bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of peptide bond formation on the ribosome
Authors: Rodnina Marina V. , Beringer Malte , Wintermeyer Wolfgang 
Published: August 2006

1. The ribosome 2042. Peptide bond formation is catalyzed by RNA 2053. Characteristics of the uncatalyzed reaction 2074. Potential catalytic strategies of the ribosome 2075. Experimental systems 2086. Substrate binding in the PT center 2107. Induced fit in the active site 2118. pH dependence of peptide bond formation 2129. Reaction with full-length aa-tRNA 21410. Role of active-site residues 21511. pH-dependent structural changes of the active site 21612. Entropic catalysis 21713. Role of 2′-OH of A76 in P-site tRNA 21814. Catalysis by proton shuttling 21915. Plasticity of the active site 22016. Conclusions 22117. Acknowledgments 22218. References 222Peptide bond formation is the fundamental reaction of ribosomal protein synthesis. The ribosome's active site – the peptidyl transferase center – is composed of rRNA, and thus the ribosome is the largest known RNA catalyst. The ribosome accelerates peptide bond formation by 107-fold relative to the uncatalyzed reaction. Recent progress of structural, biochemical and computational approaches has provided a fairly detailed picture of the catalytic mechanisms employed by the ribosome. Energetically, catalysis is entirely entropic, indicating an important role of solvent reorganization, substrate positioning, and/or orientation of the reacting groups within the active site. The ribosome provides a pre-organized network of electrostatic interactions that stabilize the transition state and facilitate proton shuttling involving ribose hydroxyl groups of tRNA. The catalytic mechanism employed by the ribosome suggests how ancient RNA-world enzymes may have functioned.
PKCα: a versatile key for decoding the cellular calcium toolkit
Authors: Reither Gregor , Schaefer Michael , Lipp Peter 
Published: August 2006

Conventional protein kinases C (cPKCs) play an essential role in signal transduction and are believed to integrate both global Ca2+ transients and diacylglycerol signals. We provide evidence that PKCα is a ubiquitous readout sensor for the cellular Ca2+ toolkit, including highly restricted elementary Ca2+ release.
Threshold stimulations of cells with Ca2+-mobilizing agonists resulted in PKCα translocation events with limited spatial spreads (&lt;4 μm) comprising two groups of lifetimes; brief events (400–1,500 ms) exclusively mediated by Ca2+–C2 domain membrane interactions and long-lasting events (&gt;4 s) resulting from longer DAG-C1a domain–mediated membrane interactions.
Although upon uncaging NP-EGTA, which is a caged Ca2+ compound, WT-PKCα displayed rapid membrane translocations within &lt;250 ms, PKCα constructs with C2 domains mutated in their Ca2+-binding region lacked any Ca2+-dependent translocation. Flash photolysis of diazo-2, a photosensitive caged Ca2+ buffer, revealed a biphasic membrane dissociation (slow and fast period) of WT-PKCα. The slow phase was absent in cells expressing PKCα-constructs containing mutated C1a-domains with largely reduced DAG binding. Thus, two groups of PKCα membrane interactions coexist; C2- and C1a-mediated interactions with different lifetimes but rapid interconversion.
We conclude that PKCα can readout very fast and, spatially and temporally, very complex cellular Ca2+ signals. Therefore, cPKCs are important transducers for the ubiquitous cellular Ca2+ signaling toolkit.
Public injecting and the need for ‘safer environment interventions’ in the reduction of drug‐related harm
Authors: Rhodes Tim , Kimber Jo , Small Will , Fitzgerald John , Kerr Thomas , Hickman Matthew , Holloway Greg 
Published: August 2006

