Searching for MIND: MicroRNAs in Neurodegenerative Diseases

In few years our understanding of microRNA (miRNA) biogenesis, molecular mechanisms by which miRNAs regulate gene expression, and the functional roles of miRNAs has been expanded. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system, suggesting that their posttrascriptional regulation may be particularly relevant in neural development and function. MiRNA studies in neurobiology showed their involvement in synaptic plasticity and brain diseases. In this review ,correlations between miRNA-mediated gene silencing and Alzheimer's, Parkinson's, and other neurodegenerative diseases will be discussed. Molecular and cellular neurobiological studies of the miRNAs in neurodegeneration represent the exploration of a new Frontier of miRNAs biology and the potential development of new diagnostic tests and genetic therapies for neurodegenerative diseases

Th.o.m.a.s.: An exploratory assessment of Theory of Mind in schizophrenic subjects

A large body of literature agrees that persons with schizophrenia suffer from a Theory of Mind (ToM) deficit. However, most empirical studies have focused on third-person, egocentric ToM, underestimating other facets of this complex cognitive skill. Aim of this research is to examine the ToM of schizophrenic persons considering its various aspects (first vs. second order, first vs. third person, egocentric vs. allocentric, beliefs vs. desires vs. positive emotions vs. negative emotions and how each of these mental state types may be dealt with), to determine whether some components are more impaired than others. We developed a Theory of Mind Assessment Scale (Th.o.m.a.s.) and administered it to 22 persons with a DSM-IV diagnosis of schizophrenia and a matching control group. Th.o.m.a.s. is a semi-structured interview which allows a multi-component measurement of ToM. Both groups were also administered a few existing ToM tasks and the schizophrenic subjects were administered the Positive and Negative Symptoms Scale and the WAIS-R. The schizophrenic persons performed worse than control at all the ToM measurements; however, these deficits appeared to be differently distributed among different components of ToM. Our conclusion is that ToM deficits are not unitary in schizophrenia, which also testifies to the importance of a complete and articulated investigation of ToM

Intranasal “painless” Human Nerve Growth Factors Slows Amyloid Neurodegeneration and Prevents Memory Deficits in App X PS1 Mice

Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. We show that “painless” hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8), hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of “painless” hNGF variants as a new generation of therapeutics for neurodegenerative diseases

"Open Ticket Request System-OTRS": manuale d\u27uso per la gestione dell\u27helpdesk nell\u27unit? Relazioni Esterne del Registro del ccTLD "it"

This work describes the operating instructions of the \u27Open Ticket Request System - OTRS\u27 used by the helpdesk of the External Relations Unit of the Italian \u27ccTLD.it\u27 Registry.Il presente documento descrive le modalit? operative delle persone addette all\u27helpdesk di primo livello dell\u27unit? Relazioni Esterne del Registro, a seguito dell\u27introduzione del sistema \u27Open Ticket Request System - OTRS\u27 per la gestione delle richieste che arrivano all\u27helpdesk. Il sistema \u27Open Ticket Request System - OTRS\u27 ? stato introdotto per l\u27ottimizzazione del servizio dell\u27helpdesk e per rispondere al meglio all\u27aumento delle richieste sia telefoniche che email, che cartacee. Con questo nuovo sistema di Trouble Ticket, che mantiene traccia in modo organizzato dei casi trattati, ? possibile gestire in maniera pi? rapida e veloce le richieste in arrivo permettendo ad ogni operatore l\u27identificazione univoca delle segnalazioni stesse: ogni operatore seguir? infatti l\u27inizio di un caso e il suo evolversi

Targeting microRNAs in neurons: Tools and perspectives

In the past few years, the understanding of microRNA (miRNA) biogenesis, the molecular mechanisms by which miRNAs regulate gene expression, and the functional roles of miRNAs has been expanded. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system, suggesting that their post-transcriptional regulation may be particularly relevant in neural development and function. miRNA studies in neurobiology have shown their involvement in synaptic plasticity and brain diseases. Approaches for manipulating miRNA levels in neuronal cells in vitro and in vivo are described here. Recent applications of miRNA antisense oligonucleotides, miRNA gene knockout and miRNA sponges in neuronal cells are reviewed. Finally, miRNA-based therapies for neurological pathologies related to alterations in miRNA functions are discussed. (c) 2011 Elsevier Inc. All rights reserved