Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

Evaluation of the use of Global Youth Tobacco Survey (GYTS) data for developing evidence-based tobacco control policies in Turkey

Introduction The tobacco control effort in Turkey has made significant progress in recent years. Turkey initiated its tobacco control effort with the passing of Law 4207 (The Prevention of Harmful Effects of Tobacco Products) in 1996 and ratified the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) in 2004. It is important to base policy decisions on valid and reliable evidence from population-based, representative studies that are periodically repeated to enable policy makers to monitor the results of their interventions and to appropriately tailor anti-tobacco activities towards future needs. Methods The Global Youth Tobacco Survey (GYTS) was developed to track tobacco use among young people and enhance the capacity of countries to design, implement, and evaluate tobacco control and prevention programs. Turkey conducted the GYTS in 2003 and data from this survey can be used as baseline measures for evaluation of the tobacco control programs implemented by the Ministry of Health (MOH) of the Turkish government. Results The GYTS was conducted in 2003 on a representative sample of students aged 13 to 15 years. It indicated that almost 3 in 10 students in Turkey had ever smoked cigarettes, with significantly higher rates among boys. Current cigarette smoking rates were lower, at 9% for boys and 4% for girls. The prevalence of current use of other tobacco products was about half these figures for each gender. About 80% were exposed to secondhand smoke. Exposure to pro-smoking media messages was not rare. Almost half of the smokers 'usually' bought their tobacco from a store, despite the law prohibiting this. Exposure to teaching against smoking in schools was not universal. Conclusion Findings from the GYTS, with periodic repeats of the survey, can be used to monitor the impact of enforcing various provisions of the present law (No: 4207), the progress made in achieving the goals of the WHO FCTC, and the effectiveness of various preventive interventions against smoking. Such data would inform and help in the development of public health strategy.PubMedWoSScopu

Tobacco use among students aged 13–15 years in Greece: the GYTS project

BACKGROUND: Data on the prevalence of tobacco use among teenagers in Greece are limited. We examined the prevalence of smoking among middle-school students in Greece using the Global Youth Tobacco Survey (GYTS). METHODS: The Global Youth Tobacco Survey was implemented in Greece during the academic year 2004 – 2005 by the University of Thessaly and the National School of Public Health. Data were collected using the GYTS self-administered anonymous questionnaire, which was distributed by specifically trained field workers to a nationally representative sample of middle-school students aged 13–15 years (through randomly selected schools and classes), randomly selected through a two-stage cluster sample design. Data processing and statistical analyses were performed at the Centers for Disease Control and Prevention (CDC). RESULTS: About one third of the students 32.1% (29.4 – 35.0) reported that they had tried tobacco in the past, while 16.2% (14.3 – 18.4) reported being current users of tobacco products. In addition, 1 in 4 of ever smokers reported that they began smoking before the age of 10 years old. Almost 1 in 5 never smokers reported being susceptible to initiate smoking in the next year and about 89.8% (88.3 – 91.1) of the respondents were exposed to environmental tobacco smoke in their homes and 94.1% (93.2 – 94.9) in public places. Finally, a strikingly high number of students 95% (89.5 – 97.7) reported that they were able to buy their own cigarettes without restrictions. CONCLUSION: The results of the GYTS show that the prevalence of smoking in middle-school children is alarmingly high in Greece. Smoking among young people constitutes a significant problem that is destined to worsen in the absence of any comprehensive efforts focused on strict anti-smoking legislation, policies and tobacco control interventions targeting children at a young age

Current use of smokeless tobacco among adolescents in the Republic of Congo

<p>Abstract</p> <p>Background</p> <p>Tobacco use is a leading cause of global morbidity and mortality. Much of the epidemiologic research on tobacco focuses on smoking, especially cigarette smoking, but little attention on smokeless tobacco (SLT).</p> <p>Methods</p> <p>Using data from the Republic of Congo Global Youth Tobacco Survey (GYTS) of 2006, we estimated the prevalence of SLT use among in-school adolescents. We also assessed the association between SLT use and cigarette smoking as well as the traditional factors which are associated with cigarette smoking among adolescents (e.g. age, sex, parental or peer smoking). Unadjusted odds ratios (OR) and adjusted odds ratios (AOR) together with their 95% confidence intervals (CI) were used to measure magnitudes of associations.</p> <p>Results</p> <p>Of the 3,034 respondents, 18.0% (18.0% males and 18.1% females) reported having used smokeless tobacco (chewing tobacco, sniff or dip) in the last 30 days. In multivariate analysis, no significant associations were observed between age and sex on one hand and current smokeless tobacco use on the other. Cigarette smokers were more than six times likely to report current use of smokeless tobacco (AOR = 6.65; 95% CI [4.84, 9.14]). Having parents or friends smokers was positively associated with using smokeless tobacco (AOR = 1.98; 95% CI [1.51, 2.59] for parents who smoked cigarettes, AOR = 1.82; 95% CI [1.41, 2.69] for some friends who smoked cigarettes, and AOR = 2.02; 95% CI [1.49, 2.47] for most or all friends who smoked cigarettes). Respondents who reported have seen tobacco advertisement on TV, billboards and in newspapers/magazines were 1.95 times more likely to report current use of smokeless tobacco (AOR = 1.95; 95% CI [1.34, 3.08]). Perception that smoking was harmful to health was negatively associated with current use of smokeless tobacco (AOR = 0.60; 95% CI [0.46, 0.78]).</p> <p>Conclusions</p> <p>Prevention programs aimed to reduce teen [cigarette] smoking must also be designed to reduce other forms of tobacco use. The teenagers environment at home, at school and at leisure must also be factored in order to prevent their uptake or maintenance of tobacco use.</p

