A new book in Endocrinology

In General

These days I am burdened with the correction of The Endocrine System, our book in an English version. We decided on American English and had to adopt names and terms to that language. Furthermore there were many tiny mistakes in the translation process which have now been eliminated. Thanks to Stuart Evans who has the tremendous job of copyediting my translation. I am fairly optimistic that we will meet the deadline end of the year, and that the book will be published in the middle of the next year.

In the meantime I have read many different articles some of them very interesting on the endocrinological site: a review on gonadotropin inhibiting hormone (GnIH) in General Comparative Endocrinology  which is not heavily involved in man, but in birds controls the Gonadotropin releasing Hormone (GnRH) due to the season with melatonin, the hormone that measures the night length and thus beginning of spring when reproductional activity is initiated. There was the paper of Krause et al. in Nature  on the origin of Europeans which is astonishly complex and full of molecular biology some issues beyond my understanding. The list of contributors is enormous, all the people who privided samples. I still donot know where the meeting was where the data were presented first. And many more papers, however, none catching the eye.

How best to attack a frog being a bat:

In General, ,

Some times the ways we gain our knowledge are intricate: In Nature this week there was an article about fructose-1,6-bisphatase (FBP1) and its role in renal carcinoma which caught my eyes. But today I will not tell this story which is highly interesting mostly for the reason this enzym is essential in normal renal metabolism and inhibits cancers, but fall back to a comment in the same edition “Wooing frogs are bat bait” about a paper in The Journal of Experimental Biology “Risks of multimodal signaling: bat predators attend to dynamic motion in frog sexual displays” which is unfortunately not online.

It is about the tungaro frog (Engystomops pustulosus) and its predator, the fringe-lipped bat (Trachops cirrhosus). It was known before that the bat hunts tungaro frogs. The author Wouter Halfwerk in Panama and his team wanted to know whether the bat is going after the remarkable vocal sac of the frog or its calls. They did not use living frog for this task but dummy frogs which had a vocal sac blowing out and called or dummy frogs which just called. The bats attacked preferentially the dummies with a vocal sac which were calling. I have asked the author for the paper and he sent it to me.

I find the issue interesting for several reason. These are tiny frog (3 cm in size) otherwise the bats which are just 7 to 8 cm long would not be able to catch them and fly away with them. The bats use their optical and echolocation cues to locate male frogs unless European bats which use mostly echolocation. And the third why this is interesting (and found its way in Nature) there is the tremendous risk involved being a male frog and call for a women. You might be caught by a bat before you succeed to copulate. It would be interesting to know whether selection is against the most proud callers and the most foolish that way.

The subject gives you ideas.

Read also the Inside JEB by Kathryn Knight which is free with a picture of the Robofrog.

A supercomputer to enroll patients

Database Management, Genetics

The Mayo Clinic must be really desparate. Otherwise the news about a partnerships of her and the IBM and its Watson supercomputer is not understandable. Forbes reports about this new cooperation. Or the article is a mess: At the origin is the search for an effective search for patients. That the doctor needs an hour to read the study protocol is very optimistic. Normally it is presented at a meeting which takes one or two days. Then there is the issue of informed consent which should be individualized and performed not by medical staff but by a doctor involved and listed in the study. That alone should take more than 30 min, otherwise it is not thoroughfull and complete. You see that streamlining the selection process will not save very much time for the doctor.  Not in the way the Mayo clinic hopes.

 

Mixed origin for Europeans

Genetics, History

 The historic origin of Europeans is obviously much more complex than initially thought. Sciene reports from a meeting of biomolecular archaeology: Johannes Krause (Tübingen University, Germany) presented data that the European history started as late as there was migration from Africa: some 60000 years ago. These people were not the first settlers in Europe. They met the Neanderthals. And they were gatherers and hunters. These hunters eventually were invaded 9000 years ago by farmers from the Middle East. Note the farmers invaded the hunters/gatherers and not vice versa. To the great surprise of scientist involved there is a third source of DNA of Eurasian origin which was found in Scandinavia and Letonia, but not in the South of Europe. This “ghost” DNA was then found in boy from Sibiria who died some 24000 years ago.  You will not find a person with the same genome today, but part of it is present in North America and in Europe. The picture is a crude scheme of this development. We were told that an article will appear soon and we will tell you about.European Origin

Has an Italian avian virus affair the potiential for a biothriller?

In General

It has ingredients of a thriller and might be picked up by Hollywood: A incredible story of crime, bribe and corruption is revealed from Italy. Where else, you might think. It involves the avian influenza viruses in different strains, scientists who sold
the viruses to an interested company, vaccines from these strains which were illegally sold to farmers, state officials who did not interrupt the illegal trafficking. 40 people involved so far. It is a biothriller if all the allegations can be substantiated.

Science this week reports an investigation taking place in Italy in the last 10 years. It claims that the Merial company has bought avian virus strains from two virologists,
Ilaria Capua and Stefano Merangon, and developed a vaccine. Against European law this vaccine was sold to Italian farmers. This is forbidden for the following reason: Infected
and vaccinated animals can not be distinguished and would be culled anyhow. Thus, the animals when tested would be killed independently whether they were vaccinated or not since the appear infected. It might be that they will not be tested when they show no sign of the illness. Furthermore the report raises the possibility that the researchers have deliberately spread the virus which endangered not only the animals, but some farmers got ill.

The person in the center of the investigation, Capua,  is now a member of Parliament and enjoys immunity. One person, Romano Mirabelli, former general secretary of the Ministry of Health stepped down from his post. All the others refute the allegations, on the contrary, they sue an Italian journal, L’Espresso, which has leaked the story. Meraial declines any
illegal action.

