Systematic analysis of the PTEN 5 ' leader identifies a major AUU initiated proteoform

Abundant evidence for translation within the 5' leaders of many human genes is rapidly emerging, especially, because of the advent of ribosome profiling. In most cases, it is believed that the act of translation rather than the encoded peptide is important. However, the wealth of available sequencing data in recent years allows phylogenetic detection of sequences within 5' leaders that have emerged under coding constraint and therefore allow for the prediction of functional 5' leader translation. Using this approach, we previously predicted a CUG-initiated, 173 amino acid N-terminal extension to the human tumour suppressor PTEN. Here, a systematic experimental analysis of translation events in the PTEN 5' leader identifies at least two additional non-AUG-initiated PTEN proteoforms that are expressed in most human cell lines tested. The most abundant extended PTEN proteoform initiates at a conserved AUU codon and extends the canonical AUG-initiated PTEN by 146 amino acids. All N-terminally extended PTEN proteoforms tested retain the ability to downregulate the PI3K pathway. We also provide evidence for the translation of two conserved AUG-initiated upstream open reading frames within the PTEN 5' leader that control the ratio of PTEN proteoforms

AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation.

In addition to acting as template for protein synthesis, messenger RNA (mRNA) often contains sensory sequence elements that regulate this process1,2. Here we report a new mechanism that limits the number of complete protein molecules that can be synthesized from a single mRNA molecule of the human AMD1 gene encoding adenosylmethionine decarboxylase 1 (AdoMetDC). A small proportion of ribosomes translating AMD1 mRNA stochastically read through the stop codon of the main coding region. These readthrough ribosomes then stall close to the next in-frame stop codon, eventually forming a ribosome queue, the length of which is proportional to the number of AdoMetDC molecules that were synthesized from the same AMD1 mRNA. Once the entire spacer region between the two stop codons is filled with queueing ribosomes, the queue impinges upon the main AMD1 coding region halting its translation. Phylogenetic analysis suggests that this mechanism is highly conserved in vertebrates and existed in their common ancestor. We propose that this mechanism is used to count and limit the number of protein molecules that can be synthesized from a single mRNA template. It could serve to safeguard from dysregulated translation that may occur owing to errors in transcription or mRNA damage

Systematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoform

Abundant evidence for translation within the 5′ leaders of many human genes is rapidly emerging, especially, because of the advent of ribosome profiling. In most cases, it is believed that the act of translation rather than the encoded peptide is important. However, the wealth of available sequencing data in recent years allows phylogenetic detection of sequences within 5′ leaders that have emerged under coding constraint and therefore allow for the prediction of functional 5′ leader translation. Using this approach, we previously predicted a CUG-initiated, 173 amino acid N-terminal extension to the human tumour suppressor PTEN. Here, a systematic experimental analysis of translation events in the PTEN 5′ leader identifies at least two additional non-AUG-initiated PTEN proteoforms that are expressed in most human cell lines tested. The most abundant extended PTEN proteoform initiates at a conserved AUU codon and extends the canonical AUG-initiated PTEN by 146 amino acids. All N-terminally extended PTEN proteoforms tested retain the ability to downregulate the PI3K pathway. We also provide evidence for the translation of two conserved AUG-initiated upstream open reading frames within the PTEN 5′ leader that control the ratio of PTEN proteoforms

The relationship between dark triad personality traits and sexting behaviors among adolescents and young adults across 11 countries

Background: Sexting is an increasingly common phenomenon among adolescents and young adults. Some studies have investigated the role of personality traits in different sexting behaviors within mainstream personality taxonomies like Big Five and HEXACO. However, very few studies have investigated the role of maladaptive personality factors in sexting. Therefore, the present study investigated the relationship between Dark Triad Personality Traits and experimental (i.e., sharing own sexts), risky (i.e., sexting under substance use and with strangers), and aggravated sexting (i.e., non-consensual sexting and sexting under pressure) across 11 countries. Methods: An online survey was completed by 6093 participants (Mage = 20.35; SDage = 3.63) from 11 different countries which covered four continents (Europe, Asia, Africa, and America). Participants completed the Sexting Behaviors Questionnaire and the 12-item Dark Triad Dirty Dozen scale. Results: Hierarchical regression analyses showed that sharing own sexts was positively predicted by Machiavellianism and Narcissism. Both risky and aggravated sexting were positively predicted by Machiavellianism and Psychopathy. Conclusions: The present study provided empirical evidence that different sexting behaviors were predicted by Dark Triad Personality Traits, showing a relevant role of Machiavellian-ism in all kinds of investigated sexting behaviors. Research, clinical, and education implications for prevention programs are discussed

