Sandberg Lundberg (tyvekquart0)

The RING-finger protein Pirh2 is a p53 family-specific E3 ubiquitin ligase. Pirh2 also ubiquitinates several other important cellular factors and is involved in carcinogenesis. However, its functional role in other cellular processes is poorly understood. To address this question, we performed a proteomic search for novel interacting partners of Pirh2. Using the GST-pulldown approach combined with LC-MS/MS, we revealed 225 proteins that interacted with Pirh2. We found that, according to the GO description, a large group of Pirh2-associated proteins belonged to the RNA metabolism group. Importantly, one of the identified proteins from that group was an RNA-binding protein ELAVL1 (HuR), which is involved in the regulation of splicing and protein stability of several oncogenic proteins. We demonstrated that Pirh2 ubiquitinated the HuR protein facilitating its proteasome-mediated degradation in cells. Importantly, the Pirh2-mediated degradation of HuR occurred in response to heat shock, thereby affecting the survival rate of HeLa cells under elevated temperature. Functionally, Pirh2-mediated degradation of HuR augmented the level of c-Myc expression, whose RNA level is otherwise attenuated by HuR. Taken together, our data indicate that HuR is a new target of Pirh2 and this functional interaction contributes to the heat-shock response of cancer cells affecting their survival.Obtaining accurate blood pressure readings is vital. However, students and health professionals do not always receive adequate training on blood pressure measurement, especially regarding new technologies, leading to insufficient knowledge. Therefore, the aim of this study is to analyze Brazilian health professionals' perceptions and knowledge about automated blood pressure monitors. This cross-sectional study involved 1734 Brazilian nurses, nursing technicians, and doctors who reported having some experience of using automated monitors. Perceptions about differences between readings obtained through the auscultatory and oscillometric methods, influence of small differences in clinical decision-making, confidence in automated monitors, and knowledge about contraindications for the use of these devices were assessed. Most medical and nursing professionals considered differences of up to 5 mmHg (40.94%) between auscultatory and oscillometric measurements acceptable. Of these, 69.02% reported that even small differences can influence clinical decisions. Confidence in readings obtained using automated blood pressure monitors was reported by 53.92%. Cetuximab Among the motivations for making these devices available in health services, the most frequent was the saving of time (48.85%) and the least frequent, the perception that the use of this technology requires less training (9.40%). Arrhythmia was the most recognized contraindication for the use of automated monitors (28.49%), followed by obesity (28.14%) and blood pressure readings above 160 × 100 mmHg. In conclusion, there is a lack of knowledge about the functionalities and indications of blood pressure monitors and a low tolerance for measurements different from those obtained through manual mercury sphygmomanometers or aneroids.A chronic low-grade inflammation within adipose tissue (AT) seems to be the link between obesity and some of its associated diseases. One hallmark of this AT inflammation is the accumulation of AT macrophages (ATMs) around dead or dying adipocytes, forming so-called crown-like structures (CLS). To investigate the dynamics of CLS and their direct impact on the activation state of ATMs, we established a laser injury model to deplete individual adipocytes in living AT from double reporter mice (GFP-labeled ATMs and tdTomato-labeled adipocytes). Hence, we were able to detect early ATM-adipocyte interactions by live imaging and to determine a precise timeline for CLS formation after adipocyte death. Further, our data indicate metabolic activation and increased lipid metabolism in ATMs u