Dexamethasone affect on the expression of bcl-2 and mTOR genes in T-lymphocytes from healthy donors

Synthetic glucocorticoids are able to activate apoptosis in the cells by regulating the transcription of the respective genes. Effect of dexamethasone on apoptosis is an established fact. However, its influence on another program of cell death autophagy, is currently unproven. Therefore, in this paper we have analyzed the influence of dexamethasone on the expression of bcl-2 and mTOR genes in T-lymphocytes from healthy donors. The results showed that dexamethasone reduced the expression of bcl-2 and mTOR genes. However, the nature of the effect of dexamethasone on mTOR and bcl-2 expression was different: the expression of bcl-2 gene in the long-term cultivation was maintained at the same reduced level, while the expression of mTOR was first reduced and then increased

Relations as executable specifications: taming partiality and non-determinism using invariants

Comunicação publicada em "Lecture Notes in Computer Science", vol. 7560 (2012), pag. 146-161The calculus of relations has been widely used in program specification and reasoning. It is very tempting to use such specifications as running prototypes of the desired program, but, even considering finite domains, the inherent partiality and non-determinism of relations makes this impractical and highly inefficient. To tame partiality we prescribe the usage of invariants, represented by coreflexives, to characterize the exact domains and codomains of relational specifications. Such invariants can be used as pre-condition checkers to avoid runtime errors. Moreover, we show how such invariants can be used to narrow the non-deterministic execution of relational specifications, making it viable for a relevant class of problems. In particular, we show how the proposed techniques can be applied to execute specifications of bidirectional transformations, a domain where partiality and non-determinism are paramount.Fundação para a Ciência e a Tecnologi

The Role of T-Lymphocytes Autophagy in Severe Atopic Asthma Pathogenesis

© 2016, Springer Science+Business Media New York.The apoptosis suppression in T-lymphocyte has been implicated with asthma pathogenesis. It was proposed that resistance to apoptosis in T-lymphocytes in asthmatic patients could be due to increased autophagy rate in these cells. While being a vital cellular waste disposal mechanism, autophagy was shown to be involved in asthma pathogenesis. However, the role of autophagy in severe atopic asthma (SAA) is not well understood. To further explore this, we investigated T-lymphocytes autophagy in SAA patients and healthy controls by utilizing transmission electron microscopy (TEM) and immunoblotting analyses. We found an increased number of autophagic T-lymphocytes in the patients with SAA versus healthy controls. Dexamethasone-induced apoptosis in T-lymphocytes of healthy donors revealed an activation of the autophagy in these cells, although SAA T-lymphocytes were not responsive. Presence of autophagolysosomes in SAA T-lymphocytes correlated with high expression levels of membrane protein LC3-II. These data suggest that autophagy may play an important role in the pathogenesis of SAA, facilitate T-lymphocytes activation and survival, and ultimately increase the level of airway inflammation in patients with this disease

Demographic history and genomic response to environmental changes in a rapid radiation of wild rats

For organisms to survive and prosper in a harsh environment, particularly under rapid climate change, poses tremendous challenges. Recent studies have highlighted the continued loss of megafauna in terrestrial ecosystems and the subsequent surge of small mammals, such as rodents, bats, lagomorphs, and insectivores. However, the ecological partitioning of these animals will likely lead to large variation in their responses to environmental change. In the present study, we investigated the evolutionary history and genetic adaptations of white-bellied rats (Niviventer Marshall, 1976), which are widespread in the natural terrestrial ecosystems in Asia but also known as important zoonotic pathogen vectors and transmitters. The southeastern Qinghai-Tibet Plateau (QHTP) was inferred as the origin center of this genus, with parallel diversification in temperate and tropical niches. Demographic history analyses from mitochondrial and nuclear sequences of Niviventer demonstrated population size increases and range expansion for species in Southeast Asia, and habitat generalists elsewhere. Unexpectedly, population increases were seen in N. eha, which inhabits the highest elevation among Niviventer species. Genome scans of nuclear exons revealed that among the congeneric species, N. eha has the largest number of positively selected genes. Protein functions of these genes are mainly related to olfaction, taste and tumor suppression. Extensive genetic modification presents a major strategy in response to global changes in these alpine species

