Candida albicans double-stranded DNA can participate in the host defense against disseminated candidiasis

In the present work, we studied the in vitro immunomodulatory properties of double-stranded Candida albicans DNA and its protective effect in murine disseminated candidiasis. DNA induced the production of TNF-alpha by peritoneal macrophages and splenocytes in vitro through a chloroquine-dependent mechanism. Yeast DNA acted synergistically with IFN-gamma in triggering the secretion of nitric oxide by macrophages and enabled them to stimulate the proliferation of T cells in response to soluble anti-CD3. The effect of DNA on splenocytes is associated with an enhanced synthesis of IFN-gamma, IL-2 and IL-10. In vivo, DNA decreased the mortality and lowered the kidney contamination in mice intraperitoneally inoculated with C. albicans simultaneously with an increase in the specific proliferative response and cytokine production. The present results indicate that C. albicans DNA can provide protection against disseminated infection.     

Comparison of the activity levels and localization of dipeptidyl peptidase IV in normal and tumor human lung cells

Dipeptidyl peptidase IV (DPPIV) was studied in three human lung cells - P (fetal lung-derived cells), A549 (lung adenocarcinoma) and SK-MES-1 (squamous cell carcinoma) using a fluorescent cytochemical procedure developed on the basis of the substrate 4-(glycyl-l-prolyl hydrazido)-N-hexyl-1,8-naphthalimide. The observed differences in the enzyme expression were confirmed by measuring the enzyme hydrolysis of glycyl-l-prolyl-para-nitroanilide. The surface and total dipeptidyl peptidase activities of P cells were correspondingly 7-8 and 3-10 times higher than those of SK-MES-1 and A549 cells. The ratio surface per total activity showed that in P (95%) and A549 (93%) cells the enzyme is associated with the plasmalemma while in SK-MES-1 cells (35%) it is bound to intracellular membranes. In order to compare the results from cell cultures with those in human tumor, the enzyme activity was investigated in cryo-sections of three cases of diagnosed squamous lung carcinoma. DPPIV activity was restricted to the connective tissue stroma surrounding the DPPIV-negative tumor foci.     

Chaotic pairwise competition

We investigate a kind of competition possible in a system of at least three populations competing for the same limited resource. As a model we use generalised Volterra equations in which the growth rates and competition coefficients of populations depend on the number of members of all populations. Because of the nonconstant values of the last quantities the system could be repelled from the state of cyclic pairwise competition described by May and Leonard (SIAM J. Appl. Math. 29 (1975) 243.). We investigate the competition in a chaotic regime of evolution of the number of members of populations. We show that the nonconstant competition coefficients can lead to a regularisation of the time intervals of domination of each population and the non-constant growth rates can lead to decreasing length of the time intervals of domination as well as to chaotisation of the occurrence of these intervals. A quantity characterising the time intervals between the successive maxima of the number of the populations individuals is discussed. By means of the wavelet transform modulus maxima method we calculate the tau(q)-spectrum and the H?lder exponent for the time series of this quantity. The results of the theory are illustrated by an example of competition among the three main political parties in Bulgaria and we discuss qualitative aspects of the dynamics of change of preferences of voters.     

Interpretation of EMG integral or RMS and estimates of “neuromuscular efficiency” can be misleading in fatiguing contraction

In occupational and sports physiology, reduction of neuromuscular efficiency (NME) and elevation of amplitude characteristics, such as root mean square (RMS) or integral of surface electromyographic (EMG) signals detected during fatiguing submaximal contraction are often related to changes in neural drive. However, there is data showing changes in the EMG integral (I_EMG) and RMS due to peripheral factors. Causes for these changes are not fully understood. On the basis of computer simulation, we demonstrate that lengthening of intracellular action potential (IAP) profile typical for fatiguing contraction could affect EMG amplitude characteristics stronger than alteration in neural drive (central factors) defined by number of active motor units (MUs) and their firing rates. Thus, relation of these EMG amplitude characteristics only to central mechanisms can be misleading. It was also found that to discriminate between changes in RMS or I_EMG due to alterations in neural drive from changes due to alterations in peripheral factors it is better to normalize RMS of EMG signals to the RMS of M-wave. In massive muscles, such normalization is more appropriate than normalization to either peak-to-peak amplitude or area of M-wave proposed in literature.     

