All posts by bk

Hormones and the Endocrine System

Endocrinology, Hormone book

Two days ago the new book has gone to the producer. It will be on the market in the middle of 2015. This version is in its major parts a translation of the 3rd German Edition with corrections with respect to invertebrate hormones. 

We are facing now a new production process. Whereas up to the 2nd edition the publisher took the pdf version for production, now they take the raw LaTeX files and translate them into XML. This process is not automatic and the LaTeX macros are not fully supported. Therefore the 3rd edition was more expensive than envisaged. To overcome these problems, I took care and succeeded to provide a XML version which can be then translated into any format you wish. The XML is far from perfect, but there should be something to do for the producer. However, it is complete and has all the references, and cross references, any figure (chemical structures included) either as png or in pdf and svg format, the citations and the index. Large part of it have already been expertly edited by Springer’s copy editor Stuart Evans. Thanks to everyone who provided information and expertise for the content and the LaTeX process.

Seeing that they see differently

Biochemistry, Cell physiology,

What we see is determined by the visual pigments of the human eye. We have often asked what our dog might see. Colour vision was thought restricted to the primates. Totally wrong. Thanks to a paper by Justin Marshall & Kentaro Arikawa in Current Biology we know now that colour vision is very common in the animal kingdom. There are several species that use a much broader spectrum to look at their surroundings. Honey bees for example can identify objects in the UV part of the spectrum. They have, however, three different photoreceptors like humans. Waterflees or the Blue Tit have four different ones the former sensing the whole spectrum from 300 nm to 700 nm. The latter misses some light in the infrared part. Horses and dogs have only two different photoreceptors, they are in way green–red blind. Dogs, however, have a much more discriminating capacity in the dark.

What comes as a surprise is that butterflies and other insects can differentiate the visual reception with up to 8 different photoreceptors. And this is not the end: Shrimps have 20: (cited from the paper)”Twenty receptor types have been defined: twelve for colour, six for polarisation and two with overlapping function for luminance tasks”.

An eye-opener. Nice and Recommende!

Gray matters in grass research

Brain, Cell physiology, THC

Whether long-term marijuana smoking has robust effects for the human brain has been a matter of debate. In a paper in PNAS Silbey and colleagus from Dallas, Frisco, and Albuquerque have addressed this question using “multimodal measures in a large group of chronic marijuana” smokers. They claim that marijuna smokers the longer the more have decreasing gray matter in orbitofrotal cortex (OFC).

This part of the brain (citation from wikipedia:)

is considered anatomically synonymous with the ventromedial prefrontal cortex.[2] Therefore the region is distinguished due to the distinct neural connections and the distinct functions it performs.[3] It is defined as the part of the prefrontal cortex that receives projections from the magnocellular, medial nucleus of the mediodorsal thalamus, and is thought to represent emotion and reward in decision making.[4] It gets its name from its position immediately above the orbits in which the eyes are located. Considerable individual variability has been found in the OFC of both humans and non-human primates.

The authors are very cautious to attribute these changes to THC. They also found increased connectivity within the OFC and suggest that the OFC gray matter is more vulnerable to the THC effects.

Recommended!

 

it’s an animal – still

Placazoa, Trichoplax adhaerens
Seawater aqurium in Prof. Fasshauer's lab
Seawater aqurium in Prof. Fasshauer’s lab; fishes are in uproar because they heard the fodder box shaken.

Yesterday, I visited  the laboratory of Prof. Fasshauer at the UNIL – Université de Lausanne. It was an interesting day in Lausanne. While Prof. Fasshauer is specialists in vesicles and SNARE, his wife is working in the field of an extremely tiny animal, Trichoplax adhaerens, a placozoan, which are very simple organisms consisting of only 6 different cell types. I have presented a paper in Current Biology earlier. I was very much interested in Trichoplax and they showed to me a beautifull seawater aquarium where they have among other beautiful animals algae growing on the glass slides (on the left and back site of the tank) and found them eventually full with Trichoplax.