Rabies outbreak in Greece during 2012-2014: use of Geographical Information System for analysis, risk assessment and control

The objectives of this work were (i) geographical analysis of the 2012–2014 outbreak of rabies in Greece using GIS and (ii) comparative analysis of animal cases with data of potential human exposure to rabies together with environmental data, in order to provide information for risk assessment, effective monitoring and control. Most animal cases (40/48) involved red foxes, while domestic animals were also diagnosed with rabies. Overall, 80% of the cases were diagnosed in central northern Greece; 75% of the cases were diagnosed in low altitudes (<343·5 m), within a distance of 1 km from human settlements. Median distance from livestock farms was 201·25 m. Most people potentially exposed to rabies (889/1060) presented with dog bite injuries. Maximum entropy analysis revealed that distance from farms contributed the highest percentage in defining environmental niche profiles for rabid foxes. Oral vaccination programmes were implemented in 24 administrative units of the country during 2013 and 2014, covering a total surface area of ~60 000 km2. Rabies re-occurrence in Greece emphasizes the need for ongoing surveillance in cross-border areas and in areas with intense human activity

LIMPRINT study - the Turkish experience

Background: Lymphedema and chronic oedema is a major healthcare problem in both developed and non-developed countries The LIMPRINT study is an international health service based study to determine the prevalence and functional impact in adult populations of member countries of the International Lymphoedema Framework (ILF). Methods: 1051 patients from 8 centers in Turkey were recruited using the LIMPRINT study protocol. Data were collected using the core and module tools which assess the demographic and clinical properties as well as disability and QoL. Results: Most of the Turkish patients were recruited from specialist lymphedema services and were found to be female, housewives and having secondary lymphedema due to cancer treatment. The duration of lymphedema was commonly less than 5 years and most of them had ISL Grade 2 lymphedema. Cellulitis, infection and wounds were uncommon. The majority of patients did not get any treatment or advice before. Most of the patients had impaired QoL and decreased functionality, but psychological support was neglected. Although most had social health security access to Lymphedema centres nevertheless access seemed difficult due to distance and cost. Conclusion: The study has shown the current status and characteristics of lymphedema patients, treatment conditions, the unmet need for the diagnosis and treatment as well as burden of the disease in both patients and families in Turkey. National health policies are needed for the prevention, diagnosis and treatment in Turkey that utilise this informative data

Mining and linking open economic data from governmental communities

In this paper, we propose a model conceptualization (Linked Open Economy - LOE) capable of exploiting the massive amount and variety of open economic data that are gradually becoming available by governments and open source communities. The main aim is to unleash the power of open data and open source systems and create a common ground to serve as a catalyst in providing more efficient answers in important economic activities. © 2018, IFIP International Federation for Information Processing

A high degree of dyspnea is associated with poor maximum exercise capacity in subjects with copd with the same severity of air-flow obstruction

