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Temporal prediction (TP) influences our perception and cognition. The cerebellum could mediate this multi-level ability in a context-dependent manner. We tested whether a modulation of the cerebellar neural activity, induced by transcranial Direct Current Stimulation (tDCS), changed the TP ability according to the temporal features of the context and the duration of target interval. Fifteen healthy participants received anodal, cathodal, and sham tDCS (15 min × 2 mA intensity) over the right cerebellar hemisphere during a TP task. We recorded reaction times (RTs) to a target during the task in two contextual conditions of temporal anticipation: rhythmic (i.e., interstimulus intervals (ISIs) were constant) and single-interval condition (i.e., the estimation of the timing of the target was based on the prior exposure of the train of stimuli). Two ISIs durations were explored: 600 ms (short trials) and 900 ms (long trials). Cathodal tDCS improved the performance during the TP task (shorter RTs) specifically in the rhythmic condition only for the short trials and in the single-interval condition only for the long trials. Our results suggest that the inhibition of cerebellar activity induced a different improvement in the TP ability according to the temporal features of the context. In the rhythmic context, the cerebellum could integrate the temporal estimation with the anticipatory motor responses critically for the short target interval. In the single-interval context, for the long trials, the cerebellum could play a main role in integrating representation of time interval in memory with the elapsed time providing an accurate temporal prediction., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cholesterol esterification and smooth muscle cell (SMC) proliferation are the crucial events in the development of atherosclerotic lesions. The objective of this study was to analyse cholesterol esterification and the expression of MDR1 (multidrug resistance), ACAT (acyl-CoA:cholesterol acyltransferase) and caveolin-1 genes in atherosclerotic and healthy vascular walls, in SMCs obtained from atherosclerotic lesions and saphenous veins. Results demonstrated higher levels of cholesterol esters, ACAT and MDR1 mRNAs and lower levels of caveolin-1 mRNA in atherosclerotic segments compared to adjacent serial sections of the same artery and the corresponding non-atherosclerotic arteries from cadaveric donors. SMCs isolated from atherosclerotic plaques manifested an increased capacity to esterify cholesterol and to grow at a faster rate than SMCs isolated from saphenous veins. In addition, when SMCs from atherosclerotic plaques were cultured in the presence of progesterone, a potent inhibitor of cholesterol esterification, significant growth suppression was observed. An increase in ACAT and MDR1 expression and a concomitant decrease in caveolin-1 expression were also observed in SMCs isolated from atherosclerotic arteries as early as 12 h after serum stimulation. An opposite pattern was found when SMCs were treated with progesterone. These findings support the idea that cholesterol esterification plays a role both in early atherogenesis and in clinical progression of advanced lesions and raise the possibility that the cholesterol ester pathway might directly modulate the proliferation of SMCs.

Laron-type dwarfism (LTD) is an autosomal recessive disorder due to mutations in the GH receptor (GHR) gene. We report the case of a Sardinian boy affected by LTD in which we found by direct genomic sequencing a nonsense mutation in the fourth exon of the GHR gene (R43X) that determines a premature termination in the protein translation process. As the result of the absence of the extracellular portion of the GHR this patient had undetectable GH binding protein. This molecular defect is identical to that observed in other patients with LTD of mediterranean origin.