All posts by bk

Parathyroid hormone essential for gill formation in zebrafish

A paper by Kwong and Perry from Ottawa in Endocrinlogy reveals that parathyroid hormone 1 (PTH1) in addition to its effects on bone formation is also necessary for the development of proper gills. This is a nice addition to the functions of PTH1 as a regulator of calcium availability.

The paper demonstrates convincingly this new role for PTH1. Recommended!

Tools as old as 3.3 Million years – question remains who used them – no homo at that time

The theory that tools are a characteristic feature of homo is challenged: At a site near Lake Turkana in Kenya a team  led by Sonia Harmand of Stony Brook University in New York found a number of artifacts that were by flaking. However, the place was dated later 3.3 Millions year ago, eliminating as the possibility that a homo has done the flaking since they did not exist at that time. The run is now open for the any ancestor who preceded the homo genus and still used tools. (from nature)

South Americans – only one wave of settlers?

Nature reports: The meeting of the Society of American Archeology listened to Dr. Fehren-Schmitz, who presented the sequencing of human bone found in Peru at a site called Lauricocha. The remnants are from five individuals, two of them died around 9000 years ago, a third 2.500 years later and another a further 2300 years later, the fifth was dated. The sequences were derived from mitochondria and from the Y chromosome.

The results are in agreement with a single wave of migration. There might be earler migration but not necessarily. It is now up to investigator to sequence the actual indigenous population to see whether there are dicrepancies to this determination

Angiotensin-Receptor in 3D

Almost all the physiological actions of angiotensin II, the effective mediator after renal renin has cleaved the precursor angiotensinogen and the angiotensin-converting enzyme (ACE) of the lung has liberated angiotensin II from angiotensin I, are mediated by by the angiotensin II type 1 receptor. It is a G-protein coupled receptor (GPcR) like many hormone receptors of the rhodopsin family (Omin 106165). Like many GPcR it has been difficult to crystallize to dertermine its threedimensional structure.

Zhang and colleagues from Los Angeles and other places have now used femtosecond chrystallography to reveal the structure with the high-affinity agonist ZD71DD as ligand.

AT1R (image with the free tool Cn3D from NIH and the sequence 4YAY from MMDB)

The depicted image is nothing compared to the images in the paper. You can, however, see how the ligand fits in a binding pocket in the transmembrane domain with its numerous helices. The domain on top is a extracellular domain.

The structure should help to resolve questions concerning the regulation of blood pressure, how mutations influence the binding of angiotensin II and may help to develop other drugs.

This is a very nice piece of work. Highly recommended!

Melatonin required to fall asleep – in fish

Reading about circadian rhymth in flies I happened to see the Neuron paper by Gandhi et al. about melatonins role in fish. Melatonin – the hormone of the pineal gland – has been shown already to be active in the determination of seasons, its amount produced during the night being measure in so-called calendar cells in the vicinity of the hyphyseal stalk. Now the authors in Pasadena show that melatonin is necessary to fall asleep: zebrafish without the critical enzyme of melatonin systhesis: aanat2 (arylalkylamine N-acetyltransferase 2) take much longer to fall asleep and do not sleep as long as control animals.

Whether the data do apply to men and mammals is open. This is, however, a nice piece of work. It does not explain while I can start sleeping extensively during day time when there is not any melatonin in my circulation.

Estrogen in insects: again — No Nein njet non

Another paper in Gen.Comp.Endo. addresses the issue “Vertebrate estrogen regulates the development of female characteristics in silkworm, Bombyx mori”. While they use vertebrate estradiol to see its effect on vitellogenin expression, they also analyse whether endogenous estrogen is present. They claim that an endogenous estrogen analogue exists in B. mori.

Very strange, to be polite. Or bullshit, to be honest. The silkworm genome has been almost fully sequenced. The side-chain cleavage enzyme (cyp11a1) are definitely not present as well as the aromatase (cyp19). Without these no chance for any estradiol or analogue.

