No, this is not a post about another case of scientific misconduct (the sigma factor in transcription initiation published in Cell last October) but about Six Sigma, a process developed at Motorola in 1986 for measuring defects and improving quality of the production process (Motorola owns the trademark for Six Sigma). Read more at the excellent Wikipedia article – applying these principles could also help scientific projects, yea, yea.

The 3 Rs of regulating animal research are Refinement (to minimize suffering), Reduction and Replacement (to minimize the number of animals used). A Nature news feature now has a critical appraisal of current knockout projects where each of the 25,000 genes will be knocked out in the next future. Although current technology represent an advantage over recent undirected mutagenesis projects

… the number of mice needed to establish a line stretches from 50 to several 100. On top of this, another couple of 100 animals are needed for basic analysis of genetic make-up and phenotype…

Many genes cannot be knocked out – some knockouts may even be lethal.
We are also not so much interested in permanent destruction of genes in all tissues but in conditional and temporal shutdown of gene function.
And many researchers are not so much interested in the current 129 background than in BL6 (at least in immunology and allergology).
Finally (in human genetics) we are not dealing with knockouts but with multiple genomic variants of a gene. The question therefore is

Is the spirit of the knockout projects in line with [3R] principle[s]?

although I acknowledge that these industrial projects may generate many “nice to know” facts.

It was an interesting experiment that started on June, 1 in the Nature office: a first trial of of open peer review. Of the 10,000 papers received every year, 6,000 are immediately rejected and eventually 700 published after peer review. The result of the trial, however, is disappointing:

We sent out a total of 1,369 papers for review during the trial period. The authors of 71 (or 5%) of these agreed to their papers being displayed for open comment. Of the displayed papers, 33 received no comments, while 38 (54%) received a total of 92 technical comments.

The trial provoked some web traffic with approx. 800 page views/day. Welcome back to the altruism thread, the discussion may be followed at their blog, yea, yea.

In a previous paper I have questioned if LPS

nanogram exposure on the pulmonary epithelium will supersede the gram-wise exposure on the gut mucosa.

This may indeed work as now shown by Eyal Raz in a commentary in Nature Immunology where previous TLR studies

typically reproduce the splenic version of innate immunity (the spleen is used here as a metaphor for the sterile internal environment).

In the lung only the alveolar space is thought to be sterile while macrophages should not be in a constant state of activation (as inflammation would compromise gas exchange).

There are now several indicators for a lung-specific regulation of innate immunity: TLR9 is expressed in human plasmacytoid dendritic cells while TLR4 is only on myeloid DCs; TGFB-ß mediated crosstalk between alveolar macrophages and epithelial cells seems to be unique in the lung; in addition indeolamine induction or surfactant production is not found elsewhere. Yea, yea.