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.

Serum chemistry profiling and prognostication in systemic mastocytosis: a registry-based study of the ECNM and GREM.

Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter.

Conservation energetics of beluga whales: using resting and swimming metabolism to understand threats to an endangered population.

The balance between energetic costs and acquisition in free-ranging species is essential for survival, and provides important insights regarding the physiological impact of anthropogenic disturbances on wild animals. For marine mammals such as beluga whales (Delphinapterus leucas), the first step in modeling this bioenergetic balance requires an examination of resting and active metabolic demands. Here, we used open-flow respirometry to measure oxygen consumption during surface rest and submerged swimming by trained beluga whales, and compared these measurements with those of a commonly studied odontocete, the Atlantic bottlenose dolphin (Tursiops truncatus).

Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis: A retrospective analysis of the DRST and GREM registries.

We identified 71 patients with AdvSM (aggressive SM [ASM], SM with an associated hematologic neoplasm [SM-AHN, e.g., acute myeloid leukemia, SM-AML], mast cell leukemia [MCL]) in two national registries (DRST/GREM) who received an allogeneic hematopoietic cell transplantation (alloHCT) performed in Germany from 1999-2021.

Poor Applicability of Currently Available Prognostic Scoring Systems for Prediction of Outcome in D816V-Negative Advanced Systemic Mastocytosis.

Within our nationwide registry, we identified a D816V mutation ( D816V in 280/299 (94%) patients with advanced systemic mastocytosis (AdvSM). Age, cytopenias and the presence of additional somatic mutations confer inferior overall survival (OS). However, little is known about the characteristics of D816V-negative (D816V) AdvSM.

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.

Prognostic Impact of Organomegaly in Mastocytosis: An Analysis of the European Competence Network on Mastocytosis.

Background: Organomegaly, including splenomegaly, hepatomegaly, and/or lymphadenopathy, are important diagnostic and prognostic features in patients with cutaneous mastocytosis (CM) or systemic mastocytosis (SM).

Objectives: To investigate the prevalence and prognostic impact of 1 or more organomegalies on clinical course and survival in patients with CM/SM.

Methods: Therefore, 3155 patients with CM (n = 1002 [32%]) or SM (n = 2153 [68%]) enrolled within the registry of the European Competence Network on Mastocytosis were analyzed.

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.

Capitalizing on paradoxical activation of the mitogen-activated protein kinase pathway for treatment of Imatinib-resistant mast cell leukemia.

Prevention of fatal side effects during cancer therapy of cancer patients with high-dosed pharmacological inhibitors is to date a major challenge. Moreover, the development of drug resistance poses severe problems for the treatment of patients with leukemia or solid tumors. Particularly drug-mediated dimerization of RAF kinases can be the cause of acquired resistance, also called "paradoxical activation.

Mast cell leukemia: clinical and molecular features and survival outcomes of patients in the ECNM Registry.

Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by ≥20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN).

Immunoglobulins to mitigate paraneoplastic Lambert Eaton Myasthenic Syndrome under checkpoint inhibition in Merkel cell carcinoma.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare, autoimmune or paraneoplastic condition characterized by muscle weakness and fatigability. In cancer therapy, immune checkpoint inhibitors (ICI) sensitize the immune system for tumor antigens. We report a 62-year-old, female patient with paraneoplastic LEMS as first manifestation of Merkel cell carcinoma.

Genetic Structure of a Worldwide Germplasm Collection of L. Reveals Three Major Diffusion Routes for Varieties Coming From the Species' Center of Origin.

The characterization of the largest worldwide representative data set of apricot ( L.) germplasm was performed using molecular markers. Genetic diversity and structure of the cultivated apricot genetic resources were analyzed to decipher the history of diffusion of this species around the world.

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.

Outcome of non-mold effective anti-fungal prophylaxis in patients at high-risk for invasive fungal infections after allogenic stem cell transplantation.

Patients who develop severe graft-versus-host disease (GvHD) after allogeneic stem cell transplantation (alloSCT) have a higher risk for invasive fungal infection (IFI). At our center, fluconazole prophylaxis is standard and upfront mold-effective prophylaxis performed only in patients with specific risk constellations. A total of 290 patients undergoing alloSCT between May 2002 and August 2011 were analyzed.

[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.

[Leukopenia - A Diagnostic Guideline for the Clinical Routine].

Reasons for leukopenia can be numerous. To get close to the diagnosis it's always useful to check previous blood counts of the patient to get a feeling for the dynamic development of the leukopenia. Furthermore, it's important to check the red blood cell count and platelet count as well; a bi- or a pancytopenia usually implies an insufficient production in the bone marrow.

A collection of European sweet cherry phenology data for assessing climate change.

Professional and scientific networks built around the production of sweet cherry (Prunus avium L.) led to the collection of phenology data for a wide range of cultivars grown in experimental sites characterized by highly contrasted climatic conditions. We present a dataset of flowering and maturity dates, recorded each year for one tree when available, or the average of several trees for each cultivar, over a period of 37 years (1978-2015).