PROGRESSIONE DA MILD COGNITIVE IMPAIRMENT A MALATTIA DI ALZHEIMER: IDENTIFICAZIONE DI PROFILI NEUROCOGNITIVI PREDITTIVI E CORRELAZIONE CON BIOMARCATORI LIQUORALI

Objective: To correlate neuropsychological testing with cerebrospinal fluid Amyloid beta (AD), tau and Ptau levels in patients with Mild Cognitive Impairment (MCI) Background: Principal diagnostic instrument to define global cognitive state is the Mini Mental State Examination (MMSE). Cognitive domains that best predict progression from amnestic MCI to AD are episodic memory and executive functioning. Were selected two neuropsychological tests for both domains: Story Recall Test (SRT) and Paired-Associate Learning (PAL) to examine episodic verbal memory, and Coloured Progressive Matrices of Raven (CPMR) and Clock Drawing Test (CDT) to investigate executive functioning. Methods: Forty subjects with amnestic MCI were recruited. All of them underwent neurological exam, neuropsychological testing and lumbar puncture at time of diagnosis. Cognition were explored by MMSE (global cognitive functioning), CPMR and CDT (executive functions), SRT and PAL (episodic verbal memory). Statistical analysis was carried out by using t-test and Spearman test for correlations. Results: In the whole population, no significant correlation between cognitive and biological markers was observed. Considering CSF biomarker level of amiloid\u3b2, thirteen subjects showed an altered pattern and converted to AD after few months, the other subjects whit a normal profile did not convert. MMSE show a significant difference between converters/no converters groups (26.4 versus 27.6 p=0.066). Also CDT and SRT had a significant difference between two groups (3 versus 5 p= 0.003 and 5.85 versus 8.32, p=0.03). Conclusion: According to these results, MMSE value is lower in converters, in according to patological biomarkers profile. PAL and CDT are more specific to predict conversion from MCI to AD

Muscle biopsy and cell cultures: potential diagnostic tools in hereditary skeletal muscle channelopathies.

Hereditary muscle channelopathies are caused by dominant mutations in the genes encoding for subunits of muscle voltage- gated ion channels. Point mutations on the human skeletal muscle Na+ channel (Nav1.4) give rise to hyperkalemic periodic paralysis, potassium aggravated myotonia, paramyotonia congenita and hypokalemic periodic paralysis type 2. Point mutations on the human skeletal muscle Ca2+ channel give rise to hypokalemic periodic paralysis and malignant hyperthermia. Point mutations in the human skeletal chloride channel ClC-1 give rise to myotonia congenita. Point mutations in the inwardly rectifying K+ channel Kir2.1 give rise to a syndrome characterized by periodic paralysis, severe cardiac arrhythmias and skeletal alterations (Andersen's syndrome). Involvement of the same ion channel can thus give rise to different phenotypes. In addition, the same mutation can lead to different phenotypes or similar phenotypes can be caused by different mutations on the same or on different channel subtypes. Bearing in mind, the complexity of this field, the growing number of potential channelopathies (such as the myotonic dystrophies), and the time and cost of the genetic procedures, before a biomolecular approach is addressed, it is mandatory to apply strict diagnostic protocols to screen the patients. In this study we propose a protocol to be applied in the diagnosis of the hereditary muscle channelopathies and we demonstrate that muscle biopsy studies and muscle cell cultures may significantly contribute towards the correct diagnosis of the channel involved. DNAbased diagnosis is now a reality for many of the channelopathies. This has obvious genetic counselling, prognostic and therapeutic implications

Strong electric fields induced on a sharp stellar boundary

Due to a first order phase transition, a compact star may have a discontinuous distribution of baryon as well as electric charge densities, as e.g. at the surface of a strange quark star. The induced separation of positive and negative charges may lead to generation of supercritical electric fields in the vicinity of such a discontinuity. We study this effect within a relativistic Thomas-Fermi approximation and demonstrate that the strength of the electric field depends strongly on the degree of sharpness of the surface. The influence of strong electric fields on the stability of compact stars is discussed. It is demonstrated that stable configurations appear only when the counter-pressure of degenerate fermions is taken into consideration.Comment: 13 pages, 2 figure

Biomolecular identification of (CCTG)n mutation in myotonic dystrophy type 2 (DM2) by FISH on muscle biopsy

