Translocating the blood-brain barrier using electrostatics

Copyright © 2012 Ribeiro,Domingues, Freire,Santos and Castanho. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.Mammalian cell membranes regulate homeostasis, protein activity, and cell signaling. The charge at the membrane surface has been correlated with these key events. Although mammalian cells are known to be slightly anionic, quantitative information on the membrane charge and the importance of electrostatic interactions in pharmacokinetics and pharmacodynamics remain elusive. Recently, we reported for the first time that brain endothelial cells (EC) are more negatively charged than human umbilical cord cells, using zeta-potential measurements by dynamic light scattering. Here, we hypothesize that anionicity is a key feature of the blood-brain barrier (BBB) and contributes to select which compounds cross into the brain. For the sake of comparison, we also studied the membrane surface charge of blood components—red blood cells (RBC), platelets, and peripheral blood mononuclear cells (PBMC).To further quantitatively correlate the negative zeta-potential values with membrane charge density, model membranes with different percentages of anionic lipids were also evaluated. From all the cells tested, brain cell membranes are the most anionic and those having their lipids mostly exposed, which explains why lipophilic cationic compounds are more prone to cross the blood-brain barrier.Fundação para a Ciência e Tecnologia — Ministério da Educação e Ciência (FCT-MEC, Portugal) is acknowledged for funding (including fellowships SFRH/BD/42158/2007 to Marta M.B. Ribeiro, SFRH/BD/41750/2007 to Marco M. Domingues and SFRH/BD/70423/2010 to João M. Freire) and project PTDC/QUI-BIQ/119509/2010. Marie Curie Industry-Academia Partnerships and Pathways (European Commission) is also acknowledged for funding (FP7-PEOPLE-2007-3-1-IAPP, Project 230654)

The very faint hard state of the persistent neutron star X-ray binary SLX 1737-282 near the Galactic centre

We report on a detailed study of the spectral and temporal properties of the neutron star low mass X-ray binary SLX 1737-282, which is located only ~1degr away from Sgr A. The system is expected to have a short orbital period, even within the ultra-compact regime, given its persistent nature at low X-ray luminosities and the long duration thermonuclear burst that it has displayed. We have analysed a Suzaku (18 ks) observation and an XMM-Newton (39 ks) observation taken 7 years apart. We infer (0.5-10 keV) X-ray luminosities in the range 3-6 x10^35erg s-1, in agreement with previous findings. The spectra are well described by a relatively cool (kTbb = 0.5 keV) black body component plus a Comptonized emission component with {\Gamma} ~1.5-1.7. These values are consistent with the source being in a faint hard state, as confirmed by the ~ 20 per cent fractional root mean square amplitude of the fast variability (0.1 - 7 Hz) inferred from the XMM-Newton data. The electron temperature of the corona is >7 keV for the Suzaku observation, but it is measured to be as low as ~2 keV in the XMM-Newton data at higher flux. The latter is significantly lower than expected for systems in the hard state. We searched for X-ray pulsations and imposed an upper limit to their semi-amplitude of 2 per cent (0.001 - 7 Hz). Finally, we investigated the origin of the low frequency variability emission present in the XMM-Newton data and ruled out an absorption dip origin. This constraint the orbital inclination of the system to 65 degr unless the orbital period is longer than 11 hr (i.e. the length of the XMM-Newton observation).Comment: 7 pages, 4 figures, 1 table. Accepted for publication in MNRA

Swimmers in thin films: from swarming to hydrodynamic instabilities

We investigate theoretically the collective dynamics of a suspension of low Reynolds number swimmers that are confined to two dimensions by a thin fluid film. Our model swimmer is characterized by internal degrees of freedom which locally exert active stresses (force dipoles or quadrupoles) on the fluid. We find that hydrodynamic interactions mediated by the film can give rise to spontaneous continuous symmetry breaking (swarming), to states with either polar or nematic homogeneous order. For dipolar swimmers, the stroke averaged dynamics are enough to determine the leading contributions to the collective behaviour. In contrast, for quadrupolar swimmers, our analysis shows that detailed features of the internal dynamics play an important role in determining the bulk behaviour. In the broken symmetry phases, we investigate fluctuations of hydrodynamic variables of the system and find that these destabilize order. Interestingly, this instability is not generic and depends on length-scale.Comment: 4 pages, 2 figures, references added, typos corrected, new introductio

In vitro ion chelating, antioxidative mechanism of extracts from fruits and barks of tetrapleura tetraptera and their protective effects against fenton mediated toxicity of metal ions on liver homogenates

The aim of the present study was to investigate the antioxidant activity and protective potential of T. tetraptera extracts against ion toxicity. The antioxidant activity of the extracts was investigated spectrophotometrically against several radicals (1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS•), hydroxyl radical (HO•), and nitric oxide (NO•)), followed by the ferric reducing power, total phenols, flavonoid, and flavonol contents. The effects of the extracts on catalase (CAT), superoxide dismutase (SOD), and peroxidase activities were also determined using the standard methods as well as the polyphenol profile using HPLC. The results showed that the hydroethanolic extract of T. tetraptera (CFH) has the lowest ICvalue with the DPPH, ABTS, OH, and NO radicals. The same extract also exhibited the significantly higher level of total phenols (37.24 ± 2.00 CAE/g dried extract); flavonoids (11.36 ± 1.88 QE/g dried extract); and flavonols contents (3.95 ± 0.39 QE/g dried extract). The HPLC profile of T. tetraptera revealed that eugenol (958.81 ± 00 mg/g DW), quercetin (353.78 ± 00 mg/g DW), and rutin (210.54 ± 00 mg/g DW) were higher in the fruit than the bark extracts. In conclusion, extracts from T. tetraptera may act as a protector against oxidative mediated ion toxicity. © 2015 Bruno Moukette Moukette et al

