The twenty-nine amino acid C-terminal cytoplasmic domain of poliovirus 3AB is critical for nucleic acid chaperone activity

Poliovirus 3AB protein is the first picornavirus protein demonstrated to have nucleic acid chaperone activity. Further characterization of 3AB demonstrates that the C-terminal 22 amino acids (3B region (also referred to as VPg), amino acid 88–109) of the protein is required for chaperone activity, as mutations in this region abrogate nucleic acid binding and chaperone function. Protein 3B alone has no chaperone activity as determined by established assays that include the ability to stimulate nucleic acid hybridization in a primer-template annealing assay, helix-destabilization in a nucleic acid unwinding assay or aggregation of nucleic acids. In contrast, the putative 3AB C-terminal cytoplasmic domain (C terminal amino acids 81–109, 3B + the last 7 C-terminal amino acids of 3A, termed 3B+7 in this report) possesses strong activity in these assays, albeit at much higher concentrations than 3AB. The characteristics of several mutations in 3B+7 are described here, as well as a model proposing that 3B+7 is the site of the “intrinsic” chaperone activity of 3AB while the 3A N-terminal region (amino acids 1–58) and/or membrane anchor domain (amino acids 59–80) serve to increase the effective concentration of the 3B+7 region leading to the potent chaperone activity of 3AB

Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction

Over the past few years, substantial progress has been made in the field of stem cell regeneration of the intervertebral disc. Autogenic mesenchymal stem cells in animal models can arrest intervertebral disc degeneration or even partially regenerate it and the effect is suggested to be dependent on the severity of degeneration. Mesenchymal stem cells (MSCs) are able to escape alloantigen recognition which is an advantage for allogenic transplantation. A number of injectable scaffolds have been described and various methods to pre-modulate MSCs’ activity have been tested. In future, work will need to address the use of mesenchymal stem cells in large animal models and the fate of the implanted mesenchymal stem cells, particularly in the long term, in animals. This review examines the state-of-the-art in the field of stem cell regeneration of the intervertebral disc, and critically discusses, with scientific support, the issues involved, before stem cells could be used in human subjects

Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated discs: Results from in-vivo serial post-contrast MRI studies in 365 human lumbar discs

Degenerative disc disease (DDD) is still a poorly understood phenomenon because of the lack of availability of precise definition of healthy, ageing and degenerated discs. Decreased nutrition is the final common pathway for DDD and the status of the endplate (EP) plays a crucial role in controlling the extent of diffusion, which is the only source of nutrition. The vascular channels in the subchondral plate have muscarinic receptors but the possibility of enhancing diffusion pharmacologically by dilation of these vessels has not been probed. Although it is well accepted that EP damage will affect diffusion and thereby nutrition, there is no described method to quantify the extent of EP damage. Precise definitions with an objective method of differentiating healthy, ageing and degenerated discs on the basis of anatomical integrity of the disc and physiological basis of altered nutrition will be useful. This information is an urgent necessity for better understanding of DDD and also strategizing prevention and treatment