The Effect of the Environment on alpha-Al_2O_3 (0001) Surface Structures

We report that calculating the Gibbs free energy of the alpha-Al_2O_3 (0001) surfaces in equilibrium with a realistic environment containing both oxygen and hydrogen species is essential for obtaining theoretical predictions consistent with experimental observations. Using density-functional theory we find that even under conditions of high oxygen partial pressure, the metal terminated surface is surprisingly stable. An oxygen terminated alpha-Al_2O_3 (0001) surface becomes stable only if hydrogen is present on the surface. In addition, including hydrogen on the surface resolves discrepancies between previous theoretical work and experimental results with respect to the magnitude and direction of surface relaxations.Comment: 4 pages including 2 figures. Submitted to Phys. Rev. Lett. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Features of modeling fatty liver disease in rats of different ages based on a high-calorie diet

BACKGROUND: The problem of diagnosis, treatment and prevention of fat liver disease (FLD) is one of the actual problems of modern medicine. In this regard, the need for the creation of reliable experimental models of the FLD, which would be as close as possible to the pathogenetic patterns of the development of this disease in humans.AIM: To create an experimental model of FLD and compare the efficiency of its reproduction in rats of different ages.MATERIALS AND METHODS: The study was conducted on male Wistar rats, whose ages at the beginning of the experiment were 3 and 18 months. Control animals were fed a standard diet. The experimental rats were kept on a diet with excess fat (45 %) and carbohydrates (31 %) for 12 weeks. The liver tissue samples were taken for morphological studies of FLD. Histological preparations were made according to the standard technique. Morphometry on digital images of micropreparations was conducted using the computer program «IMAGE J». The concentration of lipids, cholesterol, and triglecerides in the liver tissue was determined, and the concentration of ALT in the blood serum was determined. To assess the biophysical properties of the liver tissue, the method of multifrequency bioimpedance measurement was used.RESULTS: The transfer of animals to a high-calorie diet developed by us led to the development of FLD. This was evidenced by an increase of the liver mass, its pale shade and soft consistency. Morphometric signs of FLD were also revealed. Hypertrophy of hepatocytes was observed with a simultaneous decrease in the nuclear-cytoplasmic ratio; accumulation of numerous lipid inclusions in the cytoplasm and the appearance of large lipid droplets replacing the voids of dead hepatocytes. The number of binuclear hepatocytes and nucleolus in the nucleus, the relative area of the sinusoid network were decreased. An increase in the concentration of lipids, cholesterol and triglecerides in the liver tissue of experimental rats, as well as the activity of ALT in the blood serum, was observed. Changes in the bioimpedance measurements of the liver tissue also indicated the  development of severe fatty degeneration of the liver in both young (to a greater extent) and old rats.CONCLUSION: The model of FLD we have advanced based on a combined (fat-carbohydrate) high-calorie diet. It leads to the development of pronounced morphological, biochemical and biophysical signs of this pathology in all experimental rats. The most pronounced manifestations of FLD are observed in young animals

Влияние прерывистой гипо- и гипероксии на состояние респираторного отдела легких

Summary. An influence of normobaric hypoxic (10 % of oxygen in nitrogen) and hyperoxic (40 % of oxygen in nitrogen) breathing sessions on the respiratory part of the lungs was investigated in rats of 3 month of age. After 28 daily hypoxic sessions, 30 min each, we detected lung hyperinflation, an enlargement of the total alveolar area and reduction in connecting tissue elements in the lungs. After 28 daily hyperoxic sessions, 60 min each, we found reduction in mean diameter, depth, cross-sectional area and the entrance size of alveoli, increased the amount of collagen fibers, the alveolar wall thickness and increased oxyproline concentration in the lungs. These findings could indicate the connecting tissue growth in the respiratory part of the lungs and worsening of oxygen diffusion through the blood-air barrier.Резюме. Исследовалось влияние сеансов дыхания нормобарической гипо- (10 % кислорода в азоте) и гипероксической (40 % кислорода в азоте) газовой смесью на состояние респираторного отдела легких 3-месячных крыс. После 28 ежедневных (по 30 мин) сеансов гипоксии обнаружилось увеличение воздушности респираторного отдела и общей площади альвеолярной поверхности, снижение количества элементов соединительной ткани в легких, уменьшение среднего диаметра, глубины, площади поперечного сечения альвеол, ширины входа в альвеолу, увеличение количества коллагеновых волокон, толщины межальвеолярной перегородки и концентрации общего оксипролина в легких. Это может свидетельствовать о разрастании соединительной ткани в респираторном отделе легких, ухудшении условий диффузии кислорода через аэрогематический барьер

Cryptococcus neoformans induces IL-8 secretion and CXCL1 expression by human bronchial epithelial cells

