Dr. PIAS: an integrative system for assessing the druggability of protein-protein interactions

<p>Abstract</p> <p>Background</p> <p>The amount of data on protein-protein interactions (PPIs) available in public databases and in the literature has rapidly expanded in recent years. PPI data can provide useful information for researchers in pharmacology and medicine as well as those in interactome studies. There is urgent need for a novel methodology or software allowing the efficient utilization of PPI data in pharmacology and medicine.</p> <p>Results</p> <p>To address this need, we have developed the 'Druggable Protein-protein Interaction Assessment System' (Dr. PIAS). Dr. PIAS has a meta-database that stores various types of information (tertiary structures, drugs/chemicals, and biological functions associated with PPIs) retrieved from public sources. By integrating this information, Dr. PIAS assesses whether a PPI is druggable as a target for small chemical ligands by using a supervised machine-learning method, support vector machine (SVM). Dr. PIAS holds not only known druggable PPIs but also all PPIs of human, mouse, rat, and human immunodeficiency virus (HIV) proteins identified to date.</p> <p>Conclusions</p> <p>The design concept of Dr. PIAS is distinct from other published PPI databases in that it focuses on selecting the PPIs most likely to make good drug targets, rather than merely collecting PPI data.</p

Extremely short duration high intensity interval training substantially improves insulin action in young healthy males

Background: Traditional high volume aerobic exercise training reduces cardiovascular and metabolic disease risk but involves a substantial time commitment. Extremely low volume high-intensity interval training (HIT) has recently been demonstrated to produce improvements to aerobic function, but it is unknown whether HIT has the capacity to improve insulin action and hence glycemic control. Methods: Sixteen young men (age: 21 ± 2 y; BMI: 23.7 ± 3.1 kg·m-2; VO2peak: 48 ± 9 ml·kg-1·min-1) performed 2 weeks of supervised HIT comprising of a total of 15 min of exercise (6 sessions; 4-6 × 30-s cycle sprints per session). Aerobic performance (250-kJ self-paced cycling time trial), and glucose, insulin and NEFA responses to a 75-g oral glucose load (oral glucose tolerance test; OGTT) were determined before and after training. Results: Following 2 weeks of HIT, the area under the plasma glucose, insulin and NEFA concentration-time curves were all reduced (12%, 37%, 26% respectively, all P < 0.001). Fasting plasma insulin and glucose concentrations remained unchanged, but there was a tendency for reduced fasting plasma NEFA concentrations post-training (pre: 350 ± 36 v post: 290 ± 39 μmol·l-1, P = 0.058). Insulin sensitivity, as measured by the Cederholm index, was improved by 23% (P < 0.01), while aerobic cycling performance improved by ∼6% (P < 0.01). Conclusion: The efficacy of a high intensity exercise protocol, involving only ∼250 kcal of work each week, to substantially improve insulin action in young sedentary subjects is remarkable. This novel time-efficient training paradigm can be used as a strategy to reduce metabolic risk factors in young and middle aged sedentary populations who otherwise would not adhere to time consuming traditional aerobic exercise regimes