Don't try to bluff a physicist in molecular biology

I remember this funny english book series, with the title "Bluff your way in ....", wherein "...." can be anything from history, philosophy to quantum mechanics or AI. As a physicist/biophysicist working in genetics and molecular biology research, I never felt the necessity to fake anything, though. Because both disciplines are very logical, complex and, (in case of genetics) even axiomatic. So quite suitable for a physicists brain to find enough challenges.

And I met many biologists and even medics who, on the other hand, feel a great attraction towards logic and quantitative thinking. But this week I had 2 really shoking encounters with colleagues, of whom one is even an institute director in molecular biology. Both have a PhD in biology, one is a full professor, the other a PI in cytogenetics. The cytogeneticist started to argue with me about the status of mammalian cell nucleus during mitosis (i.e. cell division, when the chromomes condense and become visible). The guy (who published many papers in cancer cytogenetics) was convinced that the chromosomes in metaphase are still confined within the nucleus. I told him that in metaphase there is no nucleus any more, because the nuclear envelop disappeares, and hence the condensed chromosomes are in the cytoplasm. He (at the age of 60 or so) had never heared about this.

In mammalian cells, chromosomes in metaphase are not confined in a nucleus any more, but entirely located in the cytpplasm.

And today I had a talk aside a thesis committee meeting with the mol.biol. professor. The guy really thought that mRNA splicing is happening in the cytoplasm, rather than in the nucleus. This is fundamentally so wrong, that it really made be jaw-dropping. Thats probably the whole difference between prokaryotes (nucleus-less bacteria) and eukaryotes (yeast, plants, animals, all of which have a nucleus in their cells). All organisms with a nucleus (eukaryotes) used to splice most of their messanger RNAs. Prokaryotes simply can not do this; their cells have not the necessary enzymes to do this complicate process. Therefore it is also logical that eukaryotic cells do mRNA splicing in their nuclei, and not in cytoplasm. 

Splicing of ncRNA into the mature mRNA is a process entirely in the nucleus. Only the spliced mRNA is exported to the cytoplasm (in order to be translated into proteins at the ribosomes)

For the mol.biol. professor (64 years old, 1 year before retirement), this was new information (hic!). One has to know that he is not only head of an institute, but also doing the exams for master- and doctoral-students (in molecular-biology, as one would easily guess).

So who has faked his entire professional career here ? Me, a self-trained geneticist with biophysic PhD, or them with their biology/molecular biology degrees ? I don't think that I am a nerd, such as the notorious Sheldon Lee Cooper, Ph.D., Sc.D from the freak show "Big Bang Theory". But at least I can put one and one together, and maybe in contrast to the biologists, who in part are still trained in the tradition of botanical encyclopedists, I always want to get a more comprehensive picture. And for me such a comprehensive picture of the processes in living organisms should be free of contradictions.

The two mechanisms described above, chromosomal segregation during metaphase and pre-mRNA splicing, are absolute essential processes that mark a cornerstone of higher evolution. Random chromosomal segregation outside of a nucleus not only happens in somatic cells a thousand of times every minute throughout our body, but it also takes place during meiosis in our reproductive organs (generation of sperms and oocytes). Sexual reproduction allows a much faster genetic drift as compared to asexual reproduction (clonal expansion), in which only genetic mutations could generate heritable variations in a phenotype. mRNA splicing is also a rather recent "invitation" by nature. Whereas the earliest know prokaryotic living cells (of the Archea domain) appeared on earth about 3.5 billion years ago, the first eukaryotes entered the stage of nature approximately 1.6–2.7 billion years ago (I can not remember the exact date sorry !!!). Splicing makes it possible to generate in multicellular organisms (metazoa) a huge variability of cell types, by differentially splicing the 35 thousand genes (estimation from the human genome) into at least 10 times more different mRNA species, which later can give rise to several hundred thousand different proteins. This makes the rather small genome of higher vertebrates (in comparison to protozoae fungi or even plants) so much more versatile. By fully exploiting the potential of differential splicing, higher vertebrates can much quicker respond to environmental challenges. Our immune system and our highly complex and adaptive brain makes heavy use of constantly changing the splicing pattern of some essential genes, thereby generating a lot of cellular plasticity.

