Testosterone insulin-like effects: an in vitro study on the short-term metabolic effects of testosterone in human skeletal muscle cells

Testosterone by promoting different metabolic pathways contributes to short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue and the primary site for insulin-stimulated glucose utilization. Despite evidences indicate a close relationship between testosterone and glucose metabolism, the molecular mechanisms responsible for a possible testosterone-mediated insulin-like effects on skeletal muscle are still unknown

Reading a GEM with a VLSI pixel ASIC used as a direct charge collecting anode

In MicroPattern Gas Detectors (MPGD) when the pixel size is below 100 micron and the number of pixels is large (above 1000) it is virtually impossible to use the conventional PCB read-out approach to bring the signal charge from the individual pixel to the external electronics chain. For this reason a custom CMOS array of 2101 active pixels with 80 micron pitch, directly used as the charge collecting anode of a GEM amplifying structure, has been developed and built. Each charge collecting pad, hexagonally shaped, realized using the top metal layer of a deep submicron VLSI technology is individually connected to a full electronics chain (pre-amplifier, shaping-amplifier, sample and hold, multiplexer) which is built immediately below it by using the remaining five active layers. The GEM and the drift electrode window are assembled directly over the chip so the ASIC itself becomes the pixelized anode of a MicroPattern Gas Detector. With this approach, for the first time, gas detectors have reached the level of integration and resolution typical of solid state pixel detectors. Results from the first tests of this new read-out concept are presented. An Astronomical X-Ray Polarimetry application is also discussed.Comment: 11 pages, 14 figures, presented at the Xth Vienna Conference on Instrumentation (Vienna, February 16-21 2004). For a higher resolution paper contact [email protected]

Sport, doping and male fertility

It is universally accepted that lifestyle interventions are the first step towards a good overall, reproductive and sexual health. Cessation of unhealthy habits, such as tobacco, alcohol and drug use, poor nutrition and sedentary behavior, is suggested in order to preserve/improve fertility in humans. However, the possible risks of physical exercise per se or sports on male fertility are less known. Being fit does not only improve the sense of well-being, but also has beneficial effects on general health: in fact physical exercise is by all means a low-cost, high-efficacy method for preventing or treating several conditions, ranging from purely physical (diabetes and obesity) to psychological (depression and anxiety), highly influencing male reproduction. If male sexual and reproductive health could be positively affected by a proper physical activity, inadequate bouts of strength - both excessive intensity and duration of exercise training - are more likely to have detrimental effects. In addition, the illicit use of prohibited drugs (i.e. doping) has reached pandemic proportions, and their actions, unfortunately very often underestimated by both amateur and professional athletes, are known to disrupt at different levels and throughout various mechanisms the male hypothalamic-pituitary-gonadal axis, resulting in hypogonadism and infertility

Waking up dormant tumor suppressor genes with zinc fingers, TALEs and the CRISPR/dCas9 system

The aberrant epigenetic silencing of tumor suppressor genes (TSGs) plays a major role during carcinogenesis and regaining these dormant functions by engineering of sequence-specific epigenome editing tools offers a unique opportunity for targeted therapies. However, effectively normalizing the expression and regaining tumor suppressive functions of silenced TSGs by artificial transcription factors (ATFs) still remains a major challenge. Herein we describe novel combinatorial strategies for the potent reactivation of two class II TSGs, MASPIN and REPRIMO, in cell lines with varying epigenetic states, using the CRISPR/dCas9 associated system linked to a panel of effector domains (VP64, p300, VPR and SAM complex), as well as with protein-based ATFs, Zinc Fingers and TALEs. We found that co-delivery of multiple effector domains using a combination of CRISPR/dCas9 and TALEs or SAM complex maximized activation in highly methylated promoters. In particular, CRISPR/dCas9 VPR with SAM upregulated MASPIN mRNA (22,145-fold change) in H157 lung cancer cells, with accompanying re-expression of MASPIN protein, which led to a concomitant inhibition of cell proliferation and induction of apoptotic cell death. Consistently, CRISPR/dCas9 VP64 with SAM upregulated REPRIMO (680-fold change), which led to phenotypic reprogramming in AGS gastric cancer cells. Altogether, our results outlined novel sequence-specific, combinatorial epigenome editing approaches to reactivate highly methylated TSGs as a promising therapy for cancer and other diseases