<p>Abstract</p> <p>Background</p> <p><it>Cryptococcus neoformans </it>(<it>C. neoformans</it>) is a globally distributed fungal pathogen with the potential to cause serious disease, particularly among immune compromised hosts. Exposure to this organism is believed to occur by inhalation and may result in pneumonia and/or disseminated infection of the brain as well as other organs. Little is known about the role of airway epithelial cells in cryptococcal recognition or their ability to induce an inflammatory response.</p> <p>Methods</p> <p>Immortalized BEAS-2B bronchial epithelial cells and primary normal human bronchial epithelium (NHBE) were stimulated <it>in vitro </it>with encapsulated or acapsular <it>C. neoformans </it>cultivated at room temperature or 37°C. Activation of bronchial epithelial cells was characterized by analysis of inflammatory cytokine and chemokine expression, transcription factor activation, fungal-host cell association, and host cell damage.</p> <p>Results</p> <p>Viable <it>C. neoformans </it>is a strong activator of BEAS-2B cells, resulting in the production of the neutrophil chemokine Interleukin (IL)-8 in a time- and dose-dependent manner. IL-8 production was observed only in response to acapsular <it>C. neoformans </it>that was grown at 37°C. <it>C. neoformans </it>was also able to induce the expression of the chemokine CXCL1 and the transcription factor CAAT/enhancer-binding protein beta (CEBP/β) in BEAS-2B cells. NHBE was highly responsive to stimulation with <it>C. neoformans</it>; in addition to transcriptional up regulation of CXCL1, these primary cells exhibited the greatest IL-8 secretion and cell damage in response to stimulation with an acapsular strain of <it>C. neoformans</it>.</p> <p>Conclusion</p> <p>This study demonstrates that human bronchial epithelial cells mediate an acute inflammatory response to <it>C. neoformans </it>and are susceptible to damage by this fungal pathogen. The presence of capsular polysaccharide and <it>in vitro </it>fungal culture conditions modulate the host inflammatory response to <it>C. neoformans</it>. Human bronchial epithelial cells are likely to contribute to the initial stages of pulmonary host defense <it>in vivo</it>.</p

Role of CD45 Signaling Pathway in Galactoxylomannan-Induced T Cell Damage

Previously, we reported that Galactoxylomannan (GalXM) activates the extrinsic and intrinsic apoptotic pathways through an interaction with the glycoreceptors on T cells. In this study we establish the role of the glycoreceptor CD45 in GalXM-induced T cell apoptosis, using CD45+/+ and CD45−/− cell lines, derived from BW5147 murine T cell lymphoma. Our results show that whereas CD45 expression is not required for GalXM association by the cells, it is essential for apoptosis induction. In CD45+/+ cells, CD45 triggering by GalXM reduces the activation of Lck, ZAP70 and Erk1/2. Conversely, in CD45−/− cells, Lck was hyperphosphorylated and did not show any modulation after GalXM stimulation. On the whole, our findings provide evidence that the negative regulation of Lck activation occurs via CD45 engagement. This appears to be related to the capacity of GalXM to antagonize T cell activation and induce T cell death. Overall this mechanism may be responsible for the immune paralysis that follows GalXM administration and could explain the powerful immunosuppression that accompanies cryptococcosis

Development of an In Vitro Model for the Multi-Parametric Quantification of the Cellular Interactions between Candida Yeasts and Phagocytes

We developed a new in vitro model for a multi-parameter characterization of the time course interaction of Candida fungal cells with J774 murine macrophages and human neutrophils, based on the use of combined microscopy, fluorometry, flow cytometry and viability assays. Using fluorochromes specific to phagocytes and yeasts, we could accurately quantify various parameters simultaneously in a single infection experiment: at the individual cell level, we measured the association of phagocytes to fungal cells and phagocyte survival, and monitored in parallel the overall phagocytosis process by measuring the part of ingested fungal cells among the total fungal biomass that changed over time. Candida albicans, C. glabrata, and C. lusitaniae were used as a proof of concept: they exhibited species-specific differences in their association rate with phagocytes. The fungal biomass uptaken by the phagocytes differed significantly according to the Candida species. The measure of the survival of fungal and immune cells during the interaction showed that C. albicans was the more aggressive yeast in vitro, destroying the vast majority of the phagocytes within five hours. All three species of Candida were able to survive and to escape macrophage phagocytosis either by the intraphagocytic yeast-to-hyphae transition (C. albicans) and the fungal cell multiplication until phagocytes burst (C. glabrata, C. lusitaniae), or by the avoidance of phagocytosis (C. lusitaniae). We demonstrated that our model was sensitive enough to quantify small variations of the parameters of the interaction. The method has been conceived to be amenable to the high-throughput screening of mutants in order to unravel the molecular mechanisms involved in the interaction between yeasts and host phagocytes

Cryptococcus neoformans Capsular Enlargement and Cellular Gigantism during Galleria mellonella Infection

