Mental Indigestion

by Jim Caryl

Month: February, 2010

Telling tales…

The following is an excerpt about the current interplay between science and the media, taken from an article in this week’s Nature by Colin Macilwain:

…thanks to the massive growth in public relations and to online media’s insatiable appetite for ‘content’, journalism in science, as in other spheres, has evolved into an ugly machine — called ‘churnalism’ by media-watcher Nick Davies and others. This machine delivers inexpensive and safe content, masquerading as news, to an increasingly underwhelmed public.

The machine prospers because it serves the short-term interests of its participants. Editors get coherent and up-to-date copy. Writers get bylines. Researchers, universities and funding agencies get clips that show that their work has had ‘impact’. And readers get snippets, such as how red or white wine makes you live longer or less long, to chat about at the water-cooler.

None of these groups is benefiting strategically from the arrangement. Science is being misrepresented as a cacophony of sometimes divergent but nonetheless definitive ‘findings’, each warmly accepted by colleagues, on the record, as deeply significant. The public learns nothing about the actual cut and thrust of the scientific process, and as a result is beginning to adopt a weary cynicism that can only rebound on science in the long run.

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A radical source of antibiotic resistance…

This post was chosen as an Editor's Selection for ResearchBlogging.orgA FEW years ago, a Boston University team headed by Jim Collins published findings that suggested the means by which bactericidal antibiotics result in cell death. Rather than the cause being the cellular target of the drug, the team showed it was the secondary effects of stimulating the production of hydroxyl radicals, a reactive oxygen species 1. The hydroxyl radical is known to cause significant damage to cellular DNA, proteins and cell wall, leading to cell death.

Their 2007 study 1 was initially met with a few raised eyebrows in some quarters, coming in for some criticism for having a few gaps; namely whether the role of the hydroxyl radical was even pertinent in a real world infections settings, which are often in the low-oxygen environment of biofilms 2. There was also some question of whether it was adequately demonstrated that the oxidative stress was a source or the result of cell damage. However, subsequent studies reported by Kohanski, as well as other labs, have described a more defined link between a bactericidal drug and resulting hydroxyl radical formation 3.

In the latest edition of Molecular Cell, a new article from Mike Kohanski, Mark DePristo and Jim Collins reports that prolonged exposure to sub-lethal concentrations of antibiotics can induce multiple drug resistance in E. coli and Staphylococcus aureus strains that were initially drug sensitive 4. E. coli strains were tested with sub-lethal levels of  three major classes of bactericidal antibiotics (quinolone, B-lactam and aminoglycoside), which were found to significantly increase the mutation rate, confirming their expectations.

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Heat shocking adaptive evolution…

Research bloggingIN evolutionary theory there is a phenomenon known as canalisation, a process in which the phenotype (i.e. the outward physical appearance of an organism) remains unchanged, despite genetic or environmental influences.  This suggests that a mechanism exists to buffer the physical appearance from such changes, which may explain why some species can remain mostly unchanged for millions of years.

The buffering afforded by this mechanism permits the accumulation of genetic variation, in effect storing it up like an evolutionary capacitor. Also, presumably the accumulated genetic variation may be released by an event that overcomes the evolutionary capacitor, releasing fuel (in the form of variation) that provides a substrate for natural selection and potentially accelerating evolution. But how?

The idea of capacitance was first suggested by Rutherford and Lindquist 1 following experiments on a protein called heat shock protein 90 (Hsp90) in fruitflies. Generally speaking, heat shock proteins assist in the maintenance and correct folding of cellular proteins, especially when under temperature stress; Hsp90 plays a particular role in maintaining the unstable signalling proteins that act as key regulators of growth and development.

They suggested that in nature, a stressing event such as high or low temperatures may overcome the protective buffering effect that Hsp90 has on maintaining these key regulators. As Hsp90 becomes diverted from its usual role, due to an increase of stress-damaged proteins in the cell, those cell signalling proteins it normally maintains are free to adopt a range of altered behaviours, interfering with the development of the organism. The result is morphological variants upon which natural selection can act. Rutherford and Lindquist found as much, with chemically and environmentally compromised Hsp90 resulting in flies with abnormal wings, legs or eyes, they observed a broad variety of phenotypes.

Rutherford and Lindquist went on to demonstrate that the capacity for such remarkable variation was pre-existing, i.e. it was encoded genetically prior to the stressing event, but had been silenced. Evolutionary capacitance may therefore provide a mechanism of adaptive evolution in which a population under stress may release previously silent variation, resulting in the appearance of certain individuals with more desirable traits in that changed environment. When such revealed traits are selected for they can become fixed and independently of the buffering action of Hsp90.

This week, in a letter to Nature, Valeria Specchia et al.2 report some fascinating evidence that indicates that beyond merely acting as a gate-keeper to unleash variation, mutations of Hsp90 that compromise its functionality result in new, rather than pre-exisiting, variation. They observed that mutations in Hsp90 affect the production of piRNAs. These are small RNA molecules that are involved in the silencing of genes, particularly those involved in development, i.e. sex cells like eggs and sperm, and all the cell types that give rise to these cells. These piRNAs are also responsible for repressing genetic elements called transposons.

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