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Vitamin-D mediates antimicrobial response

If you are but moderately involved in research in innate immunity and Toll like receptors, the Science paper by Philip T. Liu et al, led by Robert Modlin entitled Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response will cross your path soon - in a journal club or on a coffee table conversation.

If your are just interested but have not been exposed to the questions of molecular biology in innate immunity, the publication is noteworthy as it reviews (and probably adds to) the challenges and controversies in the field of Toll like receptors (TLR) mediated signalling. TLRs are a *hot* class of molecules involved in recognition of pathogenic stimuli but are poorly understood given the amount of research they have been attracting.

The researchers focus on the known differences in the susceptibility of population groups to infections of Mycobacterium tuberculosis and on a particular group of TLR, the TLR 1 and 2 heterodimer. Tuberculosis was previously described to be influenced - amongst many other factors - by UV exposure which is involved in the production of vitamin D. The levels of skin melanin and consequently skin color limit the levels of UV light that reach lower regions of the skin where the vitamin is produced.

The hypothesis that vitamin D plays a role in the mediation of TLR signaling in the infection with Mycobacterium tuberculosis is experimentally augmented by showing that one of the key molecules, VDR is expressed upon stimulation with TLR-ligands in human monocytes. The differences in TLR between a caucasian and an afro-american group could be removed by adding the compound 25D3, a precursor to vitamin D, which suggests that it is directly involved in the signaling, not providing an overall benefit - the key finding of the study.

Finally, the authors argue that the some of differences in antimicrobial pathways of mice and humans might be explained by the nocturnal life style of the rodents, which relay TLR signals via nitric oxide instead of vitamin D.

Somehow, this sounds like it would be a good idea to spend some time in the sun to fight prevent infections. The work will be discussed in our lab for sure - if I learn some new insights from our experts, I'll comments it here.

[Links of interest to the article in The Scientist]

Fairy tales of actin tails

This Valentines Day greeting depicts Shigella flexneri (green) and its actin tails used to escape the phagosomes of macrophages[w]. Gullible people like me could think that the was a genuine finding - but it was photoshopped.
Shigella flexneri in a macrophage
Following the stem cell fallout, journals are in the process of reviewing their publishing policies for scientific papers. Nature's is published in the current issue, including the requirement that all "enhancements" performed on the complete picture. I wonder whether such manipulations could be detected reliably and whether there are cases where image manipulation was the main route to a publication. My impression is
that the submission of a positive control as a confirming sample is the most travelled route in fraud.

[More on actin tails in Nature Reviews Microbiology[s]. Thanks for the picture, Sebastian!]

Genome-wide knockout mutants for E. coli K-12

Three years after the yeast set, a complete set of knockouts of all genes in E. coli K-12 was published in Molecular Systems Biology[s]. Mutants resulting from transposon mutagenesis were available for about half of the genes previously but this study used the popular knockout method by Datsenko and Wanner to target each gene specifically.

The same group reports[s] the sequencing of another closely related K-12 strain - and probably provides the best sequence information we have for genomes currently.

Next on my wishlist: A complete set of double or triple knockout mutants for paralogous gene families in E.coli or yeast.

Recent additions

The following blogs have been in my blogroll for some time - I'd like to point them out anyway. While it shows that they started recently, all of them have potential to contribute to the blogosphere and arrive in the magic middle.

Nature erratum is my preference amongst the grad student blogs that uses anonymity to reflect on the process, hence other PhD students might get the most out of it. The advice to fedex your application (and hopefully its positive results) are worth following up.

The initial reason to read Blogging the biotech revolution by "Francis Crick" was to make fun of it, I have to confess - that combination was just too much. However, the content - mostly conference coverage - reads well versed and I hope to see more of it.

Unlike the two above, Deepakh Sing has no intentions of hiding himself in anonymity at business|bytes|genes|molecules. His rather playful blog connects nanotechnology and bioninformatics in a unique way.
[Thanks for the link, Robin]

The main shortcoming of the above blogs is the small number of posts per time - I can only advise to continue.

Most mashups suck fail to deliver suck - aggregating feeds from other authors by subject and placing google ads around them is the despicable and brainless end of web2.0. is one of notable exceptions, released by Stew (of Flags & Lollipops fame) that delivers information for science bloggers that you won't get out of your RSS reader easily, such as statistics on cited publication and an aggregation of meeting reports (pretty close to what I had dreamed of). It's still in the making and might be more alpha than beta but certainly not gaga. Tres cool!

[More explanations at F&L]

Funding for BIND (update)

The BIND database for protein-protein interactions ran out of funding in November 2005. An editorial[s] in the current issue of Nature Biotech provides additional insights. In particular, the funding problems of the Alliance for Cellular Signaling, one of the largest and earliest systems biology initiatives, seems noteworthy. Perhaps, thinking big was simply not enough.

[via public rambling]



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