Calibrating the IXPE Observatory from Ground to Space

The Imaging X-ray Polarimetry Explorer (IXPE) will be the next SMEX mission launched by NASA in 2021 in collaboration with the Italian Space Agency (ASI). IXPE will perform groundbreaking measurements of imaging polarization in X-rays for a number of different classes of sources with three identical telescopes, finally (re)opening a window in the high energy Universe after more than 40 years since the first pioneering results. The unprecedented sensitivity of IXPE to polarization poses peculiar requirements on the payload calibration, e.g. the use of polarized and completely unpolarized radiation, both on ground and in orbit, and can not rely on a systematic comparison with results obtained by previous observatories. In this paper, we will present the IXPE calibration plan, describing both calibrations which will be performed on the detectors at INAF-IAPS in Rome (Italy) and the calibration on the mirror and detector assemblies which will be carried out at Marshall Space Flight Center in Huntsville, Alabama. On orbit calibrations, performed with calibrations sources mounted on a filter wheel and placed in front of each detector when necessary, will be presented as well

On possible interpretations of the high energy electron-positron spectrum measured by the Fermi Large Area Telescope

The Fermi-LAT experiment recently reported high precision measurements of the spectrum of cosmic-ray electrons-plus-positrons (CRE) between 20 GeV and 1 TeV. The spectrum shows no prominent spectral features, and is significantly harder than that inferred from several previous experiments. Here we discuss several interpretations of the Fermi results based either on a single large scale Galactic CRE component or by invoking additional electron-positron primary sources, e.g. nearby pulsars or particle Dark Matter annihilation. We show that while the reported Fermi-LAT data alone can be interpreted in terms of a single component scenario, when combined with other complementary experimental results, specifically the CRE spectrum measured by H.E.S.S. and especially the positron fraction reported by PAMELA between 1 and 100 GeV, that class of models fails to provide a consistent interpretation. Rather, we find that several combinations of parameters, involving both the pulsar and dark matter scenarios, allow a consistent description of those results. We also briefly discuss the possibility of discriminating between the pulsar and dark matter interpretations by looking for a possible anisotropy in the CRE flux.Comment: 29 pages, 12 figures. Final version accepted for publication in Astroparticle Physic

Local Star formation triggered by SN shocks in magnetized diffuse neutral clouds

In this work, considering the impact of a SNR with a neutral magnetized cloud we derived analytically a set of conditions which are favorable for driving gravitational instability in the cloud and thus star formation. We have built diagrams of the SNR radius, versus the cloud density, that constrain a domain in the parameter space where star formation is allowed. The diagrams are also tested with fully 3-D MHD simulations involving a SNR and a self-gravitating cloud and we find that the numerical analysis is consistent with the results predicted by the diagrams. While the inclusion of a homogeneous magnetic field approximately perpendicular to the impact velocity of the SNR with an intensity ~1 $mu$G results only a small shrinking of the star formation triggering zone in the diagrams, a larger magnetic field (~10 $mu$G) causes a significant shrinking, as expected. Applications of the diagrams to a few regions of our own galaxy have revealed that star formation in those sites could have been triggered by shock waves from SNRs. Finally, we have evaluated the effective star formation efficiency for this sort of interaction and found that it is smaller than the observed values in our own Galaxy (sfe ~0.01-0.3). This result is consistent with previous work in the literature and also suggests that the mechanism presently investigated, though very powerful to drive structure formation, supersonic turbulence and eventually, local star formation, does not seem to be sufficient to drive global star formation in normal star forming galaxies, not even when the magnetic field in the neutral clouds is neglected. (abridged)Comment: 19 pages, 13 figures, accepted for pubblication in MNRA