Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment

Myostatin (Mstn) is a skeletal muscle growth inhibitor involved in metabolic disorders and heart fibrosis. In this study we sought to verify whether Mstn is also operative in atherosclerosis of abdominal aorta. In human specimens, Mstn expression was almost absent in normal vessels, became detectable in the media of non-progressive lesions and increased with the severity of the damage. In progressive atherosclerotic lesions, Mstn was present in the media, neointima, plaque shoulder and in infiltrating macrophages. Mstn co-localized with \uce\ub1-smooth muscle actin (\uce\ub1-SMA) staining and with some CD45+ cells, indicating Mstn expression in VSMCs and bloodstream-derived leukocytes. In vitro, Mstn was tested in VSMCs and monocytes. In A7r5 VSMCs, Mstn downregulated proliferation and Smoothelin mRNA, induced cytoskeletal rearrangement, increased migratory rate and MCP-1/CCR2 expression. In monocytes (THP-1 cells and human monocytes), Mstn acted as a chemoattractant and increased the MCP-1-dependent chemotaxis, F-actin, \uce\ub1-SMA, MCP-1 and CCR2 expression; in turn, MCP-1 increased Mstn mRNA. Mstn induced JNK phosphorylation both in VSMCs and monocytes. Our results indicate that Mstn is overexpressed in abdominal aortic wall deterioration, affects VSMCs and monocyte biology and sustains a chronic inflammatory milieu. These findings propose to consider Mstn as a new playmaker in atherosclerosis progression

Molecular Cytogenetic Analysis of the European Hake Merluccius merluccius (Merlucciidae, Gadiformes): U1 and U2 snRNA Gene Clusters Map to the Same Location

The European hake (Merluccius merluccius) is a highly valuable and intensely fished species in which a long-term alive stock has been established in captivity for aquaculture purposes. Due to their huge economic importance, genetic studies on hakes were mostly focused on phylogenetic and phylogeographic aspects; however chromosome numbers are still not described for any of the fifteen species in the genus Merluccius. In this work we report a chromosome number of 2n = 42 and a karyotype composed of three meta/submetacentric and 18 subtelo/telocentric chromosome pairs. Telomeric sequences appear exclusively at both ends of every single chromosome. Concerning rRNA genes, this species show a single 45S rDNA cluster at an intercalary location on the long arm of subtelocentric chromosome pair 12; the single 5S rDNA cluster is also intercalary to the long arm of chromosome pair 4. While U2 snRNA gene clusters map to a single subcentromeric position on chromosome pair 13, U1 snRNA gene clusters seem to appear on almost all chromosome pairs, but showing bigger clusters on pairs 5, 13, 16, 17 and 19. The brightest signals on pair 13 are coincident with the single U2 snRNA gene cluster signals. Therefore, the use of these probes allows the unequivocal identification of at least 7 of the chromosome pairs that compose the karyotype of Merluccius merluccius thus opening the way to integrate molecular genetics and cytological data on the study of the genome of this important species.Versión del editor4,411

Pigmented nodular melanoma: the predictive value of dermoscopic features using multivariate analysis

BACKGROUND: Nodular melanoma (NM), representing 10-30% of all melanomas, plays a major role in global mortality related to melanoma. Nonetheless, the literature on dermoscopy of NM is scanty. OBJECTIVES: To assess odds ratios (ORs) to quantify dermoscopic features of pigmented NM vs. pigmented superficial spreading melanoma (SSM), and pigmented nodular nonmelanocytic and benign melanocytic lesions. METHODS: To assess the presence or absence of global patterns and dermoscopic criteria, digitized images of 457 pigmented skin lesions from patients with a histopathological diagnosis of NM (n = 75), SSM (n = 93), and nodular nonmelanocytic and benign melanocytic lesions (n = 289; namely, 39 basal cell carcinomas, 85 seborrhoeic keratoses, 81 blue naevi, and 84 compound/dermal naevi) were retrospectively collected and blindly evaluated by three observers. RESULTS: Multivariate analysis showed that ulceration (OR 4.07), homogeneous disorganized pattern (OR 10.76), and homogeneous blue pigmented structureless areas (OR 2.37) were significantly independent prognostic factors for NM vs. SSM. Multivariate analysis of dermoscopic features of NM vs. nonmelanocytic and benign melanocytic lesions showed that the positive correlating features leading to a significantly increased risk of NM were asymmetric pigmentation (OR 6.70), blue-black pigmented areas (OR 7.15), homogeneous disorganized pattern (OR 9.62), a combination of polymorphous vessels and milky-red globules/areas (OR 23.65), and polymorphous vessels combined with homogeneous red areas (OR 33.88). CONCLUSIONS: Dermoscopy may be helpful in improving the recognition of pigmented NM by revealing asymmetric pigmentation, blue-black pigmented areas, homogeneous disorganized pattern and abnormal vascular structures, including polymorphous vessels, milky-red globules/areas and homogeneous red areas

