Clinically relevant aspects of the mechanism of action of botulinum neurotoxin

Botulinum neurotoxin is a highly potent substance obtained from organisms such as Clostridium botulinum, Clostridium barati and Clostridium butyricum. The toxin is synthesized as a single chain polypeptide that is cleaved to yield a heavy chain (100,000 Da) and a light chain (50,000 Da) linked by a disulfide bond. The neurotoxin is tissue-targeted to peripheral cholinergic nerve endings, where it acts to poison transmission. The toxin binds to the cell surface, undergoes receptor-mediated endocytosis, then acts intracellularly to block exocytosis. Because the toxin blocks neuromuscular transmission, it is useful for treating neurologic disorders revealed as spastic dystonias.     

Tripartite quantum state sharing

We demonstrate a multipartite protocol to securely distribute and reconstruct a quantum state. A secret quantum state is encoded into a tripartite entangled state and distributed to three players. By collaborating, any two of the three players can reconstruct the state, while individual players obtain nothing. We characterize this (2,3) threshold quantum state sharing scheme in terms of fidelity, signal transfer, and reconstruction noise. We demonstrate a fidelity averaged over all reconstruction permutations of 0.73+/-0.04, a level achievable only using quantum resources.     

Postsynthetic modification at the focal point of a hyperbranched polymer

Functionalization at the focal point of hyperbranched polyester was achieved using a series of amines and a postsynthetic reaction utilizing an activated p-nitrophenyl ester unit. An element of dense packing was also detected, as evident from differences in levels of incorporation between linear and bulky reagents.     

Detection of intracellular lactate with localized diffusion {1H-13C}-spectroscopy in rat glioma in vivo

The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of (13)C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). (13)C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, {(1)H-(13)C}-lactate and {(1)H-(13)C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into {(1)H-(13)C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/microm(2)). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, (1)H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([(13)C] lactate) originates from an intracellular compartment.