What they may have found is an estrogen receptor agonist. The literature is full of these. They are usually called endocrine disruptors since they disturb normal estrogen functions. The structures of estrogen receptor agonists are diverse and no clearcut picture has emerged to my knowledge. Such a molecule may well be present in Bombyx mori.

Caution! Not always when estrogen is claimed there is estradiol present!

Not seeing what is obvious

Sometimes we need an eye-opener to notice things which are in our reach and still beyond comprehesion. We smite our forehead and confess how could we be such blinds. The paper “The essence of female–male physiological dimorphism: Differential Ca2+-homeostasis enabled by the interplay between farnesol-like endogenous sesquiterpenoids and sex-steroids? The Calcigender paradigm” by Arnold de Loof in “General and Comparative Endocrinology” is such an eye-opener. It puts the Calcium (Ca) metabolism in an entire new prospective. De Loof argues that Ca is a toxin which has to be kept away and that reproductive activities such as egg laying and mild production have developed for this purpose since the Ca that an egg contains and which is in milk deplete the organism of much Ca.

The Ca concentration in blood is in the range of 1-3 mM in man and are conserved in evolution. In the cell however, there are only 100 nM, ten times less. The cell membrane is partially permeable for Ca so that the cell always has to deal with an excess of Ca which is permanently depleted by Ca export or/and storage in entoplasmatic reticulum vesicles.

The surprise of the paper is that de Loof finds a function for farnesol in eukaryotes: A Ca transporter in the ER that is only regulated by farnesol-like substances is common to vertebrates and insects.

Whether all the ideas of the paper will survive experimental scrutiny is to be seen, but two ideas stick: Calcium as a toxin and its role or more to the point the removal of Calcium at the origin of reproductional activity.

The paper is open access and and a must.

Sirtuin protein at the start of GnRH neuron migration

The GnRH neurons are unique among the hypothalamic neurons that they originate not in hypothalamus itself, but in the vomeronasal organ of the olfactory bulb and move (in the mouse) between day 10 and 17 of embryonic development into the hypothalamus via the forebrain. When this wandering is impaired, there is not any GnRH synthesis in the hypothalamus due to missing GnRH neurons, a phenomen called Kallmann syndrome, and subsequently the patient undergo hypogonadotrophic hypogonadism.

In a report in Molecular Endocrinology this week Gabriel Di Sante and colleagues from Philadelphia with the help of Canadian coworkers from Ottawa describe in mice another protein involved in this wandering of neurons. They found that the Sirt1 protein is necessary to start the migration of GnRH neurons. Sirt1 is the analogue of sirtuin protein originally found in yeast as Silent regulatory protein and has diverse physiological functions. Sirt1 defective mutants are not viable and die in utero.

The paper shows that the migration is initiated intracellularly due to the interaction of FGF8 and the FGF receptor, Sirt1, and corstatin, whereupon the sirtuin protein leaves the nucleus and deacylates the cytoplasmatically located corstatin. This interaction then makes the neuron migrate. There are other mechanisms listed in the introduction of the article which effect the migration. But none is as near to the origin of the migration as this one.

A nice piece of work! Recommended!

Prediction of the prey’s path by dragonflies

Hunting a moving target involves reaction to the prey’s movement, so you would think. It involves, however, in vertebrates also a model how the prey may move, to be able to predict the possible flight routes. This model was thought to be lacking in invertebrates.

In a paper in Nature Mischiati and colleagues describe that dragonflies have this internal model, too. They show that vision is to react to the prey’s escape but underlying the dragonfly’s steering is brain model how the prey might fly. You have to keep in mind that dragonflies hunt in 3D and not in 2D as tetrapods do. We are proud that comet lander does find and land on the target some 100000 miles away, and use immense computer power for this task. Dragonflies have it all in their tiny heads.

The paper uses fly models in the lab as prey. It will be some time before it will be possible to test the facts on free flying dragonfly. But it is a nice piece of information already.