: October 2005

The purpose of this study was to develop a three-dimensional finite-element model (FEM) of the human orbit, containing the globe, to predict orbital deformation in subjects following a blunt injury. This study investigated the hypothesis that such deformation could be modelled using finite-element techniques. One patient who had CT-scan examination to the maxillofacial skeleton including the orbits, as part of her treatment, was selected for this study. A FEM of one of the orbits containing the globe was constructed, based on CT-scan images. Simulations were performed with a computer using the finite-element software
NISA
(EMRC, Troy, USA). The orbit was subjected to a blunt injury of a 0.5 kg missile with 30 m s
−1
velocity. The FEM was then used to predict principal and shear stresses or strains at each node position. Two types of orbital deformation were predicted during different impact simulations: (i) horizontal distortion and (ii) rotational distortion. Stress values ranged from 213.4 to 363.3 MPa for the maximum principal stress, from −327.8 to −653.1 MPa for the minimum principal stress, and from 212.3 to 444.3 MPa for the maximum shear stress. This is the first finite-element study, which demonstrates different and concurrent patterns of orbital deformation in a subject following a blunt injury. Finite element modelling is a powerful and invaluable tool to study the multifaceted phenomenon of orbital deformation.
On the Camassa–Holm equation and a direct method of solution. III.
N
-soliton solutions
Authors: Parker Allen
Published: October 2005

In the concluding study (designated III), we modify the direct bilinear transformation method for solving the Camassa–Holm (CH) equation that was set down in part II of this work. We demonstrate its efficacy for finding
analytic
multisoliton solutions of the equation and give explicit expressions for the first few solitons. It is shown that, at each order
N
, the
N
-soliton has a non-standard representation that is characterized by an ‘extra’ parameter. The stucture of this parameter is investigated and a procedure for constructing the general
N
-soliton solution of the CH equation is presented.
Multiple gene evidence for expansion of extant penguins out of Antarctica due to global cooling
Authors: Baker Allan J , Pereira Sergio Luiz , Haddrath Oliver P , Edge Kerri-Anne
Published: October 2005

Classic problems in historical biogeography are where did penguins originate, and why are such mobile birds restricted to the Southern Hemisphere? Competing hypotheses posit they arose in tropical–warm temperate waters, species-diverse cool temperate regions, or in Gondwanaland ∼100 mya when it was further north. To test these hypotheses we constructed a strongly supported phylogeny of extant penguins from 5851 bp of mitochondrial and nuclear DNA. Using Bayesian inference of ancestral areas we show that an Antarctic origin of extant taxa is highly likely, and that more derived taxa occur in lower latitudes. Molecular dating estimated penguins originated about 71 million years ago in Gondwanaland when it was further south and cooler. Moreover, extant taxa are inferred to have originated in the Eocene, coincident with the extinction of the larger-bodied fossil taxa as global climate cooled. We hypothesize that, as Antarctica became ice-encrusted, modern penguins expanded via the circumpolar current to oceanic islands within the Antarctic Convergence, and later to the southern continents. Thus, global cooling has had a major impact on penguin evolution, as it has on vertebrates generally. Penguins only reached cooler tropical waters in the Galapagos about 4 mya, and have not crossed the equatorial thermal barrier.
Global warming is changing the dynamics of Arctic host–parasite systems
Authors: Kutz S.J , Hoberg E.P , Polley L , Jenkins E.J
Published: October 2005

Global climate change is altering the ecology of infectious agents and driving the emergence of disease in people, domestic animals, and wildlife. We present a novel, empirically based, predictive model for the impact of climate warming on development rates and availability of an important parasitic nematode of muskoxen in the Canadian Arctic, a region that is particularly vulnerable to climate change. Using this model, we show that warming in the Arctic may have already radically altered the transmission dynamics of this parasite, escalating infection pressure for muskoxen, and that this trend is expected to continue. This work establishes a foundation for understanding responses to climate change of other host–parasite systems, in the Arctic and globally.
Thermodynamics in solid mechanics: a commentary
Authors: Baker Graham
Published: October 2005

This commentary on thermodynamics in solid mechanics aims to provide an overview of the main concepts of thermodynamic processes as they apply to, and may be exploited for, studies in nonlinear solid mechanics. We give a descriptive commentary on the (physical) interpretation of these concepts, and relate these where appropriate to behaviour of solids under thermo-mechanical conditions. The motivation is firstly that students of solid mechanics have often had less exposure to thermodynamics than those in other branches of science and engineering, yet there is great value in analytical formulations of material behaviour derived from the principles of thermodynamics. It also sets the contributions in this Theme Issue in context. Along with the deliberately descriptive treatment of thermodynamics, we do outline the main mathematical statements that define the subject, knowing that full details are provided by the authors in their corresponding contributions to this issue. The commentary ends on a lighter note. In order to aid understanding and to stimulate discussion of thermodynamics in solid mechanics, we have invented a number of very basic and completely fictitious materials. These have strange and extreme behaviours that describe certain thermodynamics concepts, such as entropy, in isolation from the complexities of real material behaviour.
Change of the unbinding mechanism upon a mutation: A molecular dynamics study of an antibody–hapten complex
Authors: Curcio Raffaele , Caflisch Amedeo , Paci Emanuele
Published: September 2005

