Mechanism of Ca²⁺-triggered ESCRT assembly and regulation of cell membrane repair.

In muscle and other mechanically active tissue, cell membranes are constantly injured and their repair depends on the injury induced increase in cytosolic calcium. Here we show that injury-triggered Ca(2+) increase results in assembly of ESCRTIII and accessory proteins at the site of repair. This process is initiated by the calcium binding protein - Apoptosis Linked Gene (ALG)-2. ALG-2 facilitates accumulation of ALG-2 interacting protein X (ALIX), ESCRT III, and Vps4 complex at the injured cell membrane, which in turn results in cleavage and shedding of the damaged part of the cell membrane. Lack of ALG-2, ALIX, or Vps4B each prevents shedding, and repair of the injured cell membrane. These results demonstrate Ca(2+)-dependent accumulation of ESCRTIII-Vps4 complex following large focal injury to the cell membrane and identify the role of ALG-2 as the initiator of sequential ESCRTIII-Vps4 complex assembly that facilitates scission and repair of the injured cell membrane

The S505A thrombopoietin receptor mutation in childhood hereditary thrombocytosis and essential thrombocythemia is S505N: single letter amino acid code matters.

Dear Editor, Myeloproliferative neoplasms (MPNs) are rare diseases in children [1] when compared to adults [2]. Targeted sequencing revealed differences in the mutational landscape of pediatric and adult MPNs [1]. Children exhibit a lower frequency of mutations in the MPN driver genes JAK2, MPL, and CALR, and a much higher proportion of children exhibit no mutation among the 104 classically involved genes; these children exhibiting a trend towards essential thrombocythemia (ET) [1]. We were surprised to read about an activating thrombopoietin receptor (TpoR/Mpl) S505A transmembrane domain (TM) mutation in childhood hereditary thrombocytosis (HT) and ET [3–5]. [...

A GPU-Based Backtracking Algorithm for Permutation Combinatorial Problems

International audienceThis work presents a GPU-based backtracking algorithm for permutation combinatorial problems based on the Integer-Vector-Matrix (IVM) data structure. IVM is a data structure dedicated to permutation combinatorial optimization problems. In this algorithm, the load balancing is performed without intervention of the CPU, inside a work stealing phase invoked after each node expansion phase. The proposed work stealing approach uses a virtual n-dimensional hypercube topology and a triggering mechanism to reduce the overhead incurred by dynamic load balancing. We have implemented this new algorithm for solving instances of the Asymmetric Travelling Salesman Problem by implicit enumeration, a scenario where the cost of node evaluation is low, compared to the overall search procedure. Experimental results show that the dynamically load balanced IVM-algorithm reaches speed-ups up to 17X over a serial implementation using a bitset-data structure and up to 2X over its GPU counterpart