As you can see, I am eating my own food here – writing all links in standard notation but giving them a different outlook.
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Vitamin D and asthma
My previous work on vitamin D focused mainly on allergy but according to new research of Bosse et al vitamin D also stimulates bronchial smooth muscle and airway remodeling
Genetic variants in the vitamin D receptor (VDR) gene were recently associated with asthma. The biological mechanisms explaining this association is unknown, but are likely to involve many cell types given the pleiotropic effect of its ligand … The most significant network of up-regulated genes included genes involved in morphogenesis, cell growth and survival as well as genes encoding structural proteins, which are potentially involved in airway remodelling.
Another study published more or less at the same time by Wittke shows
Conversely, WT splenocytes, Th2 cells and hematopoetic cells induced some symptoms of experimental asthma when transferred to VDR KO mice, but the severity was less than that seen in the WT controls … Lipopolysaccharide (LPS) induced inflammation in the lungs of VDR KO mice was also less than in WT mice. Together the data suggest that vitamin D and the VDR are important regulators of inflammation in the lung…
Science elite in Germany
Three German universities that have been elected into an excellence cluster. This oracle isn´t too bad for me ;-) as I have been raised close to the first and teached at both other universities.
Yes, I agree, there are some differences but – as science is done mainly by individuals or at least local teams – the differences are not so large and this election (for whatever criteria) doesn’t have so much meaning.
I believe, however, there will be some self-fulfilling prophecy, as on the longterm run these Universities will attract more excellent people – a point being missed in the current discussion. Yea, yea.
Addendum
Another 8 universitites enter the club: HU Berlin, FU Berlin, Göttingen, Freiburg, Heidelberg, Konstanz, Aachen and Bochum.
Scientific spam
I am sending here a trackback to David who asked if a new series of spam email may be
nothing more than an intricate social engineering endeavour and that I’ve been duped into responding in this way.
I found me also answering an email where a 15 year old asked (after having smoked a few cigarettes) if she will now have an increased lung cancer risk. Only 10 minutes later at the coffee machine I heard that a dozen people had just answered exactly the same email. Think of it like an April Fool’s joke, yea, yea.
Three things can not hide for long: the moon, the sun and the truth
This is the slogan of Wikileaks a website under construction that
is developing an uncensorable Wikipedia for untraceable mass document leaking and analysis. Our primary interests are oppressive regimes […]. We aim for maximum political impact; this means our interface is identical to Wikipedia and usable by non-technical people.
We also have some experience in science with whistleblowers leading to further investigations. How will this site guarantee the correctness of any information?
A longe fuse
Mutation accumulation in the human genome is a largely neglected research field. Most mutations have a very small effect (if any) and may be compensated by environmental improvements. I have already argued in that way in my 2003 Triple T paper and will reiterate it soon in PLOS medicine (just found that James Crow 1997 in PNAS and 2000 in nat gen rev had the same opinion). In principle, the improvement of sanitation and better medical care is leading to a retention of mutations that would be otherwise subject of purifying selection.
Another important factor seems to be the increase of parental age in Western societies. A 20 year old man had about 150 chromosome replications while a 40 year old had about 610 replications. To count the number of your somatic mutations, you need to add all events of your lifetime plus the age of your father at birth minus 9 months … Even with the high fidelity of polymerases, DNA replication remains an error prone process leading eventually to an increase of germline mutations (as may be seen with achondroplasia, Apert syndrome, neurofibromatosis and prostate cancer). With the increasing age of fathers we are now nearly doubling the absolute number of mutations every generation – and we keep them in the pool in contrast to previous centuries. Crow in PNAS 1997 even said
I do regard mutation accumulation as a problem. It is something like the population bomb, but it has a much longer fuse
Addendum 20 Nov 2013
In another post, I detailed the 3,93 figure derived from cancer tissues. The best human estimate at the moment is in this Cell paper that shows a rate between 2.0 and 3.8 x 10^-8 cells. Sperm sequencing may not represent a good model as there are too many degenerate cells.
Addendum 1 Jan 2021
Here is a new nature medicine paper on cell turnover.
What I do not understand – shouldn’t we have a much higher leukemia rate in the population? Leukemia is only on the11th place.
Addendum 29 Apr 2021
Another Nature study shows
Differentiated cells in blood and colon displayed remarkably similar mutation loads and signatures to their corresponding stem cells, despite mature blood cells having undergone considerably more divisions. We then characterized the mutational landscape of post-mitotic neurons and polyclonal smooth muscle, confirming that neurons accumulate somatic mutations at a constant rate throughout life without cell division, with similar rates to mitotically active tissues …
this could be the answer to my previous question
These mutations may result from the interplay between endogenous DNA damage and repair that occurs in cells at all times. The similar mutation burden and signatures in granulocytes and hae- matopoietic stem cells, despite a different divisional load, could also be consistent with a time-dependent rather than a division-dependent accumulation of somatic mutations during haematopoiesis
although it will need independent corroboration before making any conclusion that damage repair is more important than replication.
Online statistical analysis
There are many occasions where I quickly need a calculator for example when reviewing a paper. My favorite links are statpages and VassarStats; for confidence intervals I use Poisson confidence intervals.
