The E3 Ligase TRIM32 is a Novel Effector of the RAS Family GTPase Rap2

Classical RAS oncogenes are mutated in approximately 30% of human tumours and RAP proteins are closely related to classical RAS proteins. RAP1 has an identical effector domain to RAS whereas RAP2 differs by one amino acid. RAP2 not only shares effectors with other classical RAS family members, but it also has its own specific effectors that do not bind to RAP1 or classical RAS family proteins. Thus, although closely related, RAP2 performs distinct functions, although these have been poorly characterised. Using RAP2 as bait in Tandem Affinity Purifications, we have identified several RAP2 interacting proteins including TRIM32; a protein implicated in diverse pathological processes such as Limb-Girdle Muscular Dystrophy (LGMD2H), and Bardet-Biedl syndrome (BBS). TRIM32 was shown to interact specifically with RAP2 in an activation- and effector domain-dependent manner; demonstrating stronger interaction with the RAP2 V12 mutant than the wild-type RAP2 and defective binding to the effector mutant RAP2 V12A38. The interaction was mapped to the C-terminus of TRIM32 (containing the NHL domains) while mutations found in LGMD2H (R394H, D487N, Δ588) were found to disrupt binding to RAP2. The TRIM32 P130S mutant linked to BBS did not affect binding to RAP2, suggesting that the RAP2-TRIM32 interaction may be functionally involved in LGMD2H. Because TRIM32 is an E3 ubiquitin ligase, the possible ubiquitination of interacting proteins by TRIM32 was assessed along with the potential for modulation by RAP2. RAP2 stimulates the ubiquitin ligase activity of TRIM32 against some substrates but not others. We propose that RAP2 uses TRIM32 to regulate the signalling properties of other RAP2 effectors. Furthermore, our data also shows that the overexpression of TRIM32 may increase C2C12 mouse myoblast cell differentiation whereas the inhibition of RAP2 expression decreases differentiation in C2C12 cells. Further study could lead to a potential link to Limb-Girdle Muscular Dystrophy that remains to be elucidated

A multi-site study on walkability, data sharing and privacy perception using mobile sensing data gathered from the mk-sense platform

Walking is a fundamental part of a physically active lifestyle, it is one of everyday activities that positively impacts health and wellbeing. In this paper we describe the challenges and experiences of conducting a sensing campaign in the wild. We make use of mk-sense; a software platform to facilitate the deployment of collaborative sensing campaigns. We elaborate on two cross-cultural studies conducted in four different countries (Mexico, Turkey, Spain, and Switzerland) with a total of 77 participants. We present a detailed description of the data collected from one of the studies aimed at measuring walkability around three different university campuses. The analysis of the data shows that walkability can be assessed using information from the sensors in the smartphones and results from surveys answered by participants. In addition, we analyze issues about data sharing and privacy awareness

Türkiye’de bulunan yoğun bakımlarda sabun, kağıt havlu ve alkol bazlı el dezenfektanı yeterli mi?: Phokai çalışması sonuçları

Introduction: Hand hygiene is one of the most effective infection control measures to prevent the spread of healthcare-associated infections (HCAI). Water, soap, paper towel and hand disinfectant must be available and adequate in terms of effective hand hygiene. The adequacy of hand hygiene products or keeping water-soap and paper towel is still a problem for many developing countries like Turkey. In this multicenter study, we analyzed the adequacy in number and availability of hand hygiene products.Materials and Methods: This study was performed in all intensive care units (ICUs) of 41 hospitals (27 tertiary-care educational, 10 state and four private hospitals) from 22 cities located in seven geographical regions of Turkey. We analyzed water, soap, paper towel and alcohol-based hand disinfectant adequacy on four different days, two of which were in summer during the vacation time (August, 27th and 31st 2016) and two in autumn (October, 12th and 15th 2016).Results: The total number of ICUs and intensive care beds in 41 participating centers were 214 and 2357, respectively. Overall, there was no soap in 3-11% of sinks and no paper towel in 10-18% of sinks while there was no alcohol-based hand disinfectant in 1-4.7% of hand disinfectant units on the observation days. When we compared the number of sinks with soap and/or paper towel on weekdays vs. weekends, there was no significant difference in summer. However, on autumn weekdays, the number of sinks with soap and paper towel was significantly lower on weekend days (p<0.0001, p<0.0001) while the number of hand disinfectant units with alcohol-based disinfectant was significantly higher (p<0.0001).Conclusion: There should be adequate and accessible hand hygiene materials for effective hand hygiene. In this study, we found that soap and paper towels were inadequate on the observation days in 3-11% and 10-18% of units, respectively. Attention should be paid on soap and paper towel supply at weekends as well

Cost-effectiveness of six strategies for Helicobacter pylori diagnosis and management in uninvestigated dyspepsia assuming a high resource intensity practice pattern

<p>Abstract</p> <p>Background</p> <p>Initial assessment of dyspepsia often includes noninvasive testing for <it>Helicobacter pylori </it>infection. Commercially available tests vary widely in cost and accuracy. Although there is extensive literature on the cost-effectiveness of <it>H. pylori </it>treatment, there is little information comparing the cost-effectiveness of various currently used, noninvasive testing strategies.</p> <p>Methods</p> <p>A Markov simulation was used to calculate cost per symptom-free year and cost per correct diagnosis. Uncertainty in outcomes was estimated using probabilistic sensitivity analysis.</p> <p>Results</p> <p>Under the baseline assumptions, cost per symptom-free year was $122 for empiric proton pump inhibitor (PPI) trial, and costs for the noninvasive test strategies ranged from$123 (stool antigen) to $129 (IgG/IgA combined serology). Confidence intervals had significant overlap.</p> <p>Conclusions</p> <p>Under our assumptions for how testing for <it>H. pylori </it>infection is employed in United States medical practice, the available noninvasive tests all have similar cost-effectiveness between one another as well as with empiric PPI trial.</p

Bilateral renal infarctions complicating fibromuscular dysplasia of renal arteries in a young male.

Fibromuscular dysplasia (FMD) is an uncommon disorder, accounting for less than 10% of cases of renal artery stenosis, and typically presenting with hypertension in young women. This article reports the case of a previously healthy 37-year-old man presenting with acute-onset, severe, bilateral flank pain. Initially treated for ureteral colic and urinary tract infection, he was transferred to the nephrology clinic upon recognition of a rising serum creatinine. He was found to have FMD of bilateral renal arteries with a stenotic pattern on the right side and a dissecting aneurysm on the left side with resultant infarctions in both kidneys. On the basis of negative serological markers of vasculitis, a diagnosis of FMD complicated by bilateral renal infarctions was made. A stent was placed to the right stenotic renal artery, which resulted in sufficient lumen patency. No invasive procedure was performed on the other side owing to the complexity of the lesion. After 2.5 years of follow-up, the patient remained in good condition with normal renal function and adequate blood pressure control with dual antihypertensive therapy. Renal infarction complicating FMD of renal arteries is rare in the literature, with most of the cases having causative cardiovascular risk factors including coagulopathy, ischaemic heart disease, atrial fibrillation or structural cardiac abnormalities, none of which was present in this case. In conclusion, FMD may occur in atypical asymmetric presentations causing renal infarctions in both kidneys. Radiological interventions in such cases should focus on stabilizing renal lesions and renal function