Do you believe this? Science has to report more.

Implantation revisited

Biochemistry, Endocrinology, Nuclear receptors, ,

Successful fertilization is only one half of the coin, implantation is the other half that is necessary that pregnancy can begin. As it is extremely difficult to observe normal human implantation not only for experimental, but for ethical reasons, too, the mouse is for several reasons the model of choice: implantation to occur at the blastocyst stage, only a narrow window for reception, decidualization of the stroma, invasion of the embryo into this stromal bed and a common hemochorial placentation.

In an excellent review in Molecular Endocrinology, Pawar, Hantak and Bagchi have summarized the actual knowledge about mouse implantation biology: crosstalk of estrogens and progesterons for proliferation and differentiation, estrogen and progesteron receptors at the start of signal cascades, paracrine factors as LIF, IHH, STATs, FGFs and EGF, the role of the stroma and the epithel. How the (experimental) lack of some of these proteins leads to infertility is convincingly described. It has not been a great surprise that they offer a explanation for endometriosis the disease where there is aberrant decidualisation in the peritoneum of women patients.

A must for gynaecologists!

A Structure for NO Synthase

Biochemistry, Immunology, Structure determination,

The NO synthases structures have been elusive so far. As these are fairly complex structures with different functional domains this is not very surprising. The role of these molecules in signal transduction is established and errors therein might lead to hypertension, erectile dysfunction, neurodegeneration, stroke or heart disease.

A PNAS paper this week has solved all the three structures of eNOS, iNOS, and nNOS. They used a high through put Electron microscopy single particle method to obtain the many different conformation in which these enzyme occurs. They have also solved the role of calmodulin in the enzymatic reaction and shown why the binding of calmodulin is a time limiting step (for two of the enzymes). Given the complexity of the molecular structures shown and the different confirmation obtained this is some nice piece of work: from the structure to the function. Beautifully done!

At least a bacterial ligand for the ArH

Bacteria, Cell physiology, Immunology, Innate defense, Tuberculosis, ,

The aryl hydrocarbon receptor ArH is a nuclear receptor and as such a transcription factor which has been shown to be activated by dioxins and other environmental toxins. Upon ligand binding it is translocated to the nucleus, binds dioxin responsive elements on the DNA, and triggers gene activation notably of CYP 1 monoxygenases, which in turn degradate dioxins to more soluble compounds thus facilitating their removal. It not only binds dioxins, but polyaromatic substances like benzopyrenes in tobacco smoke and a variety of plant substances like e.g. indigo.

Its structure as basic helix loop helix (bHLH) protein has been determined.

It has been questionable how a molecule with such a ligand profile has survived evolution. Groups from Berlin have now determined bacterial secondary products as ligands of the receptor, too. In a paper in Nature this week they describe Pseudomonas aeruginosa phenazines and Mycobacterium tuberculosis phthiols as ligands which activate anti-bacterial responses in mice. This role makes much more sense in terms of evolution. It would be more beneficial to have the protein than not to have it. Nicely done.

A StAR is everywhere!

Biochemistry, Endocrinology, Translation,

Steriod acute regulator protein (StAR) is the protein involved in the time-limiting step of stereogenesis since one molecule StAR must be produced to transport one molecule cholesterol  from the cell membrane to the mitochondrium. There, the side-chain cleavage enzyme converts the cholesterol to pregnenolone to begin the steroid synthesis for androgens and estrogens, mineralocorticoids and cortisols. StAR is therefore an important molecule for the Endocrinologist. Whereever StAR is expressed, steroids are supposed to be made. Its characteristic structure – a pocket to acquire just one molecule of cholesterol – has been crystallized and determined by X-ray spectrometry. What is much less known that it has homologues throughout the animal kingdom, even other taxa share the structure which is thus fairly old and that is used not only for cholesterol, but for numerous lipids, too.

Strange enough, a molecule which is at the beginning of a specialized reaction chain such as steroidogenesis is widely used. Sometimes the introduction to an article is an eye-opener: In Current Biology the paper by Schrick shows just such a case. They are concerned with StAR homologues in the plant Arabidopsis and their role as transcription factors. Maybe not so interesting to the general audience, but the introduction resumes the role of StAR and StAR-like proteins fairly well. Recommended.

90 Years of Renal Dialysis

History, In General, Medicinal technique,

Correct are the dates for 90 years of renal dialysis. A German doctor used a precursor of todays technique in 1924 for filtration of blood to get rid of deleterious low molecular weight (mass)  substances. The semipermeable membrane he used – and which is in principle still used today while the material itself has changed – is permeable only to low molecular weight substances which will cross the membrane and which will be diluted in the process. High molecular weight substances do not cross the membrane. If you pass blood along through such a filter which has on the outside a liquid (e.g. isotonic salt solution) , then the unwanted products cross the membrane due to the concentration difference. You pump this liquid permanently away , then the salts will stay in blood since there is no concentration difference between the blood and the outer liquid, the unwanted products like urea e.g., however, will diluted into the outer liquid and reduced in the blood.

The method applies to toxins and is used during renal failure for whatever reason.

Georg Haas was the first who applied this method to a patient in 1924. While he treated up to 11 patients the method was dismissed by collegues because it did not heal the patient, “only” approved the symptoms. Haas was very much engaged as the clinic head that he could not spent any further time for dialysis.

The breakthrough came with Willem Kolff (NL) 20 years later who used the easily available cellophane tubes which were originally produced to make sausages.