Characterization of complex biological systems by matrix invariants.

One direction in exploring similarities among biological sequences (such as DNA, RNA, and proteins), is to associate with such systems ordered sets of sequence invariants. These invariants represent selected properties of mathematical objects, such as matrices, that one can associate with biological sequences. In this article, we are exploring properties of recently introduced Line Distance matrices, and in particular we consider properties of their eigenvalues. We prove that Line Distance matrices of size n have one positive and n - 1 negative eigenvalues. Visual representation of Cauchy's interlacing property for Line Distance matrices is considered. Matlab programs for line distance matrices and examples are available on the following website: www.fmf.uni-lj.si/ approximately jaklicg/ldmatrix.html.     

Radiosensitizing and damaging effects of hyperthermia on different biological systems. Ehrlich ascites carcinoma cells

The cytotoxic and radiosensitizing effects of hyperthermia was shown on Ehrlich ascites tumor cells heated in vitro. The effect of hyperthermia resulted in the formation of local lesions in membranes of dying cells.     

Chemical mutagens: Dosimetry,Haber's rule and linear systems

We present an overall scheme for chemical mutagen risk assessment, which leads naturally to consideration of Haber's rule, a classical concept of toxicology. A rationale is given for considering compartmental models based on mammalian anatomy and physiology as the most reasonable and practical conceptual framework for risk assessment. Haber's rule is extended to the area of chemical dosimetry, defined in terms of our compartmental models. Then it is proved that Haber's rule holds for any system of linear ordinary differential equations with constant coefficients which is physically realizable. Finally, we comment on non-linearities and on the Blum-Druckey model for time-to-occurrence of tumors.     

Immunosuppressive molecules produced by Sertoli cells cultured in vitro: biological effects on lymphocytes.

In the present study we have analyzed the proteins secreted in vitro by murine Sertoli cells to identify immunosuppressive factors. Our data show that Sertoli cells secrete molecules capable to inhibit proliferation of lymphocytes activated in vitro. Cytophluorimetric analysis indicates that treated cells are arrested in the G1 phase of cell cycle. The inhibitory activity is specific for both B or T lymphocytes but not for other non-lymphoid cells and is associated to proteins, heat and freeze stable, with Mr of more than 30 kDa. Lymphocytes treated with Sertoli immunosuppressive proteins drastically reduce the secretion of interleukin-2.     

Study of the biological effects and DNA damage exerted by a new dipalladium-Hmtpo complex on human cancer cells

The new dipalladium complex [Pd(2)(mu-mtpo-N(3),N(4))(2)(phen)(2)](NO(3))(2) (where phen=1,10-phenantroline; Hmtpo=5,7-dihydro-7-oxo-5-methyl[1,2,4]triazolopyrimidine), (Pd(2)-Hmtpo, or complex I), interacts effectively with DNA plasmid (pBS), as studied by circular dichroism spectroscopy (CD), causing large helix distortions, altering the direction of the main DNA helix axis and producing unwinding of the DNA double helix. DNA damage induced by complex I was highly significant at 2.81 microM (ovarian carcinoma TG cell line), as assessed by comet assay, a dose at which all treated nuclei showed more than 30% DNA migration to the comet tail. DNA damage effect is a consequence of genotoxicity and not a false positive response caused by cytotoxicity. In vitro cytotoxic assay on the two human tumor cell lines TG and BT-20 (breast carcinoma), shows that doses of 0.47, 1.41 and 2.81 microM produce significant antiproliferative effects after 4 days of treatment compared with control. Complex I was highly cytotoxic at 2.81 microM causing an inhibition of viable cells of 65.5%. Cisplatin (cis-DDP) exhibits lower cytotoxic activity in TG cells than dipalladium complex (a cisplatin dose of 6.67 microM inhibits 30.3%) and does not cause migration of DNA to comet tail.     

Organic transformations catalyzed by engineered yeast cells and related systems

Asymmetric ketone reductions remain the most popular application of baker's yeast (Saccharomyces cerevisiae) in organic synthesis and data from the genome sequencing project is beginning to have an impact on improving the stereoselectivities of these reactions, augmenting traditional approaches based on selective inhibition. In addition, the catalytic repertoire of yeast has been expanded to include chiral ketone oxidations by overexpression of a bacterial Baeyer-Villiger monooxygenase.     

Honeydew honey: biological effects on skin cells

Multiple myeloma (MM) remains incurable by conventional chemotherapy. Sphingosine-1-phosphate (S1P) receptor-mediated signaling has been recently demonstrated to have critical roles in cell survival and drug resistance in a number of hematological malignancies. To dissect the roles of S1P receptor pathway in MM, we systematically examined cell viability and protein expression associated with cell survival and drug resistance in MM cell lines upon treatment with either pathway activator (S1P) or inhibitor (FTY720). Our results reveal that FTY720 inhibits cell proliferation by downregulating expression of target genes, while S1P has an opposite effect. Knocking down of S1P receptor S1P5R results in a reduction of cell survival-related gene expression; however, it does not have impacts on expression of drug resistance genes. These results suggest that S1P signaling plays a role in cell proliferation and drug resistance in MM, and targeting this pathway will provide a new therapeutic direction for MM management.     

