NatF Contributes to an Evolutionary Shift in Protein N-Terminal Acetylation and Is Important for Normal Chromosome Segregation

N-terminal acetylation (N-Ac) is a highly abundant eukaryotic protein modification. Proteomics revealed a significant increase in the occurrence of N-Ac from lower to higher eukaryotes, but evidence explaining the underlying molecular mechanism(s) is currently lacking. We first analysed protein N-termini and their acetylation degrees, suggesting that evolution of substrates is not a major cause for the evolutionary shift in N-Ac. Further, we investigated the presence of putative N-terminal acetyltransferases (NATs) in higher eukaryotes. The purified recombinant human and Drosophila homologues of a novel NAT candidate was subjected to in vitro peptide library acetylation assays. This provided evidence for its NAT activity targeting Met-Lys- and other Met-starting protein N-termini, and the enzyme was termed Naa60p and its activity NatF. Its in vivo activity was investigated by ectopically expressing human Naa60p in yeast followed by N-terminal COFRADIC analyses. hNaa60p acetylated distinct Met-starting yeast protein N-termini and increased general acetylation levels, thereby altering yeast in vivo acetylation patterns towards those of higher eukaryotes. Further, its activity in human cells was verified by overexpression and knockdown of hNAA60 followed by N-terminal COFRADIC. NatF's cellular impact was demonstrated in Drosophila cells where NAA60 knockdown induced chromosomal segregation defects. In summary, our study revealed a novel major protein modifier contributing to the evolution of N-Ac, redundancy among NATs, and an essential regulator of normal chromosome segregation. With the characterization of NatF, the co-translational N-Ac machinery appears complete since all the major substrate groups in eukaryotes are accounted for

Assertive Community Treatment for alcohol dependence (ACTAD): study protocol for a randomised controlled trial

Background Alcohol dependence is a significant and costly problem in the UK yet only 6% of people a year receive treatment. Current service provision based on the treatment of acute episodes of illness and emphasising personal choice and motivation results in a small proportion of these patients engaging with alcohol treatment. There is a need for interventions targeted at the population of alcohol dependent patients who are hard to engage in conventional treatment. Assertive Community Treatment (ACT), a model of care based on assertive outreach, has been used for treating patients with severe mental illnesses and presents a promising avenue for engaging patients with primary alcohol dependence. So far there has been little research on this. Methods/Design In this single blind exploratory randomised controlled trial, a total of 90 alcohol dependent participants will be recruited from community addiction services. After completing a baseline assessment, they will be assigned to one of two conditions: (1) ACT plus care as usual, or (2) care as usual. Those allocated to the ACT plus care as usual will receive the same treatment that is routinely provided by services, plus a trained key worker who will provide ACT. ACT comprises intensive and assertive contact at least once a week, over 50% of contacts in the participant's home or local community, and comprehensive case management across social and health care, for a period of one year. All participants will be followed up at 6 months and 12 months to assess outcome post randomisation. The primary outcome measures will be alcohol consumption: mean drinks per drinking day and percentage of days abstinent measured by the Time Line Follow Back interview. Secondary outcome measures will include severity of alcohol dependence, alcohol related problems, motivation to change, social network involvement, quality of life, therapeutic relationship and service use. Other outcome variables are treatment engagement including completion of assessment, detoxification and aftercare. Discussion Results of this trial will help clarify the potential beneficial effects of ACT for people with alcohol dependence and provide information to design a definitive trial

Validation of the French version of the alcohol, smoking and substance involvement screening test (ASSIST) in the elderly

<p>Abstract</p> <p>Background</p> <p>Substance use disorders seem to be an under considered health problem amongst the elderly. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), was developed by the World Health Organization to detect substance use disorders. The present study evaluates the psychometric properties of the French version of ASSIST in a sample of elderly people attending geriatric outpatient facilities (primary care or psychiatric facilities).</p> <p>Methods</p> <p>One hundred persons older than 65 years were recruited from clients attending a geriatric policlinic day care centre and from geriatric psychiatric facilities. Measures included ASSIST, Addiction Severity Index (ASI), Mini-International Neuropsychiatric Interview (MINI-Plus), Alcohol Use Disorders Identification Test (AUDIT), Revised Fagerstrom Tolerance Questionnaire-Smoking (RTQ) and MiniMental State(MMS).</p> <p>Results</p> <p>Concurrent validity was established with significant correlations between ASSIST scores, scores from ASI, AUDIT, RTQ, and significantly higher ASSIST scores for patients with a MINI-Plus diagnosis of abuse or dependence. The ASSIST questionnaire was found to have high internal consistency for the total substance involvement along with specific substance involvement as assessed by Cronbach’s α, ranging from 0.66, to 0.89 .</p> <p>Conclusions</p> <p>The findings demonstrate that ASSIST is a valid screening test for identifying substance use disorders in elderly.</p

Predicting Levels of Policy Advocacy Engagement Among Acute-Care Health Professionals

This study aims to describe the factors that predict health professionals' engagement in policy advocacy. The researchers used a cross-sectional research design with a sample of 97 nurses, 94 social workers, and 104 medical residents from eight hospitals in Los Angeles. Bivariate correlations explored whether seven predictor scales were associated with health professionals' policy advocacy engagement and revealed that five of the eight factors were significantly associated with it (p &lt; .05). The factors include patient advocacy engagement, eagerness, skills, tangible support, and organizational receptivity. Regression analysis examined whether the seven scales, when controlling for sociodemographic variables and hospital site, predicted levels of policy advocacy engagement. Results revealed that patient advocacy engagement (p &lt; .001), eagerness (p &lt; .001), skills (p &lt; .01), tangible support (p &lt; .01), perceived effectiveness (p &lt; .05), and organizational receptivity (p &lt; .05) all predicted health professional's policy advocacy engagement. Ethical commitment did not predict policy advocacy engagement. The model explained 36% of the variance in policy advocacy engagement. Limitations of the study and its implications for future research, practice, and policy are discussed