Myotonic dystrophy type 2 (DM2) is a dominantly inherited disorder with multisystemic clinical features, caused by a CCTG repeat expansion in intron 1 of the zinc finger protein 9 (ZNF9) gene. The mutant transcripts are retained in the nucleus forming multiple discrete foci also called ribonuclear inclusions. The size and the somatic instability of DM2 expansion complicate the molecular diagnosis of DM2. In our study fluorescence-labeled CAGG-repeat oligonucleotides were hybridized to muscle biopsies to investigate if fluorescence in situ hybridization (FISH), a relatively quick and simple procedure, could be used as a method to diagnose DM2. When FISH was performed with (CAGG)5 probe, nuclear foci of mutant RNA were present in all genetically confirmed DM2 patients (n = 17) and absent in all patients with myotonic dystrophy type 1 (DM1; n = 5) or with other muscular disease (n = 17) used as controls. In contrast, foci were observed both in DM1 and DM2 myonuclei when muscle tissue were hybridized with (CAG)6CA probe indicating that this probe is not specific for DM2 identification. The consistent detection of ribonuclear inclusions in DM2 muscles and their absence in DM1, in agreement with the clinical diagnosis and with leukocyte (CCTG)n expansion, suggests that fluorescence in situ hybridization using (CAGG)5 probes, may be a specific method to distinguish between DM1 and DM2. Moreover, the procedure is simple, and readily applicable in any pathology laboratory

Testing lepton flavour universality in semileptonic Λ(b) → Λ(c)* decays

Lepton Flavour Universality tests with semileptonic Lambda(b) -> Lambda(c)* decays are important to corroborate the present anomalies in the similar ratios R-D(*), and can provide complementary constraints on possible origins of these anomalies beyond the Standard Model. In this paper we provide - for the first time - all the necessary theoretical ingredients to perform and interpret measurements of R-Lambda c* at the LHCb experiment. For this, we revisit the heavy-quark expansion of the relevant hadronic matrix elements, and provide their expressions to order alpha(s) and 1/m accuracy. Moreover, we study the sensitivity to the form factor parameters given the projected size and purity of upcoming and future LHCb datasets of Lambda(b) -> Lambda(c)*mu(v) over bar decays. We demonstrate explicitly the need to perform a simultaneous fit to both Lambda(c)* final states. Finally, we provide projections for the uncertainty of R-Lambda c* based on the form factors analysis from semimuonic decays and theoretical relations based on the heavy-quark expansion

The Reproducibility and Reusability Platform

Poster presentation at OR2020, Stellenboch, South Africa 1st - 4th June 2020

Science Reproducibility and Reusability with FutureGateway and a Zenodo-like repository: the PALMS experiment

Open Science (OS) is a powerful and novel paradigm to share knowledge across multidisciplinary scientific communities with the aim to improve the quality of science. One of the most important OS enablers are the FAIR principles, which involves the way to Find, Access, Interoperate and Reuse research data. In most of the cases published scholarship materials are not linked with computed datasets, open source software and/or virtualized computing environments and OS currently lacks of means helping to reproduce and eventually reuse cited results exploiting public or private distributed computing infrastructures (DCIs). Moreover, from the final user point of view, the best option would be the use of graphical user interfaces (GUIs) normally hosted by a Science Gateway (SG) built for a specific scientific community. The FutureGateway Framework (FGF) consists of a complete software toolkit made of different parts such as: source codes, utilities, libraries and APIs capable to comfortably build reliable Science Gateways and link them to one or more DCIs avoiding any usage complexity from the final user perspective. Moreover, since SGs based on the FGF are capable to keep track of who is accessing the DCIs, not only its usage ensures OS-compliant reproducibility and reusability but also provides a possible answer in protecting or at least simply tracking people who are accessing data and this is one of the aspects that today still makes the adoption of the OS a delicate matter. This work presents and explains how the use of the EGI's Science Software on Demand (SSOD) service, built using the FutureGatewayFramework in conjunction with the INFN Open Access Repository (OAR), based on Zenodo software, can reproduce/reuse the outputs of the agent-based Physical Activity Lifelong Modelling & Simulations (PALMS) experiment

Science Reproducibility and Reusability with FutureGateway and a Zenodo-like repository: the PALMS experiment

Open Science (OS) is a powerful and novel paradigm to share knowledge across multidisciplinary scientific communities with the aim to improve the quality of science. One of the most important OS enablers are the FAIR principles, which involves the way to Find, Access, Interoperate and Reuse research data. In most of the cases published scholarship materials are not linked with computed datasets, open source software and/or virtualized computing environments and OS currently lacks of means helping to reproduce and eventually reuse cited results exploiting public or private distributed computing infrastructures (DCIs). Moreover, from the final user point of view, the best option would be the use of graphical user interfaces (GUIs) normally hosted by a Science Gateway (SG) built for a specific scientific community. The FutureGateway Framework (FGF) consists of a complete software toolkit made of different parts such as: source codes, utilities, libraries and APIs capable to comfortably build reliable Science Gateways and link them to one or more DCIs avoiding any usage complexity from the final user perspective. Moreover, since SGs based on the FGF are capable to keep track of who is accessing the DCIs, not only its usage ensures OS-compliant reproducibility and reusability but also provides a possible answer in protecting or at least simply tracking people who are accessing data and this is one of the aspects that today still makes the adoption of the OS a delicate matter. This work presents and explains how the use of the EGI's Science Software on Demand (SSOD) service, built using the FutureGatewayFramework in conjunction with the INFN Open Access Repository (OAR), based on Zenodo software, can reproduce/reuse the outputs of the agent-based Physical Activity Lifelong Modelling & Simulations (PALMS) experiment