Endoglin (CD105) is not a specific selection marker for endothelial cells in human islets of Langerhans. Reply to Wheeler-Jones CPD, Clarkin CE, Farrar CE et al [letter]

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Human Liver Stem Cell-Derived Extracellular Vesicles Target Hepatic Stellate Cells and Attenuate Their Pro-fibrotic Phenotype

Liver fibrosis occurs in response to chronic liver injury and is characterized by an excessive deposition of extracellular matrix. Activated hepatic stellate cells are primarily responsible for this process. A possible strategy to counteract the development of hepatic fibrosis could be the reversion of the activated phenotype of hepatic stellate cells. Extracellular vesicles (EVs) are nanosized membrane vesicles involved in intercellular communication. Our previous studies have demonstrated that EVs derived from human liver stem cells (HLSCs), a multipotent population of adult stem cells of the liver with mesenchymal-like phenotype, exert in vivo anti-fibrotic activity in the liver. However, the mechanism of action of these EVs remains to be determined. We set up an in vitro model of hepatic fibrosis using a human hepatic stellate cell line (LX-2) activated by transforming growth factor-beta 1 (TGF-β1). Then, we investigated the effect of EVs obtained from HLSCs and from human bone marrow-derived mesenchymal stromal cells (MSCs) on activated LX-2. The incubation of activated LX-2 with HLSC-EVs reduced the expression level of alpha-smooth muscle actin (α-SMA). Conversely, MSC-derived EVs induced an increase in the expression of pro-fibrotic markers in activated LX-2. The analysis of the RNA cargo of HLSC-EVs revealed the presence of several miRNAs involved in the regulation of fibrosis and inflammation. Predictive target analysis indicated that several microRNAs (miRNAs) contained into HLSC-EVs could possibly target pro-fibrotic transcripts. In particular, we demonstrated that HLSC-EVs shuttled miR-146a-5p and that treatment with HLSC-EVs increased miR-146a-5p expression in LX-2. In conclusion, this study demonstrates that HLSC-EVs can attenuate the activated phenotype of hepatic stellate cells and that their biological effect may be mediated by the delivery of anti-fibrotic miRNAs, such as miR-146a-5p

A model of discriminant analysis on the basis of descriptor variables for the ampelography of Vitis sp.

Use of descriptor variables in ampelography is recommended to simplify recording of data and to enable useful comparisons. Parametric assumptions are, however, poorly satisfied especially with regard to statistical interference. In the paper some statistical procedures to improve the discriminant ability of descriptor variables are considered. The use of variances and covariances of variety by year interactions is suggested for the error matrix within a multiple discriminant analysis procedure. The adequacy of this model is verified in a 3-year experiment with Italian wine varieties. The discriminant power, as evaluated on the basis of the estimated distances among varieties, is satisfactory

Statistics of Dissipation and Enstrophy Induced by a Set of Burgers Vortices

Dissipation and enstropy statistics are calculated for an ensemble of modified Burgers vortices in equilibrium under uniform straining. Different best-fit, finite-range scaling exponents are found for locally-averaged dissipation and enstrophy, in agreement with existing numerical simulations and experiments. However, the ratios of dissipation and enstropy moments supported by axisymmetric vortices of any profile are finite. Therefore the asymptotic scaling exponents for dissipation and enstrophy induced by such vortices are equal in the limit of infinite Reynolds number.Comment: Revtex (4 pages) with 4 postscript figures included via psfi

Supersonic turbulence and structure of interstellar molecular clouds

The interstellar medium (ISM) provides a unique laboratory for highly supersonic, driven hydrodynamics turbulence. We present a theory of such turbulence, confirm it by numerical simulations, and use the results to explain observational properties of interstellar molecular clouds, the regions where stars are born.Comment: 5 pages, 3 figures include

Obesity reduces the pro-angiogenic potential of adipose tissue stem cell-derived extracellular vesicles (EVs) by impairing miR-126 content: impact on clinical applications

BACKGROUND/OBJECTIVES: Soluble factors and cell-derived extracellular vesicles (EVs) are crucial tissue repair mediators in cell-based therapy. In the present study, we investigate the therapeutic impact of EVs released by adipose tissue-derived stem cells (ASCs) recovered from obese subjects' visceral and subcutaneous tissues. METHODS: ASCs were recovered from 10 obese (oASCs) and 6 non-obese (nASCs) participants and characterized. In selected experiments, nASCs and oASCs were cultured with palmitic acid (PA) or high glucose (HG), respectively. EVs from obese (oEVs) and non-obese (nEVs) subjects' visceral and subcutaneous ASCs were collected after ultracentrifugation and analyzed for their cargo: microRNA-126 (miR-126), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 2 (MMP-2), and for their biological effects on endothelial cells (ECs). Western blotting analysis and loss- and gain-of function experiments were performed. RESULTS: oEVs show impaired angiogenic potential compared with nEVs. This effect depends on EV cargo: reduced content of VEGF, MMP-2 and, more importantly, miR-126. We demonstrate, using gain- and loss-of-function experiments, that this reduced miR-126 content leads to Spred1 upregulation and the inhibition of the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway in ECs. We also show that PA treatment of nASCs translates into the release of EVs that recapitulate oEV cargo. Moreover, HG treatment of oASCs further reduces miR-126 EV content and EV-mediated in vitro angiogenesis. Finally, impaired pro-angiogenic potential is also detected in EVs released from obese subcutaneous adipose tissue-derived ASCs. CONCLUSIONS: These results indicate that obesity impacts on EV pro-angiogenic potential and may raise concerns about the use of adipose tissue-derived EVs in cell-based therapy in the obese setting

Dynamical Organization around Turbulent Bursts

The detailed dynamics around intermittency bursts is investigated in turbulent shell models. We observe that the amplitude of the high wave number velocity modes vanishes before each burst, meaning that the fixed point in zero and not the Kolmogorov fixed point determines the intermittency. The phases of the field organize during the burst, and after a burst the field oscillates back to the laminar level. We explain this behavior from the variations in the values of the dissipation and the advection around the zero fixed point.Comment: 4 pages, REVTex, 3 figures in one ps-fil