I was shocked that the english Wikipedia does not mention mRNA splicing at all in the article on eukaryotes. Thats surprising, considering Wiki shall summarize the common knowledge of mankind.  Well, seems that again it needs a physicist to edit such a proto-type molecular biology entry. I promise in the next few days, I will add an extra chapter on the Wikipedia eukaryotes article and provide the link here on my blog post. Stay tuned, please.

Could you please give me a gentle kick-in-the-ass, s.v.p. ?!?!

I am quite good in advising others how to get things started, how to overcome procrastination. 

• "Every long journey just starts with a first step forward"  
•  If too many tasks pile up on your desk, prioritize them. Make a rank list with urgencies and importances of each task. Than start with the task that has the highest product of "Importance x Urgency"
• Skip all the sweet little things that easily distract you and keep you busy the whole day long.   

Did I forgot something ? I am open for more good advises. Meanwhile, piles of papers and electronic files containing the results from several master and PhD projects from my lab are accumulating on my desk and on my computer. They would be sufficient to write at least 7 good papers for cancer biology and stem cell journals. 

I think I need someone who gives me a gentle kick-in-the-ass to start with the work. For the radiation-associated AML and Flt3 manuscript there is even a deadline by the International Journal of Molecular Science.

I should feel ashamed of letting them wait for too long time already.

Affirmative Action: Being torn between heart and reason

My reasoning brain tells me that affirmative action is something against nature. Because if nature would have allowed affirmative action, than the gazelle would have never developed into such a fast running and beautiful animal (intended to escape the predators), but evolution would have stalled at the stage of slow and lethargic goats. Instead, survival of the goats would have to be promoted by arbitrarily punishing a hunting cheetah with electric tasers, in order to fulfill a moral mission of supporting life of a creature in an unsuitable environment .

But one even does not has to go as far as to Darwinian evolution and survival of the fittest to find reasons against affirmative action:  Already on the submicroscopic level of macro molecular structure, the proper folding and hence functionality of proteins is governed by rewards and penalties which follow eternal, naturally given rules. Positively and negatively charged amino acids have a tendency of attraction, hydrophobic groups hide in the the center and hydrophilic groups are more exposed at the periphery of a protein. Affirmative action should encourage us (for the sake of justice) to equally allow also the hydrophobic amino acids to be exposed at the proteins periphery. Wouldn't it be morally wishful to give any amino acid - independent on its inherent properties- the chance to be "visible to the outer world" ? And indeed this would be possible, at least in a lab environment: Just heat up the proteins, and let them cool down slowly, and they will take any random configuration, with any of its amino acids having the same chance to pair with any other one, and equally likely being located on the outer surface or in the inner space.

By increasing the thermal energy (i.e. the temperature) the protein first unfolds to a more or less "anarchic" state. And when one reduces the temperature again, it will adopt all sorts of non-native meta-stable configurations (as shown by the local minima in the curve above), at which most of the amino acids occupy positions that are non-canonical but random. Here we might have an endless debate about what is canonical and what is not. Maybe one preferes one of the many metastable protein configurations much more than the native state. In fact you might like or dislike what you want, but fact is that the protein functions only in its native state. So whatever our moral subjectivity tries to tell us, there is only one configuration that works. And at this native configuration, all amino acids occupy their intended position. All the non-native states at which amino-acids are allowed to adopt non-canonical positions will in most cases lead to severe funtional impairment and diseases. In fact, some of the most devastating diseases - and some of the less treatable ones - are known today as being caused by protein misfolding. Alzheimer disease, Parkinson, Morbus Huntington, Cystic Fibrosis or other so-called proteopathies are of cause not the result of affirmative action by a benevolent human being, but of the detrimental interplay between genetic mutation, environmental factors and maybe a slow decline in  cellular check-up machinery. But the result is the same: The distortion of a native state and the formation of random and hence pathogenic states.

As a scientist, I therefore have big objections to a widespread use of affirmative action. I don't think it serves any good to promote - for good intention - a self-declared suppressed minority by discriminating the rest of the society. The human society is so diverse and complex that one can easily and arbitrarily define sub-groups ("tribes" to use a modern term), which by using questionable surveys can be shown to "suffer" from one or the other form of social discrimination.

