Susceptibility to proteolysis of triosephosphate isomerase from two pathogenic parasites: characterization of an enzyme with an intact and a nicked monomer

The susceptibility to subtilisin of homodimeric triosephosphate isomerase from Trypanosoma brucei (TbTIM) and Trypanosoma cruzi (TcTIM) was studied. Their amino sequence and 3D structure are markedly similar. In 36 h of incubation at a molar ratio of 4 TIM per subtilisin, TcTIM underwent extensive hydrolysis, loss of activity, and large structural alterations. Under the same conditions, only about 50% of the monomers of TbTIM were cleaved in two sites. The higher sensitivity of TcTIM to subtilisin is probably due to a higher intrinsic flexibility. We isolated and characterized TbTIM that had been exposed to subtilisin. It exhibited the molecular mass of the dimer, albeit it was formed by one intact and one nicked monomer. Its k(cat) with glyceraldehyde 3-phosphate was half that of native TbTIM, with no change in K(m). The intrinsic fluorescence of nicked TbTIM was red-shifted by 5 nm. The association between subunits was not affected. The TbTIM data suggest that there are structural differences in the two monomers or that alterations of one subunit change the characteristics of the other subunit. In comparison to the action of subtilisin on TIMs from other species, the trypanosomal enzymes appear to be unique.     

Aporphine alkaloids from Phoebe pittieri

The wood and bark of Phoebe pittieri afforded 1,2,3-trimethoxy-9,10-methylenedioxynoraporphine and 1,2,9-trimethoxy-10-hydroxynoraporphine (noraporphine), which are new alkaloids, and norpurpureine and reticuline, which have not been reported from this source before.     

Towards a morphogenetic perspective on cancer.

The purpose of this paper is to present a critique of the current view that reduces cancer to a cellular problem caused by specific gene mutations and to propose, instead, that such a problem might become more intelligible, if it is understood as a phenomenon which results from the breakdown of the morphological plan or Gestalt of the organism. Such an organism, in Aristotelian terms, is characterised for presenting a specific morpho or logos (form) and for having a telos (end) to fulfill. A malignant tumour represents an entity separated from both, the organic logos and the organic telos. According to the basic postulates of Semiophysics--a blend of Aristotelian physics and Catastrophe Theory developed by René Thom--an organism is a source (original) form individuated by a dominant pregnancy which corresponds to its morphogenetic field. Here it is suggested that cancer in aged individuals may result from the progressive exhaustion of the developmental constraints that regulate the process of ontogeny, that is expected to go from the fertilised non-differentiated zygote to the mature fully-developed organism, because there is no further point ahead in the developmental pathway past the reproductive age. Cancer in young individuals (before their reproductive maturity) may then be consequence of premature derangement of such fundamental developmental constraints. In all cases the result is the loss of morphological coherence within the organism. Thus representing a conflict between an organised morphology (the organism) and a part of such a morphology that drifts towards an amorphous state (the tumour).     

MUCILAGINOUS CAPSULE ADSORPTION AND INTRACELLULAR UPTAKE OF COPPER BY KIRCHNERIELLA APERTA (CHLOROCOCCALES)1

The purpose of the present investigation was to evaluate possible ecological and physiological functions of mucilaginous capsules produced by the freshwater algae Kirchneriella aperta Teiling (Chlorococcales) as related to copper ions. All experiments were performed using synthetic media under laboratory‐controlled conditions. Copper interactions were investigated by distinguishing between adsorption onto the mucilaginous material present at the surface of the cells, intracellular uptake, and differentiation between total dissolved copper and free copper ions in the culture medium. Kirchneriella aperta is sensitive to copper, as revealed by a 96‐h EC₅₀ value of 10 ^{? 9.22} M Cu^{2 +} . We demonstrated that the mucilaginous capsules were able to sequester copper ions from the medium through a passive mechanism, thus providing the cell with a mechanism able to postpone the toxic effects of copper. The organic material that diffuses into the test medium as well as the mucilaginous capsules produced by K. aperta both effectively complex copper; thus, toxicity must be related to free copper ions and not the total dissolved copper concentration in the medium.     

