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Genetics

Barker to the power of 2

It is certainly hard to understand how early life events are leading to later disease. Here is an incredible nutrigenomics story done in agouti mice:

We find that the somatic epigenetic state of Avy is affected by in utero methyl donor supplementation only when the allele is paternally contributed. Exposure to methyl donor supplementation during midgestation shifts Avy phenotypes not only in the mice exposed as fetuses, but in their offspring. This finding indicates that methyl donors can change the epigenetic state of the Avy allele in the germ line, and that the altered state is retained through the epigenetic resetting that takes place in gametogenesis and embryogenesis. Thus a mother’s diet may have an enduring influence on succeeding generations.

agouti.png

 

CC-BY-NC Science Surf , accessed 28.07.2026
Allergy, Vitamins

Lymphopoetin and allergy

1 Comment

This is to convince me that the thymic stromal lymphopoietin (TSLP) is a master switch in allergy

15 Aug 2004

Skin-specific overexpression of TSLP resulted in an AD-like phenotype, with the development of eczematous lesions containing inflammatory dermal cellular infiltrates, a dramatic increase in Th2 CD4+ T cells expressing cutaneous homing receptors, and elevated serum levels of IgE.

5 Jun 2006

Topical application of the physiologically active ligand [1{alpha},25-(OH)2D3; calcitriol] of the vitamin D receptor, or of its low-calcemic analog MC903 (calcipotriol; Dovonex), induces TSLP expression in epidermal keratinocytes, which results in an atopic dermatitis-like syndrome.

22 Jan 2007

TSLP, synergistically with interleukin 1 and tumor necrosis factor, stimulates the production of high levels of Th2 cytokines by human mast cells (MCs) … TSLP is released by primary epithelial cells in response to certain microbial products, physical injury, or inflammatory cytokines.

23 Jan 2007

Proinflammatory TNFalpha or IL-1alpha and Th2 (IL-4 or IL-13) cytokines synergized to induce the production of TSLP in human skin explants … Our data provide the first evidence of TSLP induction and subsequent DC activation in human skin.

25 Feb 2007

Mice with an IEC[intestinal epithelial cell]-specific deletion of IKKbeta show a reduced expression of the epithelial-cell-restricted cytokine thymic stromal lymphopoietin in the intestine and, after infection with the gut-dwelling parasite Trichuris, fail to develop a pathogen-specific CD4+ T helper type 2 (TH2) response and are unable to eradicate infection. Further, these animals show exacerbated production of dendritic-cell-derived interleukin-12/23p40.

June 2007

… (TSLP) and interleukin-7 share a common receptor chain, IL-7Rα … The gene encoding the IL-7Rα chain is polymorphic, and investigation of inhalation allergic patients compared with controls showed significant association with two alleles at position +1237 and +2087.

Aug 2007

… TSLP represents a master switch of allergic inflammation at the epithelial cell and dendritic cell interface.

 

CC-BY-NC Science Surf , accessed 28.07.2026
Uncategorized

Abstracts that are difficult to understand

Can you find the problem in the following abstract

…We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 times 10-8)…

The BMJ explained last year – why p-values (or relative risks alone) do not make so much sense

Unless ratio measures are reported with the underlying absolute risks, readers cannot judge the clinical significance of the effect. Consider the following example. Readers may be told that the relative risk of death with drug A compared with placebo is 0.5; in other words, people who take drug A are half as likely to die as people who take placebo. But without the underlying absolute risksâ€"the chance of death in each groupâ€"the information is incomplete.1 A relative risk of 0.5, for example, is compatible with a wide range of changes in the risk of death: from 20% to 10%, from 1% to 0.5%, and from 0.0004% to 0.0002%.

 

CC-BY-NC Science Surf , accessed 28.07.2026
Philosophy

Fail better

I truly liked the recent Sjoblom study while a new Science letter now raises heavy criticism:

… put into stark reality the challenges facing the Human Cancer Genome Project (HCGP). One wonders about the merits of such high-cost, low-efficiency, and ultimately descriptive-type “brute force” studies. Although previously unknown mutated genes were unearthed, the functional consequences of most of these and their actual role in tumorigenesis are unknown, and even with that knowledge we are a long way from identifying new therapeutic targets.

This seems to be the open wound of modern biology: all these high throughput driven genotyping / expression profiling / metabolome scanning approaches are mainly money & impact & activity driven – parameter or hypothesis-free has become a fashionable buzz phrase while only a few years ago it would have been an affront to every serious researcher.

Funny to see also the new Nature initiative opentextmining.org as nobody wants to read the results of these studies. So at least computers should be able to do that. Fail better…

Addendum

Similar criticism of the Neanderthal studies but a different argument

However, although such comparisons are of interest, it is not the static genome but rather the dynamic proteome that determines the phenotype of an organism. Salient examples include the caterpillar and the tadpole, which share
genomes with the butterfly and frog, respectively, but which have very different proteomes making them into very different organisms.
Thus, rather than performing untargeted comparisons of sizable genomes, we suggest that it might be more useful to address this question using a standard hypothesis-driven approach.

