Stressful conditions induce the cell to save energy and activate a rescue program modulated by mammalian target of rapamycin (mTOR). Along with transcriptional and translational regulation, the cell relies also on post-transcriptional modulation to quickly adapt the translation of essential proteins. MicroRNAs play an important role in the regulation of protein translation, and their availability is tightly regulated by RNA competing mechanisms often mediated by long noncoding RNAs (lncRNAs). In our paper, we simulated the response to growth adverse condition by bimiralisib, a dual PI3K/mTOR inhibitor, in diffuse large B cell lymphoma cell lines, and we studied post-transcriptional regulation by the differential analysis of exonic and intronic RNA expression. In particular, we observed the upregulation of a lncRNA, lncTNK2-2:1, which correlated with the stabilization of transcripts involved in the regulation of translation and DNA damage after bimiralisib treatment. We identified miR-21-3p as miRNA likely sponged by lncTNK2-2:1, with consequent stabilization of the mRNA of p53, which is a master regulator of cell growth in response to DNA damage.
Visuomotor transformations at the cortical level occur along a network where posterior parietal regions are connected to homologous premotor regions. Grasping-related activity is represented in a diffuse, ventral and dorsal system in the posterior parietal regions, but no systematic causal description of a premotor counterpart of a similar diffuse grasping representation is available. To fill this gap, we measured the kinematics of right finger movements in 17 male and female human participants during grasping of three objects of different sizes. Single-pulse transcranial magnetic stimulation was applied 100 ms after visual presentation of the object over a regular grid of 8 spots covering the left premotor cortex (PMC) and 2 Sham stimulations. Maximum finger aperture during reach was used as the feature to classify object size in different types of classifiers. Classification accuracy was taken as a measure of the efficiency of visuomotor transformations for grasping. Results showed that transcranial magnetic stimulation reduced classification accuracy compared with Sham stimulation when it was applied to 2 spots in the ventral PMC and 1 spot in the medial PMC, corresponding approximately to the ventral PMC and the dorsal portion of the supplementary motor area. Our results indicate a multifocal representation of object geometry for grasping in the PMC that matches the known multifocal parietal maps of grasping representations. Additionally, we confirm that, by applying a uniform spatial sampling procedure, transcranial magnetic stimulation can produce cortical functional maps independent of a priori spatial assumptions.
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