Extracellular cysteine in connexins: Role as redox sensors

Indexación: Scopus.Connexin-based channels comprise hemichannels and gap junction channels. The opening of hemichannels allow for the flux of ions and molecules from the extracellular space into the cell and vice versa. Similarly, the opening of gap junction channels permits the diffusional exchange of ions and molecules between the cytoplasm and contacting cells. The controlled opening of hemichannels has been associated with several physiological cellular processes; thereby unregulated hemichannel activity may induce loss of cellular homeostasis and cell death. Hemichannel activity can be regulated through several mechanisms, such as phosphorylation, divalent cations and changes in membrane potential. Additionally, it was recently postulated that redox molecules could modify hemichannels properties in vitro. However, the molecular mechanism by which redox molecules interact with hemichannels is poorly understood. In this work, we discuss the current knowledge on connexin redox regulation and we propose the hypothesis that extracellular cysteines could be important for sensing changes in redox potential. Future studies on this topic will offer new insight into hemichannel function, thereby expanding the understanding of the contribution of hemichannels to disease progression.http://journal.frontiersin.org/article/10.3389/fphys.2016.00001/ful

Computer simulation study of the nematic–vapour interface in the Gay–Berne model

We present computer simulations of the vapour–nematic interface of the Gay–Berne model. We considered situations which correspond to either prolate or oblate molecules. We determine the anchoring of the nematic phase and correlate it with the intermolecular potential parameters. On the other hand, we evaluate the surface tension associated to this interface. We find a corresponding states law for the surface tension dependence on the temperature, valid for both prolate and oblate molecules.Fundación Portuguesa para la Ciencia y la Tecnología EXCL / FIS-NAN / 0083/2012Ministerio de Economía y Competitividad FIS2012-32455Junta de Andalucía P09-FQM-493

Recovery rates of bluetongue virus serotypes 1, 2, 4 and 8 Spanish strains from orally infected Culicoides imicola in South Africa

Bluetongue (BT) is an infectious disease of ruminants that has spread northwards in Europe during the last decade. The aetiological agent of the disease is an arbovirus [bluetongue virus (BTV)] that belongs to the genus Orbivirus (family Reoviridae). The virus is transmitted by certain species of biting midge within the genus Culicoides (Diptera: Ceratopogonidae). Information on the vector status of the Culicoides species in a specific area will be essential to predict the risk for BTV incursion. Field-collected Culicoides (Avaritia) imicola Kieffer from South Africa were fed on blood containing several Spanish isolates of BTV. Despite the high virus concentrations in the bloodmeal (5.1-6.4 log10 TCID50/mL of blood), virus was recovered from 2.5 log10 TCID50/midge in individual infected C. imicola suggest virus replication with possible risk for transmission to susceptible vertebrate hosts in the field for at least two of the serotypes assayed (BTV-1 and BTV-2). A third serotype (BTV-4) was very close to the estimated threshold for transmission. The relatively low to near refractory status of C. inicola compared with other vector species such as Culicoides bolitinos supports previous results, indicating that Culicoides species other than C. imicola may play a more important role in the epidemiology of BTV.The Conselleria d’Innovacio, Interior i Justicia and the national project ‘Estudio de la Competencia Vectorial de las Especies de Culicoides (Diptera: Ceratopogonidae) Vectores de la Lengua Azul en Espana y Evaluacion de la Hibernacion del Virus en los Vectores’.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-2915ab201

The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

The energy spectrum of cosmic rays beyond the turn-down around 10^17 eV as measured with the surface detector of the Pierre Auger Observatory

We present a measurement of the cosmic-ray spectrum above 100 PeV using the part of the surface detector of the Pierre Auger Observatory that has a spacing of 750 m. An inflection of the spectrum is observed, confirming the presence of the so-called second-knee feature. The spectrum is then combined with that of the 1500 m array to produce a single measurement of the flux, linking this spectral feature with the three additional breaks at the highest energies. The combined spectrum, with an energy scale set calorimetrically via fluorescence telescopes and using a single detector type, results in the most statistically and systematically precise measurement of spectral breaks yet obtained. These measurements are critical for furthering our understanding of the highest energy cosmic rays

Comparación de distintas estrategias para la predicción de muerte a corto plazo en el paciente anciano infectado