BACKGROUND: In patients with COPD, limited data have been reported concerning the association between dyspnea perception and exercise tests. Moreover, the perception of dyspnea has not been analyzed in patients with the same severity of air-flow obstruction. The aim of our study was to evaluate the relationship between the degree of dyspnea and exercise capacity in subjects with COPD who had the same severity of air-flow obstruction. METHODS: We assessed dyspnea perception and maximum exercise capacity by using the modified Medical Research Council dyspnea scale (mMRC) questionnaire and by using the symptom-limited incremental cardiopulmonary exercise test, respectively. A propensity score matching was used to obtain the balance between the subjects with COPD and with an mMRC questionnaire score &lt; 2 and &gt;= 2 (mMRC score) according to the severity of air-flow obstruction. RESULTS: A total of 249 ambulatory adult patients with stable COPD (mean age, 68 y) were considered in the full cohort. After propensity score analysis, 160 subjects (65% men; mean +/- SD FEV1, 47.5 +/- 12.8% of predicted) were included in our study cohort. The subjects with an mMRC questionnaire score &gt;= 2 in comparison with those with an mMRC questionnaire score &lt; 2 showed lower values in oxygen uptake at peak (V-O2 max) (P = .002) and in maximum work load (P &lt;.001). In the regression models, the mMRC questionnaire score was able to predict oxygen uptake at peak (P &lt;.001) and at maximum work load (P &lt;.001). CONCLUSIONS: In subjects with COPD and with the same severity of air-flow obstruction, a high score in dyspnea was related to a poor maximum exercise capacity. Our results support the view that, in COPD, the severity of air-flow obstruction was less informative than symptoms in the combined assessment of the disease

Small airway dysfunction predicts excess ventilation and dynamic hyperinflation during exercise in patients with COPD

Introduction: Small airway dysfunction (SAD) is a pathophysiological characteristic of chronic obstructive pulmonary disease (COPD). Excess ventilation and dynamic hyperinflation (DH) are two main pathophysiological traits and limiting factors of COPD patients while exercising. We aimed to ascertain whether or not SAD, assessed by the multiple breath nitrogen washout (MBNW), may predict exercise ventilatory inefficiency and DH. Methods: Fifty stable COPD patients were prospectively studied and underwent MBNW and incremental cardio-pulmonary exercise test (CPET). Indices of conductive (Scond) and acinar (Sacin) ventilation heterogeneity as well as minute ventilation/CO2 production (VE/VCO2) linear relationship and the change in inspiratory capacity (IC) were analyzed. Results: Sacin was significantly and directly related to VE/VCO2 slope and inversely related to IC change and to peak O2 uptake (p &lt; 0.01 for all correlations). No significant correlation was found between Scond and CPET parameters. The regression equation generated by stepwise multiple regression analysis for the VE/VCO2 slope and IC change, as dependent variables, included only Sacin, as independent variable. This model accounted for 31% and 36% of the total variance for the VE/VCO2 slope and IC change, respectively. Conclusion: Our study shows the value of the SAD as determinant of the excess ventilation and DH during exercise in patients with stable COPD

Small airway dysfunction is associated to excessive bronchoconstriction in asthmatic patients.

We investigated whether a relationship between small airways dysfunction and bronchial hyperresponsiveness (BHR), expressed both in terms of ease of airway narrowing and of excessive bronchoconstriction, could be demonstrated in asthma. Methods: 63 (36 F; mean age 42 yr ± 14) stable, mild-to-moderate asthmatic patients (FEV1 92% pred ±14; FEV1/FVC 75% ± 8) underwent the methacholine challenge test (MCT). The degree of BHR was expressed as PD20 (in μg) and as ΔFVC%. Peripheral airway resistance was measured pre- and post-MCT by impulse oscillometry system (IOS) and expressed as R5-R20 (in kPa sL−1). Results: All patients showed BHR to methacholine (PD20 < 1600 μg) with a PD20 geometric (95% CI) mean value of 181(132–249) μg and a ΔFVC% mean value of 13.6% ± 5.1, ranging 2.5 to 29.5%. 30 out of 63 patients had R5-R20 > 0.03 kPa sL−1 (>upper normal limit) and showed ΔFVC%, but not PD20 values significantly different from the 33 patients who had R5-R20 ≤ 0.03 kPa sL−1 (15.8% ± 4.6 vs 11.5% ± 4.8, p < 0.01 and 156(96–254) μg vs 207 (134–322) μg, p = 0.382). In addition, ΔFVC% values were significantly related to the corresponding pre- (r = 0.451, p < 0.001) and post-MCT (r = 0.376, p < 0.01) R5-R20 values. Conclusions: Our results show that in asthmatic patients, small airway dysfunction, as assessed by IOS, is strictly associated to BHR, expressed as excessive bronchoconstriction, but not as ease of airway narrowing