ABSTRACTBackground  One key structural dimension in the distribution of drug‐related harm associated with injecting drug use is the injecting environment. Epidemiological evidence associates elevated blood‐borne viral risk with injecting in ‘public’ and ‘semipublic’ environments. Yet the quality of evidence on public injecting and related viral risk is variable, and is lacking in many countries such as the United Kingdom.Aim  This commentary considers the micro‐injecting environment as a critical dimension of risk, exploring the need for ‘safer injecting environment interventions’.Methods  We draw upon published research evidence and qualitative case examples. Results  We note the limits in epidemiological evidence on public injecting and emphasize the need for ethnographic research to determine the ‘social relations’ of how drug users and risk practices interact with injecting environments. We identify three main forms of ‘safer environment intervention’: purpose‐built drug consumption rooms; interventions within existing spatial relations; and spatial programming and urban design. While drug consumption rooms find evidence‐based support, they are not a panacea. We emphasize the potential of interventions embedded within existing spatial and social relations. These include low‐cost pragmatic interventions enhancing facilities and safety at public and semipublic injecting sites and, primarily, peer‐based interventions, including peer‐supervised injecting sites. We caution against spatial programming and urban design interventions which can cause the displacement of socially marginalized populations and the redistribution of harm.Conclusions  Public health interventions in the addictions field have in the past focused upon individual behavioural change at the cost of social interventions and environmental change. We wish to focus greater attention on reducing risks related to public injecting and encourage greater debate on ‘safer environment interventions’ in harm reduction.
HIV prevalence among injection drug users in rural Guangxi China
Authors: Liu Wei , Chen Jie , Rodolph Michelle , Beauchamp Geetha , Mâsse Benoît , Wang Shaoping , Li Rongjian , Ruan Yuhua , Zhou Feng , Leung Man‐kit , Lai Shenghan , Shao Yiming , Jackson J. Brooks 
Published: August 2006

ABSTRACTAims  To determine the HIV‐1 seroprevalence, risk behaviors and demographic characteristics associated with HIV‐1 infection among injection drug users (IDU) in rural Guangxi, China.Design and setting  Between July and November 2002, 702 IDU were screened for HIV‐1 antibody through community outreach in rural Guangxi, China for enrollment in an HIV sero‐incidence study.Participants  A total of 702 active high‐risk IDU were screened. High‐risk injection was defined as anyone who reported injecting drugs at least three times per week in the last month or injected drugs with shared equipment on at least three occasions in the last 3 months. Measurements  HIV‐1 antibody testing with confirmation by Western blot was performed on all subjects. Demographic and risk assessment survey data were collected at screening from everyone whose baseline HIV antibody status was known. Findings  HIV‐1 antibody prevalence among 702 IDU at baseline was 25% with a median age of 26.7 years (18.2–43.2). Based on a multivariate logistic regression model using risk factors identified in univariate analyses, the following risk factors were associated significantly with an increase in risk for HIV seropositivity: age > 26 years (OR 1.50; 95% CI 1.04, 2.17), sharing of rinse water (OR = 1.24; 95% CI 1.09, 1.40), not having sex in the last 6 months (OR = 1.62; 95% CI 1.08, 2.43).Conclusions  HIV infection among IDU in Guangxi, one of China’s major HIV epidemic regions, is high and the infection occurs predominantly among older IDU males who share rinse water.
Stimulant effects of 3,4‐methylenedioxymethamphetamine (MDMA) 75 mg and methylphenidate 20 mg on actual driving during intoxication and withdrawal
Authors: Ramaekers J. G. , Kuypers K. P. C. , Samyn N. 
Published: August 2006

