Evaluation of thermal resistance of <Emphasis Type="Italic">Azotobacter chroococcum</Emphasis> 66 using atomic force microscopy

A possibility to use atomic force microscopy (AFM) for comparative analysis of thermal resistance of Azotobacter chroococcum 66 cells has been studied. The sizes of bacteria cells and the structuredness of the cytoderm have been shown to vary depending on the dose of hyperthermic action and on the composition of the media for heating and subsequent incubation. A thermally induced increase of a standard roughness parameter (R _a) and of cell sizes has been revealed to reflect an increased level of their resistance to hyperthermia.     

Characteristic of the genetic variability of four polymorphic variants (rs2069705, rs17880053, rs11126176, and rs804271) in representative samples of indigenous and arrived populations of Siberia

Russian Journal of Genetics - The variability of potentially important functional polymorphic variants rs2069705 (5'UTR of the IFNG gene), rs17880053 (near 5'UTR of the IFNGR2), rs11126176...     

Pulmonary lymphangioleiomyomatosis (LAM): progress and current challenges

Lymphangioleiomyomatosis (LAM), a rare lung disease, is characterized by the progressive proliferation, migration, and differentiation of smooth muscle (SM)-like LAM cells, which lead to the cystic destruction of the lung parenchyma, obstruction of airways and lymphatics, and loss of pulmonary function. LAM is a disease predominantly affecting women and is exacerbated by pregnancy; only a lung transplant can save the life of a patient. It has been discovered that in LAM, somatic or genetic mutations of tumor suppressor genes tuberous sclerosis complex 1 (TSC1) or TSC2 occur and the TSC1/TSC2 protein complex functions as a negative regulator of the mTOR/S6K1 signaling pathway. These two pivotal observations paved the way for the first rapamycin clinical trial for LAM. The recent discoveries that TSC1/TSC2 complex functions as an integrator of signaling networks regulated by growth factors, insulin, nutrients, and energy heightened the interest regarding this rare disease because the elucidation of disease-relevant mechanisms of LAM will promote a better understanding of other metabolic diseases such as diabetes, cancer, and cardiovascular diseases. In this review, we will summarize the progress made in our understanding of TSC1/TSC2 cellular signaling and the molecular mechanisms of LAM; we will also highlight some of the lesser explored directions and challenges in LAM research.     

Influence of dietary vitamin E (DL-alpha-tocopheryl acetate) and diludine (diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate) levels on growth and lipid peroxidation in rainbow trout,Oncorhynchus mykiss

We aimed to investigate the influence of dietary vitamin E and diludine on growth and lipid peroxidation (malondialdehyde; MDA) in rainbow trout. Fish (1.5 g) were fed different dietary levels of vitamin E (0, 50 and 100 mg/kg) and diludine (0, 0.5 and 1 g/kg) for 10 weeks. Growth performance and feed conversion ratio (FCR) were significantly affected by dietary vitamin E (p < .05) but not diludine. Fish fed 50 mg/kg dietary vitamin E with no diludine had significantly better growth and lower FCR than those fed vitamin E free diets. Liver vitamin E content was significantly influenced by dietary vitamin E and diludine (p < .05). The highest hepatic vitamin E was in fish fed the highest dietary vitamin E and diludine levels. Hepatic MDA level was significantly affected by dietary vitamin E and diludine (p < .05), decreasing with the increase in both dietary vitamin E and diludine. According to our results, diludine had no significant effect on growth; however, decreased hepatic lipid peroxidation independent of vitamin E. Our results reveal that 50 mg/kg vitamin E content is suitable for optimal growth and FCR in rainbow trout juveniles. However, dose dependent effects of dietary diludine remain uncertain and need further researches.     

Secretory activity of the stomach during modeling of enhanced filling of abdominal veins

Determination of the secretory activity of the stomach and ultrasound scanning of human gastroduodenal organs and vessels in experiments with −12° and −15° head-down tilting (HDT) hypokinesia were performed. As a result of short-term (12–24 h) HDT hypokinesia with the minimized hypokinesia factor, parenchymatous organs enlarged, and the walls of hollow organs thickened. Enhanced blood filling of abdominal veins was accompanied by elevated pepsinogen levels in blood and urine and increased gastric contents in fasting subjects. The increased tonicity of the pylorus and the delayed evacuation of stomach contents indicated the activation of hydrochloric acid secretion. Simultaneously, the bile and pancreatic juice were secreted more profusely, and the intestinal contents in the duodenum increased. It has been shown that the modeled enhancement of blood filling of abdominal veins stimulates gastric secretion on an empty stomach, which is accompanied by activation of secretion in the liver and pancreas.     