When I will eventually visit again the lab there will a bino with which it will be possible to make pictures. This time I will only show the image from the wikipedia. You can see the cells moving on the petri dish.

Lichtmikroskopisches Bild von Trichoplax (Individuum ca. 0,5 mm im Durchmesser) Oliver Voigt (2006)
Lichtmikroskopisches Bild von Trichoplax
(Individuum ca. 0,5 mm im Durchmesser) Oliver Voigt (2006)

 The point is that this animal is one the earliest metazoan we have. There are poriferes, there are choanaflagellates, but that’s it, earlier goes not 🙂 . And the group of Prof. Fasshauer found out that they can be stained with antibodies which are specific for neuronal structures they donot have. The studies about this phenomenon will be extended in the future. It is a very exciting project from the point of evolution and of endocrinology, too.  We had a lot of talk about methods and technology.

When timing matters

Biochemistry, Cell physiology, Circadian Clock, Drug, Translation

When you are an endocrinologist you know that hormones are released into the circulation in pulses and that melatonin is only produced in the dark, that glucocortoids concentrations in the blood are high during the night and low during the day, that many hormones have their rhythm. Every hormone has its time, as the prophet sayed.

However, what has not been known until now is that to the same extend more than 40 % of all genes are expressed in a circadian (day long) rhythm.  Zhang and colleagues measured in the mouse ( and the might be the only shortcoming of the study ) the gene expression with arrays to determine many gene simultaneously in every hour of the day and night. They found 43 % of all genes expressed in a circadian rhythm. They also determined noncoding RNAs  and found 1000 of them cycling.

There are consequences for medicine and therapy: The targets of the top most drugs are expressed all in (specific) rhythms: When a drug like aspirin for example is taken at the wrong time, it would be gone before the target is fully expressed. The scale of this problem seems tremendous. Any pharmaceutical company has to do its home work again. But on the other hand, therapy might become more reliable which would be a large improvement.

The circadian rhythm in the 12 organs analysed are quite different. It might take some time to get used to the thinking that genes in question are not stable during the day but change the level of expression. It will be interesting to follow the aftermath of that paper. The paper is open access and therefore free to everybody.

A must.

 

Who is my neighbor?

Biochemistry, Cell physiology, Protein folding

To form stable connections to your neighbors is  a way to make daily life predictable even if the relations are inimical. Looking at an amino acid in a three-dimensional structure is likewise to look for neighbors at the amino acid level. This problem of protein folding has occupied biochemists for quite some time. Even with the biggest supercomputers it could not sufficiently be simulated.

In a Perspective article in PNAS Englander and Mayne from the Univ. Pennsylvania present the problem and the new technology which has helped to solve at least one structure’s folding. They show what is possible now and what cannot be done. At the origin of the problem are small units of folding which the form or donot form extended structures. Deuterium/hydrogen exchange experiments and their fast time-line-records are what can give information about the ways protein fold. This is an actual picture what has been achieved in the field. It is more that one could expect from the outside, but not enough to solve the puzzle. It seems at least that a mechanism of protein folding has been found.

Worth reading!

How an ABC transporter gets rid of arsenic

Biochemistry, Cell physiology,

Not only from Agatha Christie’s books we know that arsenic is toxic. It is even a carcinogen and, most importantly, is contaminating the groundwater in a lot of countries. Removing arsenic from water and food is a tremendous task and will improve the health of many people.

Therefore a paper on an ABC transporter in rice which excludes arsenic from the grains is a welcome addition to the tasks involved. ABC transporter are evolutionary very old molecules which transports ligands across membranes with the help of ATP. Song and colleagues found out that the rice (Oryza sativa) the ABC transporter C1 (OrABCC1) lowers the arsenic content in the grain therefore the food is not contaminated in the way the water it is grown is. The molecule is also expressed in other parts of rice. When genetically engineered into wheat, it could transfer the resistance to arsenic. In rice, its expression is increased when arsenic gets higher. It is arsenic specific, since when knock-out the arsenic resistance was gone but not the cadmium resistance.

