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

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

Prevalence and determinants of traditional sexist attitudes in Germany—an analysis based on Allbus data

Traditional sexism is still often present in Germans of both genders. To elucidate the mechanism of its development the paper is seeking for determinants of gender roles. Based on the ALLBUS 2008 data set structural equation models were calculated to separate direct from indirect factors. Both, socialization as well as the situation, play a role in development of traditional sexism. The following determinants where found as most relevant in both genders: (insufficient) education, origin from the western part of Germany, birth earlier than 1949, anti-egalitarian values and, a factor previously not investigated, anomia. Surprisingly two other determinants of sexism were only seen in men: Not working mother and the feeling of economic deprivation. These results provide starting points to reduce sexist attitudes in the future

(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