Enzymes of pentose biosynthesis. The quaternary structure and reacting form of transketolase from baker's yeast

Transketolase from baker's yeast is a dimeric enzyme with a molecular weight of 158,000 ± 4000. Sedimentation velocity and sedimentation equilibrium experiments indicate that the enzyme dissociates at low concentrations (less than 0.1 mg/ml) in the absence of the coenzyme, thiamine pyrophosphate. However, no such dissociation was detected in the presence of coenzyme. Reacting enzyme sedimentation velocity measurements showed that the reacting species of the enzyme is a dimer with an s_20,w of 7.7 S.     

In vitro cultured cells as probes for space radiation effects on biological systems

Near future scenarios of long-term and far-reaching manned space missions, require more extensive knowledge of all possible biological consequences of space radiation, particularly in humans, on both a long-term and a short-term basis. In vitro cultured cells have significantly contributed to the tremendous advancement of biomedical research. It is therefore to be expected that simple biological systems such as cultured cells, will contribute to space biomedical sciences. Space represents a novel environment, to which life has not been previously exposed. Both microgravity and space radiation are the two relevant components of such an environment, but biological adaptive mechanisms and efficient countermeasures can significantly minimize microgravity effects. On the other hand, it is felt that space radiation risks may be more relevant and that defensive strategies can only stem from our deeper knowledge of biological effects and of cellular repair mechanisms. Cultured cells may play a key role in such studies. Particularly, thyroid cells may be relevant because of the exquisite sensitivity of the thyroid gland to radiation. In addition, a clone of differentiated, normal thyroid follicular cells (FRTL5 cells) is available in culture, which is well characterized and particularly fit for space research.     

Reduction enhances yields of nitric oxide trapping by iron-diethyldithiocarbamate complex in biological systems.

The mechanism of NO trapping by iron-diethylthiocarbamate complexes was investigated in cultured cells and animal and plant tissues. Contrary to common belief, the NO radicals are trapped by iron-diethylthiocarbamates not only in ferrous but in ferric state also in the biosystems. When DETC was excess over endogenous iron ligands like citrate, ferric DETC complexes were directly observed with EPR spectroscopy at g=4.3. This was the case when isolated spinach leaves, endothelial cultured cells were incubated in the medium with 2.5mM DETC or mouse liver was perfused with 100mM DETC solution. After trapping NO, the nitrosylated Fe-DETC adducts are mostly in diamagnetic ferric state, with only a minor fraction having been reduced to paramagnetic ferrous state by endogenous biological reductants. In actual in vivo trapping experiments with mice, the condition of excess DETC was not met. The substantial quantities of iron in animal tissues were bound to ligands other than DETC, in particular citrate. These non-DETC complexes appear as roughly equal mixtures of ferric and ferrous iron. The presence of NO favors the replacement of non-DETC ligands by DETC. In all biological systems considered here, the nitrosylated Fe-DETC adducts appear as mixture of diamagnetic and paramagnetic states. The diamagnetic ferric nitrosyl complexes may be reduced ex vivo to paramagnetic form by exogenous reductants like dithionite. The trapping yields are significantly enhanced upon exogenous reduction, as proven by NO trapping experiments in plants, cell cultures and mice.     

Effect of oils and fatty acids on molasses fermentation by distillers' yeast

Some vegetable oils, and the mixed fatty acids derived from them, stimulate sugar utilization and both the rate of alcohol production and yield of alcohol during molasses fermentation by yeast. The effect is particularly prominent during fermentation at a higher temperature of 40°C.     

Toxic effects of fatty acids on yeast cells: possible mechanisms of action.

As shown in a previous paper, threshold concentrations of lower and intermediate fatty acids inhibit the uptake of inorganic phosphate, growth, and cell division in yeast cells. This demonstrates that, apart from these effects, the acids cause an increase in the respiration quotient (RQ), inhibition of CO2 fixation, production of ethanol at the expense of anabolic processes, and inhibition of active amino acid transport in the yeast Candida utilis. On the other hand, the threshold concentrations have no effect on intracellular pH. The inhibition of the inorganic phosphate uptake cannot be the sole primary mode of action of fatty acids since the omission of inorganic phosphate in the incubation medium brings about an inhibition of anabolic processes that is lower than that brought about by fatty acids since the omission of inorganic phosphate in the incubation medium brings about an inhibition of anabolic processes that is lower than that brought by fatty acids at concentrations still premitting some phosphate uptake. Although 2,4-dinitrophenol and caproic acid at low concentrations cause an analogous decrease in biomass yield, their combination does not bring about any marked increase in the effect. Considering the physicochemical properties of fatty acids and their preferential action on energy-requiring processes, one of the key sites of action can be assumed to be the mitochondrial membrane. Fatty acids might inhibit the transport of anions, especially phosphate, across the membrane, and disturb the membrane potential by affecting the transport protons. The physiocochemical properties of fatty acids may also give rise to their binding to other intracellular membranes and to a subsequent interference with the function of the corresponding organelles.