The mechanism of the development of the epidemic process in Sonne dysentery

An epidemic outbreak of Sonne dysentery has been studied. The data of epidemiological monitoring before and after the epidemic have been analyzed. The real prognostication value of controlling the biological properties of Shigella sonnei and the increase of their intrapopulation heterogeneity at the period of the activation of the epidemic process of Sonne dysentery has been established.     

The role of mu- and delta-opiate receptors in the realization of the autonomic effects of opioid peptides

In the first series of experiments on the isolated mouse vas deferens and guinea-pig ileum the capacity of 10 opioid peptides to activate mu- and delta-receptors was evaluated. [DAla2, DLeu5]-enkephalin (DADLE) and [DAla2, MePhe4, Gly5-ol]-enkephalin (DAMPGE) were the most selective agonists of delta- and mu-opiate receptors, respectively. In the second series of experiments on urethan-anesthetized rats it was shown, that intravenous administration of DADLE or DAMPGE (10(-7) M/kg each) elicited hypotension, bradycardia and expiratory apnoe. These effects disappeared both after naloxone injection and bilateral cervical vagotomy. A reflex nature of the vegetative effects of opioid peptides and the role of both mu- and delta-receptors in their realization are suggested.     

Conjugal transfer and mobilization capacity of the completely sequenced naphthalene plasmid pNAH20 from multiplasmid strain Pseudomonas fluorescens PC20

The complete 83 042-bp nucleotide sequence of the IncP-9 naphthalene degradation plasmid pNAH20 from Pseudomonas fluorescens PC20 exhibits striking similarity in size and sequence to another naphthalene (NAH) plasmid pDTG1. However, the positions of insertion sequence (IS) elements significantly alter both catabolic and backbone functions provided by the two plasmids. In pDTG1, insertion of a pCAR1 IS Pre1 -like element disrupts expression of the lower naphthalene operon and this strain utilizes the chromosomal pathway for complete naphthalene degradation. In pNAH20, this operon is intact and functional. The transfer frequency of pNAH20 is 100 times higher than that of pDTG1 probably due to insertion of the pCAR1 IS Pre2 -like element into the mpfR gene coding for a putative repressor of the mpf operon responsible for mating pilus formation. We also demonstrate in situ plasmid transfer – we isolated a rhizosphere transconjugant strain of pNAH20, P. fluorescens NS8. The plasmid pNS8, a derivative of pNAH20, lacks the ability to self-transfer as a result of an additional insertion event of IS Pre2 -like element that disrupts the gene coding for VirB2-like major pilus protein MpfA. The characteristics of the strain PC20 and the conjugal transfer/mobilization capacity of pNAH20 (or its backbone) make this strain/plasmid a potentially successful tool for bioremediation applications.     

AtRLI2 is an Endogenous Suppressor of RNA Silencing

RNA silencing is a mechanism involved in gene regulation during development and anti-viral defense in plants and animals. Although many viral suppressors of this mechanism have been described up to now, this is not the case for endogenous suppressors. We have identified a novel endogenous suppressor in plants: RNase L inhibitor (RLI) of Arabidopsis thaliana. RLI is a very conserved protein among eukaryotes and archaea. It was first known as component of the interferon-induced mammalian 2′–5′ oligoadenylate (2–5A) anti-viral pathway. This protein is in several organisms responsible for essential functions, which are not related to the 2–5A pathway, like ribosome biogenesis and translation initiation. Arabidopsis has two RLI paralogs. We have described in detail the expression pattern of one of these paralogs (AtRLI2), which is ubiquitously expressed in all plant organs during different developmental stages. Infiltrating Nicotiana benthamiana green fluorescent protein (GFP)-transgenic line with Agrobacterium strains harboring GFP and AtRLI2, we proved that AtRLI2 suppresses silencing at the local and at the systemic level, reducing drastically the amount of GFP small interfering RNAs.     

Activation of mast cells after experimental myocardial infarction in 3 week-old rats

It is known that mast cells (MC) take an active part in regeneration processes in postinfarction heart in adult rats and humans. Behaviour of population of cardial MCs has been studied 20, 60, 75 and 90 days after experimental myocardial infraction induced in 3 week-old and adult rats by ligation of left coronary artery. The density of MC of different degrees of maturity was estimated in atrium and ventricle on paraffin sections stained with Alcian blue - Safranin. Findings were compared with MC density obtained in hearts of intact rats. The MC density in intact 1.5-2.5 month-old rats in atrium and ventricle was about 0.6 cells/mm2, in intact 3.5-4.0 month-old rats in atrium--1.2 cells/mm2, in ventricle--0.6 cells/mm2. The MC density in 3 week-old rats with infarction was significantly higher than in intact rats: 5-fold increase in 20 and 60 days in atrium, and 2-fold increase in 60 and 75 days in ventricle. In 60 days after infarction the MC density in adult rats was 3 times lower in atrium and 2 times lower in ventricle than in the same heart compartments of 3 week-old rats with infarction. After infarction in 3 week-old rats, a relative share of young cells with alcian-positive granules sharply increased in 20 days and then decreased by 60-75 days. This indicates a migration of immature MCs to infracted myocardium and their subsequent differentiation. The MC activation after infraction in young rats may result from a more active immune reaction in younger rats and/or functional peculiarities of their MC.     

Three steps to the immortality of cancer cells: senescence,polyploidy and self-renewal

Background

Hepatocellular carcinoma (HCC) exhibits strong intrinsic and acquired drug resistance which is the main obstacle to chemotherapy. Overexpression of ATP binding cassette (ABC) proteins correlates with activation of mitogen activated protein kinase (MAPK) pathway in HCC. Here, we systematically investigated the inhibition of MAPK pathway and its role in regulating HCC cell growth as well as ABC proteins MRP1 and MRP3 expression.