I require 1,000,000 dollars
Most scientists are urged to spend much of their time for getting research funds. Here is a another anecdote about Otto Warburg reported by Hans Krebs / p 57:
One day he [Warburg] asked the office of the Director-General [of Kaiser-Wilhelm-Gesellschaft, later Max Plack Society] to allocate 10,000 marks for his research. He was told that that the organization had no spare money; he should therefore write an application, which the Director-General would support, to the Notgemeinschaft (an emergency fund made available by the government for the promotion of research). Warburg replied that he had no secretary; the Director-General should put a secretary at his disposal. This was agreed. Warburg handed the secretary a sheet of paper and told her to type ‘Top left: Dr.Otto Warburg; top right: the date; underneath this: I require 10,000 (zehntausend) mark.’ This Warburg signed. The ‘application’ was succesful.
Yea, yea.
Clear science
If you ever need to safely dispose a computer, here is an instruction: download an ISO image of DBAN, burn it and boot your computer from CD, that´s it. Take care, at least in Germany, you need to store research data for 10 years.
R-type and E-type
This afternoon I attended a talk at MPI of Yurii Aulchenko about his R package genABEL. He uses a nice trick to convert genotypes into 8 bit (as there are is no 2 bit format 00,01,10,11) which saves quite a lot of memory.
And here is the E type that I have seen a couple of months ago:
Autophagy
Crohn`s disease is still a mystery. Associated gene variants have been described in CARD15, DLG5, SLC22A4, CARD4, TNFSF15, IL23R and many more genes that explain altogether less than one quarter of the disease risk. My friends in Kiel now add ATG16L1 to this list. They looked for nonsynonymous SNPs and voila rs2241880 (A/G*, T300A*) a new disease SNP is born.
What is remarkable in their study that the top 9 SNPs (as judged by significance in the range of 10^-14>p<10^-4) could NOT be replicated for whatever reason. I guess it would be even worse to see also panel C in this table. Expression of ATG16L1 is rather weak in the small intestine, not influenced by the reported SNP, not different in the gut of Crohns patients and not related to disease location.
Genecards say that the subcellular location of ATG16L1 is close to a peripheral membrane protein complex known as preautophagosomal structure. Autophagy is an intracellular degradation system delivering cytoplasmic components to the lysosomes (L is not related to ligand or L1 transposon but indicates "like"). The gene has been tested so far in yeast and mouse. Unfortunately, information about ATG16L1 is scarce but there is some work on yeast ATG16 (which seems to miss the domain with the disease SNP).
Some authors believe that macroautophagy is process induced by nutrient starvation in eukaryotic cells, which could explain some of the Crohns’ disease characteristics. Autophagy seems to have some developmental effect and may be related to even more diseases. It seems that there are now even more mysteries to solve, yea, yea.
Tono-Bungay
No, this is not about H.G. Wells’ book, but about Paul Pearsall (who quotes Wells) and what he has to say about the ever increasing self-help-, Dr. Phil-, Dr. Laura- and Dr. Ruth- and whatsoever market The Last Self-Help Book You’ll Ever Need: Repress Your Anger, Think Negatively, Be a Good Blamer, and Throttle Your Inner Child.
Publisher Weekly says that he is
… arguing against the “platitudes of self-empowerment” that dominate the self-help bookshelves. Their relentlessly upbeat tone and unrealistic idea of happiness will only make you feel worse, he says. Using research studies to bolster his points … Dr. Phil. Pearsall, an adjunct clinical professor at the University of Hawaii at Manoa, wants readers to stop being so self-centered. It’s more important, he says, to love others before oneself, and appropriate guilt and anxiety are essential to learning to live a better life.
I enjoyed every sentence of this book, the inner pages fulfill what the title promises: A realistic approach that follows sound scientific principles.
One origin, one race, one earth
Conference One origin, one race, one earth
Speakers include:
Dr. Gregory Stock (author of Redesigning Humans: Our Inevitable Genetic Future)
Bartha Knoppers (author, CartaGene Project)
Karen Van Kampen (author of The Golden Cell)
Ikechi Mgbeoji (author, Biopiracy: Patents, Plants, and Indigenous Peoples, Knowledge Patents)
Do what you will this life’s a fiction and is made up of contradiction
If you also like William Blake’s poetry you might be interested in more quotes that have a true scientific background.
Pol III cross country skiing over nucleosome rocks
The relationship of gene expression and DNA methylation looks still like a mystery to me but fortunately there is now a second Arabidopsis paper that has some news. As the authors write in the discussion the mechanism how DNA methylation interferes with transcript initiation is still unclear – it is assumed that methylated DNA is carrying repressive histone modifications.
A clear (and repeated) finding, however, is the strong influence of DNA methylation on gene expression, where LOW and HIGH expressed genes are not so much methylated than MEDIUM expressed genes. Another bias of methylation is found AWAY from gene ends. Gene size seems to be also somehow relevant for gene expression. Taken that all together they develop a model of Pol III moving along DNA strand between nucleosome rocks (POL III may disrupt these rocks that cross country skiiers cannot ;-) ).
Version A: Far distant nucleosomes – the transiting RNA polymerase exposes cryptic initiation sites that allow aberrant transcipts be processed by dicer into siRNA that will methylate DNA (and create nucleosomes?)
Version B: Average distant nucleosomes – continuous flow of disrupted nucleosomes by closely spaced polymerase working along DNA strand – normal situation?
Version C+D: Close distance nucleosomes – high polymerase density – polymerase stalling and collision – as a repression mechanism?