We study forced unbinding of fluorescein from the wild type (WT) and a mutant [H(H58)A] of the single‐chain variable‐fragment (scFv) anti‐fluorescein antibody FITC‐E2 by molecular dynamics simulations using various pulling techniques. A large number of long simulations were needed to obtain statistically meaningful results as both the wild type and the H(H58)A mutant unbinding occurs through multiple pathways, often with metastable intermediates. For the wild type, the rate‐limiting step in the unbinding process corresponds to the breaking of the non‐native interactions characteristic of a specific intermediate. The H(H58)A mutation disfavors the occurrence of this intermediate. Two events where the hapten partially unbinds in the absence of pulling force are observed in extensive equilibrium simulations of the wild type, and their analysis indicates that forced unbinding and spontaneous unbinding proceed along similar pathways. The different unbinding mechanisms observed in the simulations suggest a possible reason for the difference in the experimental off‐rate between the two antibodies. We predict mutations that are expected to modulate the occurrence of the unbinding intermediate. For two such new mutants [H(H58)A and S(H52)A], our predictions are validated in silico by additional simulations. The accompanying paper in this issue by Honegger et al. reports the X‐ray structure of FITC‐E2 with a derivative of fluorescein, which was used as the starting conformation for the work presented here.
Evidence from 13C solid‐state NMR spectroscopy for a lamella structure in an alanine–glycine copolypeptide: A model for the crystalline domain of Bombyx mori silk fiber
Authors: Asakura Tetsuo , Nakazawa Yasumoto , Ohnishi Erika , Moro Fumika
Published: September 2005

13C high‐resolution solid‐state NMR coupled with selective 13C isotope‐labeling of different Ala one methyl carbons was used to clarify the structure of (AG)15 peptide in the silk II structure as a model for the crystalline domain of Bombyx mori silk fiber. At the inner part of the peptide, the fraction of the peak at 16.6 ppm of the Ala Cβ resonance assigned to β‐turn structure increased at 11th and 19th positions. These data indicate the appearance of the most probable lamellar structure having a turn structure at these two positions, although the position of turn was distributed along the chain.
Expression of human peripheral cannabinoid receptor for structural studies
Authors: Yeliseev Alexei A. , Wong Karen K. , Soubias Olivier , Gawrisch Klaus
Published: September 2005

Human peripheral‐type cannabinoid receptor (CB2) was expressed inEscherichia colias a fusion with the maltose‐binding protein, thioredoxin, and a deca‐histidine tag. Functional activity and structural integrity of the receptor in bacterial protoplast membranes was confirmed by extensive binding studies with a variety of natural and synthetic cannabinoid ligands.E. colimembranes expressing CB2 also activated cognate G‐proteins in an in vitro coupled assay. Detergent‐solubilized receptor was purified to 80%–90% homogeneity by affinity chromatography followed by ion‐exchange chromatography. By high‐resolution NMR on the receptor in DPC micelles, it was determined that purified CB2 forms 1:1 complexes with the ligands CP‐55,940 and anandamide. The receptor was successfully reconstituted into phosphatidylcholine bilayers and the membranes were deposited into a porous substrate as tubular lipid bilayers for structural studies by NMR and scattering techniques.
Parallel interrogation of covalent intermediates in the biosynthesis of gramicidin S using high‐resolution mass spectrometry
Authors: Miller Leah M. , Mazur Matthew T. , McLoughlin Shaun M. , Kelleher Neil L.
Published: September 2005

For determination of multiple covalent intermediates bound to the ultra‐large enzymes responsible for biosynthesis via nonribosomal peptide synthesis, mass spectrometry (MS) is a promising method to provide new mechanistic insight. Application of a quadrupole‐Fourier‐transform instrument (Q‐FTMS) for direct analysis of aminoacyl intermediates is demonstrated for the first two modules (127 and 120 kDa) involved in the nonribosomal synthesis of gramicidin S. Cyanogen bromide digestions of recombinant proteins afforded detection of two active site peptides (both ∼13 kDa) that provided direct evidence for modules copurifying with their preferred amino acid substrates. Given the ability to detect multiple covalent intermediates in tandem, a competition experiment among several nonnatural substrates in parallel was performed using the first module. This defined mixture of acyl‐enzyme intermediates was used to probe the selectivity of the condensation step producing a diversity of noncognate dipeptides on the second module.
Topology characterization of a benzodiazepine‐binding β‐rich domain of the GABAA receptor α1 subunit
Authors: Xu Zhiwen , Fang Shisong , Shi Haifeng , Li Hoiming , Deng Yiqun , Liao Yinglei , Wu Jiun‐Ming , Zheng Hui , Zhu Huaimin , Chen Hueih‐Min , Tsang Shui Ying , Xue Hong
Published: September 2005

