Pathophysiological Mechanisms in Sclerosing Skin Diseases

Sclerosing skin diseases represent a large number of distinct disease entities, which include systemic sclerosis, localized scleroderma, and scleredema adultorum. These pathologies have a common clinical appearance and share histological features. However, the specific interplay between cytokines and growth factors, which activate different mesenchymal cell populations and production of different extracellular matrix components, determines the biomechanical properties of the skin and the clinical features of each disease. A better understanding of the mechanisms underlying these events is prerequisite for developing novel targeted therapeutic approaches

State-of-the-art capabilities in LPJ-GUESS

LPJ-GUESS is an advanced DGVM including detailed forest demography and management, croplands, wetlands, specialised arctic processes, emissions of nonCO2 GHGs and a highly flexible land-use change scheme which tracks transitions between different land-uses. It is the vegetation component of the EC-Earth CMIP6 ESM, the RCA-GUESS regional ESM, and also has a European mode operating at tree species level

Stabilization of integrin-linked kinase by the Hsp90-CHIP axis impacts cellular force generation, migration and the fibrotic response

Integrin-linked kinase (ILK) is an adaptor protein required to establish and maintain the connection between integrins and the actin cytoskeleton. This linkage is essential for generating force between the extracellular matrix (ECM) and the cell during migration and matrix remodelling. The mechanisms by which ILK stability and turnover are regulated are unknown. Here we report that the E3 ligase CHIP–heat shock protein 90 (Hsp90) axis regulates ILK turnover in fibroblasts. The chaperone Hsp90 stabilizes ILK and facilitates the interaction of ILK with α-parvin. When Hsp90 activity is blocked, ILK is ubiquitinated by CHIP and degraded by the proteasome, resulting in impaired fibroblast migration and a dramatic reduction in the fibrotic response to bleomycin in mice. Together, our results uncover how Hsp90 regulates ILK stability and identify a potential therapeutic strategy to alleviate fibrotic diseases

Stabilization of integrin-linked kinase by the Hsp90-CHIP axis impacts cellular force generation, migration and the fibrotic response

Integrin-linked kinase (ILK) is an adaptor protein required to establish and maintain the connection between integrins and the actin cytoskeleton. This linkage is essential for generating force between the extracellular matrix (ECM) and the cell during migration and matrix remodelling. The mechanisms by which ILK stability and turnover are regulated are unknown. Here we report that the E3 ligase CHIP-heat shock protein 90 (Hsp90) axis regulates ILK turnover in fibroblasts. The chaperone Hsp90 stabilizes ILK and facilitates the interaction of ILK with a-parvin. When Hsp90 activity is blocked, ILK is ubiquitinated by CHIP and degraded by the proteasome, resulting in impaired fibroblast migration and a dramatic reduction in the fibrotic response to bleomycin in mice. Together, our results uncover how Hsp90 regulates ILK stability and identify a potential therapeutic strategy to alleviate fibrotic diseases

(In)certezze giuridiche sulla situazione della Crimea: una «mappa» dei casi pendenti o decisi davanti alle corti europee

The purpose of this chapter is to analyse the case of Crimea from an international law perspective, by reflecting on the numerous pending cases in front of the European Court of Human Rights and on two cases decided by the European Court of Justice. The chapter will not take a position on the legitimacy or not of the facts that led to the current situation. It will rather focus on the current de facto situation, case law, and on two pivotal notions in international law: sovereignty and jurisdiction.The purpose of this chapter is to analyse the case of Crimea from an international law perspective, by reflecting on the numerous pending cases in front of the European Court of Human Rights and on two cases decided by the European Court of Justice. The chapter will not take a position on the legitimacy or not of the facts that led to the current situation. It will rather focus on the current de facto situation, case law, and on two pivotal notions in international law: sovereignty and jurisdiction

Operational rater types in writing assessment: Linking rater cognition to rater behavior

This research investigated the relation between rater cognition and rater behavior, focusing on differential severity/leniency regarding criteria. Participants comprised a sample of 18 raters examined in a previous rater cognition study Recent increase in the use of constructed-response tasks in high-stakes language testing and assessment has led to an increasing need to understand how humans evaluate examinees' responses (G. T. L. As reviewed in the next two sections, there has been a considerable number of studies addressing various aspects of rater cognition involved in performance evaluations (e.g., differential weighting of criteria or selective attention to performance features), as well as research into the kind of decision-making behaviors and biased use of scoring criteria in rating examinee performance, but research directed at investigating the link between rater cognition and rater behavio