ABSTRACTBackground  3,4‐methylenedioxymethamphetamine (MDMA) is currently one of the most popular drugs of abuse in Europe. Its increasing use over the last decade has led to concern regarding possible adverse effects on driving. The aims of the present study were to investigate the acute effects of MDMA on actual driving performance during the intoxication and withdrawal phase.Methods  Eighteen recreational MDMA‐users (nine males, nine females) aged 21–39 years participated in a double‐blind, placebo‐controlled, three‐way cross‐over study. MDMA 75 mg, methylphenidate 20 mg and placebo were administered on day 1 of treatment (intoxication phase). Driving tests were conducted between 3 and 5 hours post‐drug. Subjects returned the following day for a repetition of the driving tests between 27 and 29 hours post‐drug (withdrawal phase). On‐the‐road driving tests consisted of a road‐tracking test and a car‐following test. Its main parameters were standard deviation of lateral position (SDLP), time to speed adaptation (TSA), brake reaction time (BRT) and gain.Findings  MDMA and methylphenidate significantly decreased SDLP in the road‐tracking tests by about 2 cm relative to placebo on day 1 (intoxication phase). In addition, MDMA intoxication decreased performance in the car‐following test as indicated by a significant rise in the ‘overshoot’ of the subjects’ response to speed decelerations of the leading vehicle. Driving performance was not affected by treatments during withdrawal on day 2.Conclusion  Collectively, these data indicate that MDMA is a stimulant drug that may improve certain aspects of the driving task, such as road‐tracking performance, but may reduce performance in other aspects of the driving task, such as accuracy of speed adaptation during car‐following performance.
Topiramate reduces the harm of excessive drinking: implications for public health and primary care
Authors: Ma Jennie Z. , Ait‐Daoud Nassima , Johnson Bankole A. 
Published: August 2006

ABSTRACTAims  Having demonstrated previously the efficacy of topiramate—a sulfamate‐substituted fructopyranose derivative—as pharmacotherapy for treating alcohol dependence, promoting abstinence and reducing the harmful psychosocial consequences of drinking, we investigated whether topiramate also promoted ‘safe’ levels of drinking: ≤ 1 and ≤ 2 standard drinks/day for women and men, respectively, among alcohol‐dependent individuals.Design, setting and participants  In a double‐blind, randomized, controlled, 12‐week clinical trial conducted in San Antonio, Texas, 75 alcohol‐dependent adults received topiramate and 75 received placebo as an adjunct to weekly standardized medication compliance management.Measurements  For this secondary analysis of data from that trial, we calculated, based on self‐reports, specific intervals of up to 30 days of continuous ‘safe’ drinking for each subject.Findings  The average longest ‘safe’ drinking period was 16.7 days for topiramate recipients versus 8.9 days for placebo recipients. By day 50 of treatment, 44% versus 26.4% had achieved ≥ 7 and 30.8% versus 10% had achieved ≥ 14 continuous ‘safe’ drinking days. Similarly, topiramate increased the relative likelihood of continuous ‘safe’ drinking from 77% for ≥ 7 days [relative risk (RR) for achieving continuous ‘safe’ drinking = 1.77] to threefold for ≥ 14 days (RR = 3.37) and fourfold for ≥ 28 days (RR = 4.07). Thus, participants who received topiramate were more likely to achieve longer periods of ‘safe’ drinking compared with those who received placebo.Conclusions  For alcohol‐dependent individuals who drank within an abstinence‐oriented treatment program, topiramate promoted ‘safe’ drinking. Topiramate’s potential to decrease the public health consequences of hazardous drinking needs to be established in future long‐term studies.
Substance use disorders: Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM‐IV) and International Classification of Diseases, tenth edition (ICD‐10)
Authors: Hasin Deborah , Hatzenbuehler Mark L. , Keyes Katherine , Ogburn Elizabeth 
Published: August 2006

