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?

I swear by God that I will speak the pure truth

Will you state your full name?
Will you repeat this oath after me?
I swear by God, the Almighty and Omniscient, that I will speak the pure truth, and will withhold and add nothing.
You may sit down.

I have heard this sentence now eight times – on eight new CDs from the Nuremberg trials with original material by the American Record Group 238 “Die NS-Führung im Verhör” documented by Ulrich Lampen with an introduction by Peter Steinbach. The introductory remarks are well balanced, the sound quality excellent, translation and dubbing artists outstanding, but there seems to be no documentation in the CD box in particular for CD 7, the interrogation of Prof. Dr. med. Karl Gebhard.

I am giving therefore some links here – as otherwise you will not really understand what this man did. None of the other interviews recorded such an aggressive, rude and loud tone – a big-headed, omnipotent medical professor that still believes that winning of the war would have enobled his medical research.

www.shoa.de, the largest German portal on the Holocaust has an article about Herta Oberheuser that contains some information about Gebhard; more at German Wikipedia but the most detailed account may be found in Klee, Auschwitz pp 152. Gebhard was one of the few German physicians that were hanged after the war.

Born in 1897, he studied as Mengele here in Munich, habilitated 1935 as a scholar of Sauerbruch and became associate professor in Berlin. As of 1937, he held a chair of orthopedic surgery, became head physician at the sanatorium (Heilanstalt) Hohenlychen and “Oberster Kliniker beim Reichsarzt SS”. Ravensbrück was only a few kilometer from Hohenlychen. Klee has all the terrible details of his medical research: artificial infection with Clostridium, wood and glass implantation into the lower legs, explantation of limbs, trepanation with artifical brain injuries, phosphor burning of the perineum as punishment, consecutive murdering of patients with evipan or by shooting. Gebhard was medical attendant of Heinrich Himmler and president of the German Red Cross (sic!)

Protocols

The protocols are available as microfilms. I am currently checking with the editors if they can be copied to PDF format.

Epidemiology in a fascist system

Götz Aly and Karl Heinz Roth show in their book that the German Nazi system would not have worked without counting people, identification, classification, separation and elimination. It is a detailed historical account on technical details of coding and storing information about the population, the census of 1933 and 1939, the infamy of telling people that their data of Jewish ancestry in a separate questionnaire would be treated anonymously (p 93). The 1939 census required a “supplemental card” in addition to the household card (p 32)

This card developed by security service, police as well as statistical office was used by the authorities to ask for individual descend (“Was one of you grandparent Jew?”) as well as for the education in commission of the military services. The card should be given back in a separate, closed envelope. The envelope – together with the official affirmation – should delude potential victims and let them believe by the fictitious anonymity to make absolutely true information which was indeed facilitated and guaranteed.

The supplemental cards were then used to build the “Reichskartei der Juden und jüdischen Mischlingen” – the basis of the Holocaust. The Holocaust started with a  knitting needle – the tool to lift the punched supplemental cards.

As mentioned earlier, I think there is a particular obligation with population based studies in Germany where it took 40 years to build epidemiology from scratch again. This is a must-read book for every epidemiologist.

A few hours before being executed, Eichmann was asked by Mr. Ofer, the director of the prison (in my translation)

“What should the Jews have done? How could they have resisted according to your opinion? Eichmann: Disappear, disappear. Our most sensitive point, that they would disappear before being registered and concentrated. Our command units were too weak and even when the police of the respective countries supported us with all their strength, [the Jewish] had a at least a chance of 50 : 50. A mass escape would have been a disaster for us.

p1060009.JPG

Vivat rex

Ever since I heard 1976 about the Lyon hypothesis (described already in 1961 by Mary Frances Lyon) of X inactivation I wondered how this works on a molecular level – locking this chromosome in a separate nuclear compartment, condense it or encase it? Silencing a whole chromosome probably needs a concerted action of higher order DNA structure, histone code modification and primary sequence features. The last seems to be indeed relevant as C. elegans X has a target for gene expression repression by the dosage compensation complex – small rex motifs (X recruitment elements) ?CAGGGG and ?GTAATTG. The strength of DCC recruitment is correlated with rex motif number BUT rex motifs are not enriched on X – so certainly more features need to synergize for X repression. Yea, yea.

Quick database edit from webbrowser

Frequently, I need to change only one single field in a database. For that purpose I am using a short php script – it basically outputs all fields and highlights them with a javascript popup where you can do any changes (or even delete a row) while a “return” writes the change back to the database.

sc_edit.png

You will immediately see, where the script needs some adaptation – all the trick is in line 28.
line 2: your database
line 5,9…: your mytable
line 23: your columns

 1:
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<?php
$db 
= @mysql_connect('server','user','password');
if (
$_GET['change']!='') {
    if (
$_GET['value']=='d') {
        
$sql 'DELETE FROM mytable
            WHERE mytable.Index=' 
$_GET['id'] . ' LIMIT 1';
    }
    else {
        
$sql 'UPDATE mytable ';
        if (
is_numeric($_GET['value'])) {
            
$sql $sql 'SET mytable.' $_GET['field'] . '=' $_GET['value'];
        }
        else {
            
