Autophagic Cell Death in Dictyostelium Requires the Receptor Histidine Kinase DhkM

Through random mutagenesis, the receptor histidine kinase DhkM was found essential for autophagic cell death (ACD) in Dictyostelium. DhkM is the most downstream known molecule required for this model ACD. Different DhkM mutants showed distinct non-vacuolizing ACD phenotypes and genetically separated previously undissociated late cell death events

Graph Partitioning Algorithms With Applications To Scientific Computing

Identifying the parallelism in a problem by partitioning its data and tasks among the processors of a parallel computer is a fundamental issue in parallel computing. This problem can be modeled as a graph partitioning problem in which the vertices of a graph are divided into a specified number of subsets such that few edges join two vertices in different subsets. Several new graph partitioning algorithms have been developed in the past few years, and we survey some of this activity. We describe the terminology associated with graph partitioning, the complexity of computing good separators, and graphs that have good separators. We then discuss early algorithms for graph partitioning, followed by three new algorithms based on geometric, algebraic, and multilevel ideas. The algebraic algorithm relies on an eigenvector of a Laplacian matrix associated with the graph to compute the partition. The algebraic algorithm is justified by formulating graph partitioning as a quadratic assignment p..

Structural insights into the extracellular assembly of the hematopoietic Flt3 signaling complex.

The class III receptor tyrosine kinase (RTKIII) Fms-like tyrosine kinase receptor 3 (Flt3) and its cytokine ligand (FL) play central roles in hematopoiesis and the immune system, by establishing signaling cascades crucial for the development and homeostasis of hematopoietic progenitors and antigen-presenting dendritic cells. However, Flt3 is also one of the most frequently mutated receptors in hematologic malignancies and is currently a major prognostic factor and clinical target for acute myeloid leukemia. Here, we report the structural basis for the Flt3 ligand-receptor complex and unveil an unanticipated extracellular assembly unlike any other RTKIII/V complex characterized to date. FL induces dimerization of Flt3 via a remarkably compact binding epitope localized at the tip of extracellular domain 3 of Flt3, and it invokes a ternary complex devoid of homotypic receptor interactions. Comparisons of Flt3 with homologous receptors and available mutagenesis data for FL have allowed us to rationalize the unique features of the Flt3 extracellular assembly. Furthermore, thermodynamic dissection of complex formation points to a pronounced enthalpically driven binding event coupled to an entropic penalty. Together, our data suggest that the high-affinity Flt3:FL complex is driven in part by a single preformed binding epitope on FL reminiscent of a "lock-and-key" binding mode, thereby setting the stage for antagonist design