Tobacco use, exposure to secondhand smoke, and cessation counseling among medical students: cross-country data from the Global Health Professions Student Survey (GHPSS), 2005-2008

<p>Abstract</p> <p>Background</p> <p>GHPSS is a school-based survey that collects self-administered data from students in regular classroom settings. GHPSS produces representative data at the national or city level in each country. This study aims to investigate the prevalence of tobacco use, exposure to secondhand smoke, and cessation counseling among medical students using the GHPSS data.</p> <p>Methods</p> <p>The Global Health Professions Student Survey (GHPSS) was conducted among 3^rdyear medical students in 47 countries and the Gaza Strip/West Bank from 2005-2008 to determine the prevalence of tobacco use and amount of formal training in cessation counseling.</p> <p>Results</p> <p>In 26 of the 48 sites, over 20% of the students currently smoked cigarettes, with males having higher rates than females in 37 sites. Over 70% of students reported having been exposed to secondhand smoke in public places in 29 of 48 sites. The majority of students recognized that they are role models in society (over 80% in 42 of 48 sites), believed they should receive training on counseling patients to quit using tobacco (over 80% in 41 of 48 sites), but few reported receiving formal training (less than 40% in 46 of 48 sites).</p> <p>Conclusion</p> <p>Tobacco control efforts must discourage tobacco use among health professionals, promote smoke free workplaces, and implement programs that train medical students in effective cessation-counseling techniques.</p

Falciparum malaria and HIV-1 in hospitalized adults in Maputo, Mozambique: does HIV-infection obscure the malaria diagnosis?

<p>Abstract</p> <p>Background</p> <p>The potential impact of HIV-1 on falciparum malaria has been difficult to determine because of diagnostic problems and insufficient epidemiological data.</p> <p>Methods</p> <p>In a prospective, cross-sectional study, clinical and laboratory data was registered consecutively for all adults admitted to a medical ward in the Central Hospital of Maputo, Mozambique, during two months from 28^thOctober 2006. Risk factors for fatal outcome were analysed. The impact of HIV on the accuracy of malaria diagnosis was assessed, comparing "Presumptive malaria", a diagnosis assigned by the ward clinicians based on fever and symptoms suggestive of malaria in the absence of signs of other infections, and "Verified malaria", a malaria diagnosis that was not rejected during retrospective review of all available data.</p> <p>Results</p> <p>Among 333 included patients, fifteen percent (51/333) had "presumptive malaria", ten percent (28 of 285 tested persons) had positive malaria blood slides, while 69.1% (188/272) were HIV positive. Seven percent (n = 23) had "verified malaria", after the diagnosis was rejected in patients with neck stiffness or symptom duration longer than 2 weeks (n = 5) and persons with negative (n = 19) or unknown malaria blood slide (n = 4). Clinical stage of HIV infection (CDC), hypotension and hypoglycaemia was associated with fatal outcome. The "presumptive malaria" diagnosis was rejected more frequently in HIV positive (20/31) than in HIV negative patients (2/10, p = 0.023).</p> <p>Conclusion</p> <p>The study suggests that the fraction of febrile illness attributable to malaria is lower in HIV positive adults. HIV testing should be considered early in evaluation of patients with suspected malaria.</p

Cyclin-dependent kinase 5 mediates pleiotrophin-induced endothelial cell migration

Pleiotrophin (PTN) stimulates endothelial cell migration through binding to receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and ανβ3 integrin. Screening for proteins that interact with RPTPβ/ζ and potentially regulate PTN signaling, through mass spectrometry analysis, identified cyclin-dependent kinase 5 (CDK5) activator p35 among the proteins displaying high sequence coverage. Interaction of p35 with the serine/threonine kinase CDK5 leads to CDK5 activation, known to be implicated in cell migration. Protein immunoprecipitation and proximity ligation assays verified p35-RPTPβ/ζ interaction and revealed the molecular association of CDK5 and RPTPβ/ζ. In endothelial cells, PTN activates CDK5 in an RPTPβ/ζ- and phosphoinositide 3-kinase (PI3K)-dependent manner. On the other hand, c-Src, ανβ3 and ERK1/2 do not mediate the PTN-induced CDK5 activation. Pharmacological and genetic inhibition of CDK5 abolished PTN-induced endothelial cell migration, suggesting that CDK5 mediates PTN stimulatory effect. A new pyrrolo[2,3-α]carbazole derivative previously identified as a CDK1 inhibitor, was found to suppress CDK5 activity and eliminate PTN stimulatory effect on cell migration, warranting its further evaluation as a new CDK5 inhibitor. Collectively, our data reveal that CDK5 is activated by PTN, in an RPTPβ/ζ-dependent manner, regulates PTN-induced cell migration and is an attractive target for the inhibition of PTN pro-angiogenic properties

Bayesian Cue Integration as a Developmental Outcome of Reward Mediated Learning

Average human behavior in cue combination tasks is well predicted by Bayesian inference models. As this capability is acquired over developmental timescales, the question arises, how it is learned. Here we investigated whether reward dependent learning, that is well established at the computational, behavioral, and neuronal levels, could contribute to this development. It is shown that a model free reinforcement learning algorithm can indeed learn to do cue integration, i.e. weight uncertain cues according to their respective reliabilities and even do so if reliabilities are changing. We also consider the case of causal inference where multimodal signals can originate from one or multiple separate objects and should not always be integrated. In this case, the learner is shown to develop a behavior that is closest to Bayesian model averaging. We conclude that reward mediated learning could be a driving force for the development of cue integration and causal inference