Objective. The aim of this study was to determine the utility of a post hoc lactate added to SIRS and qSOFA score to predict 30-day mortality in older non-severely dependent patients attended for infection in the Emergency Department (ED). Methods. We performed an analytical, observational, prospective cohort study including patients of 75 years of age or older, without severe functional dependence, attended for an infectious disease in 69 Spanish ED for 2-day three seasonal periods. Demographic, clinical and analytical data were collected. The primary outcome was 30-day mortality after the index event. Results. We included 739 patients with a mean age of 84.9 (SD 6.0) years; 375 (50.7%) were women. Ninety-one (12.3%) died within 30 days. The AUC was 0.637 (IC 95% 0.587-0.688; p= 2 and 0.698 (IC 95% 0.635- 0.761; p= 2. Comparing receiver operating characteristic (ROC) there was a better accuracy of qSOFA vs SIRS (p=0.041). Both scales improve the prognosis accuracy with lactate inclusion. The AUC was 0.705 (IC95% 0.652-0.758; p<0.001) for SIRS plus lactate and 0.755 (IC95% 0.696-0.814; p<0.001) for qSOFA plus lactate, showing a trend to statistical significance for the second strategy (p=0.0727). Charlson index not added prognosis accuracy to SIRS (p=0.2269) or qSOFA (p=0.2573). Conclusions. Lactate added to SIRS and qSOFA score improve the accuracy of SIRS and qSOFA to predict short-term mortality in older non-severely dependent patients attended for infection. There is not effect in adding Charlson index

Multiwavelength observations of 3C 454.3. III. Eighteen months of agile monitoring of the "crazy diamond"

We report on 18 months of multiwavelength observations of the blazar 3C 454.3 (Crazy Diamond) carried out in the period 2007 July-2009 January. In particular, we show the results of the AGILE campaigns which took place on 2008 May-June, 2008 July-August, and 2008 October-2009 January. During the 2008 May-2009 January period, the source average flux was highly variable, with a clear fading trend toward the end of the period, from an average γ-ray flux F E>100 MeV ≳ 200 × 10-8photonscm -2s-1 in 2008 May-June, to F E>100 MeV 80 × 10-8photonscm-2s-1 in 2008 October-2009 January. The average γ-ray spectrum between 100 MeV and 1 GeV can be fit by a simple power law, showing a moderate softening (from ΓGRID ∼ 2.0 to ΓGRID ∼ 2.2) toward the end of the observing campaign. Only 3σ upper limits can be derived in the 20-60 keV energy band with Super-AGILE, because the source was considerably off-axis during the whole time period. In 2007 July-August and 2008 May-June, 3C 454.3 was monitored by Rossi X-ray Timing Explorer (RXTE). The RXTE/Proportional Counter Array (PCA) light curve in the 3-20 keV energy band shows variability correlated with the γ-ray one. The RXTE/PCA average flux during the two time periods is F 3-20 keV = 8.4 × 10-11ergcm-2s -1, and F 3-20 keV = 4.5 × 10 -11ergcm-2s-1, respectively, while the spectrum (a power law with photon index ΓPCA = 1.65 0.02) does not show any significant variability. Consistent results are obtained with the analysis of the RXTE/High-Energy X-Ray Timing Experiment quasi-simultaneous data. We also carried out simultaneous Swift observations during all AGILE campaigns. Swift/XRT detected 3C 454.3 with an observed flux in the 2-10 keV energy band in the range (0.9-7.5) × 10-11ergcm-2s-1 and a photon index in the range ΓXRT = 1.33-2.04. In the 15-150 keV energy band, when detected, the source has an average flux of about 5mCrab. GASP-WEBT monitored 3C 454.3 during the whole 2007-2008 period in the radio, millimeter, near-IR, and optical bands. The observations show an extremely variable behavior at all frequencies, with flux peaks almost simultaneous with those at higher energies. A correlation analysis between the optical and the γ-ray fluxes shows that the γ-optical correlation occurs with a time lag of τ = -0.4+0.6-0.8 days, consistent with previous findings for this source. An analysis of 15 GHz and 43 GHz VLBI core radio flux observations in the period 2007 July-2009 February shows an increasing trend of the core radio flux, anti-correlated with the higher frequency data, allowing us to derive the value of the source magnetic field. Finally, the modeling of the broadband spectral energy distributions for the still unpublished data, and the behavior of the long-term light curves in different energy bands, allow us to compare the jet properties during different emission states, and to study the geometrical properties of the jet on a time-span longer than one year. © 2010. The American Astronomical Society. All rights reserved