$sql $sql 'SET mytable.' $_GET['field'] . '="' $_GET['value'] . '"';
        }
        
$sql $sql ' WHERE mytable.Index=' $_GET['id'];
    }
    
$result mysql_db_query('test',$sql);
}
$sql 'SELECT DISTINCTROW *
    FROM mytable'
;
$result mysql_db_query('test',$sql);
$sc_vars = array("FirstCol","SecndCol","ThrdCol");
echo 
'<table>';
while(
$row mysql_fetch_array($result)){
    echo 
'<tr>';
    for (
$i=0;$i<9;$i++) {
        echo 
'<td><a href="javascript:void(str=prompt(\'(d)el\',\'' $row[$sc_vars[$i]] . '\'));if(str)void(window.location.href=\'liste.php?change=T&field=' $sc_vars[$i] . '&id=' $row['Index'] . '&value=\'+escape(str));">' $row[$sc_vars[$i]] . '</td></a>';
    }
    echo 
'</tr>';
}
echo 
'</table>';
?>

Cell podcast with an interesting fact

Cell has a first podcast online. It features interviews with two of this year’s Nobel Laureates, Dr. Craig Mello and Dr. Roger Kornberg, as well as a talk to Dr. Paul Nurse about current funding prospects in the US ( “dont give up”). It is quite easy to hear that on my morning ride – and liked very much Craig Mello saying (please wind forward to 6:19) “the entire genome is probably described in some level” which is quite different to the prevailing junk theory. Yea, yea.

Mercy and truth

Doing science and seeking truth may be occasionally unkind to others. Watching a beautiful movie (“Babette’s Feast“, Oscar 1988) I was deeply moved by the speech of the officer Lorens Löwenhjelm about “Barmherzigkeit und Wahrheit” or “mercy and truth” – it goes back to

Ps 85:10 (KJ) Mercy and truth are met together; righteousness and peace have kissed each other.

Also Martin Luther found that remarkable as well as Wolfgang Huber. Yea, yea.

Dangerous DNA – nullomers or nullintells

New Scientist reports that

Could there be forbidden sequences in the genome – ones so harmful that they are not compatible with life? One group of researchers thinks so. Unlike most genome sequencing projects which set out to search for genes that are conserved within and between species, their goal is to identify “primes”: DNA sequences and chains of amino acids so dangerous to life that they do not exist.

Read the full article – I am hesitating what to say now, yea, yea.

Celebrities on science

BBC reports about celebrities speaking on scientific issues – and comments by experts. I would like another BBC news feature about scientists speaking on scientific issues from different disciplines, for example famous molecular biologists about ethics.

A tragedy if you don’t feel pain

A highly successfull study of the molecular pathways of nociception (and identification of a loss of function mutation in the alpha subunit of SCN9A, a voltage gated sodium channel) has a sad story from Northern Pakistan

The index case for the present study was a ten-year-old child, well known to the medical service after regularly performing ‘street theatre’. He placed knives through his arms and walked on burning coals, but experienced no pain. He died before being seen on his fourteenth birthday, after jumping off a house roof.

It is so difficult for us humans to accept that pain has an important function in life, yea, yea.

Here’s lookin’ at you, kid

In German Humphrey Bogart’s immortal expression “Here’s lookin’ at you, kid” was translated “Ich seh’ Dir in die Augen, Kleines” which translates back to “I look in your eyes, honey”. Seems that this was a spontaneous idea of Bogart on 3rd July 1942 in the Burbank Studios of Warner Brothers if we believe this website.

I am now looking in your eyes with a new study by my long-term penpal David Duffy – 3 OCA2 intron 1 SNPs (rs7495174-rs6497268-rs11855019) are sufficient to explain most human eye colors: T-G-T/T-G-T diplotype is found in 62% blue/gray, 28% green/hazel and 10% brown eyes.

In a (soon to be published) study of European population stratification we also typed 2 OCA2 SNPs but unfortunately not the same ones; I checked also the Affymetrix 500K panel but it doesn`t included these SNPs as well.

Read this if you own a Porsche

and read it also if you are not so much interested in German cars but in population-based DNA registries.

  1. In 1996 all 750 Porsche car owner here in Munich were asked for a DNA identity test – the High Court in Karlsruhe later decided, that this approach was adequate. All test results, however, were discarded after that screening as
  2. forensic DNA testing (invented in 1985 by Sir Jeffreys) is only allowed for severe criminal offense and needs the decision of a judge.
  3. Some German authorities now want to change the rules – allowing DNA testing also in less severe cases, without order of a judge and infinite computer storage of DNA profiles. They get support by police investigators who complain about unresolved crimes and by victims that fear repeaters (boostered by the success in the Moshammer case)
  4. A considerable fraction of these DNA profiles has errors – lab errors, chimera, twins…
  5. Scientists fear that the acceptance to take part in genetic studies will drop if these profiles can be easily matched to research data sets.
  6. A large part of the population is interested in genetic privacy and do not want their government to store their genetic profiles: Ethnic data have been abused in the past to discriminate and kill people – politics and government may change in the future.

German BKA seems to have already 3900,000 DNA fingerprints in stock (other European countries store DNA profiles without any consent). Is there any way out? Here is an idea that I had on my morning daily bike trip:

  1. It is a waste of time and money to discard any test result – and both parties have strong arguments to use these data and to delete it.
  2. Why couldn’t the DNA test result be encoded, saved on a credit-card-like “DNAcard” including a PIN and given to the DNA owner before being deleted from the lab files? It would even be possible to reduce information content – to allow only for a 99% probability for identification.
  3. This would leave any individual the right to identify himself whenever he or she wants to be identified. In case of crime persecution, individuals may asked to insert their “DNAcard” in a public reader that will check the hash of his profile against the hash of any wanted profile (without storing the individual profile on any computer).
    1. Is that a solution?