Correlation between the anaesthetic effect of halothane and saturable binding in brain

Two theories of the molecular mechanism of volatile anaesthetic action suggest either that anaesthetics cause a generalized perturbation of neuronal membrane structure, probably through a nonspecific interaction with membrane lipids, or that anaesthetics bind to sets of sites of appropriate molecular dimension on membrane proteins. Based on the recent finding that fluorinated anaesthetics can be observed in animal tissue by 19F nuclear magnetic resonance (19F-NMR) spectroscopy, we have used 19F-NMR to quantify the interaction between the volatile anaesthetic halothane and rat brain tissue. Steady-state brain halothane concentration was found to be a non-linear function of inspired concentration, with apparent saturation of brain occurring at inspired halothane concentrations above 2.5% by volume. Using a spin-echo pulse sequence it was found that halothane exists in two distinct chemical environments in brain, characterized by different spin-spin relaxation times (T2), chemical shifts and kinetics of occupancy. Halothane concentration in one of these environments (T2 = 3.6 ms) was saturated at approximately 2.5% inspired halothane; occupancy of this environment was found to correlate with the anaesthetic effect of the drug. In the other environment (T2 = 43 ms), brain halothane concentration was a linear function of inspired concentration. These data suggest the existence of a saturable anaesthetic site for halothane in brain and do not support the concept that anaesthetics act by nonspecific membrane perturbation.     

Accurate whole human genome sequencing using reversible terminator chemistry

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.     

The Meaning of Volunteering: The General and Constant Versus the Differentiating and Shifting

This comment concerns a two-fold phenomenon, namely differentiations within the wide array of what is called civic engagement, including voluntary action; and shifts that sometimes blur the demarcation lines between the worlds of voluntary action and working life. How do these two developments affect the meaning of volunteering both on an analytical and on a public discourse level?