Colon: Colorectal adenocarcinoma

Review on Colon: Colorectal adenocarcinoma, with data on clinics, and the genes involved

Hobo elements and their deletion-derivative sequences in Drosophila melanogaster and its sibling species D simulans, D mauritiana and D sechellia

International audienc

A two-directional target optimization model.

This paper presents an algorithm for computing the optimal target path for two aircraft traversing a target area from different directions. There are constraints on the maneuverability of each aircraft which prohibit it from attacking every target. The algorithm chooses a subset of targets whose destruction will yield maximum value to the attacking force. The basis of the algorithm is the branch and bound method, with upper bounds computed by dynamic programming. Several variations are considered, such as payload limit, an increased number of aircraft from each direction, and a three-directional attack. An example problem is solved using the basic model. A Fortran IV computer program is included. Computation time versus problem characteristics is discussed.http://archive.org/details/twodirectionalta00hameLieutenant, United States NavyApproved for public release; distribution is unlimited

P53 (protein 53 kDa)

Review on P53 (protein 53 kDa), with data on DNA, on the protein encoded, and where the gene is implicated

Involvement of Plasmodium falciparum protein kinase CK2 in the chromatin assembly pathway

<p>Abstract</p> <p>Background</p> <p>Protein kinase CK2 is a pleiotropic serine/threonine protein kinase with hundreds of reported substrates, and plays an important role in a number of cellular processes. The cellular functions of <it>Plasmodium falciparum </it>CK2 (PfCK2) are unknown. The parasite's genome encodes one catalytic subunit, PfCK2α, which we have previously shown to be essential for completion of the asexual erythrocytic cycle, and two putative regulatory subunits, PfCK2β1 and PfCK2β2.</p> <p>Results</p> <p>We now show that the genes encoding both regulatory PfCK2 subunits (PfCK2β1 and PfCK2β2) cannot be disrupted. Using immunofluorescence and electron microscopy, we examined the intra-erythrocytic stages of transgenic parasite lines expressing hemagglutinin (HA)-tagged catalytic and regulatory subunits (HA-CK2α, HA-PfCK2β1 or HA-PfCK2β2), and localized all three subunits to both cytoplasmic and nuclear compartments of the parasite. The same transgenic parasite lines were used to purify PfCK2β1- and PfCK2β2-containing complexes, which were analyzed by mass spectrometry. The recovered proteins were unevenly distributed between various pathways, with a large proportion of components of the chromatin assembly pathway being present in both PfCK2β1 and PfCK2β2 precipitates, implicating PfCK2 in chromatin dynamics. We also found that chromatin-related substrates such as nucleosome assembly proteins (Naps), histones, and two members of the Alba family are phosphorylated by PfCK2α <it>in vitro</it>.</p> <p>Conclusions</p> <p>Our reverse-genetics data show that each of the two regulatory PfCK2 subunits is required for completion of the asexual erythrocytic cycle. Our interactome study points to an implication of PfCK2 in many cellular pathways, with chromatin dynamics being identified as a major process regulated by PfCK2. This study paves the way for a kinome-wide interactomics-based approach to elucidate protein kinase function in malaria parasites.</p

Singularities in ternary mixtures of k-core percolation

Heterogeneous k-core percolation is an extension of a percolation model which has interesting applications to the resilience of networks under random damage. In this model, the notion of node robustness is local, instead of global as in uniform k-core percolation. One of the advantages of k-core percolation models is the validity of an analytical mathematical framework for a large class of network topologies. We study ternary mixtures of node types in random networks and show the presence of a new type of critical phenomenon. This scenario may have useful applications in the stability of large scale infrastructures and the description of glass-forming systems.Comment: To appear in Complex Networks, Studies in Computational Intelligence, Proceedings of CompleNet 201

Function-guided proximity mapping unveils electrophilic-metabolite sensing by proteins not present in their canonical locales.

Enzyme-assisted posttranslational modifications (PTMs) constitute a major means of signaling across different cellular compartments. However, how nonenzymatic PTMs-despite their direct relevance to covalent drug development-impinge on cross-compartment signaling remains inaccessible as current target-identification (target-ID) technologies offer limited spatiotemporal resolution, and proximity mapping tools are also not guided by specific, biologically-relevant, ligand chemotypes. Here we establish a quantitative and direct profiling platform (Localis-rex) that ranks responsivity of compartmentalized subproteomes to nonenzymatic PTMs. In a setup that contrasts nucleus- vs. cytoplasm-specific responsivity to reactive-metabolite modification (hydroxynonenylation), ∼40% of the top-enriched protein sensors investigated respond in compartments of nonprimary origin or where the canonical activity of the protein sensor is inoperative. CDK9-a primarily nuclear-localized kinase-was hydroxynonenylated only in the cytoplasm. Site-specific CDK9 hydroxynonenylation-which we identified in untreated cells-drives its nuclear translocation, downregulating RNA-polymerase-II activity, through a mechanism distinct from that of commonly used CDK9 inhibitors. Taken together, this work documents an unmet approach to quantitatively profile and decode localized and context-specific signaling/signal-propagation programs orchestrated by reactive covalent ligands