Drosophila melanogaster as a model for studying the function of animal viral proteins

Studies in which Drosophila melanogaster individuals carrying transgenes of animal viruses were used to analyze the action of animal viral proteins on the cell are reviewed. The data presented suggest that host specificity of viruses is determined by their proteins responsible for the penetration of the virus into the cell, while viral proteins responsible for interactions with the host cell are much less host-specific. Due to this, the model of Drosophila with its developed system of searching for genetic interactions can be used to find intracellular targets for the action of viral proteins of the second group.     

Stochastic analysis of the GAL genetic switch in Saccharomyces cerevisiae: Modeling and experiments reveal hierarchy in glucose repression

Background

Most mathematical models of biochemical pathways consider either signalling events that take place within a single cell in isolation, or an 'average' cell which is considered to be representative of a cell population. Likewise, experimental measurements are often averaged over populations consisting of hundreds of thousands of cells. This approach ignores the fact that even within a genetically-homogeneous population, local conditions may influence cell signalling and result in phenotypic heterogeneity. We have developed a multi-scale computational model that accounts for emergent heterogeneity arising from the influences of intercellular signalling on individual cells within a population. Our approach was to develop an ODE model of juxtacrine EGFR-ligand activation of the MAPK intracellular pathway and to couple this to an agent-based representation of individual cells in an expanding epithelial cell culture population. This multi-scale, multi-paradigm approach has enabled us to simulate Extracellular signal-regulated kinase (Erk) activation in a population of cells and to examine the consequences of interpretation at a single cell or population-based level using virtual assays.

Results

A model consisting of a single pair of interacting agents predicted very different Erk activation (phosphorylation) profiles, depending on the formation rate and stability of intercellular contacts, with the slow formation of stable contacts resulting in low but sustained activation of Erk, and transient contacts resulting in a transient Erk signal. Extension of this model to a population consisting of hundreds to thousands of interacting virtual cells revealed that the activated Erk profile measured across the entire cell population was very different and may appear to contradict individual cell findings, reflecting heterogeneity in population density across the culture. This prediction was supported by immunolabelling of an epithelial cell population grown in vitro, which confirmed heterogeneity of Erk activation.

Conclusion

These results illustrate that mean experimental data obtained from analysing entire cell populations is an oversimplification, and should not be extrapolated to deduce the signal:response paradigm of individual cells. This multi-scale, multi-paradigm approach to biological simulation provides an important conceptual tool in addressing how information may be integrated over multiple scales to predict the behaviour of a biological system.     

The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 10. Cooperative immune reactions in different generations of mice]

The immune status of mice has been assessed by the whole complex of data. The permanent action of low-level radiation has been shown to suppress considerably the rate of reactions of the delayed-type hypersensitivity and "graft versus host" disease, as well as NK and specific cytolytic T-lymphocyte activity. The dynamics of accumulation and the levels of antiviral antibodies in the serum, lung and trachea extracts are virtually invariable. The resistance of experimental animals to influenza is lower than that of non-irradiated mice of the same line and age. The data obtained indicate that the immune disturbances revealed are connected not only with the alteration of lymphoid cell populations, but also with the alteration of the immune regulation mechanisms.     

Various characteristics of lipid metabolism of Bacillus brevis var. G.-B

Some characteristic features of the lipid metabolism of Bacillus brevis var. G.-B. natural variants and Bacillus brevis mutant 101 were studied. The authors found that upon submerged cultivation gramicidine S-producing P+-variant and B. brevis mutant 101 synthesized higher amounts of tocopherols as compared to other colonial-morphological variants. The highest tocopherol content was observed in P+-variant, whose cells contained the highest amount of total lipids as compared to other gramicidine S-producers.     

Monomorphism of isoenzyme loci in natural and cultivated amaranth (Amaranthus L.) populations

Starch gel electrophoresis was used for isozyme analysis of ADH, GDH, MDH, IDH, and ME in populations of amaranth. Experiments were performed with 93 populations and 4 cultivars. Some populations proved to be polymorphic, and this fact allowed analysis of the genetic control of the enzymes listed. The populations examined showed poor allozyme variability. Monomorphism for all loci studied was observed in 73 populations and 4 varieties. Starch gel electrophoresis was used for isozyme analysis ofADH, GDH, MDH, IDH, and ME in populations of amaranth. Experiments were performed with 93 populations and 4 cultivars. Some populations proved to be polymorphic, and this fact allowed analysis of the genetic control of the enzymes listed. The populations examined showed poor allozyme variability. Monomorphism for all loci studied was observed in 73 populations and 4 varieties. Only some populations demonstrated rare polymorphism for a single locus each: Adh, Mdh 2, Gdh, Idh 1, Idh 2, or Mod 2. The results demonstrate genetic monomorphism of amaranth for the studied loci.     

