Dissociating Explicit and Implicit Timing in Parkinson\u2019s Disease Patients: Evidence from Bisection and Foreperiod Tasks

A consistent body of literature reported that Parkinson\u2019s disease (PD) is marked by severe deficits in temporal processing. However, the exact nature of timing problems in PD patients is still elusive. In particular, what remains unclear is whether the temporal dysfunction observed in PD patients regards explicit and/or implicit timing. Explicit timing tasks require participants to attend to the duration of the stimulus, whereas in implicit timing tasks no explicit instruction to process time is received but time still affects performance. In the present study, we investigated temporal ability in PD by comparing 20 PD participants and 20 control participants in both explicit and implicit timing tasks. Specifically, we used a time bisection task to investigate explicit timing and a foreperiod task for implicit timing. Moreover, this is the first study investigating sequential effects in PD participants. Results showed preserved temporal ability in PD participants in the implicit timing task only (i.e., normal foreperiod and sequential effects). By contrast, PD participants failed in the explicit timing task as they displayed shorter perceived durations and higher variability compared to controls. Overall, the dissociation reported here supports the idea that timing can be differentiated according to whether it is explicitly or implicitly processed, and that PD participants are selectively impaired in the explicit processing of time

Dust formation in the winds of AGBs: the contribution at low metallicities

We present new models for the evolution of stars with mass in the range 1Msun < M < 7.5Msun, followed from the pre-main-sequence through the asymptotic giant branch phase. The metallicity adopted is $Z=3*10^{-4} (which, with an alpha-enhancement of +0.4, corresponds to [Fe/H]=-2). Dust formation is described by following the growth of dust grains of various types as the wind expands from the stellar surface. Models with mass M>3Msun experience Hot Bottom Burning, thus maintaining the surface C/O below unity. Unlike higher Z models, the scarcity of silicon available in the envelope prevents the formation of silicates in meaningful quantities, sufficient to trigger the acceleration of the wind via radiation pressure on the dust grains formed. No silicate formation occurs below a threshold metallicity of Z=10^{-3}. Low--mass stars, with M< 2.5Msun become carbon stars, forming solid carbon dust in their surroundings. The total dust mass formed depends on the uncertain extent of the inwards penetration of the convective envelope during the Third Dredge--Up episodes following the Thermal Pulses. Carbon grains have sizes 0.08 micron < a_C < 0.12 micron and the total amount of dust formed (increasing with the mass of the star) is M_C=(2-6)*10^{-4}Msun. Our results imply that AGB stars with Z=3*10^{-4} can only contribute to carbon dust enrichment of the interstellar medium on relatively long timescales, > 300 Myr, comparable to the evolutionary time of a 3Msun star. At lower metallicities the scarcity of silicon available and the presence of Hot Bottom Burning even in M< 2Msun, prevents the formation of silicate and carbon grains. We extrapolate our conclusion to more metal--poor environments, and deduce that at Z < 10^{-4} dust enrichment is mostly due to metal condensation in supernova ejecta.Comment: 13 pages, 8 figures, accepted for publication on MNRA

Reading with method. Exploring the relationship between the Pizzigoni method and the learning of reading and writing

On the current Italian school scene, choosing an effective method for the teaching-learning of reading and writing has become a key priority for teachers. This is reflected in the increasing number of schools offering the Montessori method or with other distinctive approaches, which are well received, and indeed sought after, by parents. The distinctiveness of a given method appears to be perceived as a guarantee of quality teaching-learning, including in the area of reading and writing. In light of these trends, this paper offers an analysis of the method devised by Giuseppina Pizzigoni, for which the annual demand on the part of families exceeds the current supply. The typical practices and methodological peculiarities of the Pizzigoni method are examined by reviewing Pizzigoni’s own writings and comparing her proposals with data on their implementation, obtained by administering questionnaires.   Leggere con “metodo”. Una riflessione sulla relazione tra il metodo Pizzigoni e l’apprendimento della lettura e scrittura Nell’attuale panorama scolastico italiano l’attenzione puntuale alla scelta di un metodo d’insegnamento-apprendimento efficace nell’ambito della lettura e della scrittura è diventato un elemento che interroga fortemente i docenti. In contemporanea si assiste all’aumento dell’offerta in molti istituti scolastici di scuole a metodo Montessori, o ad altre proposte accolte e richieste con molto favore dai genitori. La garanzia di una precisa identificabilità pare essere un elemento che assicura una qualità delle proposte di insegnamento-apprendimento, anche legate alla lettura e alla scrittura. Alla luce di questi cambiamenti il contributo si focalizza sul metodo di Giuseppina Pizzigoni, richiesto ogni anno da moltissime famiglie, ben oltre le sue possibilità di accoglienza. L’indagine osserverà le sue attività e scelte metodologiche in questo ambito, tramite l’analisi degli scritti della pedagogista e il confronto con le evidenze delle sue applicazioni, ottenute grazie a una serie di questionati e interviste con i docenti

improved solubility and increased biological activity of neosol rcl40 a novel red clover isoflavone aglycones extract preparation