Structural investigation of GABAA receptors has been limited by difficulties imposed by its trans‐membrane‐complex nature. In the present study, the topology of a membrane‐proximal β‐rich (MPB) domain in the C139–L269 segment of the receptor α1 subunit was probed by mapping the benzodiazepine (BZ)‐binding and epitopic sites, as well as fluorescence resonance energy transfer (FRET) analysis. Ala‐scanning and semiconservative substitutions within this segment revealed the contribution of the phenyl rings of Y160 and Y210, the hydroxy group of S186 and the positive charge on R187 to BZ‐binding. FRET with the bound BZ ligand indicated the proximity of Y160, S186, R187, and S206 to the BZ‐binding site. On the other hand, epitope‐mapping using the monoclonal antibodies (mAbs) against the MPB domain established a clustering of T172, R173, E174, Q196, and T197. Based on the lack of FRET between Trp substitutionally placed at R173 or V198 and bound BZ, this epitope‐mapped cluster is located on a separate end of the folded protein from the BZ‐binding site. Mutations of the five conserved Cys and Trp residues in the MPB domain gave rise to synergistic and rescuing effects on protein secondary structures and unfolding stability that point to a CCWCW‐pentad, reminiscent to the CWC‐triad “pin” of immunoglobulin (Ig)‐like domains, important for the structural maintenance. These findings, together with secondary structure and fold predictions suggest an anti‐parallel β‐strand topology with resemblance to Ig‐like fold, having the BZ‐binding and the epitopic residues being clustered at two different ends of the fold.
Ionic liquids as refolding additives: N′‐alkyl and N′‐(ω‐hydroxyalkyl) N‐methylimidazolium chlorides
Authors: Lange Christian , Patil Ganesh , Rudolph Rainer
Published: September 2005

The purpose of this work was to investigate the influence of a series of N′‐alkyl and N′‐(ω‐hydroxy‐alkyl)‐N‐methylimidazolium chlorides on the renaturation of two model proteins, namely hen egg white lysozyme and the single‐chain antibody fragment ScFvOx. All tested ionic liquids acted as refolding enhancers, with varying efficacies and efficiencies. The results of the refolding screening could be interpreted by taking into account the effect of the studied ionic liquids on protein aggregation, together with the systematic variations of their influence on the stability of native proteins in solution. More hydrophobic imidazolium cations carrying longer alkyl chains were increasingly destabilizing, while terminal hydroxylation of the alkyl chain made the salts more compatible with protein stability. The studied ionic liquids can be classified as preferentially bound, slightly to moderately chaotropic cosolvents for proteins.
Solution structure of the low‐molecular‐weight protein tyrosine phosphatase from Tritrichomonas foetus reveals a flexible phosphate binding loop
Authors: Gustafson Christin L.T. , Stauffacher Cynthia V. , Hallenga Klaas , Van Etten Robert L.
Published: September 2005

Eukaryotic low‐molecular‐weight protein tyrosine phosphatases (LMW PTPs) contain a conserved serine, a histidine with an elevated pKa, and an active site asparagine that together form a highly conserved hydrogen bonding network. This network stabilizes the active site phosphate binding loop for optimal substrate binding and catalysis. In the phosphatase from the bovine parasite Tritrichomonas foetus (TPTP), both the conserved serine (S37) and asparagine (N14) are present, but the conserved histidine has been replaced by a glutamine residue (Q67). Site‐directed mutagenesis, kinetic, and spectroscopic experiments suggest that Q67 is located near the active site and is important for optimal catalytic activity. Kinetic experiments also suggest that S37 participates in the active site/hydrogen bonding network. Nuclear magnetic resonance spectroscopy was used to determine the three‐dimensional structure of the TPTP enzyme and to further examine the roles of S37 and Q67. The backbone conformation of the TPTP phosphate binding loop is nearly superimposable with that of other tyrosine phosphatases, with N14 existing in a strained, left‐handed conformation that is a hallmark of the active site hydrogen bonding network in the LMW PTPs. As expected, both S37 and Q67 are located at the active site, but in the consensus structure they are not within hydrogen bonding distance of N14. The hydrogen bond interactions that are observed in X‐ray structures of LMW PTPs may in fact be transient in solution. Protein dynamics within the active site hydrogen bonding network appear to be affected by the presence of substrate or bound inhibitors such as inorganic phosphate.
Structural and functional features of an NDP kinase from the hyperthermophile crenarchaeon Pyrobaculum aerophilum
Authors: Pédelacq Jean‐Denis , Waldo Geoffrey S. , Cabantous Stéphanie , Liong Elaine C. , Terwilliger Thomas C.
Published: September 2005