Outcome of Tuberculosis Treatment in Patients with Diabetes Mellitus Treated in the Revised National Tuberculosis Control Programme in Malappuram District,Kerala, India

Settings

Kerala State, India has reported the greatest dual burden of Tuberculosis (TB) and Diabetes Mellitus (DM). Malappuram district in Kerala has monitored and recorded DM status and its control from 2010 under Revised National Tuberculosis Control Program (RNTCP).

Objectives

To assess, under programme conditions, comprehensiveness of recording DM status among TB cases and the TB treatment outcomes among DM patients (disaggregated by glycemic control) and compare with-non DM patients.

Design

This retrospective record review included 3,116TB patients from April 2010 to September 2011.DM was defined as per international guidelines and TB treatment outcomes were categorized as favourable(cured and treatment completed) and unfavourable(death, default, failure and transfer out). Relative Risk (RR) and 95% confidence intervals(CI) were calculated to assess the risk of unfavourable outcomes.

Results

DM status was recorded in 90% of TB cases and 667 (24%) had DM. 17% of DM patients and 23% of patients with unknown DM status had unfavourable outcomes but this difference was not statistically significant. Unadjusted RR for poor glycemic control or unknown control status for unfavourable outcome were (2.00; 95% CI 0.97–4.13) and (2.14; 95% CI 1.11–4.13).

Conclusion

This study could not confirm an adverse association between DM or its control during treatment and the course of response to TB treatment.DM screening in TB cases and recording of DM care needs to be improved to enable more conclusive evidence.     

Effect of amyxin--a domestic analog of tilorone--on characteristics of interferon and immune status of man

The influence of amyxin, the Russian oral analog of tilorone, on the human interferon and immune status has been evaluated. As revealed by this investigation the administration of amyxin has produced a rise in the content of serum interferon, an increase in the capacity of leukocytes and lymphocytes for synthesizing alpha- and gamma-interferon, the activation of NK and phagocytizing cells of peripheral blood. No essential influence of amyxin on the amount of B and T lymphocytes, their subpopulations and the levels of the main classes of immunoglobulins has been established.     

Cell biology and life cycle of the testate amoeba Corythion delamarei

Corythion delamarei Bonnet, Thomas, 1960, a typical testate amoeba with hyaline, filiform pseudopodia (Filosea Leidy, 1879), is a mass and widely spread species in the forest soil of Leningrad district. This species has been studied in natural and experimental conditions by means of morphological, cytochemical and morphometrical methods, including original culturing in vitro. The complex life cycle of C. delamarei involves the number of phases: trophozoites, precysts, resting cysts, copulating trophozoits, cystozygotes, cells with spores inside the shell, small amoeboid cells producing spores after germination. Different stages display structural peculiarities reflecting adaptation to exogenous environment. In C. delamarei sexual process has been first discovered. It represents a primitive form of isogamic copulation of morphologically similar trophozoites copulation and results in uninuclear cystozygote formation. The zygote nucleus is a synkaryon meiosis is zygotic, and is accomplished in two steps. Copulation occurs only between two trophozoites of one and the same species. Further zygote development includes its excystation that eventually gives rise to a trophozoite which then undergoes several metagamic divisions resulting in spore formation, thus starting a new generation of trophozoites.     

Formulation and evaluation of ketorolac tromethamine-loaded albumin microspheres for potential intramuscular administration

The objective of this work was to prepare and evaluate ketorolac tromethamine-loaded albumin microspheres using a factorial design. Albumin microspheres were prepared by emulsion cross-linking method. Selected formulations were characterized for their entrapment efficiency, particle size, surface morphology, and release behavior. Analysis of variance (ANOVA) for entrapment efficiency indicated that entrapment efficiency is best fitted to a response surface linear model. From the statistical analysis it was observed that as the drug:polymer (D∶P) ratio and volume of glutaraldehyde increased, there was a significant increase in the encapsulation efficiency. Scanning electron microscopy of the microspheres revealed a spherical, nonporous and uniform appearance, with a smooth surface. Based on the entrapment efficiency and physical appearance, 9 formulations were selected for release study. The maximum particle size observed was below 40 μm. The release pattern was biphasic, characterized by an initial burst effect followed by a slow release. All selected microspheres, except those having less polymer proportion (D∶P ratio is 1∶1), exhibited a prolonged release for almost 24 hours. On comparingr ² values for Higuchi and Peppas kinetic models, different batches of microspheres showed Fickian, non-Fickian, and diffusion kinetics. The release mechanism was regulated by D∶P ratio and amount of cross-linking agent. From the experimental data obtained with respect to particle size and extent of drug relaase, it could be concluded that the prepared microspheres are useful for once-a-day intramuscular administration of ketorolac tromethamine. Published: February 23, 2007