Cleaved intracellular SNARE peptides are implicated in a novel cytotoxicity mechanism of botulinum serotype C

Recent advances in intracellular protein delivery have enabled more in-depth analyses of cellular functions. A specialized family of SNARE proteases, known as Botulinum Neurotoxins, blocks neurotransmitter exocytosis, which leads to systemic toxicity caused by flaccid paralysis. These pharmaceutically valuable enzymes have also been helpful in the study of SNARE functions. As can be seen in Figure 1A, SNARE bundle formation causes vesicle docking at the presynapse. Although these toxins are systemically toxic, no known cytotoxic effects have been reported with the curious exception of the Botulinum serotype C [1]. This enzyme cleaves intracellular SNAP25, as does serotype A and E, but also, exceptionally, cleaves Syntaxin 1. Using an array of lipid and polymer transfection reagents we were able to deliver different combinations of Botulinum holoenzymes into the normally unaffected, Neuro2A, SH-SY5Y, PC12, and Min6 cells to analyze the individual contribution of each SNARE protein and their cleaved peptide products

Botulinum neurotoxin type C protease induces apoptosis in differentiated human neuroblastoma cells

Neuroblastomas constitute a major cause of cancer-related deaths in young children. In recent years, a number of translation-inhibiting enzymes have been evaluated for killing neuroblastoma cells. Here we investigated the potential vulnerability of human neuroblastoma cells to protease activity derived from botulinum neurotoxin type C. We show that following retinoic acid treatment, human neuroblastoma cells, SiMa and SH-SY5Y, acquire a neuronal phenotype evidenced by axonal growth and expression of neuronal markers. Botulinum neurotoxin type C which cleaves neuron-specific SNAP25 and syntaxin1 caused apoptotic death only in differentiated neuroblastoma cells. Direct comparison of translation-inhibiting enzymes and the type C botulinum protease revealed one order higher cytotoxic potency of the latter suggesting a novel neuroblastoma-targeting pathway. Our mechanistic insights revealed that loss of ubiquitous SNAP23 due to differentiation coupled to SNAP25 cleavage due to botulinum activity may underlie the apoptotic death of human neuroblastoma cells

Stopping of relativistic ions in multicomponent plasmas

Investigation of the processes of stopping of charged particles moving in different media is of significant interest for many realms of Physics, such that Nuclear Physics, Condensed Matter Physics, Plasma Physics, etc. The problem of evaluation of energy losses of relativistic protons has acquired special importance recently [1] and, due to the experimental conditions, it is necessary to estimate relativistic corrections to the asymptotic form of energy losses in non-ideal multicomponent plasmas..

Stopping of relativistic ions in multicomponent plasmas

Investigation of the processes of stopping of charged particles moving in different media is of significant interest for many realms of Physics, such that Nuclear Physics, Condensed Matter Physics, Plasma Physics, etc. The problem of evaluation of energy losses of relativistic protons has acquired special importance recently [1] and, due to the experimental conditions, it is necessary to estimate relativistic corrections to the asymptotic form of energy losses in non-ideal multicomponent plasmas..

The stopping power and straggling of strongly coupled electron fluids revisited

Measuring energy losses of beams of charged particles is an important diagnostic tool in both modern condensed matter and plasma physics..

Random to chaotic temperature transition in low-field Fano-Feshbach resonances of cold thulium atoms

Here, we report on the observation of a random to chaotic temperature transition in the spacing of Fano-Feshbach resonances in the ultracold polarized gas of thulium atoms. This transition is due to the appearance of so-called d-resonances, which are not accessible at low temperatures, in the spectra at high temperatures, which drastically changes thulium's overall resonance statistic. In addition to this statistical change, it has been observed that s- and d-resonances experience quite different temperature shifts: s-resonances experience almost no shift with the temperature, while d-resonances experience an obvious positive shift. In addition, careful analysis of the broad Fano-Feshbach resonances enabled the determination of the sign of thulium's background scattering length. A rethermalization experiment made it possible to estimate a length value of a=144+-38a.u.. This proves that thulium atoms are suitable for achieving Bose-Einstein Condensation