Take for instance something very obvious: your home address. When we lived in London, our house was in the nice middleclass neighborhood of Battersea/Wandsworth. Our postal code was SW11 2AZ. A friend at work then asked me how it feels to live in such a wealthy borough.  Wealthy boroug ??? I asked him, after I had been involved in a fight with a drunken neighbor a few days before. It appeared that SW11 is in general considered to be of a good socio-economic background, and indeed just a few hundred meters away lived bankers, layers and folks from the media business. I was told that with my address and the SW11 postcode, I could easily apply for a well paid job in the financial industry. In the UK (and apparently other coutries like the US as well) your address postcode is used as a synonyme for your social status. On the other hand, of course, living at the "wrong" postcode (for instance Bethnal Green E2 6AU or Peckham SE15 5RJ) can be a really obstacle if you want to get a good job or intend to apply for a mortgage ("location, location, location, that's what counts"). When we believe in the beneficial effects of affirmative action, then we should turn this upside down and provide special quota of job positions or mortgages to be given to applicants from "dodgy postcodes".  With my SW11 postcode, I would have than been blocked from getting a good job or an affordable mortgage. But wait, our address in Battersea/Wandsworth was Jansen Walk 13, and isn't number 13 known to be considered also a bid scary ? Maybe I should have tried to promote myself as member of the discriminated tribe of No.13 residents. With some lobby work and some social media activities it should be possible to raise enough attention to fight for my (or OUR) case. At least in the case of getting a negative answer to a job application I could accuse the employer of discrimination because of my house number 13.

Janson Walk 13 in London SW11 2AZ: Excellent postcode, but suspicious house number.

Affirmative action is not such a big issue here in Germany, (except for womans quota) and maybe that was the reason that against my own judgement I recently followed my heart and not my mind. It happened at the refugee camp nearby, where I regularily help the school kids of the asylum seekers with their home work. And sometimes the parents of the kids also ask me for help with the language or with some beaurocratic issues. Nilab, a young mother from Afghanistan initially wanted me to help her with the language. She currently attends an integrative school to make her fit for a proper job training. For this, she already applies for apprenticeships as construction draftswoman. After a written application at a technical college she was asked to participate in an online test (obviously, the college forwared all applications to an assesment center).  Nilab was pretty nervous, considering that she is still not 100% familiar with the German language, and the online test requires a really quick understanding and answering.  So I agreed to "assist" her with the online test, which of course is against the rules. And "assisting" did not ment explaining her the question (which would have taken much to long), but I answered about 80% of the questions myself. I knew that this was not right, somehow in violation of my feeling that one should not positively discriminate a person to provide her with an advantage in a competitive situation.  I found the proper term for my doing, "Affirmative Action" only recently in the book "12 rules for life " by Jordan Peterson. Whereas in many points I can agree with his arguments, in the special situation of Nilab, a war refugee from Afghanistan, who is running her young family, living in a single studio of a refugee camp, learning a difficult new language, and above all is committed to learn a good and ambitious profession I saw no problem of promoting her against many obstacles of a western society.

Big Data shows Male-Female Imballance in Arts

Just for fun, and because the time between the years (i.e. 25th of December till 6th of January) generates silly ideas, I tried my first big data analysis today. I was inspired by the frequent notion of woman curating arts exhibitions. Was it just my selective perception, or is there something real behind ?

I used a public German website that provides information on all arts exhibitions during a selected time period. The site http://www.kunstausstellungen.de/suche/ I searched for all exhibitions between 01.01.2018 - 31.12.2018. I got a long list (perhaps still anything from complete) of 210 events, covering private galeries, municipal exhibiton halls and big and famous museums of national and international fame. Of those 210 exhibitions, 181 could be associated with a single artist (the remaining 29 were group exhibitions). Counting the male and female artists, these are the results:

144 male artists (79.6 %)

37 female artists (20.4 %).

The common (PC) interpretation of such a gender inequality is always, that men in their networks support each other, and restrict access of the talented woman. 

Well, we all know who selects the artists to be exhibit in museums and galeries, and these are the above mentioned curators.  

Thanks god, at least for some of the 210 exhibitions, also the names of the curators are listed in www.kunstausstellungen.de. But in particular the big and famous institutions (like Munich Pinakothek, Schirn Kunsthalle Frankfurt, Museum Ludwig Koeln etc) don't like to give names. But of the 123 exhibitions were the curators are known, the picture looks almost like a mirror image than what I found for the artists. Here the gender distribution is as following:

34 male curators (27.5%)

89 female curators (72.5%).

