Systematic analysis of the Hippo pathway organization and oncogenic alteration in evolution.

The Hippo pathway is a central regulator of organ size and a key tumor suppressor via coordinating cell proliferation and death. Initially discovered in Drosophila, the Hippo pathway has been implicated as an evolutionarily conserved pathway in mammals; however, how this pathway was evolved to be functional from its origin is still largely unknown. In this study, we traced the Hippo pathway in premetazoan species, characterized the intrinsic functions of its ancestor components, and unveiled the evolutionary history of this key signaling pathway from its unicellular origin. In addition, we elucidated the paralogous gene history for the mammalian Hippo pathway components and characterized their cancer-derived somatic mutations from an evolutionary perspective. Taken together, our findings not only traced the conserved function of the Hippo pathway to its unicellular ancestor components, but also provided novel evolutionary insights into the Hippo pathway organization and oncogenic alteration

Obesity care pathway

This paper recognises that obesity is a growing problem within the UK with Britain with one of the highest rates for overweight children in Europe and with one in three adults predicted to be obese by 2012. Within the UK, nearly 25 per cent of men and women are now obese which has created enormous implications for health service providers (NICE, 2006). This paper focuses specifically on North East Lincolnshire where life expectancy is less than the national average with males (76) and females (80.8). Within North East Lincolnshire we developed an evidence-based adult obesity care pathway based on the NICE obesity guidance, incorporating local referral criteria and input. The pathway is benefiting patients by helping to reduce obesity through an increase in lifestyle referrals. Since the pathway was developed we have seen a reduction in referrals for unnecessary bariatic surgery which is reducing the cost to the NHS. This paper shares our learning and best practice from stakeholder engagement, partnership working, successfully implementing and evaluating the adult obesity care pathway across all general practices

Knockdown of piRNA pathway proteins results in enhanced Semliki forest virus production in mosquito cells

The exogenous siRNA pathway is important in restricting arbovirus infection in mosquitoes. Less is known about the role of the PIWI-interacting RNA pathway, or piRNA pathway, in antiviral responses. Viral piRNA-like molecules have recently been described following infection of mosquitoes and derived cell lines with several arboviruses. The piRNA pathway has thus been suggested to function as an additional small RNA-mediated antiviral response to the known infection-induced siRNA response. Here we show that piRNA-like molecules are produced following infection with the naturally mosquito-borne Semliki Forest virus in mosquito cell lines. We show that knockdown of piRNA pathway proteins enhances the replication of this arbovirus and defines the contribution of piRNA pathway effectors, thus characterizing the antiviral properties of the piRNA pathway. In conclusion, arbovirus infection can trigger the piRNA pathway in mosquito cells, and knockdown of piRNA proteins enhances virus production

Multiple Arrhythmogenic Substrate for Tachycardia in a Patient with Frequent Palpitations

We report a 26-year-old woman with frequent episodes of palpitation and dizziness. Resting electrocardiography showed no evidence of ventricular preexcitation. During electrophysiologic study, a concealed right posteroseptal accessory pathway was detected and orthodromic atrioventricular reentrant tachycardia incorporating this pathway as a retrograde limb was reproducibly induced. After successful ablation of right posteroseptal accessory pathway, another tachycardia was induced using a concealed right posterolateral accessory pathway in tachycardia circuit. After loss of retrograde conduction of second accessory pathway with radiofrequency ablation, dual atrioventricular nodal physiology was detected and typical atrioventricular nodal reentrant tachycardia was repeatedly induced. Slow pathway ablation was done successfully. Finally sustained self-terminating atrial tachycardia was induced under isoproterenol infusion but no attempt was made for ablation. During 8-month follow-up, no recurrence of symptoms attributable to tachycardia was observed

A technology platform for enabling behavioural change as a “PATHway” towards better self-management of CVD

We describe a technology platform developed as part of a novel approach to technology-enabled exercise-based Cardiac Rehabilitation (CR), termed PATHway. We explain the overall concept and explain how technology can facilitate remote participation and better adherence to communitybased long-term Phase III CR. The demo will showcase the user experience of interacting with the PATHway system, including navigation and manual data entry, whilst also demonstrating real-time sensing and analysis of exercise movements and automatic adaptation of exercise based on physiological response