ABSTRACTAims  Two major nomenclatures, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM‐IV) and International Classification of Diseases, tenth edition (ICD‐10), currently define substance use disorders for broad audiences of users with different training, experience and interests. A comparison of these definitions and their implications for DSM‐V and ICD‐11 has not been available.Methods  The background for the dependence concept and abuse, harmful use, withdrawal, substance‐induced disorders and remission and other substance‐related conditions is reviewed. Reliability evidence is presented, as is validity evidence from approaches including psychometric, genetic and animal studies. The relevance of the DSM‐IV and ICD‐10 compared to alternative systems (e.g. the Addiction Severity Index) is considered.Results  Reliability and psychometric validity evidence for substance dependence is consistently strong, but more mixed for abuse and harmful use. Findings on the genetics of alcohol disorders support the validity of the dependence concept, while animal studies underscore the centrality of continued use despite negative consequences to the concept of dependence. While few studies on substance‐induced disorders have been conducted, those published show good reliability and validity when elements of DSM‐IV and ICD‐10 are combined. Conclusions  Dependence in DSM‐V and ICD‐11 should be retained, standardizing both criteria sets and adding a severity measure. The consequences of heavy use should be measured independently of dependence; add cannabis withdrawal if further research supports existing evidence; conduct further studies of the substance‐induced psychiatric categories; standardize their criteria across DSM‐V and ICD‐11; develop a theoretical basis for better remission criteria; consider changing substance ‘abuse’ to substance ‘dysfunction disorder’; and conduct clinician education on the value of the diagnostic criteria.
Should there be both categorical and dimensional criteria for the substance use disorders in DSM‐V?
Authors: Helzer John E. , Van Den Brink Wim , Guth Sarah E. 
Published: August 2006

ABSTRACTAims As discussed in the following literature review, the relative advantages of categorical and dimensional criteria for classifying the substance use disorders (SUDs) have been debated for many years. The scheduled revision of theDiagnostic and Statistical Manual(DSM) offers an opportunity to re‐examine this question. Both categorical and dimensional approaches to diagnosis offer advantages, both may in fact be necessary for a comprehensive taxonomy.Methods One means of resolving debate about the direction to take in revising DSM‐V and simultaneously of achieving maximum taxonomic utility is to include both categorical and dimensional criteria in DSM‐V. This could be accomplished by first defining a set of categorical criteria, as in the previous editions of the DSM. Corresponding dimensional criteria could then be created using a more empirical methodology. In this paper we review some of the relevant literature, offer a specific proposal for a dimensional component for the DSM‐V substance use disorders that also preserves the categorical definitions and suggest areas for additional research relevant the this agenda.Results There is evidence that alcohol and other forms of substance abuse and dependence are heterogeneous categories and that the SUDs can be conceptualized viably as arrayed along a continuum. Amplifying clinically derived categorical definitions with more empirically derived dimensional components to better capture this variability is a particularly important consideration for a substance use research agenda for DSM‐V.Conclusion It is crucial that a dimensional approach be offered in some form in DSM‐V; but it is also vital that any dimensional approach be linked to the categorical definition. The proposal offered herein provides a model for amplifying categorical definitions with a dimensional component in a way that is evolutionary and not disruptive to the existing taxonomy.
Should criteria for drug dependence differ across drugs?
Authors: Hughes John R. 
Published: August 2006

ABSTRACTAim To examine the pros and cons of using the same diagnostic criteria for dependence across all drugs versus using dependence criteria specific to the drug of interest.Methods A qualitative review of the similarities and differences in nicotine versus alcohol and opiate dependence is used as an example of the utility of using generic versus drug‐specific criteria.Results Many scientists implicitly recognize that nicotine dependence is different when they do not include nicotine dependence when studying ‘drug dependence’. Nicotine and alcohol/opiate dependence have many similarities (e.g. both can cause withdrawal). Among the several differences, the most important is that nicotine dependence does not cause acute behavioral impairment. Some of the generic dependence criteria do not apply to nicotine dependence (e.g. giving up activities to use the drug) and some well‐validated measures of nicotine dependence (e.g. time to first cigarette) are not included in the generic criteria.Conclusion Empirical tests of the relative utility of generic versus drug‐specific criteria are needed.
Characteristics of nosologically informative data sets that address key diagnostic issues facing the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM‐V) and International Classification of Diseases, eleventh edition (ICD‐11) substance use disorders workgroups
Authors: Cottler Linda B. , Grant Bridget F. 
Published: August 2006

