Cyclin D1 and D3 expression in melanocytic skin lesions

Cyclins, cyclin-dependent kinases, as well as proteins cooperating with them are responsible for cell cycle regulation which is crucial for normal development, injury repair, and tumorigenesis. D-type cyclins regulate G1 cell cycle progression by enhancing the activities of cyclin-dependent kinases, and their expression is frequently altered in tumors. Disturbances in cyclin expression were also reported in melanocytic skin lesions. The objective of the study was to evaluate the expression of cyclins D1 and D3 in common, dysplastic, and malignant melanocytic skin lesions. Forty-eight melanocytic skin lesions including common nevi (10), dysplastic nevi (24), and melanomas (14) were diagnosed by dermoscopy and excised. Expression of cyclin D1 and D3 was detected by immunohistochemistry and quantified as percentage of immunostained cell nuclei in each sample. In normal skin, expression of cyclins D1 and D3 was not detected. The mean percentage of cyclin D1-positive nuclei was 7.75% for melanoma samples, 5% for dysplastic nevi samples, and 0.34% for common nevi samples. For cyclin D3, the respective values were 17.8, 6.4, and 1.8%. Statistically significant differences in cyclin D1 expression were observed between melanomas and common nevi as well as between dysplastic and common nevi (p = 0.0001), but not between melanomas and dysplastic nevi. Cyclin D3 expression revealed significant differences between all investigated lesion types (p = 0.0000). The mean cyclin D1 and D3 scores of melanomas with Breslow thickness <1 mm and >1 mm were not significantly different. G1/S abnormalities are crucial for the progression of malignant melanoma, and enhanced cyclin D1 and D3 expression leading to increased melanocyte proliferation is observed in both melanoma and dysplastic nevi. In histopathologically ambiguous cases, lower cyclin D3 expression in dysplastic nevi can be a diagnostic marker for that lesion type

MoS2 monolayer catalyst doped with isolated Co atoms for the hydrodeoxygenation reaction

The conversion of oxygen-rich biomass into hydrocarbon fuels requires efficient hydrodeoxygenation catalysts during the upgrading process. However, traditionally prepared CoMoS2 catalysts, although efficient for hydrodesulfurization, are not appropriate due to their poor activity, sulfur loss and rapid deactivation at elevated temperature. Here, we report the synthesis of MoS2 monolayer sheets decorated with isolated Co atoms that bond covalently to sulfur vacancies on the basal planes that, when compared with conventionally prepared samples, exhibit superior activity, selectivity and stability for the hydrodeoxygenation of 4-methylphenol to toluene. This higher activity allows the reaction temperature to be reduced from the typically used 300 °C to 180 °C and thus allows the catalysis to proceed without sulfur loss and deactivation. Experimental analysis and density functional theory calculations reveal a large number of sites at the interface between the Co and Mo atoms on the MoS2 basal surface and we ascribe the higher activity to the presence of sulfur vacancies that are created local to the observed Co–S–Mo interfacial sites

Mechanotransduction and Vascular Resistance

International audienceMechanotransduction is the process by which any cell transduces (converts) a mechanical signal into chemical cues. The vessel wall is permanently sheared by the moving blood particles as well as stretched and compressed by the pressure applied by the blood. Multiple types of mechanical stress fields are associated with flow patterns and unsteadiness.Mechanosensing occurs locally at the plasma membrane. It relies on detection of local changes in protein conformation that lead to ion channel opening, protein unfolding, modified enzyme kinetics, and variations in molecular interactions following exposure of buried binding site or, conversely, hiding them.Mechanotransduction initiates several signaling pathways. Multiple mediators include: At the cell surface, G-protein-coupled and protein tyrosine kinase receptors, ion channels, enzymes, adhesion molecules, and specialized plasmalemmal nanodomains At the cell cortex, the cortical actin network that regulates the cell-surface mechanics and signaling adaptors and effectors (e.g., small monomeric guanosine triphosphatases and heterotrimeric guanine nucleotide-binding proteins, kinases, phosphatases, and ubiquitins, among others) In the cytosol, enzymes, scaffolds, carriers such as endosomes, calcium concentration, and transcription factors In the nucleus, nuclear pore carriers, enzymes, and the transcriptional and translational machineryMechanotransduction by vascular cells regulate the contraction–relaxation state of vascular smooth myocytes, thereby regulating locally and quickly the size of the vascular lumen, that is, the local vascular resistance to blood flow. Once experiencing an unusual mechanical stress, vascular smooth myocytes react by contracting or relaxing according to the magnitude of the mechanical stress, the value of which rises above or falls below the range in which it fluctuates in normal conditions. Moreover, they receive chemical and electrochemical signals from endotheliocytes, themselves sensing the wall shear stress at their wetted (luminal) surface.Mechanotransduction thus regulates locally blood flow more rapidly than the endocrine regulation by remote tissues and even than that of the nervous system, which transmits signals very rapidly via afferent nerves and, after processing in the centers of the spinal cord and brain, efferent nerves