In Science this week there is a paper by Brommer et al. from Berlin and Jena, Germany, who reports the structure of the enzyme dehalogenase from
Sulfurospirillum multivorans in complex with trichlorethane and a pseudo-vitamine B12 providing the cobalt ion for electron transfer. A Perspectives article by E.A. Edwards further explains the findings: the pseudo-vitamine B12 is protected from the outside by the dehalogenase and a channel of open for the substrate and its analog.
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Who we are
Sometimes it might be difficult to assess who I am, for examplt if I am seriously ill and dependent on other’s care, I feel like a baby. Or I might be fully absent due to heavy thinking or alcohol, and unaware of my surroundings. Then I will look most probably like the idiot who I believe I am not. But in the title of a paper in Current Biology, we learn very clear who we are: This paper is entitled “Rapid Evolution of the Cerebellum in Humans and Other Great Apes”. Thus we are just another great ape. I wonder whether that is fortious or not. I have not yet read the paper but the title stuck.
Anybody may decide whether the intonation stays with “Other” or “Great” or “Apes”, unfortunately I do not have an image of the author of that article. I would have added it, too.
(The images are all from Wikipedia and believed to be free. If otherwise I will change them.)
HIV vaccine, only fraud in Iowa?
A doctor in Iowa State University spiked the rabbits he had immunized, with human anti-Hiv antibodies to show that his vaccine was successfull; he was caught and faces now up to 20 years of federal justice, says a report by CNN of yesterday.
Obviously not enough criminal intelligence on the side of this doctor. Still one wonders where he got the human antibodies to spike the rabbits, and whether the test applied did not discriminate human from rabbit antibodies. How the head of department got suspicious? Maybe we will never get answers to these questions?
Sad!
The immune system in jawless fish
That sharks share the antibody structure with men is already known for quite some time. Whether other animals, earlier in evolution, have also antibodies and T cells like ourselves has been a open question. The answer is yes, but….
An article in PNAS from the Max-Planck-Institute for Immunobiology, Freiburg, Germany (with contributions from the Emory Univ. Atlanta, the Univ. of Maryland and from National Library of Medicine, NIH) reports in detail about one (of three) antigen receptors in lampreys. These jawless fishes (whether they belong to vertebrates is open to discussion) have a repertoire of different receptors, but unlike antibodies where the variable region is composed of variable and constant elements and linked by diversity and joining elements they are build of a variable number of leucin-rich repeats which form a structure which is reminescent of glycoprotein receptors with a very similar organization: Continue reading The immune system in jawless fish
Oxytocin for pairing — in mice
Oxytoxin is the hormone of social interactions, the mechanism of the interaction mostly unknown. Therefore, it is a nice surprise that Nakajima, Görlich, and Heintz from the Rockefeller Univ. in New York report in Cell on a newly identified subset of somatostatin interneurons from the prefrontal cortex of mice which bear the oxytocin receptor.
They silenced then this receptor in some mice. The females in these silenced mice with the oxytocin receptor inactive lacked the social interactions with male mice only during the estrus phase, when copulation would ensure progeny. The interactions with female mice were normal. In the diestrus phase interactions with males were not disturbed.
Similarily they could produce mice where the oxytocin gene was removed in the prefrontal cortex. The female mice showed the same deficit. Even mice treated with an oxytocin antagonist blocking the action of oxytocin had the same effect on the social interactions of the females thus treated.
We do not know whether oxytoxin is acting here in an endocrine way via the blood or as a neurotransmitter via synapses. It is not to far fetched to think oxytocin stimulating these interneurons is required – in mice – for social interactions leading to progeny although it is not in the paper.
A nice bit of information!
Phtalate exposure during pregnancy impairs insulin signalling – at least in rats
Phtalates are present in many plastics as softener and thus ubiquitarily distributed. They have been regarded as endocrine disruptors that means they will bind to for example the estrogen receptor and trigger that molecule to start gene activation. That has been shown for quite some time.
What is new in the paper of Rajesh and Balasubramanian in the Journal of Endocrinology is the detail of the analysis: They have looked for glucose in di(ethylhexyl)phthalate (DEHP) treated mothers and their pubs and found elevated glucose, as well as glucose and insulin tolerance. The analysis went to the insuline receptor, the insulin receptor substrate, to the glucose transporter, to all the molecules thought involved in the regulation of insulin and glucose. But not the proteins alone, the RNAs were measured, even the methylation of the DNA was estimated. And the message is very clear: with DEHP exposure in utero you will encounter a disturbed metabolism throughout life.
