Influence of interstitial fluid dynamics on growth and therapy of angiogenic tumor. Analysis by mathematical model

We have developed a spatially distributed mathematical model of angiogenic tumor growth in tissue with account of interstitial fluid dynamics and bevacizumab monotherapy. In this model the process of neovascularization is initiated by tumor cells in a state of metabolic stress, vascular endothelial growth factor (VEGF) being its main mediator. The model takes into consideration the convection flows arising in dense tissue due to active proliferation and migration of tumor cells as well as interstitial fluid inflow from blood vascular system, its outflow through lymphatic system and redistribution in the area of tumor growth. The work considers the diffusive approximation of interstitial fluid dynamics in tumor and normal tissue. Numerical study of the model showed that in absence of therapy a peritumoral edema is formed due to the increase of interstitial fluid inflow from angiogenic capillaries. In the case of rapid interstitial fluid outflow through lymphatic system and its fast transport from necrotic zone to normal tissue the regimes of full growth stop are observed in case of low-invasive tumor. Under bevacizumab monotherapy the peritumoral edema vanishes and low-invasive tumor may not only decelerate its growth, but also start shrinking for a large range of parameters.     

The quaternary structure of bovine brain kinesin.

In the present work we have studied the subunit composition of kinesin, the microtubule-activated, mechanochemical ATPase, isolated from bovine brain. Polypeptides with mol. wts of 120 and 62 kd are the major components of the kinesin preparation. These polypeptides could not be separated by electrophoresis under nondenaturing conditions or by FPLC on a MonoQ column, and are therefore assumed to form a tight complex. As shown by immunoblotting with polyclonal and monoclonal antibodies to the 120-kd polypeptide and by one-dimensional peptide mapping, the 62-kd polypeptide does not appear to be a proteolytic product of the 120-kd component. Densitometric scanning of polyacrylamide-SDS gels shows that these polypeptides are present in a complex in a 1:1 molar ratio. The mol. wt of native kinesin was studied by sedimentation equilibrium and was found to be 386 +/- 14 kd. A comparison of the mol. wts of individual polypeptides with the mol. wt of the intact molecule indicates that the native molecule contains two 120-kd subunits and two 62-kd subunits.     

Planktonic viruses,heterotrophic bacteria,and nanoflagellates in fresh and coastal marine waters of the Kara Sea Basin (the Arctic)

In August–September 2009, the concentration of dissolved organic matter and quantitative distribution of virioplankton, bacterioplankton, and heterotrophic nanoflagellates were studied in the coastal waters of the Kara Sea, the fresh waters of the islands and the coasts of the sea, and the estuaries of the Ob’ and Yenisei rivers. A high positive correlation was observed between the abundances of viruses and bacteria. The frequency of visibly infected bacteria in marine waters ranged from 0.6 to 4.3% (an average of 1.6%); in the fresh waters of islands and coastline and in estuaries, it ranged from 0.3 to 3.9% (an average of 1.5%) and from 0.5 to 1.6% (an average of 1.1%) respectively. In most surveyed water bodies, the role of viruses in bacterioplankton mortality was considerably higher than that of heterotrophic flagellates.     

Pre-steady-state kinetics shows differences in processing of various DNA lesions by Escherichia coli formamidopyrimidine-DNA glycosylase

Formamidopyrimidine-DNA-glycosylase (Fpg pro tein, MutM) catalyses excision of 8-oxoguanine (8-oxoG) and other oxidatively damaged purines from DNA in a glycosylase/apurinic/apyrimidinic-lyase reaction. We report pre-steady-state kinetic analysis of Fpg action on oligonucleotide duplexes containing 8-oxo-2′-deoxyguanosine, natural abasic site or tetrahydrofuran (an uncleavable abasic site analogue). Monitoring Fpg intrinsic tryptophan fluorescence in stopped-flow experiments reveals multiple conformational transitions in the protein molecule during the catalytic cycle. At least four and five conformational transitions occur in Fpg during the interaction with abasic and 8-oxoG-containing substrates, respectively, within 2 ms to 10 s time range. These transitions reflect the stages of enzyme binding to DNA and lesion recognition with the mutual adjustment of DNA and enzyme structures to achieve catalytically competent conformation. Unlike these well-defined binding steps, catalytic stages are not associated with discernible fluorescence events. Only a single conformational change is detected for the cleavable substrates at times exceeding 10 s. The data obtained provide evidence that several fast sequential conformational changes occur in Fpg after binding to its substrate, converting the protein into a catalytically active conformation.     

Relative occurrence of amino acid-nucleotide contacts assessed by Voronoi-Delaunay tessellation of protein-DNA interfaces

The data for 1109 protein-DNA complexes in PDB were analyzed for direct contacts between particular amino acid residues and nucleotides by rigorous space partitioning (Voronoi-Delaunay tessellation). When the actual occurrence of each kind of residue-nucleotide contact in the interface was related to its chance expectation, the most abundant contacts (made by Arg or Lys as well as by Ser or Thr) proved indiscriminate to heterocyclic bases, whereas a number of other, rarer contacts were clearly nonrandom, being significantly overrepresented or underrepresented in the sample of interfaces. Especially remarkable was the high overrepresentation of G/C contacts with negatively charged Asp/Glu. The nonrandom combinations showed no distinctions between purines and pyrimidines. This first step in formal analysis provides some hints concerning the accessibility of the “protein-DNA recognition code.”     

Parthenogenetic activation of bovine oocytes maturing in vitro]

The effect of hyaluronidase (0.3%) and killed bull spermatozoa on the parthenogenetic activation of cow oocytes matured in vitro until metaphase II was studied. It is shown that hyaluronidase, killed spermatozoa, and both agents in combination activate 3.4, 15.0 and 29.6% oocytes, respectively.