Modeling the biocoenose of parasitic diseases using remote sensing and geographic information systems

Application of growing degree day-water budget analysis concepts to snail-borne diseases are reviewed to demonstrate use of the unique thermal-hydrological preferences and limits of tolerance of individual parasite-vector systems to define the environmental niche of disease agents in the landscape by modern geospatial analysis tools.     

Microtubule dynamics: new surprises from an old MAP

Dis1/XMAP215 family microtubule-binding proteins are essential for cell division in animals, plants and fungi, suggesting a conserved cell-division mechanism used by all eukaryotes. Two new studies, however, reveal that different family members can have very different effects on microtubule dynamics.     

Nesprin-1alpha self-associates and binds directly to emerin and lamin A in vitro

The mitogen-stimulated protein kinase p70(s6k)/p85(s6k) (S6K) plays an essential role in cell proliferation and growth, with inhibitors of the S6K signalling pathway showing promise as anti-tumour therapeutics. Here, we report that the bisindolylmaleimide derivative Ro 31-6045, previously reported to be inactive as a kinase inhibitor, inhibited S6K activity in vivo with an IC50=8 microM. Structure/function analysis using mutant forms of S6K indicates that Ro 31-6045 inhibition is independent of the upstream activator mTOR. Ro 31-6045 will prove useful in elucidating the complex activation mechanism of S6K and its independence from mTOR will allow confirmation of functional data obtained using the mTOR inhibitor rapamycin.     

Design and in vivo immunogenicity of a polyvalent vaccine based on SIVmac regulatory genes

Most vaccine modalities for human immunodeficiency virus type 1 (HIV-1) tested for immunogenicity and efficacy in the SIVmac (simian immunodeficiency virus) macaque model do not include the viral regulatory proteins. Because viral regulatory proteins are expressed early during the virus life cycle and represent an additional source of antigens, their inclusion as a vaccine component may increase the overall virus-specific immune response in vaccinees. However, at least two of the early proteins, Tat and Nef, may be immunosuppressive, limiting their usefulness as components of an SIV vaccine. We have constructed a polyvalent chimeric protein in which the open reading frames for Tat and Nef have been reassorted and the nuclear localization sequence for Tat and Rev and the myristoylation site for Nef have been removed. The resulting DNA plasmid (pDNA-SIV-Retanef) (pDNA-SIV-RTN) encodes a protein of 55 kDa (Retanef) that localizes at the steady state in the cytoplasma of transfected cells. Both the DNA-SIV-RTN and the highly attenuated recombinant poxvirus vector NYVAC-SIV-RTN were demonstrated to be immunogenic in SIVmac251-infected macaques treated with ART as well as in naive macaques. An equivalent strategy may be used for the generation of polyvalent antigens encoding the regulatory proteins in a HIV-1 vaccine candidate.