The medium is the message: glycosphingolipids and their soluble analogues

We have made adamantylGSLs by substituting the fatty acids of primarily, globotriaosyl ceramide(Gb(3)) and sulfogalactosyl ceramide(SGC), with the rigid alpha-adamantane hydrocarbon frame. These analogues have proven to be remarkably water-soluble but retain the receptor function of the parent membrane GSL. AdaGb(3) prevents the binding of verotoxins to target cells but increased pathology in vivo, likely due to the partitioning into receptor negative target cells to provide pseudo-receptors. Preincubation of HIV with adaGb(3) prevents cellular infection in vitro and viral-host cell fusion. Cellular accumulation of Gb(3) reduces HIV susceptibility in vitro, whereas lack of Gb(3) promotes infection, suggesting that Gb(3) expression could be a novel risk factor for HIV susceptibility. AdaGb(3) has proven to be a new inhibitor for the MDR1 drug pump (P-glycoprotein) and can reverse drug resistance in cell culture. AdaSGC is bound by hsp70/hsc70 within the N-terminal ATPase domain and inhibits chaperone function. When added to cells transfected with the DeltaF508 CFTR mutant, adaSGC was able to decrease ER degradation of this mutant protein, an hsc70 dependent process. Our finding that DeltaF508 CFTR expressing cells show reduced SGC biosynthesis suggests that SGC could be an additional natural regulator of the hsp70 chaperone ATPase cycle.     

Motion processing: where the medium is the message

The primate retina serves up three channels for visual entertainment, of which just one is used for the primary analysis of motion. A prominent, unique class of neuron has a dominant role in transmission from cortical area V1.     

McMaster's pioneer in evidence-based medicine now spreading his message in England.

Dr. David Sackett, formerly of McMaster University and now at Oxford University in England, is considered one of the pioneers of the evidence-based medicine movement. This article looks at his colleagues'' assessment of Sackett''s contributions to medicine and at Sackett''s own views on his lengthy career.     

Metabolic footprinting and systems biology: the medium is the message

One element of classical systems analysis treats a system as a black or grey box, the inner structure and behaviour of which can be analysed and modelled by varying an internal or external condition, probing it from outside and studying the effect of the variation on the external observables. The result is an understanding of the inner make-up and workings of the system. The equivalent of this in biology is to observe what a cell or system excretes under controlled conditions - the 'metabolic footprint' or exometabolome - as this is readily and accurately measurable. Here, we review the principles, experimental approaches and scientific outcomes that have been obtained with this useful and convenient strategy.     

The future of genomic medicine is here

A report on the 6th annual Future of Genomic Medicine conference, held at the Scripps Seaside Forum, La Jolla, CA, USA, March 7-8, 2013.On his flight over to San Diego to lead the Future of Genomic Medicine (FoGM) conference, Dr Eric Topol (Scripps Translational Science Institute, USA) used a heart monitor device attached to his smartphone to diagnose a distressed passenger with atrial fibrillation. Already, mobile technologies such as this one are beginning to transform medicine, and genome sequencing, with its rapidly decreasing costs, is no exception. As we get closer to mini-sequencers and what George Church (Harvard Medical School, USA) termed ''wearable sequencing'', a future of genomically informed medicine becomes possible. The FoGM conference integrated the patient-oriented perspective of genomic medicine, along with cutting-edge technologies and data integration, and developing methods and models in the aim of clinical utility.     

The mutant vasopressin gene from diabetes insipidus (Brattleboro) rats is transcribed but the message is not efficiently translated

The vasopressin gene from normal and diabetes insipidus (Brattleboro) rats has been isolated and sequenced. Except for a single deletion of a G residue in region coding for the neurophysin carrier protein the approximately 2300 nucleotides of both genes are identical. Blot analysis of hypothalamic RNA as well as transfection and microinjection experiments indicate that the mutant gene is correctly transcribed and spliced, however the resulting mRNA is not efficiently translated.     

Translating the message

The "one gene = one protein" model for understanding the genome is well-known. But, as with most biological "rules", it has its exceptions. The viral family that brings polio, the common cold and foot-and-mouth disease translates its entire genome into one long "polyprotein". The study of this translation strategy is bringing to light new targets for fighting disease and new techniques for the biotech industry.