Project description:We identified Tf2, the first β-scorpion toxin from the venom of the Brazilian scorpion Tityus fasciolatus. Tf2 is identical to Tb2-II found in Tityus bahiensis. We found that Tf2 selectively activates human (h)Nav1.3, a neuronal voltage-gated sodium (Nav) subtype implicated in epilepsy and nociception. Tf2 shifts hNav1.3 activation voltage to more negative values, thereby opening the channel at resting membrane potentials. Seven other tested mammalian Nav channels (Nav1.1-1.2; Nav1.4-1.8) expressed in Xenopus oocytes are insensitive upon application of 1 μM Tf2. Therefore, the identification of Tf2 represents a unique addition to the repertoire of animal toxins that can be used to investigate Nav channel function.
Project description:Scorpion venoms are a complex mixture of components. Among them the most important are peptides, which presents the capacity to interact and modulate several ion channel subtypes, including voltage-gated sodium channels (NaV). Screening the activity of scorpion toxins on different subtypes of NaV reveals the scope of modulatory activity and, in most cases, low channel selectivity. Until now there are approximately 60 scorpion toxins experimentally assayed on NaV channels. However, the molecular bases of interaction between scorpion toxins and NaV channels are not fully elucidated. The activity description of new scorpion toxins is crucial to enhance the predictive strength of the structural⁻function correlations of these NaV modulatory molecules. In the present work a new scorpion toxin (Tf1a) was purified from Tityus fasciolatus venom by RP-HPLC, and characterized using electrophysiological experiments on different types of voltage-gated sodium channels. Tf1a was able to modify the normal function of NaV tested, showing to be a typical β-NaScTx. Tf1a also demonstrated an unusual capability to alter the kinetics of NaV1.5.
Project description:The DNA isolated from 44 either frozen or FFPE Neuroendocrine Neoplasm (NEN) was analysed by NGS, to identify genes more likely to be subject to sequence variations among 523 cancer-related ones.
Project description:Plasma DNA from 558 malignancies, 263 benign and borderline tumors and 367 healthy control samples were collected and subjected to random short-gun whole genome sequencing.
