Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.

The secretion of proteolytic enzymes by pathogenic microorganisms is one of the most successful strategies used by pathogens to colonize and infect the host organism. The extracellular microbial proteinases can seriously deregulate the homeostatic proteolytic cascades of the host, including the kinin-forming system, repeatedly reported to he activated during bacterial infection. The current study assigns a kinin-releasing activity to secreted proteinases of Candida spp. yeasts, the major fungal pathogens of humans. Of several Candida species studied, C. parapsilosis and C. albicans in their invasive filamentous forms are shown to produce proteinases which most effectively degrade proteinaceous kinin precursors, the kininogens. These enzymes, classified as aspartyl proteinases, have the highest kininogen-degrading activity at low pH (approx. 3.5), but the associated production of bradykinin-related peptides from a small fraction of kininogen molecules is optimal at neutral pH (6.5). The peptides effectively interact with cellular B2-type kinin receptors. Moreover, kinin-related peptides capable of interacting with inflammation-induced B1-type receptors are also formed, but with a reversed pH dependence. The presented variability of the potential extracellular kinin production by secreted aspartyl proteinases of Candida spp. is consistent with the known adaptability of these opportunistic pathogens to different niches in the host organism

Solvable model of a many-filament Brownian ratchet

We construct and exactly solve a model of an extended Brownian ratchet. The model comprises an arbitrary number of heterogeneous, growing and shrinking filaments which together move a rigid membrane by a ratchet mechanism. The model draws parallels with the dynamics of actin filament networks at the leading edge of the cell. In the model, the filaments grow and contract stochastically. The model also includes forces which derive from a potential dependent on the separation between the filaments and the membrane. These forces serve to attract the filaments to the membrane or generate a surface tension that prevents the filaments from dispersing. We derive an N -dimensional diffusion equation for the N filament-membrane separations, which allows the steady-state probability distribution function to be calculated exactly under certain conditions. These conditions are fulfilled by the physically relevant cases of linear and quadratic interaction potentials. The exact solution of the diffusion equation furnishes expressions for the average velocity of the membrane and critical system parameters for which the system stalls and has zero net velocity. In the case of a restoring force, the membrane velocity grows as the square root of the force constant, whereas it decreases once a surface tension is introduced

Synthetic biology: Building the language for a new science brick by metaphorical brick

Changes in the biosciences and their relations to society over the last decades provide a unique opportunity to examine whether or not such changes leave traces in the language we use to talk about them. In this article we examine metaphors used in English-speaking press coverage to conceptualize a new type of (interdisciplinary) bioscience: synthetic biology. Findings show that three central metaphors were used between 2008 and May 2010. They exploit social and cultural knowledge about books, computers and engines and are linked to knowledge of three revolutions in science and society (the printing, information and industrial revolutions). These three central metaphors are connected to each other through the concepts of reading/writing, designing and mass production and they focus on science as a revolutionary process rather than on the end results or products of science. Overall, we observed the use of a complex bricolage of mixed metaphors and chains of metaphors that root synthetic biology in historical events and achievements, while at the same time extolling its promises for the future. © 2011 Copyright Taylor and Francis Group, LLC

The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro

Background: Fascin is overexpressed in many cancers, including colorectal, but its role in the malignant transformation of benign colorectal adenomas is unclear. Methods: Immunohistochemical analysis of fascin expression was carried out in resected human colorectal adenoma specimens. The effects of forced overexpression of fascin on adenoma cell motility were also analysed. Results: We show fascin overexpression in adenomas increasing with tumour size, histological type, and degree of dysplasia and increased cell motility in adenoma cell lines following fascin transfection. Conclusion: These data suggest an important role for fascin in the malignant progression of colorectal tumours

Properties of an alkali-thermo stable xylanase from Geobacillus thermodenitrificans A333 and applicability in xylooligosaccharides generation

An extracellular thermo-alkali-stable and cellulase-free xylanase from Geobacillus thermodenitrificans A333 was purified to homogeneity by ion exchange and size exclusion chromatography. Its molecular mass was 44 kDa as estimated in native and denaturing conditions by gel filtration and SDS-PAGE analysis, respectively. The xylanase (GtXyn) exhibited maximum activity at 70 °C and pH 7.5. It was stable over broad ranges of temperature and pH retaining 88 % of activity at 60 °C and up to 97 % in the pH range 7.5–10.0 after 24 h. Moreover, the enzyme was active up to 3.0 M sodium chloride concentration, exhibiting at that value 70 % residual activity after 1 h. The presence of other metal ions did not affect the activity with the sole exceptions of K+ that showed a stimulating effect, and Fe2+, Co2+ and Hg2+, which inhibited the enzyme. The xylanase was activated by non-ionic surfactants and was stable in organic solvents remaining fully active over 24 h of incubation in 40 % ethanol at 25 °C. Furthermore, the enzyme was resistant to most of the neutral and alkaline proteases tested. The enzyme was active only on xylan, showing no marked preference towards xylans from different origins. The hydrolysis of beechwood xylan and agriculture-based biomass materials yielded xylooligosaccharides with a polymerization degree ranging from 2 to 6 units and xylobiose and xylotriose as main products. These properties indicate G. thermodenitrificans A333 xylanase as a promising candidate for several biotechnological applications, such as xylooligosaccharides preparation

Effects of small interfering RNAs targeting fascin on human esophageal squamous cell carcinoma cell lines

<p>Abstract</p> <p>Background</p> <p>Fascin induces membrane protrusions and cell motility. Fascin overexpression was associated with poor prognosis, and its downregulation reduces cell motility and invasiveness in esophageal squamous cell carcinoma (ESCC). Using a stable knockdown cell line, we revealed the effect of fascin on cell growth, cell adhesion and tumor formation.</p> <p>Methods</p> <p>We examined whether fascin is a potential target in ESCC using <it>in vitro </it>and <it>in vivo </it>studies utilizing a specific siRNA. We established a stable transfectant with downregulated fascin from KYSE170 cell line.</p> <p>Results</p> <p>The fascin downregulated cell lines showed a slower growth pattern by 40.3% (p < 0.01) and detachment from collagen-coated plates by 53.6% (p < 0.01), compared to mock cells, suggesting that fascin plays a role in cell growth by maintaining cell adhesion to the extracellular matrix. <it>In vivo</it>, the tumor size was significantly smaller in the tumor with fascin knockdown cells than in mock cells by 95% at 30 days after inoculation.</p> <p>Conclusions</p> <p>These findings suggest that fascin overexpression plays a role in tumor growth and progression in ESCC and that cell death caused by its downregulation might be induced by cell adhesion loss. This indicates that targeting fascin pathway could be a novel therapeutic strategy for the human ESCC.</p