The Dermatan Sulfate Proteoglycan Decorin Modulates α2β1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis.

Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(-/-)) mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(-/-) mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(-/-) fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, we identified vimentin as one of the proteins that was differentially upregulated by the presence of decorin. We discovered that a decorin-deficient matrix leads to abnormal nuclear morphology in the Dcn(-/-) fibroblasts. This phenotype could be rescued by the decorin proteoglycan but less efficiently by the decorin protein core. Decorin treatment led to a significant reduction of the α2β1 integrin at day 6 in Dcn(-/-) fibroblasts, whereas the protein core had no effect on β1. Interestingly, only the decorin core induced mRNA synthesis, phosphorylation and de novo synthesis of vimentin indicating that the proteoglycan decorin in the extracellular matrix stabilizes the vimentin intermediate filament system. We could support these results in vivo, because the dermis of wild-type mice have more vimentin and less β1 integrin compared to Dcn(-/-). Furthermore, the α2β1 null fibroblasts also showed a reduced amount of vimentin compared to wild-type. These data show for the first time that decorin has an impact on the biology of α2β1 integrin and the vimentin intermediate filament system. Moreover, our findings provide a mechanistic explanation for the reported defects in wound healing associated with the Dcn(-/-) phenotype

Conceptualising computerized adaptive testing for measurement of latent variables associated with physical objects

The notion of that more or less of a physical feature affects in different degrees the users' impression with regard to an underlying attribute of a product has frequently been applied in affective engineering. However, those attributes exist only as a premise that cannot directly be measured and, therefore, inferences based on their assessment are error-prone. To establish and improve measurement of latent attributes it is presented in this paper the concept of a stochastic framework using the Rasch model for a wide range of independent variables referred to as an item bank. Based on an item bank, computerized adaptive testing (CAT) can be developed. A CAT system can converge into a sequence of items bracketing to convey information at a user's particular endorsement level. It is through item banking and CAT that the financial benefits of using the Rasch model in affective engineering can be realised

Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

Investigation of Floating Peat Wetlands, Sacramento–San Joaquin Delta, California

Tidal wetland restoration is integral to achieving the Delta coequal goals. Deeply subsided islands limit the potential for tidal wetland restoration. Floating peats may offer an opportunity to create tidal habitat in the subsided western and central Delta. We conducted a mesocosm experiment to assess the feasibility of floating peat blocks, and the potential food-web benefits, biomass production, carbon sequestration, methane emissions, and water-quality effects. We evaluated the effect of varying water residence time and initial peat-block density.The peat blocks floated during the entire experiment, and accreted biomass at rates consistent with those reported for Delta non-tidal managed wetlands. Peat blocks placed in mesocosms with 45% open water expanded horizontally about 21% per year. We estimated average vertical accretion rates of 5.5 to 8.6 cm/yr  for all the mesocosms. Vertical and horizontal expansion increase floating peat-block stability.We measured a 3-fold zooplankton population increase during the first year after deployment, relative to the Mokelumne River, which was the mesocosm’s water source. Measured and modeled methane emissions were lower than those reported in Delta non-tidal managed wetlands. Aqueous methane concentrations and methane fluxes were significantly lower for the shorter water-residence-time of about 5 days compared to longer residence times of about 11 days. Elevated dissolved oxygen (DO) concentrations generally corresponded with low methane concentrations. Our estimated net ecosystem carbon balance of – 820 +/– 137 g C m2/yr  indicates that the floating wetlands are potentially greater carbon sinks than Delta non-tidal wetlands. Nitrogen data indicated consumption by wetland plants, and denitrification and dissimilatory nitrate reduction in the mesocosms. Our preliminary results point to potential ecosystem benefits of floating peats on a larger scale

Quality Management Initiatives in Europe: an Empirical Analysis according to Their Structural Elements

"This is an Accepted Manuscript of an article published by Taylor & Francis in Total Quality Management and Business Excellence on 10 June 2010, available online: http://wwww.tandfonline.com/10.1080/14783363.2010.483064."In recent years, managers have opted for implementing Quality Management in their firms. The market offers different alternatives for QM implementation, such as EFQM model, ISO standards, Malcolm Baldrige or the recent Six Sigma methodology. Implementation difficulty of each initiative varies from case to case. This article designs a criterion for choosing among four alternatives (Quality Control, EFQM, Six Sigma and ISO 9000), according to the degree of development required for the elements that structure the alternatives. To do so, using an ANOVA analysis and mean comparison T-tests, it analyses 234 organizations in Europe that have implemented the four alternatives mentioned and observes the degree of development of nine of the elements that compose them. From the research, one can conclude that Quality Control is the simplest initiative, followed by ISO 9000 and, finally, the EFQM model and Six Sigma methodology

Demography, dynamics and data:building confidence for simulating changes in the world's forests

Summary: Vegetation demographic models (VDMs) are advanced tools for simulating forest responses to climate and land‐use changes, and are essential for projecting carbon cycling and large‐scale forest management strategies. Despite their increasing incorporation into Earth System Models, VDMs differ in their demographic assumptions, with no prior quantitative comparison of their performance. We benchmarked nine VDMs against observational data from boreal, temperate and tropical sites, assessing their accuracy in predicting tree growth, carbon turnover, biomass stocks and size distributions. Models were simulated under consistent climate conditions with postdisturbance recovery monitored for at least 420 yr. Postdisturbance carbon recovery trajectories showed significant variability while remaining within observational ranges. Initial regrowth rates varied substantially (0.03–0.60, 0.18–0.70 and 0.35–1.10 kgCm−2 yr−1 for boreal, temperate and tropical sites, respectively), influenced by each model's initial forest state. Models captured mature forest carbon content but showed compensating effects between overestimated growth and underestimated mortality rates. This first multi‐model benchmarking identifies growth and mortality rates as critical calibration targets and highlights the need to refine postdisturbance establishment conditions for model development. We outline specific benchmarking variables needed to improve predictions of forest responses to environmental change

Optimisation of Biochemical Condition and Substrates In Vitro for Tissue Engineering of Ligament

In this work, we analysed the effect of growth factors on in vitro cell proliferation and collagens synthesis by fibroblasts cultured for 72 h on different substrates (silicon sheet with or without 1% gelatin, and glass as control surface) for ligament tissue engineering. A human fibroblast cell line (CRL-2703) was used. The synthesis of type I and type III collagens were evaluated qualitatively and quantitatively by RT-PCR and confocal microscopy, respectively. Cell proliferation was evaluated by two methods: (1) MTT assay (2) cell cycle analysis. It was found that PDGF-AB stimulate the proliferation of fibroblast cultured on gelatin coated silicon sheet in dose dependant manner with a maximum effect at 10 ng ml(−1). The exogenous TGF-β1 induced the expression of type I and type III collagens in a dose and substrate-dependant manner. We deduce from this work that biochemical conditions and substrates have an important impact for optimisation of the tissue neo synthesis