Cell metabolism affects selective vulnerability in PINK1-associated Parkinson's disease

Mitochondrial dysfunction plays a primary role in the pathogenesis of Parkinson's disease (PD), particularly in autosomal recessive forms of the disease caused by mutations encoding PINK1. Although mitochondrial pathology can be demonstrated in many cell types, it is neurons that bear the brunt of cell death in PD. We studied the mitochondrial physiology of neurons and muscle cells with loss of function of the nuclear encoded mitochondrial protein PINK1. PINK1 is widely expressed in many types of tissues, but deficiency selectively induces death in neurons. We report here that the same genetic defect results in opposing phenotypes in different cell types, depending on the metabolic properties of the cell. Thus, PINK1-deficient myocytes exhibit high basal mitochondrial membrane potential (Δψm), whereas PINK1-deficient neurons have been shown to exhibit a low Δψm. PINK1 deficiency induces impaired respiration in both cell types, with a concomitant increase in glycolytic activity. We demonstrate that the high glycolytic capacity in myocytes compared with neurons enables them to produce more ATP and, therefore, compensates for the metabolic defects induced by PINK1 deficiency. Furthermore, the high Δψm generated in PINK1 knockout (KO) muscle mitochondria enables them to buffer cytosolic Ca2+ fluxes, rendering them resistant to Ca2+ stress effectively. Conversely, PINK1 KO neurons were previously shown to develop mitochondrial Ca2+ overload and Ca2+-induced mitochondrial depolarisation. Prevention of Ca2+ dysregulation in myocytes might therefore account for the sparing of these cells in PD

Entropy of semiclassical measures for nonpositively curved surfaces

We study the asymptotic properties of eigenfunctions of the Laplacian in the case of a compact Riemannian surface of nonpositive sectional curvature. We show that the Kolmogorov-Sinai entropy of a semiclassical measure for the geodesic flow is bounded from below by half of the Ruelle upper bound. We follow the same main strategy as in the Anosov case (arXiv:0809.0230). We focus on the main differences and refer the reader to (arXiv:0809.0230) for the details of analogous lemmas.Comment: 20 pages. This note provides a detailed proof of a result announced in appendix A of a previous work (arXiv:0809.0230, version 2

The NuMI Neutrino Beam and Potential for an Off-Axis Experiment

The Neutrinos at the Main Injector (NuMI) facility at Fermilab is under construction and due to begin operations in late 2004. NuMI will deliver an intense $\nu_{\mu}$ beam of variable energy 2-20 GeV directed into the Earth at 58 mrad. Several aspects of the design are reviewed, and potential limitations to the ultimate neutrino flux are described. In addition, potential measurements of neutrino mixing properties are described.Comment: talk given at NuFact '02, Imperial College London, proceedings to appear in J. Phys. G, revised to add a referenc

Local electromechanical properties of barium strontium titanate based glass-ceramics

The equipment of the Ural Center for Shared Use “Modern Nanotechnology” Ural Federal University was used. The research was made possible by Russian Foundation for Basic Research (Grant 18-52-53032)

Phase transitions for suspension flows

This paper is devoted to study thermodynamic formalism for suspension flows defined over countable alphabets. We are mostly interested in the regularity properties of the pressure function. We establish conditions for the pressure function to be real analytic or to exhibit a phase transition. We also construct an example of a potential for which the pressure has countably many phase transitions.Comment: Example 5.2 expanded. Typos corrected. Section 6.1 superced the note "Thermodynamic formalism for the positive geodesic flow on the modular surface" arXiv:1009.462