Etoposide Induces Nuclear Re-Localisation of AID

During B cell activation, the DNA lesions that initiate somatic hypermutation and class switch recombination are introduced by activation-induced cytidine deaminase (AID). AID is a highly mutagenic protein that is maintained in the cytoplasm at steady state, however AID is shuttled across the nuclear membrane and the protein transiently present in the nucleus appears sufficient for targeted alteration of immunoglobulin loci. AID has been implicated in epigenetic reprogramming in primordial germ cells and cell fusions and in induced pluripotent stem cells (iPS cells), however AID expression in non-B cells is very low. We hypothesised that epigenetic reprogramming would require a pathway that instigates prolonged nuclear residence of AID. Here we show that AID is completely re-localised to the nucleus during drug withdrawal following etoposide treatment, in the period in which double strand breaks (DSBs) are repaired. Re-localisation occurs 2-6 hours after etoposide treatment, and AID remains in the nucleus for 10 or more hours, during which time cells remain live and motile. Re-localisation is cell-cycle dependent and is only observed in G2. Analysis of DSB dynamics shows that AID is re-localised in response to etoposide treatment, however re-localisation occurs substantially after DSB formation and the levels of re-localisation do not correlate with γH2AX levels. We conclude that DSB formation initiates a slow-acting pathway which allows stable long-term nuclear localisation of AID, and that such a pathway may enable AID-induced DNA demethylation during epigenetic reprogramming.     

P2X7-mediated ATP secretion is accompanied by depletion of cytosolic ATP

Purinergic Signalling - ATP and its metabolites are important extracellular signal transmitters acting on purinergic P2 and P1 receptors. Most cells can actively secrete ATP in response to a...     

Structure of an otter (Lutra lutra) population in Germany – results of DNA and hormone analyses from faecal samples

Population size, one of the basic biological parameters is particularly difficult to estimate for nocturnal animals with cryptic life style and little individual distinctiveness like Eurasian otters (Lutra lutra). Because telemetric methods often fail and also expose the animals to a high risk of injuries and even mortality, we analysed DNA and hormones of spraints to obtain data on population density and structure of free-living otters in a Nature Park in north-eastern Germany. We were able to assign 53 different individual profiles from faecal samples and obtained six more profiles from animals found dead inside the park. The total population estimate (n=59) consisted of at least 32 males and 27 females; 33 animals were adult, 23 younger than 2 years (three of unknown age). Marking points were frequented by up to 12 individuals. Estimated density was one animal per 4.7 km of shoreline. The genotypically estimated total population size was more than 2.5 times as high as estimated in the past census. The method was also suited to compare otter population densities in different areas or at different times in the same area.     

THE FLICKER RESPONSE CONTOUR FOR THE CRAYFISH. I

The F - log I curve for threshold response to visual flicker has been determined for the crayfish Cambarus bartoni. As predicted on the basis of the higher curvature of the optic surface, the flicker response contour is more asymmetrical than for bee and dragonfly nymph under comparable conditions of temperature and light time fraction of flash cycle. The mechanical origin of this asymmetry is thus confirmed, and is further supported by the similar forms of the F - log I curves in bee, dragonfly larva, and crayfish in the lower portion of the curves (up to F = 70 per cent F_max.). The slope of the fundamental curve for crayfish, deduced by analysis of the data, is lower than for bee, dragonfly nymph, or Asellus. This signifies a wider spread of the effective distribution of elemental log I thresholds involvable in the response to flicker, and may be traced either to the greater curvature of the eye-surfaces or to their position upon movable pedicles. The results are therefore consistent with the statistical conception of the nature of effects recognizable as due to the activity of excitable elements.