The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10

The novel CXC-chemokine ligand 16 (CXCL16) functions as transmembrane adhesion molecule on the surface of APCs and as a soluble chemoattractant for activated T cells. In this study, we elucidate the mechanism responsible for the conversion of the transmembrane molecule into a soluble chemokine and provide evidence for the expression and shedding of CXCL16 by fibroblasts and vascular cells. By transfection of human and murine CXCL16 in different cell lines, we show that soluble CXCL16 is constitutively generated by proteolytic cleavage of transmembrane CXCL16 resulting in reduced surface expression of the transmembrane molecule. Inhibition experiments with selective hydroxamate inhibitors against the disintegrin-like metalloproteinases a disintegrin and metalloproteinase domain (ADAM)10 and ADAM17 suggest that ADAM10, but not ADAM17, is involved in constitutive CXCL16 cleavage. In addition, the constitutive cleavage of transfected human CXCL16 was markedly reduced in embryonic fibroblasts generated from ADAM10-deficient mice. By induction of murine CXCL16 in ADAM10-deficient fibroblasts with IFN-gamma and TNF-alpha, we show that endogenous ADAM10 is indeed involved in the release of endogenous CXCL16. Finally, the shedding of endogenous CXCL16 could be reconstituted by retransfection of ADAM10-deficient cells with ADAM10. Analyzing the expression and release of CXCXL16 by cultured vascular cells, we found that IFN-gamma and TNF-alpha synergize to induce CXCL16 mRNA. The constitutive shedding of CXCL16 from the endothelial cell surface is blocked by inhibitors of ADAM10 and is independent of additional inhibition of ADAM17. Hence, during inflammation in the vasculature, ADAM10 may act as a CXCL16 sheddase and thereby finely control the expression and function of CXCL16 in the inflamed tissue.     

Spirochaeta coccoides sp. nov., a novel coccoid spirochete from the hindgut of the termite Neotermes castaneus

A novel spirochete strain, SPN1, was isolated from the hindgut contents of the termite Neotermes castaneus. The highest similarities (about 90%) of the strain SPN1 16S rRNA gene sequence are with spirochetes belonging to the genus Spirochaeta, and thus, the isolate could not be assigned to the so-called termite clusters of the treponemes or to a known species of the genus Spirochaeta. Therefore, it represents a novel species, which was named Spirochaeta coccoides. In contrast to all other known validly described spirochete species, strain SPN1 shows a coccoid morphology and is immotile. The isolated strain is obligately anaerobic and ferments different mono-, di-, and oligosaccharides by forming formate, acetate, and ethanol as the main fermentation end products. Furthermore, strain SPN1 is able to grow anaerobically with yeast extract as the sole carbon and energy source. The fastest growth was obtained at 30 degrees C, the temperature at which the termites were also grown. The cells possess different enzymatic activities that are involved in the degradation of lignocellulose in the termite hindgut, such as beta-D-glucosidase, alpha-L-arabinosidase, and beta-D-xylosidase. Therefore, they may play an important role in the digestion of breakdown products from cellulose and hemicellulose in the termite gut.     

P300 wave: a comparative study of impulsive aggressive criminals

Event-Related potentials are a simple non-invasive neurophysiological method enabling to comprehend certain aspects of the cognitive processing of information in humans. The best-known component of Event-Related Potentials is the so-called P3 wave. Alterations in the parameters of P300 wave have been discovered in certain personality disorders and in persons with impulsively aggressive behaviour. The purpose of this study is to investigate the changes of these parameters, especially an amplitude and latency in the place of Pz electrode. We examined 15 persons with the impulsive aggressive behaviour and compared them to a population comparable of normal age, gender and approximate degree of education. We used P300 auditory and a neuropsychological Eysenck IVE battery. The results showed that significantly lower amplitudes had been found in the aggressive impulsive subjects as compared to the control group. No statistically significant differences have been discovered in the latency. These results seem to confirm previous studies.     

Rheological properties of myometrium: experimental quantification and mathematical modeling

This work answers some questions related to detection of rheological properties of soft tissues exemplified in myometrium, stressed by external tensile force. In the first stage of the experiment the tissue samples were ciclically stressed and response loops were recorded. This test proved severe plastical deformation of samples, which is not usually being stated for living tissues. In addition to course, growth and stabilizing this deformation also energetical losses of individual hysteresis loops of the response were evaluated. In the second stage of the experiment the tissue samples were exposed to a loading force changed in step-wise manner in four steps. The sample response to each force step was processed and evaluated separately to obtain basic properties of used model. In next step, the changes in model characteristics were obtained and evaluated for each element in subsequent force steps. By reason of following easier interpretation, the quite simple visco-elastic model, defined by differential equation with analytic solution, is used. The results prove necessary to introduce in model both spring and damper constants dependent on the magnitude of the loading force and one damper with even time dependent constant. The interindividual variability of characteristic values of the model elements is surprisingly low. On the other side, they are strongly dependent on load magnitude. Complete mathematical model of uterine wall tissue is obtained by amending the principal equation by formulas describing changes in individual components of the model.     

