Introductory editorial: drug-eluting stents or drug-eluting grafts? Insights from proteomic analysis

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Aspects of geodesical motion with Fisher-Rao metric: classical and quantum

The purpose of this article is to exploit the geometric structure of Quantum Mechanics and of statistical manifolds to study the qualitative effect that the quantum properties have in the statistical description of a system. We show that the end points of geodesics in the classical setting coincide with the probability distributions that minimise Shannon's Entropy, i.e. with distributions of zero dispersion. In the quantum setting this happens only for particular initial conditions, which in turn correspond to classical submanifolds. This result can be interpreted as a geometric manifestation of the uncertainty principle.Comment: 15 pages, 5 figure

Pharmacologic approaches against advanced glycation end products (ages) in diabetic cardiovascular disease

Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports

Hamilton-Jacobi approach to Potential Functions in Information Geometry

The search for a potential function $S$ allowing to reconstruct a given metric tensor $g$ and a given symmetric covariant tensor $T$ on a manifold $\mathcal{M}$ is formulated as the Hamilton-Jacobi problem associated with a canonically defined Lagrangian on $T\mathcal{M}$. The connection between this problem, the geometric structure of the space of pure states of quantum mechanics, and the theory of contrast functions of classical information geometry is outlined.Comment: 16 pages. A discussion on the Kullback-Leibler divergence has been added. To appear in Journal of Mathematical Physic

Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling in DS mice by a novel rapamycin intranasal administration protocol (InRapa) that maximizes brain delivery and reduce systemic side effects. Methods: Ts65Dn mice were administered with InRapa for 12 weeks, starting at 6 months of age demonstrating, at the end of the treatment by radial arms maze and novel object recognition testing, rescued cognition. Results: The analysis of mTOR signalling, after InRapa, demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR (reduced to physiological levels), which led, through the rescue of autophagy and insulin signalling, to reduced APP levels, APP processing and APP metabolites production, as well as, to reduced tau hyperphosphorylation. In addition, a reduction of oxidative stress markers was also observed. Discussion: These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis, thus ultimately resulting in improved cognition. Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals

The mesolithic occupation at Isolidda (San Vito Lo Capo), Sicily

‘Gruppo dell’Isolidda’ is a complex of five caves along a rocky cliff on the eastern side of the promontory of San Vito Lo Capo (Trapani) in NW Sicily. In 2004 archaeological excavations in the slope below the caves revealed a stratified deposit, partially in secondary position, containing levels with Late Epigravettian and Mesolithic stone tool assemblages. Early Mesolithic stone tool industries, characterized by backed microlithic tools, were distributed in two contiguous layers (SU 21 and SU 25), the lowest of which (SU 21) also contained Epigravettian tools, probably due to sediment reworking. Three AMS dates on Phorcus turbinatus shells (~9520-8990 cal. BP) are chronologically compatible with the Early Mesolithic materials and suggest that the bulk of the deposit accumulated then. A third level, lying above the previous ones, contained material culture associated to the Late Mesolithic or Early Neolithic. Faunal remains from the site represent mainly food refuse and included abundant shells of intertidal molluscs (e.g. Phorcus turbinatus and Patella sp.), along with few fragmented bones of terrestrial herbivores (e.g. Cervus elaphus and Sus scrofa). Oxygen isotope analyses on shell carbonates of Phorcus turbinatus show that, around 9520-9000 cal. BP, marine molluscs were exploited year-round, albeit more often in autumn and winter

Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells

Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cultured in a weightless and protected environment SGM produced by the Rotary Cell Culture System (Synthecon) and control condition in normal gravity (NG). Self-replication and differentiation toward mature cells were determined by culturing hBTSCs in Kubota's Medium (KM) and in hormonally defined medium (HDM) tailored for hepatocyte differentiation. The effects on the expression and cell exo-metabolome profiles of SMG versus NG cultures were analyzed. SMG promotes tridimensional (3D) cultures of hBTSCs and HepG2. Significative increase of stemness gene expression (p < 0.05) has been observed in hBTSCs cultured in SMG when compared to NG condition. At the same time, the expression of hepatocyte lineage markers in hBTSCs differentiated by HDM was significantly lower (p < 0.05) in SMG compared to NG, demonstrating an impaired capability of hBTSCs to differentiate in vitro toward mature hepatocytes when cultured in SMG condition. Furthermore, in HepG2 cells the SMG caused a lower (p < 0.05 vs controls) transcription of CYP3A4, a marker of late-stage (i.e. Zone 3) hepatocytes. Exo-metabolome NMR-analysis showed that both cell cultures consumed a higher amount of glucose and lower glutamate in SMG respect to NG (p < 0.05). Moreover, hBTSCs media cultures resulted richer of released fermentation (lactate, acetate) and ketogenesis products (B-hydroxybutyrate) in SGM (p < 0.05) than NG. While, HepG2 cells showed higher consumption of amino acids and release of ketoacids (3-Methyl-2-oxovalerate, 2-oxo-4-methyl-valerate) and formiate with respect to normogravity condition (p < 0.05). Based on our results, SMG could be helpful for developing hBTSCs-derived liver devices. In conclusion, SMG favored the formation of hBTSCs and HepG2 3D cultures and the maintenance of stemness contrasting cell differentiation; these effects being associated with stimulation of glycolytic metabolism. Interestingly, the impact of SMG on stem cell biology should be taken into consideration for workers involved in space medicine programs