Esterification of methyl glycoside mixtures by lipase catalysis

The acylation of a mixture of methyl -D-galacto-, methyl -D-gluco- and methyl -D-mannopyranosides by octanoic acid was catalysed by lipases from Candida antarctica, Pseudomonas cepacia, Candida rugosa OF or Mucor miehei in acetonitrile at 45°C. The methyl glycopyranosides had the same anomeric configuration as that of the softwood hemicellulose galactoglucomannan. C. rugosa OF lipase had almost no substrate specificity and P. cepacia lipase had a high substrate specificity for the esterification of methyl -D-galactopyranoside.     

An EPR determination of copper complexation by excreted high molecular weight compounds of Ankistrodesmus densus (Chlorophyceae)

Electron paramagnetic resonance (EPR) spectra were obtainedfrom dialysed and dried samples of high mol. wt compounds (HMWC)excreted by Ankistrodesmus densus: precipitated with ethanol(A); ethanol soluble (B); and capsular material (C). The singlespectrum of A shows the existence of nitrogen coordination withcopper. The spectra of B show two distinct complexes: one similarto A and another without superhyperfine lines suggesting thepresence of oxygen ligands coordinated with ion. In C the spectraare similar to B with the concentration relation inverted. About20 µ g of ion is chelated by 1 mg of dried HMWC.     

A synoptical revision of Solandra (Solanaceae)

Taxonomic account of Solandra , a neotropical genus ranging from Mexico and West Indies to South America, with phytochemical, ethnobotanical and ornamental interest. Its systematic position and affinities are discussed in connection to Trianaea , the other genus of the tribe Solandreae. Ten species are recognized: S. boliviano, S. brachycalyx, S. brevicalyx, S. grandiflora, S. longiflora, S. maxima, S. nizandensis, S. paraensis, S. guerrerensis and 5. guttata.     

The Genetic Diversity of Influenza A Viruses in Wild Birds in Peru

Our understanding of the global ecology of avian influenza A viruses (AIVs) is impeded by historically low levels of viral surveillance in Latin America. Through sampling and whole-genome sequencing of 31 AIVs from wild birds in Peru, we identified 10 HA subtypes (H1-H4, H6-H7, H10-H13) and 8 NA subtypes (N1-N3, N5-N9). The majority of Peruvian AIVs were closely related to AIVs found in North America. However, unusual reassortants, including a H13 virus containing a PA segment related to extremely divergent Argentinian viruses, suggest that substantial AIV diversity circulates undetected throughout South America.     

Protein tyrosine phosphatase 1B inhibitors isolated from Artemisia roxburghiana

Artemisia roxburghiana is used in traditional medicine for treating various diseases including diabetes. The present study was designed to evaluate the antidiabetic potential of active constituents by using protein tyrosine phosphatase 1B (PTP1B) as a validated target for management of diabetes. Various compounds were isolated as active principles from the crude methanolic extract of aerial parts of A. roxburghiana. All compounds were screened for PTP1B inhibitory activity. Molecular docking simulations were performed to investigate the mechanism behind PTP1B inhibition of the isolated compound and positive control, ursolic acid. Betulinic acid, betulin and taraxeryl acetate were the active PTP1B principles with IC₅₀ values 3.49?±?0.02, 4.17?±?0.03 and 87.52?±?0.03?µM, respectively. Molecular docking studies showed significant molecular interactions of the triterpene inhibitors with Gly220, Cys215, Gly218 and Asp48 inside the active site of PTP1B. The antidiabetic activity of A. roxburghiana could be attributed due to PTP1B inhibition by its triterpene constituents, betulin, betulinic acid and taraxeryl acetate. Computational insights of this study revealed that the C-3 and C-17 positions of the compounds needs extensive optimization for the development of new lead compounds.