Nucleoside diphosphate (NDP) kinases are ubiquitous enzymes that transfer γ‐phosphates from nucleoside triphosphates to nucleoside diphosphates via a ping‐pong mechanism. The important role of this large family of enzymes in controlling cellular functions and developmental processes along with their crystallizability has made them good candidates for structural studies. We recently determined the structure of an evolved version of an NDP kinase from Pyrobaculum aerophilum, an extreme thermophile. This NDP kinase has similarity to the 42 other NDP kinases deposited in the Protein Data Bank (PDB) but differs significantly in sequence, structure, and biophysical properties. The P. aerophilum NDP kinase sequence contains two unique segments not present in other NDP kinases, comprising residues 66–100 and 156–165. We show that deletion mutants of the P. aerophilum NDP kinase lacking either or both of these inserts have an altered substrate specificity, allowing dGTP as the phosphate donor. A structural analysis of the evolved NDP kinase in conjunction with mutagenesis experiments suggests that the substrate specificity of the P. aerophilum NDP kinase is related to the presence of these two inserts.
Design of HIV‐1‐PR inhibitors that do not create resistance: Blocking the folding of single monomers
Authors: Broglia Ricardo A. , Tiana Guido , Sutto Ludovico , Provasi Davide , Simona Fabio
Published: September 2005

The main problems found in designing drugs are those of optimizing the drug–target interaction and of avoiding the insurgence of resistance. We suggest a scheme for the design of inhibitors that can be used as leads for the development of a drug and that do not face either of these problems, and then apply it to the case of HIV‐1‐PR. It is based on the knowledge that the folding of single‐domain proteins, such as each of the monomers forming the HIV‐1‐PR homodimer, is controlled by local elementary structures (LES), stabilized by local contacts among hydrophobic, strongly interacting, and highly conserved amino acids that play a central role in the folding process. Because LES have evolved over many generations to recognize and strongly interact with each other so as to make the protein fold fast and avoid aggregation with other proteins, highly specific (and thus little toxic) as well as effective folding‐inhibitor molecules suggest themselves: short peptides (or eventually their mimetic molecules) displaying the same amino acid sequence of that of LES (p‐LES). Aside from being specific and efficient, these inhibitors are expected not to induce resistance; in fact, mutations in HIV‐1‐PR that successfully avoid the action of p‐LES imply the destabilization of one or more LES and thus should lead to protein denaturation. Making use of Monte Carlo simulations, we first identify the LES of the HIV‐1‐PR and then show that the corresponding p‐LES peptides act as effective inhibitors of the folding of the protease.
Crystal structure of yeast YER010Cp, a knotable member of the RraA protein family
Authors: Leulliot Nicolas , Quevillon‐Cheruel Sophie , Graille Marc , Schiltz Marc , Blondeau Karine , Janin Joël , Van Tilbeurgh Herman
Published: September 2005

We present here the structure of Yer010c protein of unknown function, solved by Multiple Anomalous Diffraction and revealing a common fold and oligomerization state with proteins of the regulator of ribonuclease activity A (RraA) family. In Escherichia coli, RraA has been shown to regulate the activity of ribonuclease E by direct interaction. The absence of ribonuclease E in yeast suggests a different function for this family member in this organism. Yer010cp has a few supplementary secondary structure elements and a deep pseudo‐knot at the heart of the protein core. A tunnel at the interface between two monomers, lined with conserved charged residues, has unassigned residual electron density and may constitute an active site for a yet unknown activity.
Crystal structure of the Yersinia type III secretion protein YscE
Authors: Phan Jason , Austin Brian P. , Waugh David S.
Published: September 2005

The plague‐causing bacterium Yersinia pestis utilizes a contact‐dependent (type III) secretion system (T3SS) to transport virulence factors from the bacterial cytosol directly into the interior of mammalian cells where they interfere with signal transduction pathways that mediate phagocytosis and the inflammatory response. The type III secretion apparatus is composed of 20–25 different Yersinia secretion (Ysc) proteins. We report here the structure of YscE, the smallest Ysc protein, which is a dimer in solution. The probable mode of oligomerization is discussed.