Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.Comment: 49 pages, 2 figures, 2 tables, 10 supplementary figures, 13 supplementary table

Understanding diabetes in patients with HIV/AIDS

This paper reviews the incidence, pathogenetic mechanisms and management strategies of diabetes mellitus in patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). It classifies patients based on the aetiopathogenetic mechanisms, and proposes rational methods of management of the condition, based on aetiopathogenesis and concomitant pharmacotherapy

Distortion of spores of moss Venturiella under ultra high pressure

In our previous studies on the tolerance of living organisms such as planktons and spores of mosses to the high hydrostatic pressure of 7.5 GPa, we showed that all the samples could be borne at this high pressure. These studies have been extended to the extreme high pressure of 20GPa by using a Kawai-type octahedral anvil press. It was found that the average diameter of the spores of Venturiella exposed to 20GPa for 30min was 25.5m, which is 16.5% smaller (40.0% smaller in volume) than that of the control group which was not exposed to high pressure. The inner organisms showed a further extent of plastic deformation. As a result, a gap appeared between the outer cover and the cytoplasm. A relationship has been obtained between the survival ratio and plastic deformation of spores of moss Venturiella caused by the application of ultra high pressure

Effect of very high pressure on life of plants and animals

We studied the tolerance of living organisms, such as a small animal (Milnesium tardigradum), a small crustacean (Artemia), non-vascular plants or moss (Ptichomitrium and Venturiella), and a vascular plant (Trifolium) to the extremely high hydrostatic pressure of 7.5 GPa. It turned out that most of the high pressure exposed seeds of white clover were alive. Those exposed to 7.5 GPa for up to 1 day and seeded on agar germinated roots. Those exposed for up to 1 hour and seeded on soil germinated stems and leaves. Considering the fact that proteins begins to unfold around 0.3 GPa, it seems difficult to understand that all the living samples which have been investigated can survive after exposure to 7.5 GPa