Interplay between FGFR2b-induced autophagy and phagocytosis: role of PLCγ-mediated signalling

Signalling of the epithelial splicing variant of the fibroblast growth factor receptor 2 (FGFR2b) induces both autophagy and phagocytosis in human keratinocytes. Here, we investigated, in the cell model of HaCaT keratinocytes, whether the two processes might be related and the possible involvement of PLCγ signalling. Using fluorescence and electron microscopy, we demonstrated that the FGFR2b-induced phagocytosis and autophagy involve converging autophagosomal and phagosomal compartments. Moreover, the forced expression of FGFR2b signalling mutants and the use of specific inhibitors of FGFR2b substrates showed that the receptor-triggered autophagy requires PLCγ signalling, which in turn activates JNK1 via PKCδ. Finally, we found that in primary human keratinocytes derived from light or dark pigmented skin and expressing different levels of FGFR2b, the rate of phagocytosis and autophagy and the convergence of the two intracellular pathways are dependent on the level of receptor expression, suggesting that FGFR2b signalling would control in vivo the number of melanosomes in keratinocytes, determining skin pigmentation

Influence of sinusoidal motion on Stirling engines

Stirling engines have a high potential to produce renewable energy due to their ability to use a wide range of sustainable heat sources and their high theoretical efficiencies. They have not yet achieved widespread use and commercial Stirling engines have had reduced efficiencies compared to their ideal values. This work shows that a substantial\ amount of the reduction in efficiency is due to the operation of Stirling engines using sinusoidal motion and quantities this reduction. A discrete model was developed to perform an isothermal analysis of a 100cc alpha-type Stirling engine with a 90_ phase angle offset, to demonstrate the impact of sinusoidal motion on the net work and thermal efficiency in comparison to the ideal cycle. The model was adapted to analyze beta and gamma-type Stirling configurations, and the analysis revealed similar reductions due to sinusoidal motion. Lastly, a mechanically plausible arrangement is presented and analyzed to demonstrate that non-sinusoidal operation can be accomplished

Extracorporeal Shock Wave Treatment (ESWT) enhances the in vitro-induced differentiation of human tendon-derived stem/progenitor cells (hTSPCs)

Extracorporeal shock wave therapy (ESWT) is a non-invasive and innovative technology for the management of specific tendinopathies. In order to elucidate the ESWT-mediated clinical benefits, human Tendon-derived Stem/Progenitor cells (hTSPCs) explanted from 5 healthy semitendinosus (ST) and 5 ruptured Achilles (AT) tendons were established. While hTSPCs from the two groups showed similar proliferation rates and stem cell surface marker profiles, we found that the clonogenic potential was maintained only in cells derived from healthy donors. Interestingly, ESWT significantly accelerated hTSPCs differentiation, suggesting that the clinical benefits of ESWT may be ascribed to increased efficiency of tendon repair after injury

Critical analysis of the integration of residual municipal solid waste incineration and selective collection in two Italian tourist areas

Municipal solid waste management is not only a contemporary problem, but also an issue at world level. In detail, the tourist areas are more difficult to be managed. The dynamics of municipal solid waste production in tourist areas is affected by the addition of a significant amount of population equivalent during a few months. Consequences are seen in terms of the amount of municipal solid waste to be managed, but also on the quality of selective collection. In this article two case studies are analyzed in order to point out some strategies useful for a correct management of this problem, also taking into account the interactions with the sector of waste-to-energy. The case studies concern a tourist area in the north of Italy and another area in the south. Peak production is clearly visible during the year. Selective collection variations demonstrate that the tourists' behavior is not adequate to get the same results as with the resident population. © The Author(s) 2014

Chronic heart failure is characterized by altered mitochondrial function and structure in circulating leucocytes