Gas Exchange of In Vitro and Ex Vitro Grown Grapevine Plants

Net photosynthetic rate (P _N) and dark respiration rate (R _D) were measured in Vitis vinifera L. cvs. Dimiat 4/24 (23^rd subculture), Dimiat 4/38 (22^nd subculture), and Italian Riesling 3/47 (22^nd subculture) on days 3, 2, and 1 (1^st series) before transfer from the in vitro culture and on days 14, 15, 16 (2^nd series) and 28, 29, 30 (3^rd series) after the transfer. P _N of in vitro and ex vitro plants was strongly affected by irradiance. P _N and R _D of in vitro plantlets were lower and transpiration rate (E) was higher compared to those of ex vitro plantlets. P _N, R _D, and E changed in the course of acclimation.     

Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes.     

Protein-protein interactions between hepatitis C virus nonstructural proteins

Replication of the hepatitis C virus (HCV) genome has been proposed to take place close to the membrane of the endoplasmic reticulum in membrane-associated replicase complexes, as is the case with several other plus-strand RNA viruses, such as poliovirus and flaviviruses. The most obvious benefits of this property are the possibility of coupling functions residing in different polypeptidic chains and the sequestration of viral proteins and nucleic acids in a distinct cytoplasmic compartment with high local concentrations of viral components. Indeed, HCV nonstructural (NS) proteins were clearly colocalized in association with membranes derived from the endoplasmic reticulum. This observation, together with the demonstration of the existence of several physical interactions between HCV NS proteins, supports the idea of assembly of a highly ordered multisubunit protein complex(es) probably involved in the replication of the viral genome. The objective of this study, therefore, was to examine all potential interactions between HCV NS proteins which could result in the formation of a replication complex(es). We identified several interacting viral partners by using a glutathione S-transferase pull-down assay, by in vitro and ex vivo coimmunoprecipitation experiments in adenovirus-infected Huh-7 cells allowing the expression of HCV NS proteins, and, finally, by using the yeast two-hybrid system. In addition, by confocal laser scanning microscopy, NS proteins were clearly shown to colocalize when expressed together in Huh-7 cells. We have been able to demonstrate the existence of a complex network of interactions implicating all six NS proteins. Our observations confirm previously described associations and identify several novel homo- and heterodimerizations.     

Estimate of M-wave changes in human biceps brachii during continuous stimulation.

The purpose of the present study was to validate the capability of new fatigue indexes (in the time and frequency domain) applied to experimental recordings and thus, to test some assumptions made in previous simulations. The indexes were applied to M-waves detected non-invasively from human m.biceps brachii during repetitive slightly above threshold stimulations. It was found that distance between the motor point and middle of the end-plate region could be relatively large. Under identical conditions (signals detected by monopolar electrodes and high-pass filtered at 1 Hz), the relative changes of the indexes obtained in electrophysiological experiments and simulations were similar. Changes of the intracellular action potential profile during fatigue used in the simulations were consequently supposed to be close to the actual ones for the muscle analyzed. When the high-pass cut-off frequency was higher than 1 Hz, the sensitivity of the index in the time domain was higher, while that in the frequency domain was lower. If the normalizing spectral moment was of higher order, the sensitivity of the spectral index could be even 150-times greater than that of the fatigue indexes traditionally used. Thus, the spectral index promises high capability to assess fatigue during functional electrical stimulation.     

Pretreatment with heat does not affect double-strand breaks DNA rejoining in Chlamydomonas reinhardtii

We aimed to clarify if heat pretreatment could protect Chlamydomonas reinhardtii cells from gamma rays DNA damaging action. It was studied whether: (1) heat pretreatment could accelerate DNA DSB rejoining; (2) chloroplast chaperones (HSP70B, HSP90C) could be involved in protection from radiation-induced DNA DSB.It was obtained that heat pretreatment (37–42 °C) induced minor DNA DSB levels which might be insufficient as signals for DNA DSB repair induction. No correlation between chaperones overproduction and DNA DSB rejoining was shown. These are probably the first data that HSP70B and HSP90C do not protect DNA against radiation-induced damage in a plant model system.