Polycomb group protein ezh2 controls actin polymerization and cell signaling

Polycomb group protein Ezh2, one of the key regulators of development in organisms from flies to mice, exerts its epigenetic function through regulation of histone methylation. Here, we report the existence of the cytosolic Ezh2-containing methyltransferase complex and tie the function of this complex to regulation of actin polymerization in various cell types. Genetic evidence supports the essential role of cytosolic Ezh2 in actin polymerization-dependent processes such as antigen receptor signaling in T cells and PDGF-induced dorsal circular ruffle formation in fibroblasts. Revealed function of Ezh2 points to a broader usage of lysine methylation in regulation of both nuclear and extra-nuclear signaling processes.     

Amyloid Abeta1-40 preconditions non-apoptotic signals in vivo and protects fetal rat brain from intrauterine ischemic stress

Abstract The dualistic activities of the amyloid beta (Abeta) peptide as a pro-oxidant and ubiquitous constituent of amyloid deposits in Alzheimer's disease plaques and as an antioxidant of purported physiological function has been suggested but the mechanisms are far from being understood. In this report we measure several oxidative stress parameters and signaling cascades in brains of fetal rats subjected to global ischemia in order to evaluate the putative bifunctional properties of the Abeta(1-40) peptide. Intraperitoneal injection of 6 microg Abeta(1-40) into 18-days-old rat fetuses (approximately 3 g body weight) resulted after 24 h in the appearance of the peptide in various fetal organs including brain where it enhanced the levels of glutathione (GSH), glutathione reductase, glutathione peroxidase, and stimulated the levels of pro-survival signaling activities such as Akt serine/threonine kinase, extracellular signal-regulated kinase (ERK) and protein kinase C enzymes. Moreover, pretreatment with Abeta(1-40) reversed the consequences of a transient hypovolemic/hypotensive oxidative stress by restoring GSH levels via its recycling enzymes and by lowering the production of lipid peroxides presumably by activating the aforementioned pro-survival signaling cascades. It also caused a reduction in the number of DAPI-enhanced reactive cells and a decrease in p38 kinase phosphorylation and caspase-9 and -3 activity. These data suggest that pre-exposure to Abeta(1-40) stimulates fetal tolerance to ischemia via regulation of GSH metabolism and as such may be considered as neuroprotective.     

Habitat selection in evolving mole rats

Summary The actively speciating four chromosomal species of fossorial mole rats of the Spalax ehrenbergi complex in Israel (2n=52, 58, 54 and 60) which inhabit an increasingly arid environment in this order were tested to determine their habitat preference. The testing apparatus simulated four climatic regimes based on temperature and humidity combinations corresponding to the climatic origins of the four chromosomal species: coolhumid, cool-dry, warm-humid and warm-dry, respectively. The tests involved 175 adults comprising all four chromosome species and representing 10 populations. Out of the 139 analyzed animals 88% selected the warm cages and only 12% selected the cool cages. The four karyotype progressively preferred the warm-dry cage in the following order: 53, 59, 60 and 72% for 2n=58, 52, 54 and 60 respectively, largely in accord with their increasingly arid climatic origins. Even larger differences were found in populations within karyotypes in accord with the local climatic variation within a karyotype range.The results of our analysis indicate that the chromosomal species and populations select their climatic habitat in accord with the climatic conditions of their geographic localities. The humidity index appears to be the prime differentiator of habitat selection and may have been a substantial ecological factor in species differentiation and distribution of the Spalax ehrenbergi complex in Israel.     

Poly(L-histidyl-L-alanyl-α-L-glutamic acid). II. Catalysis of p-nitrophenyl acetate hydrolysis

The hydrolysis of p-nitrophenyl acetate is catalyzed by imidazole, free in solution or as the side chain in poly(His-Ala-Glu). This is based on the observations that the reaction is first order in ester and first order in nonprotonated imidazole. Catalysis of p-nitrophenyl acetate hydrolysis is dependent on solvent conditions. The effect of low concentrations of ethanol, dioxane, and trifluoroethanol were investigated. As the concentration of organic solvent is increased, the second-order rate constant for imidazole catalysis decreases. The decrease, however, is greater for imidazole than for poly(His-Ala-Glu). In 2% trifluoroethanol/water solution, free imidazole has twice the catalytic activity of polymeric imidazole, while in 40% trifluoroethanol/water they have equal activity. Since under the latter solvent conditions poly(His-Ala-Glu) is partially α-helical, the relative improvement in polymeric–imidazole catalysis may be attributed to imidazole hydrogen-bonded to a carboxylate ion. With this assumption the carboxylate–imidazole hydrogen-bonded system has been calculated to have three times the base catalytic activity of imidazole.     

