Low degree metabolites explain essential reactions and enhance modularity in biological networks

Background  

Recently there has been a lot of interest in identifying modules at the level of genetic and metabolic networks of organisms, as well as in identifying single genes and reactions that are essential for the organism. A goal of computational and systems biology is to go beyond identification towards an explanation of specific modules and essential genes and reactions in terms of specific structural or evolutionary constraints.     

Cytogenetic characterization and H-ras associated transformation of immortalized human mammary epithelial cells

Introduction  

Immortalization is a key step in malignant transformation, but immortalization alone is insufficient for transformation. Human mammary epithelial cell (HMEC) transformation is a complex process that requires additional genetic changes beyond immortalization and can be accomplished in vitro by accumulation of genetic changes and expression of H-ras.     

Re-evaluation of how artemisinins work in light of emerging evidence of in vitro resistance

There are more than half a billion cases of malaria every year. Combinations of an artemisinin with other antimalarial drugs are now recommended treatments for Plasmodium falciparum malaria in most endemic areas. These treatment regimens act rapidly to relieve symptoms and effect cure. There is considerable controversy on how artemisinins work and over emerging indications of resistance to this class of antimalarial drugs. Several individual molecules have been proposed as targets for artemisinins, in addition to the idea that artemisinins might have many targets at the same time. Our suggestion that artemisinins inhibit the parasite-encoded sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) PfATP6 has gained support from recent observations that a polymorphism in the gene encoding PfATP6 is associated with in vitro resistance to artemether in field isolates of P. falciparum.     

Cadmium induced endothelial dysfunction: consequence of defective migratory pattern of endothelial cells in association with poor nitric oxide availability under cadmium challenge

Recent advances in cadmium toxicity research suggest an association between cadmium and vascular diseases. However, the mechanisms of cadmium implications in vascular diseases are not yet explained. The objective of our present study is to explore the mechanism of cadmium induced endothelial dysfunction. Doses of 0, 1 and 5microM cadmium chloride were used to test the effects of cadmium on nitric oxide induced tube formation, cellular migration and subcellular actin polymerization in ECV-304 endothelial cells. An egg-yolk vascular bed model was used to study the effects of cadmium on angiogenesis. Results of the present study show that 5microM cadmium chloride effectively inhibited angiogenesis, cellular migration and tube formation. Phalloidin staining, which represents actin polymerization of endothelial cells, reveals that cadmium induces an altered F-actin pattern, which could be the prime cause for cadmium mediated inhibition of cellular migration and angiogenesis. Cadmium was also found to inhibit nitric oxide production in endothelial cells in a calcium free medium, which further hints that cadmium might impair endothelial functions by inhibiting endothelial nitric oxide synthase.     

An experimental metagenome data management and analysis system

The application of shotgun sequencing to environmental samples has revealed a new universe of microbial community genomes (metagenomes) involving previously uncultured organisms. Metagenome analysis, which is expected to provide a comprehensive picture of the gene functions and metabolic capacity for microbial communities, needs to be conducted in the context of a comprehensive data management and analysis system. We present in this paper IMG/M, an experimental metagenome data management and analysis system that is based on the Integrated Microbial Genomes (IMG) system. IMG/M provides tools and viewers for analyzing both metagenomes and isolate genomes individually or in a comparative context. IMG/M is available at http://img.jgi.doe.gov/m.     

Threat-Related Acoustical Differences in Alarm Calls by Wild Bonnet Macaques (Macaca radiata) Elicited by Python and Leopard Models

Wild and urban bonnet macaques (Macaca radiata) were studied in southern India to record alarm calls during presentations of realistic models of spotted and dark leopards (Panthera pardus) and an Indian python (Python molurus). Recordings of alarm calls were made from members of four forest troops at feeding stations who observed brief and prolonged presentations of fully exposed spotted and dark leopard morphs and partially concealed views of the spotted morph. Four different forest troops were presented a slowly moving python near feeding stations. Two predator‐inexperienced urban troops from the city of Bangalore were presented either the spotted leopard morph briefly or the python. Analyses of alarm calls revealed differences in acoustic structure, such as a lower harmonic to noise ratio, which can be interpreted as reflecting the level of perceived threat rather than predator type. Noisy alarm calls likely indicate high states of physiological arousal that might provide eavesdropping troop members with information useful for assessing the urgency of the predatory threat. Lack of alarm‐call distinctiveness characterizing predator type is complemented by explicit contextual information in which alarm calling to leopards never occurred on the ground whereas nearly all initial python‐elicited alarm calls were made by individuals on the ground monitoring the python. The alarm calls of Bangalore monkeys distinguished the leopard and python models, with the latter engendering the noisiest calls and immediate flight to trees. Such flight is unnecessary with the python and suggests that, without appropriate experience with pythons, bonnet macaques adopt less predator specific refuge‐seeking behavior.     

Nitroarylhydroxymethylphosphonic acids as inhibitors of CD45

A series of nitroarylhydroxymethylphosphonic acids was synthesized and evaluated as inhibitors of CD45. It was discovered that both the alpha hydroxy and nitro groups are essential for activity. Potency is enhanced by the addition of a large lipophilic group on the aryl ring adjacent to the phosphonic acid moiety. Kinetics studies have shown that these compounds are competitive inhibitors and thus bind at the active site of this enzyme     

Neutralization of the hemorrhagic effect induced by Bothrops asper (Serpentes: Viperidae) venom with tropical plant extracts

Organic extracts representing 48 species included in 30 families of Costa Rican tropical plants were evaluated for their ability to neutralize hemorrhagic activity induced by the venom of the snake Bothrops asper. A bioassay in mice was used, based on intradermal injection of either venom or venom-extract mixtures followed by the measurement of hemorrhagic areas. Total inhibition of hemorrhage was observed with the ethanolic, ethyl acetate and aqueous extracts of Bursera simaruba, Clusia torresii, C. palmana, Croton draco, Persea americana, Phoebe brenesii, Pimenta dioica, Sapindus saponaria, Smilax cuculmeca and Virola koschnyi. Chemical analysis of these extracts identified catequines, flavones, anthocyanines and condensated tannins, which may be responsible for the inhibitory effect observed, probably owing to the chelation of the zinc required for the catalytic activity of venom's hemorrhagic metalloproteinases.