Nek1 shares structural and functional similarities with NIMA kinase

AbstractThe Aspergillus NIMA serine/threonine kinase plays a pivotal role in controlling entrance into mitosis. A major function attributed to NIMA is the induction of chromatin condensation. We show here that the founder murine NIMA-related kinase, Nek1, is larger than previously reported, and that the full-length protein conserves the structural hallmarks of NIMA. Even though Nek1 bears two classical nuclear localization signals (NLS), the endogenous protein localizes to the cytoplasm. Ectopic overexpression of various Nek1 constructs suggests that the C-terminus of Nek1 bears cytoplasmic localization signal(s). Overexpression of nuclear constructs of Nek1 resulted in abnormal chromatin condensation, with the DNA mainly confined to the periphery of the nucleus. Advanced condensation phenotype was associated with nuclear pore complex dispersal. The condensation was not accompanied by up-regulation of mitotic or apoptotic markers. A similar phenotype has been described following NIMA overexpression, strengthening the notion that the mammalian Nek1 kinase has functional similarity to NIMA

A framework for a distributed, hybrid, multiple-ontology clinical-guideline library, and automated guideline-support tools

AbstractClinical guidelines are a major tool in improving the quality of medical care. However, most guidelines are in free text, not in a formal, executable format, and are not easily accessible to clinicians at the point of care. We introduce a Web-based, modular, distributed architecture, the Digital Electronic Guideline Library (DeGeL), which facilitates gradual conversion of clinical guidelines from text to a formal representation in chosen target guideline ontology. The architecture supports guideline classification, semantic markup, context-sensitive search, browsing, run-time application, and retrospective quality assessment. The DeGeL hybrid meta-ontology includes elements common to all guideline ontologies, such as semantic classification and domain knowledge; it also includes four content-representation formats: free text, semi-structured text, semi-formal representation, and a formal representation. These formats support increasingly sophisticated computational tasks. The DeGeL tools for support of guideline-based care operate, at some level, on all guideline ontologies. We have demonstrated the feasibility of the architecture and the tools for several guideline ontologies, including Asbru and GEM

Sand fly dispersal from the five marking sites.

<p>A-yellow, B-green, C-red, D-orange, E-blue. Black stars indicate the marking sites, the annuli used for MDT calculation are marked by the concentric rings.</p

Number and proportion of marked non-dispersing sand flies, in the marking sites traps.

<p>Number and proportion of marked non-dispersing sand flies, in the marking sites traps.</p

The number of dispersing sand flies, mean (MDT) and maximal (Max) travel distances.

<p>The number of dispersing sand flies, mean (MDT) and maximal (Max) travel distances.</p

Trapping efforts and sand fly data summarized according to land use category.

<p>Trapping efforts and sand fly data summarized according to land use category.</p

Melting curve features of <i>Leishmania major</i>, <i>L</i>. <i>tropica</i>, <i>L</i>. <i>infantum/donovani</i>, <i>L</i>. <i>aethipica</i> and <i>L</i>. <i>arabica</i>.

<p>Melting curve features of <i>Leishmania major</i>, <i>L</i>. <i>tropica</i>, <i>L</i>. <i>infantum/donovani</i>, <i>L</i>. <i>aethipica</i> and <i>L</i>. <i>arabica</i>.</p