Molecular subtyping of bladder cancer using Kohonen self-organizing maps

Kohonen self-organizing maps (SOMs) are unsupervised Artificial Neural Networks (ANNs) that are good for low-density data visualization. They easily deal with complex and nonlinear relationships between variables. We evaluated molecular events that characterize high- and low-grade BC pathways in the tumors from 104 patients. We compared the ability of statistical clustering with a SOM to stratify tumors according to the risk of progression to more advanced disease. In univariable analysis, tumor stage (log rank P = 0.006) and grade (P < 0.001), HPV DNA (P < 0.004), Chromosome 9 loss (P = 0.04) and the A148T polymorphism (rs 3731249) in CDKN2A (P = 0.02) were associated with progression. Multivariable analysis of these parameters identified that tumor grade (Cox regression, P = 0.001, OR.2.9 (95% CI 1.6–5.2)) and the presence of HPV DNA (P = 0.017, OR 3.8 (95% CI 1.3–11.4)) were the only independent predictors of progression. Unsupervised hierarchical clustering grouped the tumors into discreet branches but did not stratify according to progression free survival (log rank P = 0.39). These genetic variables were presented to SOM input neurons. SOMs are suitable for complex data integration, allow easy visualization of outcomes, and may stratify BC progression more robustly than hierarchical clustering

Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines

<p>Abstract</p> <p>Background</p> <p>Airway remodeling and dysfunction are characteristic features of asthma thought to be caused by aberrant production of Th2 cytokines. Histamine H₄receptor (H₄R) perturbation has previously been shown to modify acute inflammation and Th2 cytokine production in a murine model of asthma. We examined the ability of H₄R antagonists to therapeutically modify the effects of Th2 cytokine production such as goblet cell hyperplasia (GCH), and collagen deposition in a sub-chronic model of asthma. In addition, effects on Th2 mediated lung dysfunction were also determined.</p> <p>Methods</p> <p>Mice were sensitized to ovalbumin (OVA) followed by repeated airway challenge with OVA. After inflammation was established mice were dosed with the H₄R antagonist, JNJ 7777120, or anti-IL-13 antibody for comparison. Airway hyperreactivity (AHR) was measured, lungs lavaged and tissues collected for analysis.</p> <p>Results</p> <p>Therapeutic H₄R antagonism inhibited T cell infiltration in to the lung and decreased Th2 cytokines IL-13 and IL-5. IL-13 dependent remodeling parameters such as GCH and lung collagen were reduced. Intervention with H₄R antagonist also improved measures of central and peripheral airway dysfunction.</p> <p>Conclusions</p> <p>These data demonstrate that therapeutic H₄R antagonism can significantly ameliorate allergen induced, Th2 cytokine driven pathologies such as lung remodeling and airway dysfunction. The ability of H₄R antagonists to affect these key manifestations of asthma suggests their potential as novel human therapeutics.</p

A mutated dph3 gene causes sensitivity of Schizosaccharomyces pombe cells to cytotoxic agents

Dph3 is involved in diphthamide modification of the eukaryotic translation elongation factor eEF2 and in Elongator-mediated modifications of tRNAs, where a 5-methoxycarbonyl-methyl moiety is added to wobble uridines. Lack of such modifications affects protein synthesis due to inaccurate translation of mRNAs at ribosomes. We have discovered that integration of markers at the msh3 locus of Schizosaccharomyces pombe impaired the function of the nearby located dph3 gene. Such integrations rendered cells sensitive to the cytotoxic drugs hydroxyurea and methyl methanesulfonate. We constructed dph3 and msh3 strains with mutated ATG start codons (ATGmut), which allowed investigating drug sensitivity without potential interference by marker insertions. The dph3- ATGmut and a dph3::loxP-ura4-loxM gene disruption strain, but not msh3-ATGmut, turned out to be sensitive to hydroxyurea and methyl methanesulfonate, likewise the strains with cassettes integrated at the msh3 locus. The fungicide sordarin, which inhibits diphthamide modified eEF2 of Saccharomyces cerevisiae, barely affected survival of wild type and msh3Δ S. pombe cells, while the dph3Δ mutant was sensitive. The msh3-ATG mutation, but not dph3Δ or the dph3-ATG mutation caused a defect in mating-type switching, indicating that the ura4 marker at the dph3 locus did not interfere with Msh3 function. We conclude that Dph3 is required for cellular resistance to the fungicide sordarin and to the cytotoxic drugs hydroxyurea and methyl methanesulfonate. This is likely mediated by efficient translation of proteins in response to DNA damage and replication stress

Plasma–liquid interactions: a review and roadmap

Plasma–liquid interactions represent a growing interdisciplinary area of research involving plasma science, fluid dynamics, heat and mass transfer, photolysis, multiphase chemistry and aerosol science. This review provides an assessment of the state-of-the-art of this multidisciplinary area and identifies the key research challenges. The developments in diagnostics, modeling and further extensions of cross section and reaction rate databases that are necessary to address these challenges are discussed. The review focusses on non-equilibrium plasmas

Issledovanija vitaminnogo balansa v processe parazitnojj invazii. Ch. II. Opredelenija soderzhimogo vitamina C v nekotorykh parenkhimatoznykh organakh khozjaina

The authors' observations have confirmed the opinion of Selye (1950) and other authors as regards changes in the C vitamin level of parenchymatous organs in the stress condition. Corroborated are also the quantitative, qualitative, histochemical findings of Tarczyński (1962) on the subject of parasitogenic stress

Methods of cultivating of parasitic nematodes in vitro

The review of literature referring to cultivating methods of some parasitic nematodes in vitro is presented (Ascaridia galli, Ascaris suum, Nippostrongylus brasiliensis, Strongyloides fülleborni). It refers general problems and initiate in subject of parasites cultivating in vitro. This work comprises terminology and elementary problems connected with the starting of culture of parasites in vitro, such as: obtaining of parasites to the starting of cultures, the types of cultures in vitro and forming of conditions to determine successful of culture of parasitic nematodes in vitro (sterilization, the selecting of medium, the forming of most favourable physical-chemical conditions)

The effect of vitamin A, B2 and B15 administration on the activity of alpha-amylase in lungs and kidney of guinea pig infected Ascaris suum

The guinea pigs were administrated vit. A (400 i.u.), vit. B₂ (1 mg) or vit. B₁₅ (5 mg). On the 9-th day of the experiment part of them was infectpd with 5000 invasive eggs of Ascaris suum. The invasion lasted 6 days and was controlled by lungs and kidney weight, and number of larvae in the lungs. The activity of amylase was determined by saccharogenic method in both organs. In the lungs of infected animals the activity of alpha-amylase was abouth 3 times lower than in the control. The infection of guinea pigs which were given vitamins did not cause change of enzyme's activity. In the kidney directive tendency was the same, but the differences were smaller. The infection resulted in an increase of relative mass of lungs. This index and number of larvae was considerable smaller in guinea pigs with vitamins A and B₁₅ administration. Any testing agent did not cause change of relative weight of kidney

The effect of low temperatures on the development of eggs of Ascaris suum Goeze, 1782

Eggs of A. suum were kept at -10 and -20'C for 12 weeks and subsequently incubated in a thermostat at 28°C. During the incubation, their development was checked every 5 days. It was found that storage at low temperatures slows down their development and reduces the number of eggs successfully completing their embryogenesis