The mTOR pathway controls phosphorylation of BRAF at T401.

BRAF serves as a gatekeeper of the RAS/RAF/MEK/ERK pathway, which plays a crucial role in homeostasis. Since aberrant signalling of this axis contributes to cancer and other diseases, it is tightly regulated by crosstalk with the PI3K/AKT/mTOR pathway and ERK mediated feedback loops. For example, ERK limits BRAF signalling through phosphorylation of multiple residues.

BRAF in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability.

In-frame exon 12 deletions are increasingly identified in various tumor types. The resultant BRAF oncoproteins usually lack five amino acids in the β3-αC helix linker and sometimes contain de novo insertions. The dimerization status of BRAF oncoproteins, their precise pathomechanism, and their direct druggability by RAF inhibitors (RAFi) has been under debate.

Mast cell deficiency prevents BCR::ABL1 induced splenomegaly and cytokine elevation in a CML mouse model.

The persistence of leukemic stem cells (LSCs) represents a problem in the therapy of chronic myeloid leukemia (CML). Hence, it is of utmost importance to explore the underlying mechanisms to develop new therapeutic approaches to cure CML. Using the genetically engineered ScltTA/TRE-BCR::ABL1 mouse model for chronic phase CML, we previously demonstrated that the loss of the docking protein GAB2 counteracts the infiltration of mast cells (MCs) in the bone marrow (BM) of BCR::ABL1 positive mice.

Sugar infusion into trees: A novel method to study tree carbon relations and its regulations.

Many carbon-related physiological questions in plants such as carbon (C) limitation or starvation have not yet been resolved thoroughly due to the lack of suitable experimental methodology. As a first step towards resolving these problems, we conducted infusion experiments with bonsai trees () and young maple trees () in greenhouse, and with adult Scots pine trees () in the field, that were "fed" with C-labelled glucose either through the phloem or the xylem. We then traced the C-signal in plant organic matter and respiration to test whether trees can take up and metabolize exogenous sugars infused.

Item Response Model Validation of the German ICD-11 International Trauma Questionnaire for PTSD and CPTSD.

Background: In the 11th revision of the International Classification of Diseases (ICD-11) posttraumatic stress disorder (PTSD) and the complex variant (CPTSD) were newly conceptualised. The International Trauma Questionnaire (ITQ) was developed as a brief self-report measure to screen for both disorders. The English original version has been rigorously tested and presents convincing psychometric properties.

The secreted inhibitor of invasive cell growth CREG1 is negatively regulated by cathepsin proteases.

Previous clinical and experimental evidence strongly supports a breast cancer-promoting function of the lysosomal protease cathepsin B. However, the cathepsin B-dependent molecular pathways are not completely understood. Here, we studied the cathepsin-mediated secretome changes in the context of the MMTV-PyMT breast cancer mouse model.

[Immunosuppression, Surgery, Complication?].

Immunosuppression, Surgery, Complication? Abstract. Surgical conditions sometimes pose major diagnostic and therapeutic challenges for immunosuppressed patients. Especially in patients suffering from diseases with potential septic emergencies or postoperative complications, the indication for elective surgery should be discussed at an early stage.

Deaths caused by malaria in Switzerland 1988-2002.

Despite sophisticated intensive medicine, between one and three malaria-associated deaths occur annually in Switzerland. In this retrospective study, 33 deaths (25 men and 8 women) caused by falciparum malaria reported in Switzerland from 1988 to 2002 were analyzed. The case fatality ratio (CFR) for the falciparum infections for the 15-year period was 1.

Multidimensional analysis of learning curves in laparoscopic sigmoid resection: eight-year results.

Purpose: The number of operations to reach a plateau phase in colorectal laparoscopic surgery is still under debate. There are few publications reporting on multidimensional assessment of the learning curve, including operation time and complication and conversion rates. The purpose of this study was to define a multidimensional learning curve for sigmoid resection performed by two surgeons with experience in laparoscopic surgery.