A long way to stemness

Comment on: Tanaka Y, et al. Proc Natl Acad Sci USA 2012; 109:4515-20.     

A long way to stemness

Comment on: Tanaka Y, et al. Proc Natl Acad Sci USA 2012; 109:4515-20.     

The long journey from stem cells to medical product

There is much interest in developing stem cells and the cells derived from them as therapies for treating human disease and injury, but many biological, technological and regulatory hurdles have to be overcome before these cell therapies can be brought to commercial fruition.     

From genomes to cures: the start of a long journey

The EMBO/EMBL Science and Society Conference 'From Genomes to Cures', was held in Heidelberg, Germany, 16-18 November 2001.     

The long journey to a Systems Biology of neuronal function

Computational neurobiology was born over half a century ago, and has since been consistently at the forefront of modelling in biology. The recent progress of computing power and distributed computing allows the building of models spanning several scales, from the synapse to the brain. Initially focused on electrical processes, the simulation of neuronal function now encompasses signalling pathways and ion diffusion. The flow of quantitative data generated by the "omics" approaches, alongside the progress of live imaging, allows the development of models that will also include gene regulatory networks, protein movements and cellular remodelling. A systems biology of brain functions and disorders can now be envisioned. As it did for the last half century, neuroscience can drive forward the field of systems biology.     

From the soil to the seeds: the long journey of nitrate in plants

Under temperate climates and in cultivated soils, nitrate is the most important source of nitrogen (N) available for crops and, before its reduction and assimilation into amino acids, must enter the root cells and then move in the whole plant. The aim of this review is to provide an overall picture of the numerous membrane proteins that achieve these processes by being localized in different compartments and in different tissues. Nitrate transporters (NRT) from the NRT1 and NRT2 families ensure the capacity of root cells to take up nitrate, through high- and low-affinity systems (HATS and LATS) depending on nitrate concentrations in the soil solution. Other members of the NRT1 family are involved subsequently in loading and unloading of nitrate to and from the xylem vessels, allowing its distribution to aerial organs or its remobilization from old leaves. Once in the cell, nitrate can be stored in the vacuole by passing through the tonoplast, a step that involves chloride channels (CLC) or a NRT2 member. Finally, with the exception of one NRT1 member, the transport of nitrite towards the chloroplast is still largely unknown. All these fluxes are controlled by key factors, the 'major tour operators' like the internal nutritional status of the plant but also by external abiotic factors.     

A long and winding road: the Plasmodium sporozoite's journey in the mammalian host

The Plasmodium sporozoite, the infectious stage of the malaria parasite, makes a remarkable journey in its mammalian host. Here we review our current knowledge of the molecular and cellular basis of this journey, which begins in the skin and ends in the hepatocyte.     

A journey to the world of glycobiology

Finding of the deletion phenomenon of certain oligosaccharides in human milk and its correlation to the blood types of the donors opened a way to elucidate the biochemical basis of blood types in man. This success led to the idea of establishing reliable techniques to elucidate the structures and functions of the N-linked sugar chains of glycoproteins. N-Linked sugar chains were first released quantitatively as oligosaccharides by enzymatic and chemical means, and labelled by reduction with NaB³H₄. After fractionation, structures of the radioactive oligosaccharides were determined by a series of methods developed for the studies of milk oligosaccharides. By using such techniques, structural rules hidden in the N-linked sugar chains, and organ- and species-specific N-glycosylation of glycoproteins, which afforded a firm basis to the development of glycobiology, were elucidated. Finding of galactose deficiency in the N-linked sugar chains of serum lgG from patients with rheumatoid arthritis, and malignant alteration of N-glycosylation in various tumors opened a new research world called glycopathology.However, recent studies revealed that several structural exceptions occur in the sugar chains of particular glycoproteins. Finding of the occurrence of the Gal1-4Fuc1- group linked at the C-6 position of the proximal N-acetylglucosamine residue of the hybrid type sugar chains of octopus rhodopsin is one of such examples. This finding indicated that the fucosyl residue of the fucosylated trimannosyl core should no more be considered as a stop signal as has long been believed. Furthermore, recent studies on dystroglycan revealed that the sugar chains, which do not fall into the current classification of N- and O-linked sugar chains, are essential for the expression of the functional role of this glycoprotein.It was found that expression of many glycoproteins is altered by aging. Among the alterations of the glycoprotein patterns found in the brain nervous system, the most prominent evidence was found in P₀. This protein is produced in non-glycosylated form in the spinal cord of young mammals. However, it starts to be N-glycosylated in the spinal cord of aged animals.These evidences indicate that various unusual sugar chains occur as minor components in mammals, and play important roles in particular tissues.     

A journey from neocortex to hippocampus

In the mid-1960s, it was generally agreed that the engram, the neural trace of previously experienced events, must be encoded by Hebb-like neurons in which synaptic efficacy could be modified by activity. Here, I describe my attempts as a PhD student at McGill University, Montreal, to find rules governing cortical plasticity in the neocortex, and having failed, why the hippocampus seemed to offer a far better prospect.