Immunologists will know ABC transporters involved in the transfer of degraded peptides into the ER to be loaded eventually into the histocompatibility class I molecules. Obviously, they can do much more.

Recommended!

“Sport ist Mord”

Biochemistry, Cell physiology, Endocrinology

Obviously there is no easy translation for this German proverb: No sports, no sports is what Churchill said. Sport’s a killer, sport is murder doesn’t have the rhyme the German version has. Nevertheless, the people who say so are totally wrong. Exercise was the base that the human race could go where we are now, a overweight race with many problems due to sitting most of the time in our desk chairs while exercise is beyond the horizon and reserved to leisure. It had been just the opposite: running and hunting was the professional occupation and sitting at the fire the leisure. How time changes!

I was lead to this excurs by a review in Cell: Integrative Biology of Exercise by Howard and colleagues from Melbourne (Australia), Rochester (Maine), and Stockholm (Sweden). They bring the different aspects of Exercise into an systematic overview and nail the “Major Signaling Pathways Involved in the Control of Skeletal Muscle Hypertrophy and Mitochondrial Biogenesis” down to one image. Exercise involves “Complex and Redundant Physiological Control” in CNS, muscles, heart, lung, in the metabolism and neuroendocrine systems. The pictures are straight forward and very instructive. 

Recommended!

Once a month …

Cell physiology, Development, Endocrinology, Oocyte

The selective activation of only a few of several hundred thousands primordial follicles to mature into an oocyte is a riddle which has not at all been solved. In a paper in Current Biology Chang and colleagues from Gothenburg, Sweden, place this decision onto the microenvironment of the primary cell, especially the few primordial follicular granulosa cells surrounding each primordial follicle. They show that mTORC1 activation and Kit ligand signalling are required steps in the activation, mTORC1 defective animals never develop primary follicles, the primordial follicular cells die.

They do not answer the question which follicle is to grow, but placing the decision to the surrounding is a paradigma change and will focus the experiments and the discussion away from the oocyte precursors which cells seems more or less “only” to react to the surroundings. Given that this cell is dormant and needs strong signals to be activated this is comprehensible. At least we know now who the cascade of events is initiated.

Whether this has consequences for in vitro fertilization we will see. The question why so few follicles are activated during the reproductive life of women is not answered by this article.

Nice and recommended!

Mother’s age a newborn’s risk factor — due to mitochondrial DNA

Cell physiology, Genetics,

Mitochondrial DNA (mtDNA) is used to assign traits in human evolution: for example it was claimed that the Ur-mother of modern humans lived in Africa. mtDNA may harbor fatal mutations which cannot be treated. If there occurs a mutation during the life of an individual this mutation is rarely fatal since it is well diluted. However, if a women during oogenesis transfers these mutation to the oocyte, the problem is multiplied since there are only some mtDNA molecules transferred and therefore one mutation might result in diseases like diabetes, cancer, male infertility, Parkinson, or Alzheimer. The male mtDNA does not reach the progeny.

In an article in PNAS Rebolledo-Jaramillo and colleagues have analyzed in detail mutation rates, disease accumulation and dependency of the age of the mother on the frequency of mutations in the child. They show that on average 9 mtDNA molecules are transferred to the oocyte. The mutation rate is 1.3 × 108 /year (10 times higher than for genomic DNA) which means a mutation in about every 78 th mitochondium (mitochondium has 16.5 kB).  They found also, and that is easily comprehensible, that the older the mother the higher the risk of a defect mitochondrium for the child. Ten years older means a tenfold higher risk.

This risk is independent of fathers since only the maternal mtDNA is inherited. There might be other risks due to age in man but they have to be analysed.

Nice and careful article! Recommended!