Methods

The Raf1 kinase inhibitor (GW5074) and different MEK inhibitors (U0126 and AZD6244) were used to treat HCC cells to identify their effects on HCC cell growth and ABC proteins expression in vitro. Cell viability tests were performed after the treatment of MAPK pathway inhibitors and in combination with gemcitabine or doxorubicin. Western blot was applied to assess the changes of MAPK pathway and protein expression of MRP1 and MRP3. Flow cytometry was used to measure intracellular doxorubicin accumulation after the treatment of MEK inhibitors.

Results

Both Raf1 inhibitor (GW5074) and MEK inhibitors (U0126 and AZD6244) suppressed HCC cell growth in a dose dependent manner. Pre-treatment of MEK inhibitor U0126 or AZD6244 sensitized HCC cells to gemcitabine or doxorubicin based chemotherapy. Raf1 inhibitor GW5074 had no effect on MRP1 and MRP3 protein expression. Treatment of gemcitabine or doxorubicin activated phosphorylated ERK and induced the upregulation of MRP1 and MRP3. MEK inhibitors U0126 and AZD6244 deactivated phosphorylated ERK, decreased endogenous MRP1 expression, reversed gemcitabine or doxorubicin induced MRP1 and MRP3 upregulation, and increased the intracellular doxorubicin accumulation.

Conclusion

This study provides evidence that MEK inhibitors sensitize HCC cells to chemotherapy by increasing intracellular chemodrug accumulation. MEK inhibirors U0126 and AZD6244 reduced MRP1 as well as MRP3 expression, and may contribute partially to the sensitization. The combination of MEK inhibitor and conventional chemotherapy may offer new therapeutic option for the treatment of resistant HCC.     

Mitochondrial COI and morphological specificity of the mealy aphids (Hyalopterus ssp.) collected from different?hosts in Europe (Hemiptera,Aphididae)

Forty three European population samples of mealy aphids from various winter and summer host plants were attributed to respective species of Hyalopterus by means of their partial sequences of mitochondrial COI gene. Used Hyalopterus samples emerged as monophyletic relative to outgroup and formed three major clades representing three host specific mealy aphid species in the Neighbor joining, Maximum parsimony, Maximum likelihood and Bayesian inference trees. Hyalopterus pruni and Hyalopterus persikonus emerged as a sister species, whilst Hyalopterus amygdali was located basally. Samples representing different clades in the molecular trees were used for canonical discrimination analysis based on twenty two morphological characters. Length of the median dorsal head hair enabled a 97.3 % separation of Hyalopterus amygdali from the remaining two species. No single character enabled satisfactory discrimination between apterous viviparous females of Hyalopterus pruni and Hyalopterus persikonus. A modified key for the morphological identification of Hyalopterus species is suggested and their taxonomic status discussed.     

Effect of agitation on the peptide fibrillization: Alzheimer's amyloid‐β peptide 1‐42 but not amylin and insulin fibrils can grow under quiescent conditions

Many peptides and proteins can form fibrillar aggregates in vitro, but only a limited number of them are forming pathological amyloid structures in vivo. We studied the fibrillization of four peptides – Alzheimer's amyloid‐β (Aβ) 1‐40 and 1‐42, amylin and insulin. In all cases, intensive mechanical agitation of the solution initiated fast fibrillization. However, when the mixing was stopped during the fibril growth phase, the fibrillization of amylin and insulin was practically stopped, and the rate for Aβ₄₀ substantially decreased, whereas the fibrillization of Aβ₄₂ peptide continued to proceed with almost the same rate as in the agitated conditions. The reason for the different sensitivity of the in vitro fibrillization of these peptides towards agitation in the fibril growth phase remains elusive. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Changes in some indices of the cardiovascular system in different mental tasks

In order to study the effects of the type of mental activity on the function of the cardiovascular system in humans, the following indices were used: the heart rate (HR), RR interval, variation magnitude (VM), systolic wave amplitude (SWA), and pulse wave transit time (PWTT). These indices were recorded when the subjects solved verbal-logical or spatial mental tasks. The HR was substantially increased during solving of the spatial tasks as compared to solving of the verbal-logical tasks, whereas the SWA showed the opposite changes. The latencies of the performance of the tasks of various types were similar in the subjects; therefore, the changes in the autonomic indices did not depend on the difficulties of the mental tasks. They rather depended on specific features of the mental processes involved in the performance of the tasks of different types. Thus, changes in the HR and the decreased SWA, which was related to elevated blood pressure, represent the effect of the sympathetic nervous system on the heart function during solving verbal-logical tasks. Our data demonstrate that the HR and blood pressure can be used as additional indices for the development of new techniques for assessment of different types of mental processes together with the indices of electrical brain activity.     

Thermoresponsive Aggregation Behavior of Triterpene-Poly(ethylene oxide) Conjugates in Water

Bioconjugate amphiphiles comprising triterpene and poly(ethylene oxide) (PEO) were studied according to their thermoresponsive aggregation behavior (LCST) in water. Cholesteryl-PEO (CE) and betulinyl-PEO (BE) comprising <70 wt% PEO precipitated from water upon heating. CE, but not BE, solutions contained nanoscopic aggregates at room temperature causing different thermoprecipitation behaviors. Solutions containing 5?wt% solutions of BE with short PEO chains demonstrated dual thermoresponsive behavior, precipitating at high temperature and forming hydrogel at low temperature. A BE multiblock copolymer was found to form large aggregates, presumably vesicles, in water. Results suggest that the solution properties of triterpene-PEO amphiphiles can be controlled by the chemical composition and structure.