Blanche de Castille

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-201

Fur Activates the Expression of Salmonella enterica Pathogenicity Island 1 by Directly Interacting with the hilD Operator In Vivo and In Vitro

Previous studies have established that the expression of Salmonella enterica pathogenicity island 1 (SPI1), which is essential for epithelial invasion, is mainly regulated by the HilD protein. The ferric uptake regulator, Fur, in turn modulates the expression of the S. enterica hilD gene, albeit through an unknown mechanism. Here we report that S. enterica Fur, in its metal-bound form, specifically binds to an AT-rich region (BoxA), located upstream of the hilD promoter (PhilD), at position -191 to -163 relative to the hilD transcription start site. Furthermore, in a PhilD variant with mutations in BoxA, PhilD*, Fur·Mn2+ binding is impaired. In vivo experiments using S. enterica strains carrying wild-type PhilD or the mutant variant PhilD* showed that Fur activates hilD expression, while in vitro experiments revealed that the Fur·Mn2+ protein is sufficient to increase hilD transcription. Together, these results present the first evidence that Fur·Mn2+, by binding to the upstream BoxA sequence, directly stimulates the expression of hilD in S. enterica

Classical Limit of Demagnetization in a Field Gradient

We calculate the rate of decrease of the expectation value of the transverse component of spin for spin-1/2 particles in a magnetic field with a spatial gradient, to determine the conditions under which a previous classical description is valid. A density matrix treatment is required for two reasons. The first arises because the particles initially are not in a pure state due to thermal motion. The second reason is that each particle interacts with the magnetic field and the other particles, with the latter taken to be via a 2-body central force. The equations for the 1-body Wigner distribution functions are written in a general manner, and the places where quantum mechanical effects can play a role are identified. One that may not have been considered previously concerns the momentum associated with the magnetic field gradient, which is proportional to the time integral of the gradient. Its relative magnitude compared with the important momenta in the problem is a significant parameter, and if their ratio is not small some non-classical effects contribute to the solution. Assuming the field gradient is sufficiently small, and a number of other inequalities are satisfied involving the mean wavelength, range of the force, and the mean separation between particles, we solve the integro- partial differential equations for the Wigner functions to second order in the strength of the gradient. When the same reasoning is applied to a different problem with no field gradient, but having instead a gradient to the z-component of polarization, the connection with the diffusion coefficient is established, and we find agreement with the classical result for the rate of decrease of the transverse component of magnetization.Comment: 22 pages, no figure

Radiation Hardness of Perovskite Solar Cells Based on Aluminum‐Doped Zinc Oxide Electrode Under Proton Irradiation

Due to their high specific power and potential to save both weight and stow volume, perovskite solar cells have gained increasing interest to be used for space applications. However, before they can be deployed into space, their resistance to ionizing radiations such as high‐energy protons must be demonstrated. In this report, we investigate the effect of 150 keV protons on the performance of perovskite solar cells based on aluminium‐doped zinc oxide (AZO) transparent conducting oxide (TCO). Record power conversion efficiency of 15% and 13.6% were obtained for cells based on AZO under AM1.5G and AM0 illumination, respectively. We demonstrate that perovskite solar cells can withstand proton irradiation up to 1013 protons.cm−2 without significant loss in efficiency. At this irradiation dose, Si or GaAs solar cells would be completely or severely degraded when exposed to 150 keV protons. From 1014 protons.cm−2, a decrease in short‐circuit current of the perovskite cells is observed, which is consistent with interfacial degradation due to deterioration of the Spiro‐OMeTAD HTL during proton irradiation. Using a combination of non‐destructive characterization techniques, results suggest that the structural and optical properties of perovskite remain intact up to high fluence levels. Although shallow trap states are induced by proton irradiation in perovskite bulk at low fluence levels, they can release charges efficiently and are not detrimental to the cell's performance. This work highlights the potential of perovskite solar cells based on AZO TCO to be used for space applications and give a deeper understanding of interfacial degradation due to proton irradiation

Acetylsalicylic acid prevents intermittent hypoxia-induced vascular remodeling in a murine model of sleep apnea

Study objectives: Chronic intermittent hypoxia (CIH), a hallmark feature of obstructive sleep apnea (OSA), induces accelerated atherogenesis as well as aorta vascular remodeling. Although the cyclooxygenase (COX) pathway has been proposed to contribute to the cardiovascular consequences of OSA, the potential benefits of a widely employed COX-inhibitor such (acetylsalicylic acid, ASA) on CIH-induced vascular pathology are unknown. Therefore, we hypothesized that a common non-selective COX inhibitor such as ASA would attenuate the aortic remodeling induced by CIH in mice. Methods: 40 wild-type C57/BL6malemice were randomly allocated to CIH or normoxic exposures (N) and treated with daily doses of ASA or placebo for 6 weeks. At the end of the experiments, intima-media thickness (IMT), elastin disorganization (ED), elastin fragmentation (EF), length between fragmented fiber endpoints (LFF), aortic wall collagen abundance (AC) and mucoid deposition (MD) were assessed. Results: Compared to N, CIH promoted significant increases in IMT (52.58 ± 2.82μm vs. 46.07 ± 4.18μm, p < 0.003), ED (25.29 ± 14.60% vs. 4.74 ± 5.37%, p < 0.001), EF (5.80 ± 2.04 vs. 3.06 ± 0.58, p < 0.001), LFF (0.65 ± 0.34% vs. 0.14 ± 0.09%, p < 0.001), AC (3.43 ± 1.52% vs. 1.67 ± 0.67%, p < 0.001) and MD (3.40 ± 2.73 μm2 vs. 1.09 ± 0.72 μm2, p < 0.006). ASA treatment mitigated the CIH-induced alterations in IMT: 44.07 ± 2.73μm; ED: 10.57 ± 12.89%; EF: 4.63 ± 0.88; LFF: 0.25 ± 0.17% and AC: 0.90 ± 0.13% (p<0.05 for all comparisons). Conclusions: ASA prevents the CIH-induced aortic vascular remodeling, and should therefore be prospectively evaluated as adjuvant treatment in patients with OSA.This work was supported by the Spanish Respiratory Society (SEPAR), SOCAP, the Associació Lleidatana de Respiratori (ALLER), and the Spanish Fondo de Investigaciones Sanitarias (PI14/00486 and PI14-00004), Instituto de Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”. DG is supported by National Institutes of Health grant HL130984

Integrated transcriptomics establish macrophage polarization signatures and have potential applications for clinical health and disease

Growing evidence defines macrophages (Mφ) as plastic cells with wide-ranging states of activation and expression of different markers that are time and location dependent. Distinct from the simple M1/M2 dichotomy initially proposed, extensive diversity of macrophage phenotypes have been extensively demonstrated as characteristic features of monocyte-macrophage differentiation, highlighting the difficulty of defining complex profiles by a limited number of genes. Since the description of macrophage activation is currently contentious and confusing, the generation of a simple and reliable framework to categorize major Mφ phenotypes in the context of complex clinical conditions would be extremely relevant to unravel different roles played by these cells in pathophysiological scenarios. In the current study, we integrated transcriptome data using bioinformatics tools to generate two macrophage molecular signatures. We validated our signatures in in vitro experiments and in clinical samples. More importantly, we were able to attribute prognostic and predictive values to components of our signatures. Our study provides a framework to guide the interrogation of macrophage phenotypes in the context of health and disease. The approach described here could be used to propose new biomarkers for diagnosis in diverse clinical settings including dengue infections, asthma and sepsis resolution