Category Archives: Cell physiology

Studies on the Epigenom in Human Early Embryos

Cell physiology, Epigenom, Genetics, Human evolution, imprinting

Epigenetic modification of DNA, mostly methylation, is the way which ensures lineage specity in mammalian organization and propagation of cell types. It is inherited while cells multiply.

In Nature this week (doi:10.1038/nature13648) Reik and Kelsey describe two article (Guo, H. et al. Nature 511, 606–610 (2014) and Smith, Z. D. et al. Nature 511, 611–615 (2014)) where the methylation patterns in egg, sperm, fertilized eggs and blastocysts are analyzed. As has been found in mice before, blastocysts lose most of their methylation. Later in development the DNA gets remethylated again. This has been suggested but formal proof was lacking. The imprinting – methylated gene regions due to maternal or paternal origin – is not as much removed for maternal genes, but for paternal ones.

Whether these papers will improve human stem cell research is to be seen.

Translation Errors – not so bad at all

Biochemistry, Cell physiology, Translation, Translational error

Faithfull translation of mRNA into proteins  is one of the hallmarks of life. It is generally accepted that any deviation from this pathway leads to missformed proteins and is considered deleterious per se.

A very enlightning review in Trends in Biological Sciences (TIBS; DOI: 10.1016/j.tibs.2014.06.002) shows that errors in translation are dealt with in a productive way. First of all mistranslation are obviously regulated due to species and environnement which is by itself showing that mistranslation is beneficial for the organism, at least part of it. Furthermore mistranslation is well tolerated and not deleterious for the organism. Different organisms have evolved strategies to deal with it. It seems clear that by mistranslation the organism generates alternative proteins which may help to adapt the different environmental challenges.

Recommended!

Pre-eclampsia in a line with Alzheimer, Parkinson, and mad cow disease

Biochemistry, Cell physiology,

In an IN DEPTH contribution in Science Nadia Whitehead describes a Science Translational Medicine article (DOI: 10.1126/scitranslmed.3008808) where a team around the doctors Burimshi analyzed urine from 600 pregnant women using the dye Congo red which stains only “bunched”, not properly folded proteins. Those women with a risk of preeclampsia had bunched proteins with a frequency of more than 80 % while healthy women had none. Among the five proteins mostly bunched were immunoglobulin light chains, ceruloplasmin, SERPINA1, albumin and (sic!) Alsheimer’s β-amyloid. The authors conclude that preeclampsia might also be a disease of protein misfolding.

Aside from a new way to look at the disease which affects about 10 % of birth worldwide this paper offers a cheap test for preeclampsia. Remarcable!

The repertoire of smelling

Cell physiology, Olfactory system

In a Science article (DOI: 10.1126/science.1249168) C. Bushdid, M. O. Magnasco, L. B. Vosshall, A. Keller determine the size of the olfactory repertoire. On the basis of psychological testing they find that the human nose can distinguish at least 1 Billion (european enumeration = 1012) In the English nomenclature leaving out Milliarde (109) this is even more impressive: 1 Trillion. I wonder about the number of chemically defined receptors. In the case of the immune systems the repertoire of B and T cells (1012) could finally be explained by recombination. What the olfactory system has in its stores is to be seen. This paper sets the threshold fairly high.

Tibetans are different!

Biochemistry, Cell physiology, Evolution, Human evolution

A paper in Nature (Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA Emilia Huerta-Sánchez, Xin Jin, Asan et al.) says that DNA in Tibetans to adapt to the altitude can be attributed to an extinguished hominid precursor, the Denisovan: (cited from Nature)

Admixture with other hominin species helped humans to adapt to high-altitude environments; the EPAS1 gene in Tibetan individuals has an unusual haplotype structure that probably resulted from introgression of DNA from Denisovan or Denisovan-related individuals into humans, and this haplotype is only found in Denisovans and Tibetans, and at low frequency among Han Chinese.

A role for BRCA1

Cell physiology, Oncogenes, Transformation

The Breast Cancer Risk protein BRCA1 role is becoming analysed. While the mutation/deletion of this protein makes young women (males too) susceptible to develop breast tumours prematurely, how the protein did this was not clear for some time:

While Skully and collegues (doi: 10.1073/pnas.1400783111)  claim a role in replication fork control, Palazzo et al. (doi: 10.4161/cc.27945) observe it is related to the mitotic spindel formation. Chiba and collegue (DOI: 10.1016/j.molcel.2013.10.028) show a complex pattern of BRCA1, its dimerisation partner BARD1 and  the Obg-like ATPase 1, Ola-1 in the organisation of the centrosome.

Therefore, being involved in the basics of the machinery of cellular growth it is clear that BRCA1 once mutated makes the cell instable and prone to neoplastic transformation.

Chinese-herb nephropathy

Altermative medicine, Cell physiology, Drug

A News Focus article in Science (DOI: 10.1126/science.344.6180.146 ) reports that the Balkan chronic kidney disease is caused by the weed Aristolochia clematis and its drug aristologic acid. The article is concerned that a chronic kidney disease in Central America which is thought to originate from herbicides or pesticides might be more broadly analysed.

The Balkan disease has a very particular geographic distribution: only in mountain valleys and small elevations. It was thought to originate from the kidney toxin ochratoxin A. The new data show that in specimen of tumours from there as well as from patients who suffered from a disease of A.clematis intoxication which is contain in some Chinese herbal medicine had aristologic acid-DNA complexes. Aristologic acid is now regarded  as a tumour inducing drug.

My opinion on this that herbal medicine needs to be regarded with the same scientific zeal that is shown to its brothers in the “Schulmedizin”.