Heparanase and macrophage interplay in the onset of liver fibrosis

Abstract The heparan sulfate endoglycosidase heparanase (HPSE) is involved in tumor growth, chronic inflammation and fibrosis. Since a role for HPSE in chronic liver disease has not been demonstrated to date, the current study was aimed at investigating the involvement of HPSE in the pathogenesis of chronic liver injury. Herein, we revealed that HPSE expression increased in mouse livers after carbon tetrachloride (CCl4)-mediated chronic induction of fibrosis, but with a trend to decline during progression of the disease. In mouse fibrotic liver tissues HPSE immunostaining was restricted in necro-inflammatory areas, co-localizing with F4/80 macrophage marker and TNF-α. TNF-α treatment induced HPSE expression as well as HPSE secretion in U937 macrophages. Moreover, macrophage-secreted HPSE regulated the expression of α-SMA and fibronectin in hepatic stellate LX-2 cells. Finally, HPSE activity increased in the plasma of patients with liver fibrosis but it inversely correlated with liver stiffness. Our results suggest the involvement of HPSE in early phases of reaction to liver damage and inflammatory macrophages as an important source of HPSE. HPSE seems to play a key role in the macrophage-mediated activation of hepatic stellate cells (HSCs), thus suggesting that HPSE targeting could be a new therapeutic option in the treatment of liver fibrosis

Profile Monitoring of Probability Density Functions via Simplicial Functional PCA with application to Image Data

The advance of sensor and information technologies is leading to data-rich industrial environments, where large amounts of data are potentially available. This study focuses on industrial applications where image data are used more and more for quality inspection and statistical process monitoring. In many cases of interest, acquired images consist of several and similar features that are randomly distributed within a given region. Examples are pores in parts obtained via casting or additive manufacturing, voids in metal foams and light-weight components, grains in metallographic analysis, etc. The proposed approach summarizes the random occurrences of the observed features via their (empirical) probability density functions (PDFs). In particular, a novel approach for PDF monitoring is proposed. It is based on simplicial functional principal component analysis (SFPCA), which is performed within the space of density functions, that is, the Bayes space B2. A simulation study shows the enhanced monitoring performances provided by SFPCA-based profile monitoring against other competitors proposed in the literature. Finally, a real case study dealing with the quality control of foamed material production is discussed, to highlight a practical use of the proposed methodology. Supplementary materials for the article are available online

Dynamic arrest and aging of biomolecular condensates are modulated by low-complexity domains, RNA and biochemical activity

Biomolecular condensates require suitable control of material properties for their function. Here we apply Differential Dynamic Microscopy (DDM) to probe the material properties of an in vitro model of processing bodies consisting of out-of-equilibrium condensates formed by the DEAD-box ATPase Dhh1 in the presence of ATP and RNA. By applying this single-droplet technique we show that condensates within the same population exhibit a distribution of material properties, which are regulated on several levels. Removal of the low-complexity domains (LCDs) of the protein decreases the fluidity of the condensates. Structured RNA leads to a larger fraction of dynamically arrested condensates with respect to unstructured polyuridylic acid (polyU). Promotion of the enzymatic ATPase activity of Dhh1 reduces aging of the condensates and the formation of arrested structures, indicating that biochemical activity and material turnover can maintain fluid-like properties over time

Itinerari conoscitivi in città. Test di realtà virtuale nel miglioramento del design Italiano

Five years ago, the Department of Architectural History, Theory and Composition of the University of Seville began a line of research and work on universal accessibility and historical heritage. The current Curriculum for Architecture studies, from 2012 and derived from the Bologna Plan, is based on competency-based learning. Along with the specific ones for each subject, for each area of knowledge, others of a transversal nature are established, such as universal accessibility and the reasonable use of IC

Mendelian breeding units <i>versus</i> standard sampling strategies: mitochondrial DNA variation in southwest Sardinia

We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits