Protein kinase WNK2 as a tumour suppressor gene in malignant gliomas

Malignant glioblastomas are the most common and lethal adult brain tumours, with patients dying within two years from diagnosis. Little is known about the molecular mechanisms underlying the formation and/or development of these tumours, which present a very invasive phenotype within the brain and are genetically heterogeneous and highly resistant to both chemo- and radio-therapies. Recently, the promoter region of the protein kinase WNK2 gene was found to be hypermethylated in 29 of 31 infiltrative gliomas and about 80% of meningiomas. We have previously described that the experimental depletion of WNK2 expression decreases RhoA activity whilst leading to increased Rac1 activity. Because RhoA/Rac1 activities are important for cell migration and glioblastomas are very invasive tumours, we tested the effects of WNK2 on wound-healing assays in glioma cell lines SW1088 and A172. SW1088 cells express endogenous WNK2 and we observed that wound closure was increased upon experimental depletion of endogenous WNK2. In contrast, A172 cells display complete promoter region methylation and WNK2 re-expression was found to decrease migration. Consistently, we observed an increase in Rac1 activity in SW1088 cells upon WNK2 down-regulation, but lower levels of active Rac1 in A172 cells stably expressing WNK2 cDNA when compared with an equivalent cell line stably transfected with the same empty vector. Our studies indicate that loss of WNK2 expression promotes Rac1 activation and may contribute to the highly invasive phenotype that glioblastomas present. We also observed that, in a panel of glioblastoma cell lines, WNK2 promoter methylation correlates with a marked deregulation in Akt, MEK1/2 and ERK1/2 activities, suggesting WNK2 may also be important for tumour cell survival and cell cycle progression.FC

NEOTECTÔNICA NA BACIA DO ALTO RIO GRANDE: APLICAÇÕES EM SUA PORÇÃO MANTIQUEIRENSE

O trabalho tem por objetivo levar a efeito investigações acerca do quadro neotectônico vigente na bacia do alto Rio Grande em sua porção contida na Serra da Mantiqueira, sul de Minas Gerais. A discussão se pautou nos resultados obtidos por interpretações cartográficas, trabalhos de campo e mensuração dos seguintes índices geomórficos: Fator Assimetria de Bacias de Drenagem, Fator de Simetria Topográfica Transversal, Relação Declividade X Extensão do Curso, perfil longitudinal principais canais

Cardiovascular autonomic modulation differences between moderate-intensity continuous and high-intensity interval aerobic training in women with PCOS: A randomized trial

Background: Moderate-intensity continuous training (MICT) is strongly recommended for polycystic ovarian syndrome (PCOS) treatment. However, recent studies have suggested that high-intensity interval training (HIIT) would promote great benefits for cardiac autonomic control. Therefore, we investigated whether the benefits of HIIT related to cardiovascular autonomic control were greater than those of MICT in women with PCOS. Methods: Women with PCOS were randomly allocated through a blind draw into three groups: control, MICT, and HIIT. The control group did not undergo exercise, whereas those in the MICT and HIIT groups underwent 16 weeks of aerobic physical training. All groups were evaluated before and after the 16 weeks of intervention in the following aspects: quantification of serum lipids, testosterone, fasting insulin and blood glucose; physical fitness through cardiopulmonary testing; analysis of heart rate variability (HRV) by linear (time domain and frequency domain) and non-linear (symbolic analysis) methods, analysis of blood pressure variability (BPV) and spontaneous baroreflex sensitivity (BRS). Results: The final analysis, each group comprised 25 individuals. All groups had similar baseline parameters. After 16 weeks, intragroup comparison showed that the MICT and HIIT groups had a reduction in baseline heart rate (P < 0.001; P < 0.001, respectively) and testosterone levels P < 0.037; P < 0.012, respectively) associated with an increase in VO2peak (MICT, P < 0.001; HIIT, P < 0.001). The MICT (P < 0.36) and HIIT (P < 0.17) groups also showed an increase in cardiac vagal modulation, however only observed in the non-linear analysis. The intergroup comparison showed no differences between the MICT and HIIT groups in any of the hormonal, metabolic and autonomic parameters evaluated, including testosterone, peak oxygen uptake (VO2peak), HRV, BPV and BRS. Conclusion: HIIT and MICT showed similar results for the different parameters evaluated. This suggests that both training protocols can be recommended for the treatment of PCOS. Brazilian Clinical Trials Registry (RBR-78qtwy)

Crossover and self-averaging in the two-dimensional site-diluted Ising model

Using the newly proposed probability-changing cluster (PCC) Monte Carlo algorithm, we simulate the two-dimensional (2D) site-diluted Ising model. Since we can tune the critical point of each random sample automatically with the PCC algorithm, we succeed in studying the sample-dependent $T_c(L)$ and the sample average of physical quantities at each $T_c(L)$ systematically. Using the finite-size scaling (FSS) analysis for $T_c(L)$, we discuss the importance of corrections to FSS both in the strong-dilution and weak-dilution regions. The critical phenomena of the 2D site-diluted Ising model are shown to be controlled by the pure fixed point. The crossover from the percolation fixed point to the pure Ising fixed point with the system size is explicitly demonstrated by the study of the Binder parameter. We also study the distribution of critical temperature $T_c(L)$. Its variance shows the power-law $L$ dependence, $L^{-n}$, and the estimate of the exponent $n$ is consistent with the prediction of Aharony and Harris [Phys. Rev. Lett. {\bf 77}, 3700 (1996)]. Calculating the relative variance of critical magnetization at the sample-dependent $T_c(L)$, we show that the 2D site-diluted Ising model exhibits weak self-averaging.Comment: 6 pages including 6 eps figures, RevTeX, to appear in Phys. Rev.

Geometric K-Homology of Flat D-Branes

We use the Baum-Douglas construction of K-homology to explicitly describe various aspects of D-branes in Type II superstring theory in the absence of background supergravity form fields. We rigorously derive various stability criteria for states of D-branes and show how standard bound state constructions are naturally realized directly in terms of topological K-cycles. We formulate the mechanism of flux stabilization in terms of the K-homology of non-trivial fibre bundles. Along the way we derive a number of new mathematical results in topological K-homology of independent interest.Comment: 45 pages; v2: References added; v3: Some substantial revision and corrections, main results unchanged but presentation improved, references added; to be published in Communications in Mathematical Physic

An overview of jets and outflows in stellar mass black holes

In this book chapter, we will briefly review the current empirical understanding of the relation between accretion state and and outflows in accreting stellar mass black holes. The focus will be on the empirical connections between X-ray states and relativistic (`radio') jets, although we are now also able to draw accretion disc winds into the picture in a systematic way. We will furthermore consider the latest attempts to measure/order jet power, and to compare it to other (potentially) measurable quantities, most importantly black hole spin.Comment: Accepted for publication in Space Science Reviews. Also to appear in the Space Sciences Series of ISSI - The Physics of Accretion on to Black Holes (Springer Publisher

Eschar-associated Spotted Fever Rickettsiosis, Bahia, Brazil

In Brazil, Brazilian spotted fever was once considered the only tick-borne rickettsial disease. We report eschar-associated rickettsial disease that occurred after a tick bite. The etiologic agent is most related to Rickettsia parkeri, R. africae, and R. sibirica and probably widely distributed from São Paulo to Bahia in the Atlantic Forest

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201