Mycobacterium tuberculosis cell envelope is a treasure house of biologically active lipids of fascinating molecular architecture. Although genetic studies have alluded to an array of genes in biosynthesis of complex lipids, their mechanistic, structural, and biochemical principles have not been investigated. Here, we have dissected the molecular logic underlying the biosynthesis of a virulence lipid phthiocerol dimycocerosate (PDIM). Cell-free reconstitution studies demonstrate that polyketide synthases, which are usually involved in the biosynthesis of secondary metabolites, are responsible for generating complex lipids in mycobacteria. We show that PapA5 protein directly transfers the protein bound mycocerosic acid analogs on phthiocerol to catalyze the final esterification step. Based on precise identification of biological functions of proteins from Pps cluster, we have rationally produced a nonmethylated variant of mycocerosate esters. Apart from elucidating mechanisms that generate chemical heterogeneity with PDIMs, this study also presents an attractive approach to explore host-pathogen interactions by altering mycobacterial surface coat.
Tissue engineering is a multidisciplinary area of research aimed at regeneration of tissues and restoration of organ function. This is achieved through implantation of cells/tissues grown outside the body or by stimulating cells to grow into an implanted matrix. In this short review, we discuss the use of biomaterials, in the form of scaffolds, for tissue engineering and review clinical applications to otorhinolaryngology-head and neck surgery.
Stem cells derived from adult and embryonic sources have great therapeutic potential, but much research is still needed before their clinical use becomes commonplace. There is debate about whether adult stem cells can be used instead of those derived from embryos. Rationalisation is needed but can be exercised only once the various cells have been carefully compared and contrasted under appropriate experimental conditions. Some characteristics that might help resolve the issue of cell source can already be applied to the debate. Accessibility is important; some adult cells, such as neural stem cells, are difficult to obtain, at least from living donors. Other factors include the frequency and abundance of adult stem cells and their numbers and potency, which might decline with age or be affected by disease. For embryonic stem cells, ethical concerns have been raised, and the proposed practice of therapeutic cloning tends to be misrepresented in the lay media. For both adult and embryonic stem cells, stability, potential to transmit harmful pathogens or genetic mutations, and risk of forming unwanted tissues or even teratocarcinomas have yet to be fully assessed.
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