Standardized generation of fully mature p70 IL-12 secreting monocyte-derived dendritic cells for clinical use

Dendritic cells (DC) have been shown to be efficient antigen-presenting cells (APC) and, as such, could be considered ideal candidates for cancer immunotherapy. Immature DC (iDC) efficiently capture surrounding antigens; however, only mature DC (mDC) prime naive T lymphocytes. Clinical trials using DC-based tumor vaccines have achieved encouraging, but limited, success, possibly due to the use of immature or incompletely mature DC. Thus, it was apparent that a method capable of generating large numbers of fully functional iDC, their pulsing with desired form of tumor antigens and the subsequent complete and reproducible maturation of iDC is needed. Therefore, we compared two different methods of producing large numbers of iDC. Both protocols yielded comparable numbers of cells with an iDC phenotype with phagocytic function. We next determined which of the clinically applicable activators could induce the complete and reproducible maturation of DC, in order to define the most suitable combination for future clinical trials. Only a combination of TNFalpha + Poly (I:C), or a previously described cytokine cocktail of TNFalpha + IL-1beta + IL-6 + prostaglandin E2, induced the complete activation of the whole DC population, as assessed by the cell surface expression of CD83 and costimulatory molecules. The matured DC were functionally superior to iDC in their ability to stimulate the proliferation of allogeneic lymphocytes and autologous keyhole limpet hemocyanin (KLH)-specific T lymphocytes. Furthermore, only the combination of TNFalpha + Poly (L:C) activated DC to produce large amounts of biologically active p70 IL-12. Thus DC maturation by TNFalpha + Poly (I:C) could efficiently bias T cell response towards Th1 response. Implementation of our results into clinical protocols used for DC generation could be beneficial for future immunotherapy trials.     

Red-shifted light-harvesting system of freshwater eukaryotic alga Trachydiscus minutus (Eustigmatophyta,Stramenopila)

Photosynthesis Research - Survival of phototrophic organisms depends on their ability to collect and convert enough light energy to support their metabolism. Phototrophs can extend their absorption...     

Large‐scale disturbance legacies and the climate sensitivity of primary Picea abies forests

Determining the drivers of shifting forest disturbance rates remains a pressing global change issue. Large‐scale forest dynamics are commonly assumed to be climate driven, but appropriately scaled disturbance histories are rarely available to assess how disturbance legacies alter subsequent disturbance rates and the climate sensitivity of disturbance. We compiled multiple tree ring‐based disturbance histories from primary Picea abies forest fragments distributed throughout five European landscapes spanning the Bohemian Forest and the Carpathian Mountains. The regional chronology includes 11,595 tree cores, with ring dates spanning the years 1750–2000, collected from 560 inventory plots in 37 stands distributed across a 1,000 km geographic gradient, amounting to the largest disturbance chronology yet constructed in Europe. Decadal disturbance rates varied significantly through time and declined after 1920, resulting in widespread increases in canopy tree age. Approximately 75% of current canopy area recruited prior to 1900. Long‐term disturbance patterns were compared to an historical drought reconstruction, and further linked to spatial variation in stand structure and contemporary disturbance patterns derived from LANDSAT imagery. Historically, decadal Palmer drought severity index minima corresponded to higher rates of canopy removal. The severity of contemporary disturbances increased with each stand's estimated time since last major disturbance, increased with mean diameter, and declined with increasing within‐stand structural variability. Reconstructed spatial patterns suggest that high small‐scale structural variability has historically acted to reduce large‐scale susceptibility and climate sensitivity of disturbance. Reduced disturbance rates since 1920, a potential legacy of high 19th century disturbance rates, have contributed to a recent region‐wide increase in disturbance susceptibility. Increasingly common high‐severity disturbances throughout primary Picea forests of Central Europe should be reinterpreted in light of both legacy effects (resulting in increased susceptibility) and climate change (resulting in increased exposure to extreme events).     

Expansion of the human mitochondrial proteome by intra- and inter-compartmental protein duplication

Background  

Mitochondria are highly complex, membrane-enclosed organelles that are essential to the eukaryotic cell. The experimental elucidation of organellar proteomes combined with the sequencing of complete genomes allows us to trace the evolution of the mitochondrial proteome.