A 1,4-dihydropyridine derivative reduces DNA damage and stimulates DNA repair in human cells in vitro

Compounds of the 1,4-dihydropyridine (1,4-DHP) series have been shown to reduce spontaneous, alkylation- and radiation-induced mutation rates in animal test systems. Here we report studies using AV-153, the 1,4-DHP derivative that showed the highest antimutagenic activity in those tests, to examine if it modulates DNA repair in human peripheral blood lymphocytes and in two human lymphoblastoid cell lines, Raji and HL-60. AV-153 caused a 50% inhibition of growth (IC50) of Raji and HL-60 cells at 14.9+/-1.2 and 10.3+/-0.8mM, respectively, but did not show a cytotoxic effect at concentrations <100 microM. Alkaline single-cell gel electrophoresis (comet) assays showed that AV-153 reduced the number of DNA strand breaks in untreated cells and also in cells exposed to 2 Gy of gamma-radiation, 100 microM ethylmethane sulfonate (EMS), or 100 microM H2O2. DNA damage was reduced by up to 87% at AV-153 concentrations between 1 and 10nM, and a positive dose-effect relationship was seen between 0.01 and 1 nM. Comparison of the kinetics of DNA strand-break rejoining in the presence and absence of AV-153 revealed a considerable influence on the rate of repair. In view of the resemblance of this compound's structure to that of dihydronicotinamide, a substrate for poly(ADP-rybose)polymerase, the modulation of DNA repair by AV-153 could involve an influence on poly(ADP)ribosylation.     

An approach on determining the displacements of the pelvic floor during voluntary contraction using numerical simulation and MRI

The present study was conducted in order to establish a methodology based on the finite element method to simulate the contraction of the pelvic floor (PF) muscles. In the generated finite element model, a downward pressure of 90 cm H(2)O was applied, while actively contracting the PF muscles with different degrees of muscular activation (10, 50 and 100%). The finite element methodology of the active contraction behaviour proposed in this study is adequate to simulate PF muscle contraction with different degrees of muscular activation. In this case, in particular, for an activation of 100%, the numerical model was able to displace the pubovisceral muscle in a range of values very similar to the displacement found in the magnetic resonance imaging data. In the analysed case study, it would be possible to conclude that an intensity contraction of 50% would be necessary to produce enough stiffness to avoid possible urine loss.     

Functional investigation of an universally conserved leucine residue in subunit a of ATP synthase targeted by the pathogenic m.9176 T>G mutation

Protons are transported from the mitochondrial matrix to the intermembrane space of mitochondria during the transfer of electrons to oxygen and shuttled back to the matrix by the a subunit and a ring of identical c subunits across the membrane domain (F_O) of ATP synthase, which is coupled to ATP synthesis. A mutation (m.9176?T?>?G) of the mitochondrial ATP6 gene that replaces an universally conserved leucine residue into arginine at amino acid position 217 of human subunit a (aL₂₁₇R) has been associated to NARP (Neuropathy, Ataxia and Retinitis Pigmentosa) and MILS (Maternally Inherited Leigh's Syndrome) diseases. We previously showed that an equivalent thereof in Saccharomyces cerevisiae (aL₂₃₇R) severely impairs subunit a assembly/stability and decreases by >90% the rate of mitochondrial ATP synthesis. Herein we identified three spontaneous first-site intragenic suppressors (aR₂₃₇M, aR₂₃₇T and aR₂₃₇S) that fully restore ATP synthase assembly. However, mitochondrial ATP synthesis rate was only partially recovered (40–50% vs wild type yeast). In light of recently described high-resolution yeast ATP synthase structures, the detrimental consequences of the aL₂₃₇R change can be explained by steric and electrostatic hindrance with the universally conserved subunit a arginine residue (aR₁₇₆) that is essential to F_O activity. aL₂₃₇ together with three other nearby hydrophobic residues have been proposed to prevent ion shortage between two physically separated hydrophilic pockets within the F_O. Our results suggest that aL₂₃₇ favors subunit c-ring rotation by optimizing electrostatic interaction between aR₁₇₆ and an acidic residue in subunit c (cE₅₉) known to be essential also to the activity of F_O.     

MKP-1 Is Necessary for T Cell Activation and Function

MAPKs are evolutionarily conserved immune regulators. MAPK phosphatases (MKPs) that negatively regulate MAPK activities have recently emerged as critical players in both innate and adaptive immune responses. MKP-1, also known as DUSP1, was previously shown to negatively regulate innate immunity by inhibiting pro-inflammatory cytokine production. Here, we found that MKP-1 is necessary in T cell activation and function. MKP-1 deficiency in T cells impaired the activation, proliferation, and function of T cells in vitro, associated with enhanced activation of JNK and reduced NFATc1 translocation into the nucleus. Consistently, MKP-1^−/− mice were defective in anti-influenza immunity in vivo and resistant to experimental autoimmune encephalomyelitis. Our results thus demonstrate that MKP-1 is a critical positive regulator of T cell activation and function and may be targeted in treatment of autoimmune diseases.