Metallothioneins as dynamic markers for brain disease in lysosomal disorders

Objective: To facilitate development of novel disease-modifying therapies for lysosomal storage disorder (LSDs) characterized by nervous system involvement such as metachromatic leukodystrophy (MLD), molecular markers for monitoring disease progression and therapeutic response are needed. To this end, we sought to identify blood transcripts associated with the progression of MLD. Methods: Genome-wide expression analysis was performed in primary T lymphocytes of 24 patients with MLD compared to 24 age- and sex-matched healthy controls. Genes associated with MLD were identified, confirmed on a quantitative polymerase chain reaction platform, and replicated in an independent patient cohort. mRNA and protein expression of the prioritized gene family of metallothioneins was evaluated in postmortem patient brains and in mouse models representing 6 other LSDs. Metallothionein expression during disease progression and in response to specific treatment was evaluated in 1 of the tested LSD mouse models. Finally, a set of in vitro studies was planned to dissect the biological functions exerted by this class of molecules. Results: Metallothionein genes were significantly overexpressed in T lymphocytes and brain of patients with MLD and generally marked nervous tissue damage in the LSDs here evaluated. Overexpression of metallothioneins correlated with measures of disease progression in mice and patients, whereas their levels decreased in mice upon therapeutic treatment. In vitro studies indicated that metallothionein expression is regulated in response to oxidative stress and inflammation, which are biochemical hallmarks of lysosomal storage diseases. Interpretation Metallothioneins are potential markers of neurologic disease processes and treatment response in LSDs

An underground Sagnac gyroscope with sub-prad/s rotation rate sensitivity: toward General Relativity tests on Earth

Measuring in a single location on Earth its angular rotation rate with respect to the celestial frame, with a sensitivity enabling access to the tiny Lense-Thirring effect is an extremely challenging task. GINGERINO is a large frame ring laser gyroscope, operating free running and unattended inside the underground laboratory of the Gran Sasso, Italy. The main geodetic signals, i.e., Annual and Chandler wobbles, daily polar motion and Length of the Day, are recovered from GINGERINO data using standard linear regression methods, demonstrating a sensitivity better than 1 prad/s, therefore close to the requirements for an Earth-based Lense-Thirring test.Comment: 7 pages, 5 figure

Carta esatta rappresentante l'isola di S. Domingo o sia Hispaniola / G.M. Terreni sc.

Relief shown pictorially. In: Il gazzettiere americano ... l763, v. 2, opp. p. 73. Decorative cartouche.Grayscale1:2,700,00

Parallel Neutrino Triggers using GPUs for an underwater telescope

Graphics Processing Units are high performance co-processors originally intended to improve the use and the acceleration of computer graphics applications. Because of their performance, researchers have extended their use beyond the computer graphics scope. We have investigated the possibility of implementing online neutrino trigger algorithms in the KM3Net-It experiment using a CPU-GPU system. The results of a neutrino trigger simulation on a NEMO Phase II tower and a KM3-It 14 floors tower are reported

Synthesis of novel bio-based and degradable polyurethanes using lignin oligomers

Bio-based and degradable materials were proposed to challenge the major problem of plastic disposal in the environment. In this context, polyurethane production was re-evaluated, encouraging the search for replacing both petroleum components and highly toxic species. A novel synthesis route is explored in this work, aimed to produce degradable lignin-based polyurethanes. Oligomers from steam-exploded lignin were extracted and used with e-caprolactone (e-CL) to generate a fully bio-based pre-polymer (oligo-grafted-poly(e-CL)), exploiting ringopening polymerization. We have demonstrated that tuning the main reaction parameters, such as e-CL:oligomer and catalyst:e-CL mass ratios, and reaction time, it is possible to obtain different pre-polymers enabling the synthesis of bio-based polyurethanes with variable physicochemical properties. In particular, the oligomeric content modulates the thermal and mechanical properties of the polymer (melting point range: 54-62 degrees C; Young modulus range: 3-7 kPa) and enhances the degradability (up to 13 % wt, in acid environment), highlighting the potential of the material for possible applications