Abstract Red clover (Trifolium pratense L., Fabaceae; RCL), a perennial plant rich in isoflavones, is a natural alternative for menopausal symptoms, as well as antiaging and antioxidant. Isoflavone preparations usually contain aglycones and β-glycosides. Aglycones, the active moieties, are absorbed slowly and unevenly due to reduced water solubility and biotransformation from β-glycosides. NeoSol™RCL40 is a novel RCL isoflavone aglycones preparation based on active solubilization technologies. In the present study, NeoSol™RCL40 was shown to induce solubilization of isoflavones and to increase estrogenic and antioxidative effects in comparison to a standard RCL extract (RCLE). NeoSol™RCL40 was prepared from RCLE using as host molecules either 2-pyrrolidone, 1-ethenyl homopolymer (PVP), γ-cyclodextrin, or maltodextrin. Solubilisation assays, performed by means of HPLC-UV, showed that solubilization of isoflavone aglycones was highest with RCLE processed with PVP, which was therefore selected for functional assays. In comparison to RCLE, NeoSol™RCL40 containing the same amount of isoflavone aglycones displayed 3.4 times higher estrogenicity in MCF-7 cell, 1.9–2.0 higher antioxidant activity in the DPPH and in the FRAP assay, and was cytoprotective in PC12 cells. As a whole, results support the ability of NeoSol™RCL40 to promote isoflavones solubilization leading to increased biological activity. NeoSol™RCL40 is therefore an interesting novel preparation providing improved availability of active isoflavones aglycones

Glutathione S-transferase homozygous deletions and relapse in childhood acute lymphoblastic leukemia: a novel study design in a large Italian AIEOP cohort

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Calpain digestion and HSP90-based chaperone protection modulate the level of plasma membrane F508del-CFTR

AbstractWe are here showing that peripheral mononuclear blood cells (PBMC) from cystic fibrosis (CF) patients contain almost undetectable amounts of mature 170 kDa CF-transmembrane conductance regulator (CFTR) and a highly represented 100 kDa form. This CFTR protein, resembling the form produced by calpain digestion and present, although in lower amounts, also in normal PBMC, is localized in cytoplasmic internal vesicles. These observations are thus revealing that the calpain-mediated proteolysis is largely increased in cells from CF patients. To characterize the process leading to the accumulation of such split CFTR, FRT cells expressing the F508del-CFTR mutated channel protein and human leukaemic T cell line (JA3), expressing wild type CFTR were used. In in vitro experiments, the sensitivity of the mutated channel to the protease is identical to that of the wild type, whereas in Ca2+-loaded cells F508del-CFTR is more susceptible to digestion. Inhibition of intracellular calpain activity prevents CFTR degradation and leads to a 10-fold increase in the level of F508del-CFTR at the plasma membrane, further indicating the involvement of calpain activity in the maintenance of very low levels of mature channel form. The higher sensitivity to calpain of the mutated 170 kDa CFTR results from a reduced affinity for HSP90 causing a lower degree of protection from calpain digestion. The recovery of HSP90 binding capacity in F508del-CFTR, following digestion, explains the large accumulation of the 100 kDa CFTR form in circulating PBMC from CF patients

PACSIN2 as a modulator of autophagy and mercaptopurine cytotoxicity: mechanisms in lymphoid and intestinal cells

PACSIN2 variants are associated with gastrointestinal effects of thiopurines and thiopurine methyltransferase activity through an uncharacterized mechanism that is postulated to involve auto-phagy. This study aims to clarify the role of PACSIN2 in autophagy and in thiopurine cytotoxicity in leukemic and intestinal models. Higher autophagy and lower PACSIN2 levels were observed in inflamed compared with non-inflamed colon biopsies of in-flammatory bowel disease pediatric patients at diagnosis. PAC-SIN2 was identified as an inhibitor of autophagy, putatively through inhibition of autophagosome formation by a protein- protein interaction with LC3-II, mediated by a LIR motif. Moreover, PACSIN2 resulted a modulator of mercaptopurine-induced cyto-toxicity in intestinal cells, suggesting that PACSIN2-regulated autophagy levels might influence thiopurine sensitivity. However, PACSIN2 modulates cellular thiopurine methyltransferase activity via mechanisms distinct from its modulation of autophagy