271 research outputs found
Influence of body mass index on outcomes after minimal-access aortic valve replacement through a J-shaped partial upper sternotomy
Full text linkPrenylation inhibitors stimulate both estrogen receptor α transcriptional activity through AF-1 and AF-2 and estrogen receptor β transcriptional activity
Get PDFINTRODUCTION: We showed in a previous study that prenylated proteins play a role in estradiol stimulation of proliferation. However, these proteins antagonize the ability of estrogen receptor (ER) α to stimulate estrogen response element (ERE)-dependent transcriptional activity, potentially through the formation of a co-regulator complex. The present study investigates, in further detail, how prenylated proteins modulate the transcriptional activities mediated by ERα and by ERβ. METHODS: The ERE-β-globin-Luc-SV-Neo plasmid was either stably transfected into MCF-7 cells or HeLa cells (MELN cells and HELN cells, respectively) or transiently transfected into MCF-7 cells using polyethylenimine. Cells deprived of estradiol were analyzed for ERE-dependent luciferase activity 16 hours after estradiol stimulation and treatment with FTI-277 (a farnesyltransferase inhibitor) or with GGTI-298 (a geranylgeranyltransferase I inhibitor). In HELN cells, the effect of prenyltransferase inhibitors on luciferase activity was compared after transient transfection of plasmids coding either the full-length ERα, the full-length ERβ, the AF-1-deleted ERα or the AF-2-deleted ERα. The presence of ERα was then detected by immunocytochemistry in either the nuclei or the cytoplasms of MCF-7 cells. Finally, Clostridium botulinum C3 exoenzyme treatment was used to determine the involvement of Rho proteins in ERE-dependent luciferase activity. RESULTS: FTI-277 and GGTI-298 only stimulate ERE-dependent luciferase activity in stably transfected MCF-7 cells. They stimulate both ERα-mediated and ERβ-mediated ERE-dependent luciferase activity in HELN cells, in the presence of and in the absence of estradiol. The roles of both AF-1 and AF-2 are significant in this effect. Nuclear ERα is decreased in the presence of prenyltransferase inhibitors in MCF-7 cells, again in the presence of and in the absence of estradiol. By contrast, cytoplasmic ERα is mainly decreased after treatment with FTI-277, in the presence of and in the absence of estradiol. The involvement of Rho proteins in ERE-dependent luciferase activity in MELN cells is clearly established. CONCLUSIONS: Together, these results demonstrate that prenylated proteins (at least RhoA, RhoB and/or RhoC) antagonize the ability of ERα and ERβ to stimulate ERE-dependent transcriptional activity, potentially acting through both AF-1 and AF-2 transcriptional activities
European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG registry): Study Protocol for a Prospective Clinical Registry and Proposal of Classification of Postoperative Complications
Get PDFDistributed Dynamical Computation in Neural Circuits with Propagating Coherent Activity Patterns
Get PDFActivity in neural circuits is spatiotemporally organized. Its spatial organization consists of multiple, localized coherent patterns, or patchy clusters. These patterns propagate across the circuits over time. This type of collective behavior has ubiquitously been observed, both in spontaneous activity and evoked responses; its function, however, has remained unclear. We construct a spatially extended, spiking neural circuit that generates emergent spatiotemporal activity patterns, thereby capturing some of the complexities of the patterns observed empirically. We elucidate what kind of fundamental function these patterns can serve by showing how they process information. As self-sustained objects, localized coherent patterns can signal information by propagating across the neural circuit. Computational operations occur when these emergent patterns interact, or collide with each other. The ongoing behaviors of these patterns naturally embody both distributed, parallel computation and cascaded logical operations. Such distributed computations enable the system to work in an inherently flexible and efficient way. Our work leads us to propose that propagating coherent activity patterns are the underlying primitives with which neural circuits carry out distributed dynamical computation
Prognostic Impact of Prolonged Cross-Clamp Time in Coronary Artery Bypass Grafting