While this is true for rats I might be another situation in humans, but would you risk your kids health on the assumption that man is not a rat?
Nicely done! Worth reading!
The map in your brain
How can we know where we are? This question has for centuries pestered philosophs. In the area of GPS this now is no longer even a practical question, anyone with a smartphone can easily determine her/his position in space with unprecedented certitude.
However, what is technically possible, does not bear on the perception of space in the human mind. Agreed, that this would pose problem came not even to my mind. Therefore, the announcement of the Nobelprice to the three researchers John O’ Keefe (USA) and the couple May-Britt and Edvard Moser (Norway) comes as a surprise. But it shows that there was a question and already the solution these three researchers provided. I cite from the press release of Nobel Assembly at the Carolinka Institute (Nobelprizse.org):
The discoveries of John O´Keefe, May-Britt Moser and Edvard Moser have solved a problem that has occupied philosophers and scientists for centuries – how does the brain create a map of the space surrounding us and how can we navigate our way through a complex environment?
How to Control a Stem Cell
Stem cell biology for the general public is fairly obscure and the subject overwhelming for many reasons: It is the fact that stem cell autonomously divide and create cellular progeny that sometimes is again a stem cell, sometimes a cell matured along its predetermined cell fate. In the shop there are stem cells for any major tissue, at least for mice, and it is difficult to stay informed.
Therefore the review by Clevers, Lo and Nusse (Utrecht and Stanford) on An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control in Science this week is a good primer for those who are not part of the business. It gives you very basic knowledge on Wnt, its role in stem cell biology, its regulation, and finally the role of Wnt in assymmetric cell division. This is supported by very clear figures which I highly recommend.
Do not miss this paper!
BRCA1 – a new role
Mutations in the breast tumor risk gene (BRCA1) make individual susceptible to tumors not only of breasts and ovar, but of many different origins. This is due to the role of BRCA1 in the DNA repair mechanisms.
A paper in Molecular Cell shows now an additional role for BRCA1: It is involved when the replication fork gets stuck at an interstrand cross which is likely to occur in the presence of the drug Cisplatin. With the help of BRCA1 the CMG helicases, which unwinds the strand to be replicated, are unloaded. Then DNA can be repaired and finally replicated faithfully.
Nicely done.
Clock gene necessary for implantation
Endocrinologists are aware of the circadian clock since it determines the release of many hormone likewise cortisol in a daily rhythm. There are other rhythmic hormone releases not dependent on the circadian clock, for example the prolactin release in a circannual fashion, or faster pulses for hormones of the pituitary with one to three hours pulse lengths.
In short, the circadion clock is found in the supraoptic nucleus of the hypothalamus and concists of the RNAs and proteins Per, BMAL, Clock, and cryptochrome(s). These are generated and inactivated in a way that autonomously repeats about every 24 hours. It can also adjust to a light-dark cycle.
What is new in a paper by Liu et al. from the Bradfield labaratory at the Univ. of Wisconsin in PNAS is that steroidogenesis — the synthesis of steroids –is coupled to the clock protein BMAL-1. They show that female mice which fail to express the BMAL protein in steroidogenic cells are not capable to implant an fertilized egg into the uterus and fail to generate progeny. When they transplant one normal uterus into these animals by exchanging one defective with the normal one, these mice will again produce offspring. The defect can, in addition, be rescued by soluble progesterone which shows that progesterone is a determining factor in nidation/implantation.
These experiments are nicely done. The conclusion, however, that the hormone production in the ovar is decisive is too far fetched: They have eliminated the entire steroidogenesis in these mice, therefore the only hormone producing organ of the rescued animals is the transplanted normal ovar. Progestone or other steroid hormones being soluble and acting far away from their place of synthesis could under normal conditions be generated in the adrenal or somewhere else as well. The ovar is by far not the only organ with progesterone synthesis. It will be difficult to answer the question whether the ovar’s progesterone synthesis is required for implantation, since a block in the progesteron synthesis will likely block androgen, estrogen and corticoid synthesis. You would need the 3ß-hydroxysteroid dehydrogenase 1 inactive only in the ovar. And still the animal needs androstendione substitution to allow ongoing testosterone and estrone and thus estradiol synthesis.
Worth to read!