ABSTRACTAims  Over the past two decades, many nosological issues have been addressed by the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD) substance use disorders workgroups. Even with those efforts, there are key issues that have not been resolved and must be revisited, or addressed de novo, by the workgroups. These lingering points are broad, due to the array of substances classified under the diagnostic umbrella of substance use disorders. They include substantive issues ranging from dimensional approaches, similar criteria for each substance, cut‐points and thresholds, distinct abuse and dependence classifications, new criteria and drugs, to less substantive ones, such as the adjectives used to describe the severity of the behaviors. Results  This paper describes the characteristics of the data sets that will be needed to resolve the key nosological issues. Ten points are described: (1) data must be true to nomenclature under study; (2) flexible regarding rearrangements of scoring algorithms; (3–4) able to assess substances individually and retain former versions of the criteria; (5) not rely on shortened versions; (6) utilize samples that are generalizable; (7) make diagnoses with transparent algorithms; (8) combine mixed methods for corroborating data; (9) utilize assessments that collect reliable and valid diagnoses and criteria; and (10) stretch the limits by allowing for new discoveries.Conclusions  This paper describes each of these and gives examples of the limitations and strengths of data for the purpose of defining a useful, unified concept of addictive behaviors.
Should addictive disorders include non‐substance‐related conditions?
Authors: Potenza Marc N. 
Published: August 2006

ABSTRACTAims  In anticipation of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐V), to consider whether addictive disorders should include non‐substance use disorders.Methods  The author reviewed data and provided perspective to explore whether disorders such as pathological gambling (PG) should be grouped together with substance dependence, given that they share many features.Results  PG and substance dependence currently reside in the DSM, fourth edition, text revision (DSM‐IV‐TR) within separate categories, with PG classified as an impulse control disorder (ICD) and substance dependence as a substance use disorder (SUD). Arguments can be forwarded to support each categorization, as well as to justify their inclusion together as addictions. Conclusion  The current state of knowledge suggests that there exist substantial similarities between PG and SUDs. Further research is indicated prior to categorizing PG and other ICDs together with SUDs.
Should the scope of addictive behaviors be broadened to include pathological gambling?
Authors: Petry Nancy M. 
Published: August 2006

ABSTRACTAims  Pathological gambling is currently considered an impulse control disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM). This paper considers the prospect of reclassifying and broadening the substance use disorders to include non‐pharmacological addictions such as pathological gambling.Methods  Literature reviews were conducted on areas relevant to pathological gambling and its classification and similarities to substance use disorders.Results  The diagnostic criteria for pathological gambling are outlined across the three versions of the DSM since its initial introduction. The paper also describes instruments that have been used to assess the disorder, basic epidemiology and some biological and genetic data, especially in terms of potential overlap with substance use disorders. Similarities and differences with respect to treatments are reviewed as well.Conclusions  Both advantages and disadvantages should be considered with respect to expanding the classification system to include pathological gambling within the context of addictive disorders.
Are there empirically supported and clinically useful subtypes of alcohol dependence?
Authors: Hesselbrock Victor M. , Hesselbrock Michie N. 
Published: August 2006

ABSTRACTAims This paper provides an overview of several multidimensional empirically derived typologies of alcohol use disorders that have been derived primarily for research purposes in relation to their clinical utility.Methods Studies using multivariate statistical methods for identifying homogeneous groups of subjects were selected for inclusion. Theoretically based typologies were not included in this review.Results While formal diagnostic criteria typically identify separate categories of alcohol abuse and dependence, several studies using different statistical methods consistently suggest as many as four homogeneous types of alcoholism: a chronic/severe type, a depressed/anxious type, a mildly affected type and an antisocial type.Conclusions Even though the longitudinal outcomes of few empirically derived subtypes have been examined, alcoholism typologies remain a viable and potentially valuable tool for investigating etiological pathways, the effectiveness of treatments and the long‐term course of alcohol use disorders.