We have studied infection of Cryptococcus neoformans in the non-vertebrate host Galleria mellonella with particular interest in the morphological response of the yeast. Inoculation of C. neoformans in caterpillars induced a capsule-independent increase in haemocyte density 2 h after infection. C. neoformans manifested a significant increase in capsule size after inoculation into the caterpillar. The magnitude of capsule increase depended on the temperature, being more pronounced at 37°C than at 30°C, which correlated with an increased virulence of the fungus and reduced phagocytosis at 37°C. Capsule enlargement impaired phagocytosis by haemocytes. Incubation of the yeast in G. mellonella extracts also resulted in capsule enlargement, with the polar lipidic fraction having a prominent role in this effect. During infection, the capsule decreased in permeability. A low proportion of the cells (<5%) recovered from caterpillars measured more than 30 µm and were considered giant cells. Giant cells recovered from mice were able to kill the caterpillars in a manner similar to regular cells obtained from in vivo or grown in vitro, establishing their capacity to cause disease. Our results indicate that the morphological transitions exhibited by C. neoformans in mammals also occur in a non-vertebrate host system. The similarities in morphological transitions observed in different animal hosts and in their triggers are consistent with the hypothesis that the cell body and capsular responses represent an adaptation of environmental survival strategies to pathogenesis

EMSL Geochemistry, Biogeochemistry and Subsurface Science-Science Theme Advisory Panel Meeting

This report covers the topics of discussion and the recommendations of the panel members. On December 8 and 9, 2010, the Geochemistry, Biogeochemistry, and Subsurface Science (GBSS) Science Theme Advisory Panel (STAP) convened for a more in-depth exploration of the five Science Theme focus areas developed at a similar meeting held in 2009. The goal for the fiscal year (FY) 2011 meeting was to identify potential topical areas for science campaigns, necessary experimental development needs, and scientific members for potential research teams. After a review of the current science in each of the five focus areas, the 2010 STAP discussions successfully led to the identification of one well focused campaign idea in pore-scale modeling and five longer-term potential research campaign ideas that would likely require additional workshops to identify specific research thrusts. These five campaign areas can be grouped into two categories: (1) the application of advanced high-resolution, high mass accuracy experimental techniques to elucidate the interplay between geochemistry and microbial communities in terrestrial ecosystems and (2) coupled computation/experimental investigations of the electron transfer reactions either between mineral surfaces and outer membranes of microbial cells or between the outer and inner membranes of microbial cells

A Sensitive High-Throughput Assay for Evaluating Host-Pathogen Interactions in Cryptococcus neoformans Infection

Background: Cryptococcus neoformans causes serious disease in immunocompromised individuals, leading to over 600,000 deaths per year worldwide. Part of this impact is due to the organism’s ability to thwart what should be the mammalian hosts ’ first line of defense against cryptococcal infection: internalization by macrophages. Even when C. neoformans is engulfed by host phagocytes, it can survive and replicate within them rather than being destroyed; this ability is central in cryptococcal virulence. It is therefore critical to elucidate the interactions of this facultative intracellular pathogen with phagocytic cells of its mammalian host. Methodology/Principal Findings: To accurately assess initial interactions between human phagocytic cells and fungi, we have developed a method using high-throughput microscopy to efficiently distinguish adherent and engulfed cryptococci and quantitate each population. This method offers significant advantages over currently available means of assaying hostfungal cell interactions, and remains statistically robust when implemented in an automated fashion appropriate for screening. It was used to demonstrate the sensitivity of human phagocytes to subtle changes in the cryptococcal capsule, a major virulence factor of this pathogen. Conclusions/Significance: Our high-throughput method for characterizing interactions between C. neoformans and mammalian phagocytic cells offers a powerful tool for elucidating the relationship between these cell types durin

Resistance of Mycobacterium tuberculosis strains to Rifampicin: A systematic review and meta-analysis

Introduction: Antitubercular drug resistance strain is a horrifying barrier to effective TB treatment and prevention. The present study aimed to determine the prevalence and geographical distribution of rifampicin-resistance M. tuberculosis (MTB) strains. Methods: We searched two electronic databases, PubMed and EMBASE, until 26 March 2017 and updated our search on 27 April 2018 and accessed all prevalence studies of MTB strain and their drug susceptibility patterns to rifampicin. The pooled prevalence estimate was determined using random effects model. Results: We identified 23 studies satisfying the inclusion criteria. The proportion of rifampicin resistance strains was diverged depending on the type of strains, country and Regions. The pooled estimate of rifampicin-resistance strains of MTB for the included studies was 4 (95 CI: 3-5). In subgroup analysis based on World Health Organization (WHO) Regions, the pooled estimate of rifampicin-resistance strains of MTB was 11 (95 CI: 9-13) with the Western Pacific Region 24, Europian Region 10, South-East Asian Region 6, African Region 3 and Region of American 1. Beijing family was the most dominant strain resistance to rifampicin with pooled prevalence of 14 (95 CI: 10e18). The pooled prevalence of other families, i.e. EAI, T, CAS, MANU, Haarlem, LAM and Ural, was <= 2 for each. Conclusion: High burden of rifampicin resistance MTB strains was identified in the Western Pacific Region. Of these, Beijing family was predominantly resistance to rifampicin in Western Pacific Region and South-East Asian Region and also spread to European Region and Region of American