Probing variability patterns of the Fe K line complex in bright nearby AGNs

The unprecedented sensitivity of current X-ray telescopes allows for the first time to address the issue of the Fe K line complex variability patterns in bright, nearby AGNs. We examine XMM-Newton observations of the brightest sources of the FERO sample of radio-quiet type 1 AGNs with the aim of characterizing the temporal behaviour of Fe K complex features. A systematic mapping of residual flux above and below the continuum in the 4-9 keV range is performed in the time vs energy domain, with the purpose of identifying interesting spectral features in the three energy bands: 5.4-6.1 keV, 6.1-6.8 keV and 6.8-7.2 keV, corresponding respectively to the redshifted, rest frame and blueshifted or highly ionized Fe Kalpha line bands. The variability significance is assessed by extracting light curves and comparing them with MonteCarlo simulations. The time-averaged profile of the Fe K complex revealed spectral complexity in several observations. Red- and blue-shifted components (either in emission or absorption) were observed in 30 out of 72 observations, with an average ~90 eV for emission and ~ -30 eV for absorption features. We detected significant line variability (with confidence levels ranging between 90% and 99.7%) within at least one of the above energy bands in 26 out of 72 observations on time scales of ~6-30 ks. Reliability of these features has been carefully calculated using this sample and has been assessed at ~3sigma confidence level. This work increases the currently scanty number of detections of variable, energy shifted, Fe lines and confirms the reliability of the claimed detections. We found that the distribution of detected features is peaked at high variability significances in the red- and blue-shifted energy bands, suggesting an origin in a relativistically modified accretion flow.Comment: Accepted for publication in Astronomy & Astrophysic

Establishing the nature of companion candidates to X-ray emitting late B-type stars

The most favored interpretation for the detection of X-ray emission from late B-type stars is that these stars have a yet undiscovered late-type companion (or an unbound nearby late-type star) that produces the X-rays. Several faint IR objects at (sub)-arcsecond separation from B-type stars have been uncovered in our earlier adaptive optics imaging observations, and some of them have been followed up with the high spatial resolution of the Chandra X-ray observatory, pinpointing the X-ray emitter. However, firm conclusions on their nature requires a search for spectroscopic signatures of youth. Here we report on our recent ISAAC observations carried out in low resolution spectroscopic mode. Equivalent widths have been used to obtain information on spectral types of the companions. All eight X-ray emitting systems with late B-type primaries studied contain dwarf like companions with spectral types later than A7. The only system in the sample where the companion turns out to be of early spectral type is not an X-ray source. These results are consistent with the assumption that the observed X-ray emission from late B-type stars is produced by an active pre-main sequence companion star.Comment: 6 pages, 2 figures, 3 tables, accepted for publication in MNRA

The Polytropic Equation of State of Interstellar Gas Clouds

Models are presented for the polytropic equation of state of self-gravitating, quiescent interstellar gas clouds. A detailed analysis, including chemistry, thermal balance, and radiative transfer, is performed for the physical state of the gas as a function of density, metallicity, velocity field, and background radiation field. It is found that the stiffness of the equation of state strongly depends on all these physical parameters, and the adiabatic index varies between 0.2-1.4. The implications for star formation, in particular at high redshift and in starburst galaxies, and the initial stellar mass function are discussed.Comment: Accepted by Ap

Progressive Transient Photon Beams

In this work we introduce a novel algorithm for transient rendering in participating media. Our method is consistent, robust, and is able to generate animations of time-resolved light transport featuring complex caustic light paths in media. We base our method on the observation that the spatial continuity provides an increased coverage of the temporal domain, and generalize photon beams to transient-state. We extend the beam steady-state radiance estimates to include the temporal domain. Then, we develop a progressive version of spatio-temporal density estimations, that converges to the correct solution with finite memory requirements by iteratively averaging several realizations of independent renders with a progressively reduced kernel bandwidth. We derive the optimal convergence rates accounting for space and time kernels, and demonstrate our method against previous consistent transient rendering methods for participating media

HST emission-line images of nearby 3CR radio galaxies: two photoionization, accretion and feedback modes

We present HST/ACS narrow-band images of a low-z sample of 19 3C radio galaxies to study the H$\alpha$ and [OIII] emissions from the narrow-line region (NLR). Based on nuclear emission line ratios, we divide the sample into High and Low Excitation Galaxies (HEGs and LEGs). We observe different line morphologies, extended line emission on kpc scale, large [OIII]/H$\alpha$ scatter across the galaxies, and a radio-line alignment. In general, HEGs show more prominent emission line properties than LEGs: larger, more disturbed, more luminous, and more massive regions of ionized gas with slightly larger covering factors. We find evidence of correlations between line luminosities and (radio and X-ray) nuclear luminosities. All these results point to a main common origin, the active nucleus, which ionize the surrounding gas. However, the contribution of additional photoionization mechanism (jet shocks and star formation) are needed to account for the different line properties of the two classes. A relationship between the accretion, photoionization and feedback modes emerges from this study. For LEGs (hot-gas accretors), the synchrotron emission from the jet represents the main source of ionizing photons. The lack of cold gas and star formation in their hosts accounts for the moderate ionized-gas masses and sizes. For HEGs (cold-gas accretors), an ionizing continuum from a standard disk and shocks from the powerful jets are the main sources of photoionization, with the contribution from star formation. These components, combined with the large reservoir of cold/dust gas brought from a recent merger, account for the properties of their extended emission-line regions.Comment: accepted for publication on ApJ (22 pages, 12 figures