Alternative splicing (AS) is a mechanism that generates translational diversity within a genome. Equally important is the dynamic adaptability of the splicing machinery, which can give preference to one isoform over others encoded by a single gene. These isoform preferences change in response to the cell's state and function.
View Article and Find Full Text PDFThe ability of cells to manage consequences of exogenous proteotoxicity is key to cellular homeostasis. While a plethora of well-characterised machinery aids intracellular proteostasis, mechanisms involved in the response to denaturation of extracellular proteins remain elusive. Here we show that aggregation of protein ectodomains triggers their endocytosis via a macroendocytic route, and subsequent lysosomal degradation.
View Article and Find Full Text PDFAnaplastic thyroid cancer represents a rare, highly aggressive form of thyroid cancer with a poor prognosis and an overall survival ranging from 5 to 12 months. Unfortunately, treatment options remain limited, even for patients with a targetable driver mutation. Here, we present a case of a patient with a BRAF V600E-mutated, PD-L1 positive (tumor proportion score of 95%) anaplastic thyroid cancer refractory to standard therapies, including debulking surgery, followed by chemoradiation, who had further progressed on PD-1 monotherapy, and was unable to tolerate BRAF/MEK inhibition.
View Article and Find Full Text PDFBackground: The abdominal wall expanding system (AWEX) was first applied in 2012 and published in 2017. This novel technique was developed to reconstruct complex incisional hernias and residual skin-grafted laparostoma after treatment of an open abdomen, when primary midline closure was impossible. The main aim was the anatomical reconstruction of the abdominal wall and the avoidance of dissecting techniques (component separation).
View Article and Find Full Text PDF