In a nice graphic as the consulting folks do it their whole life through, it looks like this:

Distribution of men and woman among artists and curators of 210 randomly selected exhbitions in Germany (2018) 

So this simple analysis easily disproves that male decision makers (i.e. curators) are responsibility for a larger presence of male artists in public life. At least in Germany, and at least in the year 2018, there must be another reason for the imballance of male versus female artist. The same is also true for film directors, and even more for the conductors of orchestres or composers played in the concert hall. 

Other interpretation are required, since if one wishes to reach an equal representation in the creative business of male and female actors, one has to understand the reasons for the current un-equallity. And at least the stereotypic explanation that influential men support only other men and at the same time suppress woman, seem to be vastly wrong.

More Light, (please)

From yesterday on (December 22nd or winter solstice), day length increases again (at least north of the equator). This gives me more happiness than
More sun increases our vitamin D and serotonin level, whereas Christmas usually only increases our caloric uptake.
Anyhow, to be a nice and friendly son, I took the bus today from Munich to visit my parents and sisters family in Berlin. No snow, unfortunately, so we will all sit together and tell stories of our rich skying adventures from the last 40 years. These are our Christmas carols.

Christmas festivities, which the early christian missioners set for shear marketing purposes on the same days as the pagans celebrated jule feast and the persians and ethnicities following mithraism celebrated jalda.

Higher Individual Religiosity Linked to lower Science Literacy

Past research suggests that religion and science may conflict on which is a better tool for explaining the world. This conflict implies that religiosity might negatively impact both attitudes toward science and science knowledge. However, past research has focused mostly on religious affiliation and has not consistently identified such a relation using a general religiosity measure that assesses religious beliefs and religious practice. A meta-analysis done at Rochester University recently published in PlosOne shows that religious people know less about science, possibly because they view science less positively. Surprisingly, parental religious beliefs were related to their children's attitudes about science nearly 20 years later in life.Using two large, nationally representative datasets as well as two original datasets, and controlling for relevant demographic variables, four studies (N = 9,205) showed that general measures of religiosity are negatively associated with science knowledge, a relation that was partially mediated by an association between religiosity and negative attitudes toward science. Study 2 also showed that parents’ reports about their religiosity and its role in their children’s upbringing predicted, some 20 years later, their children’s attitudes toward science. The studies are correlational but the longitudinal relations in Study 2 suggests that religiosity might undermine science literacy.

Mediation model depicting the relationship between religiosity, science attitudes, and science knowledge in stud 1.

Standardized coefficients are displayed; coefficient in parentheses is the total effect before controlling for the mediator; ^†p = .050, **p < .001.

Tim Berners-Lee, the brain behind WWW, proposes the next step

"I’ve always believed the web is for everyone. That's why I and others fight fiercely to protect it. The changes we’ve managed to bring have created a better and more connected world. But for all the good we’ve achieved, the web has evolved into an engine of inequity and division; swayed by powerful forces who use it for their own agendas.

Today, I believe we’ve reached a critical tipping point, and that powerful change for the better is possible - and necessary.

This is why I have, over recent years, been working with a few people at MIT and elsewhere to develop Solid, an open-source project to restore the power and agency of individuals on the web."

Tim Berners Lee created the world wide web in 1990, while working as external contrator for CERN. I'd be curious as to what degree the inflationary use of Twitter and other social media by Donald Ivanovich Trumpowski has prompted JB Lee to suddenly become so critical.

CNN wont make me feel guilty

Without advocating a militant Green-Peace agenda and complaining about the modern society with its addiction to more and more convenient life style, I usually feel quite in good partnership with the world and nature. I hate fast food, burgers, any convenience food (because it usually tastes like shit), I use my bike to ride to work on 95% of the time of the year, and we heat our house with renewable energy (wood pellets). And of course as good citizens, we separate our domestic waste into recyclable and organic stuff.

So in general, I have little reason to feel environmentally guilty as a member of the developed world.

But today, while watching me most favorite news channel CNN, I nearly found myself sitting right in the dock accused of spoiling the world with a torrent of micro-plastic. They argued that one of the most ignored sources of plastic waste in the environment (and finally in the world oceans) is CHEWING GUM !!!!

Shit, I thought, now they got me. Since childhood I am a regular chewer, since I could convince my West-German uncle to regular send me Wrigley's Hollywood, Juicy Fruit or Fix and Foxy for doing something good to his nephews teeth. An estimated 50 years of regular chewing gum consumption, one 50 gram pack per day, would amount to a huge 900 kg mass. I guess one would need a truck to carry this away, and most likely the local EPA authorities would classify this as hazardous waste, and charge me 10 x times more for its removal than what it had originally costed in the supermarket.