Charged particle's flux measurement from PMMA irradiated by 80 MeV/u carbon ion beam

Hadrontherapy is an emerging technique in cancer therapy that uses beams of charged particles. To meet the improved capability of hadrontherapy in matching the dose release with the cancer position, new dose monitoring techniques need to be developed and introduced into clinical use. The measurement of the fluxes of the secondary particles produced by the hadron beam is of fundamental importance in the design of any dose monitoring device and is eagerly needed to tune Monte Carlo simulations. We report the measurements done with charged secondary particles produced from the interaction of a 80 MeV/u fully stripped carbon ion beam at the INFN Laboratori Nazionali del Sud, Catania, with a Poly-methyl methacrylate target. Charged secondary particles, produced at 90$\degree$ with respect to the beam axis, have been tracked with a drift chamber, while their energy and time of flight has been measured by means of a LYSO scintillator. Secondary protons have been identified exploiting the energy and time of flight information, and their emission region has been reconstructed backtracking from the drift chamber to the target. Moreover a position scan of the target indicates that the reconstructed emission region follows the movement of the expected Bragg peak position. Exploting the reconstruction of the emission region, an accuracy on the Bragg peak determination in the submillimeter range has been obtained. The measured differential production rate for protons produced with $E^{\rm Prod}_{\rm kin} >$ 83 MeV and emitted at 90$\degree$ with respect to the beam line is: $dN_{\rm P}/(dN_{\rm C}d\Omega)(E^{\rm Prod}_{\rm kin} > 83 {\rm ~MeV}, \theta=90\degree)= (2.69\pm 0.08_{\rm stat} \pm 0.12_{\rm sys})\times 10^{-4} sr^{-1}$.Comment: 13 pages, 9 figure

Cryopreservation protocol for human biliary tree stem/progenitors, hepatic and pancreatic precursors

Human biliary tree stem/progenitor cells (hBTSCs) are being used for cell therapies of patients with liver cirrhosis. A cryopreservation method was established to optimize sourcing of hBTSCs for these clinical programs and that comprises serum-free Kubota's Medium (KM) supplemented with 10% dimethyl sulfoxide (DMSO), 15% human serum albumin (HSA) and 0.1% hyaluronans. Cryopreserved versus freshly isolated hBTSCs were similar in vitro with respect to self-replication, stemness traits, and multipotency. They were able to differentiate to functional hepatocytes,cholangiocytes or pancreatic islets, yielding similar levels of secretion of albumin or of glucose-inducible levels of insulin. Cryopreserved versus freshly isolated hBTSCs were equally able to engraft into immunocompromised mice yielding cells with human-specific gene expression and human albumin levels in murine serum that were higher for cryopreserved than for freshly isolated hBTSCs. The successful cryopreservation of hBTSCs facilitates establishment of hBTSCs cell banking offering logistical advantages for clinical programs for treatment of liver diseases

oxidative stress and proteostasis network culprit and casualty of alzheimer s like neurodegeneration

Free radical-mediated damage to proteins is particularly important in aging and age-related neurodegenerative diseases, because in the majority of cases it is a non-reversible phenomenon that requires clearance systems for removal. Major consequences of protein oxidation are loss of protein function and the formation of large protein aggregates, which are often toxic to cells if allowed to accumulate. Deposition of aggregated, misfolded, and oxidized proteins may also result from the impairment of protein quality control (PQC) system, including protein unfolded response, proteasome, and autophagy. Perturbations of such components of the proteostasis network that provides a critical protective role against stress conditions are emerging as relevant factor in triggering neuronal death. In this outlook paper, we discuss the role of protein oxidation as a major contributing factor for the impairment of the PQC regulating protein folding, surveillance, and degradation. Recent studies from our group and from others aim to better understand the link between Down syndrome and Alzheimer's disease neuropathology. We propose oxidative stress and alteration of proteostasis network as a possible unifying mechanism triggering neurodegeneration