L6E9 Myoblasts Are Deficient of Myostatin and Additional TGF-β Members Are Candidates to Developmentally Control Their Fiber Formation

This work provides evidence that the robust myoblast differentiation observed in L6E9 cells is causally linked to deficiency of myostatin, which, conversely, has been found to be expressed in C2C12 cells. However, despite the absence of endogenous myostatin, L6E9 myoblasts expressed functional Activin receptors type II (ActRIIs) and follistatin as well as the highly related TGF-β members Activins and GDF11, suggesting that in this cell line the regulation of fiber size might be under the control of multiple regulators regardless of myostatin. In line with this hypothesis, delivery of a dominant-negative ActRIIb form or the increase of follistatin, as obtained via Trichostatin treatment or stable transfection of a short human follistatin form, enhanced the L6E9 cell differentiation and further increased the size of myotubes, suggesting that L6E9 myoblasts provide a spontaneous myostatin knock-out in vitro model to study TGF-β ligands involved in developmental regulation of fiber size

The role of structural inheritance in continental break-up and exhumation of Alpine Tethyan mantle (Canavese Zone, Western Alps)

The Canavese Zone (CZ) in the Western Alps represents the remnant of the distal passive margin of the Adria microplate, which was stretched and thinned during the Jurassic opening of the Alpine Tethys. Through detailed geological mapping, stratigraphic and structural analyses, we document that the continental break-up of Pangea and tectonic dismemberment of the Adria distal margin, up to mantle rocks exhumation and oceanization, did not simply result from the syn-rift Jurassic extension but was strongly favored by older structural inheritances (the Proto-Canavese Shear Zone), which controlled earlier lithospheric weakness. Our findings allowed to redefine in detail (i) the tectono-stratigraphic setting of the Variscan metamorphic basement and the Late Carboniferous to Early Cretaceous CZ succession, (ii) the role played by inherited Late Carboniferous to Early Triassic structures and (iii) the significance of the CZ in the geodynamic evolution of the Alpine Tethys. The large amount of extensional displacement and crustal thinning occurred during different pulses of Late Carboniferous–Early Triassic strike-slip tectonics is well-consistent with the role played by long-lived regional-scale wrench faults (e.g., the East-Variscan Shear Zone), suggesting a re-discussion of models of mantle exhumation driven by low-angle detachment faults as unique efficient mechanism in stretching and thinning continental crust. Keywords: Alpine Tethys, Western Alps, Jurassic ophiolite, Structural inheritance, Continental break-up, Mantle exhumatio

Pulmonary artery thrombosis in home patient with a mild COVID-19 disease

Abstract COVID-19 has been described as the cause for a proinflammatory and hypercoagulable state that induces thrombotic vascular lesions and, in more severe cases, disseminated intravascular coagulation. Increased values of d-dimers are related to the severity of the disease and are associated with worst prognosis. Intensive care studies reported an increased risk of pulmonary embolism and venous thrombosis diseases in COVID-19 compared with the historical control group even in patients who underwent the low-molecular-weight heparin (LWMH) prophylaxis. Patients with COVID-19 who have a stable clinical condition do not require hospitalisation and are treated at home with symptomatic therapy. LWMH is reserved for those with reduced mobility. In this case report, we describe a COVID-19 patient with pulmonary artery thrombosis treated at home

Polarisation measurements with a CdTe pixel array detector for Laue hard X-ray focusing telescopes

Polarimetry is an area of high energy astrophysics which is still relatively unexplored, even though it is recognized that this type of measurement could drastically increase our knowledge of the physics and geometry of high energy sources. For this reason, in the context of the design of a Gamma-Ray Imager based on new hard-X and soft gamma ray focusing optics for the next ESA Cosmic Vision call for proposals (Cosmic Vision 2015-2025), it is important that this capability should be implemented in the principal on-board instrumentation. For the particular case of wide band-pass Laue optics we propose a focal plane based on a thick pixelated CdTe detector operating with high efficiency between 60-600 keV. The high segmentation of this type of detector (1-2 mm pixel size) and the good energy resolution (a few keV FWHM at 500 keV) will allow high sensitivity polarisation measurements (a few % for a 10 mCrab source in 106s) to be performed. We have evaluated the modulation Q factors and minimum detectable polarisation through the use of Monte Carlo simulations (based on the GEANT 4 toolkit) for on and off-axis sources with power law emission spectra using the point spread function of a Laue lens in a feasible configuration.Comment: 10 pages, 6 pages. Accepted for publication in Experimental Astronom