After sorting out what might have happened with 900 kg of chewing gum after I chew out all of the peppermint and juice fruit flavor from it, I realized that in fact I acted environmentally friendly right from childhood on, since I hated to spit out the chewing gum on the street or in the waste basket, but used to swallow it instead. So now the question arises what happened with 900 kg of chewing gum (which according to CNN is made out of synthetic rubber) in my stomach and further down the intestinal tract ? They argue that after it is broken down into tiny pieces, it accumulates in vertebrate organism such as fish or human beings. But this would violate the physical law of conservation of mass, since I myself weight 71 kg, and the 900 kg chewing gum must have left a trace. Without going much into detail, I also can confirm that no chewing gums ever left my body together with the other types of excretions. Not even the clinical analysis done during regular medical check ups gave any reason to suspect of micro-plastics in the various biological samples that I provided to them.
So it seems that our digestive system is able to degrade chewing gum completely and even turn it into something nutritionally useful. So maybe each pack of chewing gum should carry a warning saying: "To protect the nature from micro-plastic, please swallow the chewing gum after use".

Another such victory and I will be totally ruined ...

“Victory belongs to the most persevering” (Napoleon Bonaparte)

What would really interest me, if Napoleon coin this phrase before or after his invasion of Russia ended in a completed desaster and half a million french soldiers losing their life.
One should always be cautious with the egocentric and arrogant reflections of great man AND woman, in particular when they have just reached the climax of success, usually before they have to deal with the first strokes of fate. I don’t know if , on average, men are more prone to this. But there are also “successful woman” who think that they have to teach the whole world how to do it right. Usually it is just a matter of time before the house of cards start to deteriorate. Have a look to the short period of fame around the THERANOS company and its over-hyped founder Elizabeth Holmes. Still in 2014, Homes was profiled in Fortune and subsequently featured in Forbes as “the youngest self-made female billionaire in the world.” In reality, however, the company’s technology was dangerously flawed and produced erroneous results, although that did not stop Ms Holmes from launching a service that carried out tens of thousands of tests.
Read the story by John Carreyrou in the New Yorker and follow a reading at YouTube

And I think I should soon write about some fellow scientists I know myself, who were once placed on a pedestal, only to take a plunge. I would not say, however, that they experienced a sort of great misfortune. This might also happen, but usually people can recover. What is more characteristic is that people with an initial phase of success start to lose their own self-control, ignore warnings by others, and in particular in science they develop the attitude of "Fake it until you make it". This way, they become so much convinced that they are destinies darlings, that whatever they do, it must be their next big victory.

Is Trump the only one lacking a conscious will ?

In reponse to N:

Hello N., this all amounts to the problem of free will, i.e. how responsible one is for the decisions he/she makes. In academia, this is still very controverse discussed. In the most extreme version, D.M.Wegner rejected the idea of a human free will altogether. He argued that our decisions are all governed by biochemical processes, leading to neuronal activities, which the physical body (muscles, vocal organs etc) have to follow. When we believe in our own free will, we might be misled by introspection illusion. But one can also find certain arguments against this reasoning. There are human conditions (mental disorder such as Tourette syndrome or addictions such as alcoholism or eating disorders) where people really feel driven by a sort of evil force to do something they don't want to do (unvoluntary). And they are fully aware of themself acting against their own will.
One can probably find arguments pro and against the general capability of people to make free decisions, in particular in a situation when one follows instincts rather than reasoning.
But if I understand properly your question, it has more to do with "Responsibility". And this means if one is allowed to sanction or punish a person for his/her evil activity. This is a moral question, and it definitely can vary in different times or social contexts. But one can also be indirectly be punished, for instance by refusing him/her certain jobs or career paths. For instance being an alcohol addict is not a crime, and in fact deserves psychatric assistance, it is very likely that he/she is refused to become a teacher. And if one easily looses self-control in an argument, you might blame the genes or hormones for this. But he/she might have bad chances to make a career in politics (I would not call D.Trumps max 4 years in office a career, I think it is rather a dead-end road). So there are most likely medical, psychological (childhood), or social reasons, which one can find for Trumps irresponsible activities. But these should not lead us to see him as a poor victim of his social background, his alcohol addicted grand-father, his poor grades in school, his physical ugliness, and give him a bonus as politician.
Best regards, Micha