 

CC-BY-NC Science Surf , accessed 28.07.2026
Software

Powerpoint slides in wordpress

I have tested several programs for their usefulness of showing Powerpoint slides on the web- some packages create standalone pages only while others have major problems with figures, graphics or transitions (or are quite expensive).

A rather simple method works at least in part – loading a .ppt file in Open Office Impress and exporting it to .swf. The flv player, however, creates a messy display as it doesn’t use the full display area.

Another option is to export all pages as 800×600 .jpg files and mount them in File Show Maker to a standalone flash film – as seen below in a talk that I have given in 2006:

 

CC-BY-NC Science Surf , accessed 28.07.2026
Genetics, Joke

What is DANN sequencing?

Did you ever came across DANN sequencing or plasmid DANN?

Here is my explanation: Native German MS WORD always corrects DNA to DANN (“then”). So if you don’t check your text, and your editor doesn’t check your text, and your reviewer doesn’t check your text – you will get an immortal entry in PUBMED like the guys below:

dann.png

You may even earn money with typos …

 

CC-BY-NC Science Surf , accessed 28.07.2026
Genetics

Coworker ID

A nice PNAS paper gives in its supplement 4 the MCM6 and mtDNA 16209 genotypes of some prehistoric bones AND of all authors – excellent! The study itself is also interesting as we learn about the true wild-type allele in early Neolithic Europeans – they could not digest milk.

 

CC-BY-NC Science Surf , accessed 28.07.2026
Uncategorized

Sauerbruch and Rascher

Last week I went to Bavaria’s largest book market and found a book that I wanted to read for a long time – the 1950 autobiography of Ritterkreuzträger, Generalarzt, Staatsrat, Geheimrat, Prof. Dr. med., Dr. med. h.c. Ferdinand Sauerbruch, emeritus director of the surgical university clinic in Berlin – and found unexpected connections to Sigmund Rascher.

P 538
Sehr interessant war für mich ein Teilgebiet der gesamten Wehr-Medizin: die Luftfahrt-Medizin. Sie erwuchs auf der Grundlage psychologischer Untersuchungen und klinischer Erfahrungen. Es ist aber ganz selbstverständlich, und man muß es einmal aussprechen, daß die Forschung wertvollste Anregungen aus der Kriegstätigkeit der Sanitätsoffiziere gewonnen hat.
P 558
Ich will mich nicht zum sogenannten “Ärzteprozeß” in Nürnberg äußern. Ich kann hier nur versichern, daß heute manche Ärzte, die sicher nicht weniger “schuldig” waren, in aller Gemütsruhe ihrer Praxis nachgehen. Ich könnte ein Dutzend Namen nennen, aber das brächte die anderen nicht wieder zum Leben, sondern möglicherweise nur neue Opfer der so höchst zweifelhaften “irdischen Gerechtigkeit”.
translation

Mitscherlich/ Mielke reported that Sauerbruch attended the “3. Arbeitstagung der beratenden Ärzte” in May 1943 moderated by Karl Gebhardt where experiments from concentration camp Ravenbrück have been reported. According to Klee (Auschwitz, 1997, P 199) Sauerbruch issued a temporary restraining order against Mitscherlich that it had not been known that these experiments were performed on prisoners.

Reading now about Sauerbruchs’ fascination of the Rascher experiments -valuable contribution- and his speculations about -“guilt”- in quotation marks I think that this attitude can not be atrributed to dementia praecox as has been done before.

 

CC-BY-NC Science Surf , accessed 28.07.2026
Uncategorized

Doctor help yourself

Physicians do have a lower life expectancy than the average population – which argues somewhat against the health (some believe also disease) expertise of physicians. ZEIT magazine now has an article about “Guter Arzt, kranker Arzt”. It is about the hierarchic system in German hospitals, the daily indignities, the long working shifts and the hope that this will improve by climbing the next step of the career ladder.

 

CC-BY-NC Science Surf , accessed 28.07.2026
Philosophy

Don’t become a scientist?

A quick link to an open letter – I do not endorse the opinions expressed there…

Now you spend your time writing proposals rather than doing research. Worse, because your proposals are judged by your competitors you cannot follow your curiosity, but must spend your effort and talents on anticipating and deflecting criticism rather than on solving the important scientific problems. They’re not the same thing: you cannot put your past successes in a proposal, because they are finished work, and your new ideas, however original and clever, are still unproven. It is proverbial that original ideas are the kiss of death for a proposal; because they have not yet been proved to work (after all, that is what you are proposing to do) they can be, and will be, rated poorly. Having achieved the promised land, you find that it is not what you wanted after all.

Looks like ‘Research 2.0’ need to be installed there.

 

CC-BY-NC Science Surf , accessed 28.07.2026