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Biological responses to change in Antarctic sea ice habitats

Sea ice is a key habitat in the high latitude Southern Ocean and is predicted to change in its extent, thickness and duration in coming decades. The sea-ice cover is instrumental in mediating ocean–atmosphere exchanges and provides an important substrate for organisms from microbes and algae to predators. Antarctic krill, Euphausia superba, is reliant on sea ice during key phases of its life cycle, particularly during the larval stages, for food and refuge from their predators, while other small grazers, including copepods and amphipods, either live in the brine channel system or find food and shelter at the ice-water interface and in gaps between rafted ice blocks. Fish, such as the Antarctic silverfish Pleuragramma antarcticum, use platelet ice (loosely-formed frazil crystals) as an essential hatching and nursery ground. In this paper, we apply the framework of the Marine Ecosystem Assessment for the Southern Ocean (MEASO) to review current knowledge about relationships between sea ice and associated primary production and secondary consumers, their status and the drivers of sea-ice change in this ocean. We then use qualitative network modelling to explore possible responses of lower trophic level sea-ice biota to different perturbations, including warming air and ocean temperatures, increased storminess and reduced annual sea-ice duration. This modelling shows that pelagic algae, copepods, krill and fish are likely to decrease in response to warming temperatures and reduced sea-ice duration, while salp populations will likely increase under conditions of reduced sea-ice duration and increased number of days of >0°C. Differences in responses to these pressures between the five MEASO sectors were also explored. Greater impacts of environmental pressures on ice-related biota occurring presently were found for the West and East Pacific sectors (notably the Ross Sea and western Antarctic Peninsula), with likely flow-on effects to the wider ecosystem. All sectors are expected to be impacted over coming decades. Finally, we highlight priorities for future sea ice biological research to address knowledge gaps in this field

Biological responses to change in Antarctic sea ice habitats

Sea ice is a key habitat in the high latitude Southern Ocean and is predicted to change in its extent, thickness and duration in coming decades. The sea-ice cover is instrumental in mediating ocean–atmosphere exchanges and provides an important substrate for organisms from microbes and algae to predators. Antarctic krill, Euphausia superba, is reliant on sea ice during key phases of its life cycle, particularly during the larval stages, for food and refuge from their predators, while other small grazers, including copepods and amphipods, either live in the brine channel system or find food and shelter at the ice-water interface and in gaps between rafted ice blocks. Fish, such as the Antarctic silverfish Pleuragramma antarcticum, use platelet ice (loosely-formed frazil crystals) as an essential hatching and nursery ground. In this paper, we apply the framework of the Marine Ecosystem Assessment for the Southern Ocean (MEASO) to review current knowledge about relationships between sea ice and associated primary production and secondary consumers, their status and the drivers of sea-ice change in this ocean. We then use qualitative network modelling to explore possible responses of lower trophic level sea-ice biota to different perturbations, including warming air and ocean temperatures, increased storminess and reduced annual sea-ice duration. This modelling shows that pelagic algae, copepods, krill and fish are likely to decrease in response to warming temperatures and reduced sea-ice duration, while salp populations will likely increase under conditions of reduced sea-ice duration and increased number of days of >0°C. Differences in responses to these pressures between the five MEASO sectors were also explored. Greater impacts of environmental pressures on ice-related biota occurring presently were found for the West and East Pacific sectors (notably the Ross Sea and western Antarctic Peninsula), with likely flow-on effects to the wider ecosystem. All sectors are expected to be impacted over coming decades. Finally, we highlight priorities for future sea ice biological research to address knowledge gaps in this field

In vitro Inhibition of Xa/Va Procoagulant Activity and in vivo Inhibition of Neointimal Thickening after Balloon Injury in the Rabbit Aorta by N-Acetyl-L-Cysteine: Clues for a Synergistic Antithrombotic and Antiproliferative Profile.

Ruolo di Componenti Protrombotiche nella risposta al danno vascolar