Oxidative stress is currently viewed as a key factor in the genesis and progression of Heart Failure (HF). The aim of this study was to characterize the mitochondrial changes linked to oxidative stress generation in circulating peripheral blood mononuclear cells isolated from chronic HF patients (HF_PBMCs) in order to highlight the involvement of mitochondrial dysfunction in the pathophysiology of HF. To assess the production of reactive oxygen species (ROS), mitochondrial function and ultrastructure and the mitophagic flux in circulating PBMCs we enrolled 15 patients with HF and a control group of ten healthy subjects. The HF_PBMCs showed a mitochondrial population consisting of damaged and less functional organelles responsible of higher superoxide anion production both at baseline and under in vitro stress conditions, with evidence of cellular apoptosis. Although the mitophagic flux at baseline was enhanced in HF_PBMCs at level similar to those that could be achieved in control PBMCs only under inflammatory stress conditions, the activation of mitophagy was unable to preserve a proper mitochondrial dynamics upon stress stimuli in HF. In summary, circulating HF_PBMCs show structural and functional derangements of mitochondria with overproduction of reactive oxidant species. This mitochondrial failure sustains a leucocyte dysfunctional status in the blood that may contribute to development and persistence of stress conditions within the cardiovascular system in HF

Expression of miRNA-33 and miRNA-155 in symptomatic and asymptomatic carotid artery stenosis

Background: The aim of this study was to evaluate miRNA-33 and miRNA-155 expression in Peripheral Blood Mononuclear Cells (PBMC) and carotid specimens of patients affected by Critical Carotid Artery stenosis (CAS). Material and Methods: We selected 17 asymptomatic (CAS-A group) and 10 symptomatic (CAS-S group) patients with CAS. Ten patients with traditional cardiovascular risk factors (RF group), matched for age and sex, were used as control group. Results: A significant increase in miRNA-33 expression was observed both in peripheral blood and in carotid specimens of CAS-A patients (p 0.04) in comparison with CAS-S and RF, whereas no significant difference were found among the groups regarding miRNA-155 expression both in peripheral blood and in carotid specimens. Conclusions: This is to our knowledge the first report on miRNAs expression in human PBMCs from CAS patients. Results of this study suggest that miRNA-33 in involved in the process underling plaque formation and growth, but not is plaque instability and ischemic brain damage, whereas miRNA-155 is expressed during all the phases of atherosclerotic disease

The Mice Drawer System (MDS) Experiment and the Space Endurance Record-Breaking Mice

The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28th, 2009. MDS returned to Earth on November 27th, 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages

Nutrient withdrawal rescues growth factor-deprived cells from mTOR-dependent damage

Deregulated nutrient signaling plays pivotal roles in body ageing and in diabetic complications; biochemical cascades linking energy dysmetabolism to cell damage and loss are still incompletely clarified, and novel molecular paradigms and pharmacological targets critically needed. We provide evidence that in the retrovirus-packaging cell line HEK293-T Phoenix, massive cell death in serum-free medium is remarkably prevented or attenuated by either glucose or aminoacid withdrawal, and by the glycolysis inhibitor 2-deoxy-glucose. A similar protection was also elicited by interference with mitochondrial function, clearly suggesting involvement of energy metabolism in increased cell survival. Oxidative stress did not account for nutrient toxicity on serum-starved cells. Instead, nutrient restriction was associated with reduced activity of the mTOR/S6 Kinase cascade. Moreover, pharmacological and genetic manipulation of the mTOR pathway modulated in an opposite fashion signaling to S6K/S6 and cell viability in nutrient-repleted medium. Additionally, stimulation of the AMP-activated Protein Kinase concomitantly inhibited mTOR signaling and cell death, while neither event was affected by overexpression of the NAD+ dependent deacetylase Sirt-1, another cellular sensor of nutrient scarcity. Finally, blockade of the mTOR cascade reduced hyperglycemic damage also in a more pathophysiologically relevant model, i.e. in human umbilical vein endothelial cells (HUVEC) exposed to hyperglycemia. Taken together these findings point to a key role of the mTOR/S6K cascade in cell damage by excess nutrients and scarcity of growth-factors, a condition shared by diabetes and other ageing-related pathologies

Recent results and developments on double-gap RPCs for CMS

Abstract A 3 mm wide-gap Resistive Plate Chamber, as proposed for CMS, has been tested in the H2 Cern beam line. Results on efficiency, rate capability, time resolution and cluster size are reported