TPPP/p25 Promotes Tubulin Acetylation by Inhibiting Histone Deacetylase 6

TPPP/p25 (tubulin polymerization-promoting protein/p25) is an unstructured protein that induces microtubule polymerization in vitro and is aligned along the microtubule network in transfected mammalian cells. In normal human brain, TPPP/p25 is expressed predominantly in oligodendrocytes, where its expression is proved to be crucial for their differentiation process. Here we demonstrated that the expression of TPPP/p25 in HeLa cells, in doxycycline-inducible CHO10 cells, and in the oligodendrocyte CG-4 cells promoted the acetylation of α-tubulin at residue Lys-40, whereas its down-regulation by specific small interfering RNA in CG-4 cells or by the withdrawal of doxycycline from CHO10 cells decreased the acetylation level of α-tubulin. Our results indicate that TPPP/p25 binds to HDAC6 (histone deacetylase 6), an enzyme responsible for tubulin deacetylation. Moreover, we demonstrated that the direct interaction of these two proteins resulted in the inhibition of the deacetylase activity of HDAC6. The measurement of HDAC6 activity showed that TPPP/p25 is able to induce almost complete (90%) inhibition at 3 μm concentration. In addition, treatment of the cells with nocodazole, vinblastine, or cold exposure revealed that microtubule acetylation induced by trichostatin A, a well known HDAC6 inhibitor, does not cause microtubule stabilization. In contrast, the microtubule bundling activity of TPPP/p25 was able to protect the microtubules from depolymerization. Finally, we demonstrated that, similarly to other HDAC6 inhibitors, TPPP/p25 influences the microtubule dynamics by decreasing the growth velocity of the microtubule plus ends and also affects cell motility as demonstrated by time lapse video experiments. Thus, we suggest that TPPP/p25 is a multiple effector of the microtubule organization.     

Rarity,ecological memory,rate of floral change in phytoplankton—and the mystery of the Red Cock

In this article, we attempt to estimate the contemporary phytoplankton species pool of a particular lake, by assessing the rate of floral change over a period of 15 years. Phytoplankton time series data from Lake Stechlin, an oligo-mesotrophic lake in the Baltic Lake District (Germany) were used. Of the 254 algal species recorded during the 15-year of studies with roughly biweekly sampling, 212 species were planktonic. In the individual plankton years, the recorded total number of species changed between 97 and 122, of which the number of dominants (>1% contribution to the annual average of total biomass) was only 10–19. The 15-year cumulative number of species exhibited an almost linear increase after an initial saturation phase. This increase was attributed to two reasons: increase of sample size and immigration of species new to the flora. Based on a probabilistic model developed in this study, we estimated the number of co-existing planktonic species of the lake as some 180, and the rate of floral change as 1–2 species per year. Of these co-existing species, only few maintain the matter–energy processing ecosystem functions in any particular plankton year. Selection of these dominants is probably driven by mesoclimatic cycles, coupled with human-induced forcing, like eutrophication. All others are hiding as an ecological memory, in the sense of the capacity or experiences of past states to influence present or future responses of the community. Data analyses suggest that selection of the ‘memory species’ that show temporary abundance increases over shorter (several years) periods are largely dependent upon the dominants. These results show that interspecific interactions and the particular autecological features of the dominants, together with their effects on the whole ecosystem, act as a major organizing force. Some phytoplankton species, like Planktothrix rubescens, are efficient ecosystem engineers with cascading effects of both a top-down and bottom-up nature. Historical scientific data on Planktothrix blooms in Lake Stechlin suggest cyclic patterns in long-term development of phytoplankton which, as the legend of the Red Cock suggests, dates back much further than scientific archives.     

The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain

In the current investigation we tested how swimming training (T) (8 week, 5 times/week, 2 h/day), and detraining (DT) affects brain functions and oxidative stress markers in rat brain. The free radical concentration, measured by electron paramagnetic resonance, decreased in brain of T and DT rats compared to controls (C). The level of brain-derived neurotrophic factor (BDNF) increased as a result of training, but decreased below the control level after 6 weeks of detraining. In addition, the concentration of nerve growth factor (NGF) also declined with DT. The passive avoidance test was used to assess the memory of rats, and training-induced improvement was observed but the enhancement disappeared with detraining. When the content of mitochondrial electron transport complexes, as a potent free radical generator, was evaluated by the blue native gel method, no significant alterations were observed. The repair of nuclear and mitochondrial 8-oxodeoxyguanosine, as measured by the activity of OGG1, showed no significant difference. Therefore, the results suggest that regular exercise training improves memory, decreases the level of reactive oxygen species, and increase the production of BDNF and NGF. On the other hand, it appears that the beneficial effects of training are reversible in the brain, since detraining down-regulates the neurotrophin level, and memory. It is suggested that exercise training is more likely to beneficially effect the production of reactive oxygen species and the related oxidative damage.     

Telomere dysfunction: a new player in radiation sensitivity

Human individuals often exhibit important differences in their sensitivity to ionising radiation. Extensive literature links radiation sensitivity with impaired DNA repair which is due to a lack of correct functioning in many proteins involved in DNA-repair pathways and/or in DNA-damage checkpoint responses. Given that ionising radiation is an important and widespread diagnostic and therapeutic tool, it is important to investigate further those factors and mechanisms that underlie individual radiosensitivity. Recently, evidence is accumulating that telomere function may well be involved in cellular and organism responses to ionising radiation, broadening still further the currently complex and challenging scenario.