Get PDFBACKGROUND:The prognostic impact of cross-clamp time (XCT) in patients undergoing isolated coronary artery bypass grafting (CABG) has not been thoroughly investigated.MATERIAL AND METHODS:2957 patients who underwent on-pump isolated CABG from the prospective multicentre E-CABG study were the subjects of this analysis.RESULTS:The mean XCT in this series was 58±25minutes Cross-clamp time was >60 minutes in 1134 patients (38.3%), >75minutes in 619 patients (20.9%) and >90minutes in 296 patients (10.0%). Multivariate analysis showed that XCT was an independent predictor of 30-day mortality (p75minutes (2.9% vs. 1.7%, p=0.002, OR 3.479, 95%CI 1.609-7.520). Analysis of 428 propensity score matched pairs showed that XCT >75minutes was associated with significantly increased risk of early mortality, prolonged use of inotropes, postoperative use of intra-aortic balloon pump, use of extracorporeal membrane oxygenation, atrial fibrillation, prolonged stay in the intensive care unit and of composite major adverse events.CONCLUSIONS:Isolated CABG is currently performed with prolonged XCT in a significant number of patients and this seems to be a determinant of poor early outcome.</p
Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection
Get PDFPandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data
Planck intermediate results. XIX. An overview of the polarized thermal emission from Galactic dust
Get PDFThis paper presents an overview of the polarized sky as seen by Planck HFI at 353 GHz, which is the most sensitive Planck channel for dust polarization. We construct and analyse maps of dust polarization fraction and polarization angle at 1° resolution, taking into account noise bias and possible systematic effects. The sensitivity of the Planck HFI polarization measurements allows for the first time a mapping of Galactic dust polarized emission on large scales, including low column density regions. We find that the maximum observed dust polarization fraction is high (pmax = 19.8%), in particular in some regions of moderate hydrogen column density (NH < 2 × 1021 cm-2). The polarization fraction displays a large scatter at NH below a few 1021 cm-2. There is a general decrease in the dust polarization fraction with increasing column density above NH ≃ 1 × 1021 cm-2 and in particular a sharp drop above NH ≃ 1.5 × 1022 cm-2. We characterize the spatial structure of the polarization angle using the angle dispersion function. We find that the polarization angle is ordered over extended areas of several square degrees, separated by filamentary structures of high angle dispersion function. These appear as interfaces where the sky projection of the magnetic field changes abruptly without variations in the column density. The polarization fraction is found to be anti-correlated with the dispersion of polarization angles. These results suggest that, at the resolution of 1°, depolarization is due mainly to fluctuations in the magnetic field orientation along the line of sight, rather than to the loss of grain alignment in shielded regions. We also compare the polarization of thermal dust emission with that of synchrotron measured with Planck, low-frequency radio data, and Faraday rotation measurements toward extragalactic sources. These components bear resemblance along the Galactic plane and in some regions such as the Fan and North Polar Spur regions. The poor match observed in other regions shows, however, that dust, cosmic-ray electrons, and thermal electrons generally sample different parts of the line of sight.
Reproduced with permission, © ESO, 201
Endothelin-1 as a neuropeptide: neurotransmitter or neurovascular effects?
Get PDFEndothelin-1 (ET-1) is an endothelium-derived peptide that also possesses potent mitogenic activity. There is also a suggestion the ET-1 is a neuropeptide, based mainly on its histological identification in both the central and peripheral nervous system in a number of species, including man. A neuropeptide role for ET-1 is supported by studies showing a variety of effects caused following its administration into different regions of the brain and by application to peripheral nerves. In addition there are studies proposing that ET-1 is implicated in a number of neural circuits where its transmitter affects range from a role in pain and temperature control to its action on the hypothalamo-neurosecretory system. While the effect of ET-1 on nerve tissue is beyond doubt, its action on nerve blood flow is often ignored. Here, we review data generated in a number of species and using a variety of experimental models. Studies range from those showing the distribution of ET-1 and its receptors in nerve tissue to those describing numerous neurally-mediated effects of ET-1
Patient-reported health-related quality of life after a displaced intra-articular calcaneal fracture: a systematic review
Full text linkObservação do desenvolvimento de linguagem e funções auditiva e visual em lactentes
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