Primate CpG islands are maintained by heterogeneous evolutionary regimes involving minimal selection

Mammalian CpG islands are key epigenomic elements that were first characterized experimentally as genomic fractions with low levels of DNA methylation. Currently, CpG islands are defined based on their genomic sequences alone. Here, we develop evolutionary models to show that several distinct evolutionary processes generate and maintain CpG islands. One central evolutionary regime resulting in enriched CpG content is driven by low levels of DNA methylation and consequentially low rates of CpG deamination. Another major force forming CpG islands is biased gene conversion that stabilizes constitutively methylated CpG islands by balancing rapid deamination with CpG fixation. Importantly, evolutionary analysis and population genetics data suggest that selection for high CpG content is not?a significant factor contributing to conservation of CpGs in differentially methylated regions. The heterogeneous, but not selective, origins of CpG islands have direct implications for the understanding of DNA methylation patterns in healthy and diseased cells.     

Intra-Golgi protein transport depends on a cholesterol balance in the lipid membrane

Transport of proteins between intracellular membrane compartments is mediated by a protein machinery that regulates the budding and fusion processes of individual transport steps. Although the core proteins of both processes are defined at great detail, much less is known about the involvement of lipids. Here we report that changing the cellular balance of cholesterol resulted in changes of the morphology of the Golgi apparatus, accompanied by an inhibition of protein transport. By using a well characterized cell-free intra-Golgi transport assay, these observations were further investigated, and it was found that the transport reaction is sensitive to small changes in the cholesterol content of Golgi membranes. Addition as well as removal of cholesterol (10 +/- 6%) to Golgi membranes by use of methyl-beta-cyclodextrin specifically inhibited the intra-Golgi transport assay. Transport inhibition occurred at the fusion step. Modulation of the cholesterol content changed the lipid raft partitioning of phosphatidylcholine and heterotrimeric G proteins, but not of other (non) lipid raft proteins and lipids. We suggest that the cholesterol balance in Golgi membranes plays an essential role in intra-Golgi protein transport and needs to be carefully regulated to maintain the structural and functional organization of the Golgi apparatus.     

Intraglottal pressure distribution computed from empirical velocity data in canine larynx

Intraglottal velocity measurements were taken using particle image velocimetry and the corresponding estimates for the intraglottal pressure were computed using the pressure Poisson equation. Results from five canine larynges showed that when the flow separated from the divergent glottal walls during closing, the vortices that were formed in the separated region of the glottis created negative pressure near the superior aspect of the folds. The magnitude of the negative pressure was directly proportional to the subglottal pressure. At low subglottal pressure, negative pressures at the superior edge were not observed when the divergence angle of the wall was minimal and the glottal flow did not separate from the wall.     

Large eddy simulation of the pharyngeal airflow associated with obstructive sleep apnea syndrome at pre and post-surgical treatment

Obstructive Sleep Apnea Syndrome (OSAS) is the most common sleep-disordered breathing medical condition and a potentially life-threatening affliction. Not all the surgical or non-surgical OSAS therapies are successful for each patient, also in part because the primary factors involved in the etiology of this disorder are not completely understood. Thus, there is a need for improving both diagnostic and treatment modalities associated with OSAS. A verified and validated (in terms of mean velocity and pressure fields) Large Eddy Simulation approach is used to characterize the abnormal pharyngeal airflow associated with severe OSAS and its interaction with the airway wall in a subject who underwent surgical treatment. The analysis of the unsteady flow at pre- and post-treatment is used to illustrate the airflow dynamics in the airway associated with OSAS and to reveal as well, the changes in the flow variables after the treatment. At pre-treatment, large airflow velocity and wall shear stress values were found at the obstruction site in all cases. Downstream of obstruction, flow separation generated flow recirculation regions and enhanced the turbulence production in the jet-like shear layers. The interaction between the generated vortical structures and the pharyngeal airway wall induced large fluctuations in the pressure forces acting on the pharyngeal wall. After the surgery, the flow field instabilities vanished and both airway resistance and wall shear stress values were significantly reduced.