MDP, a database linking drug response data to genomic information, identifies dasatinib and statins as a combinatorial strategy to inhibit YAP/TAZ in cancer cells

Targeted anticancer therapies represent the most effective pharmacological strategies in terms of clinical responses. In this context, genetic alteration of several oncogenes represents an optimal predictor of response to targeted therapy. Integration of large-scale molecular and pharmacological data from cancer cell lines promises to be effective in the discovery of new genetic markers of drug sensitivity and of clinically relevant anticancer compounds. To define novel pharmacogenomic dependencies in cancer, we created the Mutations and Drugs Portal (MDP, http://mdp.unimore.it), a web accessible database that combines the cell-based NCI60 screening of more than 50,000 compounds with genomic data extracted from the Cancer Cell Line Encyclopedia and the NCI60 DTP projects. MDP can be queried for drugs active in cancer cell lines carrying mutations in specific cancer genes or for genetic markers associated to sensitivity or resistance to a given compound. As proof of performance, we interrogated MDP to identify both known and novel pharmacogenomics associations and unveiled an unpredicted combination of two FDA-approved compounds, namely statins and Dasatinib, as an effective strategy to potently inhibit YAP/TAZ in cancer cells

A focal plane detector design for a wide-band Laue-lens telescope

The energy range above 60 keV is important for the study of many open problems in high energy astrophysics such as the role of Inverse Compton with respect to synchrotron or thermal processes in GRBs, non thermal mechanisms in SNR, the study of the high energy cut-offs in AGN spectra, and the detection of nuclear and annihilation lines. Recently the development of high energy Laue lenses with broad energy bandpasses from 60 to 600 keV have been proposed for a Hard X ray focusing Telescope (HAXTEL) in order to study the X-ray continuum of celestial sources. The required focal plane detector should have high detection efficiency over the entire operative range, a spatial resolution of about 1 mm, an energy resolution of a few keV at 500 keV and a sensitivity to linear polarization. We describe a possible configuration of the focal plane detector based on several CdTe/CZT pixelated layers stacked together to achieve the required detection efficiency at high energy. Each layer can operate both as a separate position sensitive detector and polarimeter or work with other layers to increase the overall photopeak efficiency. Each layer has a hexagonal shape in order to minimize the detector surface required to cover the lens field of view. The pixels would have the same geometry so as to provide the best coupling with the lens point spread function and to increase the symmetry for polarimetric studies.Comment: 10 pages, 9 figure

A three-week in-hospital multidisciplinary body weight reduction program exerts beneficial effects on physical and mental health and fatiguability of elderly patients with obesity

IntroductionObesity represents one of the most serious problems of public health affecting elderly populations in an increasingly relevant way. The aim of the current study was to assess the effects of a 3-week in-hospital multidisciplinary body weight reduction program (BWRP) in a sample of elderly patients with obesity on reducing body mass index (BMI), improving fatigue, muscle performance, and psychological well-being.MethodsTwo hundred and thirty-seven consecutive elderly in-patients with obesity (males = 84; females = 153; age range = 65–86 yrs.; mean BMI = 43.7) undergoing a three-week multidisciplinary BWRP participated in the study. Data on BMI, fatiguability (measured with the Fatigue Severity Scale, FSS), muscle performance (evaluated with the Stair Climbing Test, SCT), and psychological well-being (assessed with the Psychological General Well- Being Index, PGWBI) were collected before and after the intervention.ResultsResults showed that BWRP was capable to reduce BMI [F(1.00, 235.00) = 1226.8; p < 0.001; ƞ2 = 0.024], improve perceived fatigue [F(1,234) = 296.80125; p < 0.001; ƞ2 = 0.129], physical performance [F(1.00,158.00) = 119.26; p < 0.001; ƞ2 = 0.026], and enhance psychological well-being [F(1,235) = 169.0; p < 0.001; ƞ2 = 0.103] in both males and females.DiscussionAlthough it will be necessary to demonstrate with further longitudinal studies whether the reported beneficial effects will be maintained over time, the effectiveness of a 3-week BWRP on different aspects involved in determining a level of autonomy and good quality of life of elderly obese patients appears to represent a valid attempt to counteract – at least in part – the unavoidable and progressive disability of these patients