60 research outputs found
The African swine fever virus dynein-binding protein p54 induces infected cell apoptosis
AbstractA specific interaction of ASFV p54 protein with 8 kDa light chain cytoplasmic dynein (DLC8) has been previously characterized and this interaction is critical during virus internalization and transport to factory sites. During early phases of infection, the virus induces the initiation of apoptosis triggering activation of caspase-9 and -3. To analyze the role of the structural protein p54 in apoptosis, transient expression experiments of p54 in Vero cells were carried out which resulted in effector caspase-3 activation and apoptosis. Interestingly, p54 mutants, lacking the 13 aa dynein-binding motif lose caspase activation ability and pro-death function of p54. This is the first reported ASFV protein which induces apoptosis
AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients
[Abstract] Introduction.
One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection
(AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and
treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in
HT patients can yield diagnostic and prognostic information about AMR.
Methods.
Genetic variants in 61 genes related to B-cell biology were analyzed by next generation
sequencing in 46 HT patients, 23 with and 23 without AMR.
Results.
We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G,
and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated
with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4
present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype
in control patients.
Conclusion.
We can conclude that polymorphisms in genes related to the biology of B-cells could have
an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene
could potentially increase the risk of AMR.Instituto de Salud Carlos III; PI13/0217
A new wildland fire danger index for a Mediterranean region and some validation aspects
Wildland fires are the main cause of tree mortality in Mediterranean Europe and a major threat to Spanish forests. This paper focuses on the design and validation of a new wildland fire index especially adapted to a Mediterranean Spanish region. The index considers ignition and spread danger components. Indicators of natural and human ignition agents, historical occurrence, fuel conditions and fire spread make up the hierarchical structure of the index. Multi-criteria methods were used to incorporate experts¿ opinion in the process of weighting the indicators and to carry out the aggregation of components into the final index, which is used to map the probability of daily fire occurrence on a 0.5-km grid. Generalised estimating equation models, which account for possible correlated responses, were used to validate the index, accommodating its values onto a larger scale because historical records of daily fire occurrence, which constitute the dependent variable, are referred to cells on a 10-km grid. Validation results showed good index performance, good fit of the logistic model and acceptable discrimination power. Therefore, the index will improve the ability of fire prevention services in daily allocation of resources.The authors acknowledge the support received from the Ministry of Science and Innovation through the research project Modelling and Optimisation Techniques for a Sustainable Development, Ref. EC02008-05895-C02-01/ECON.Vicente López, FJD.; Crespo Abril, F. (2012). A new wildland fire danger index for a Mediterranean region and some validation aspects. 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Joint Observation of the Galactic Center with MAGIC and CTA-LST-1
MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations
Infrared and Millimetric Study of the Young Outflow Cepheus E
The Cepheus E outflow has been studied in the mid and far infrared using the ISO CAM and LWS instruments, and at millimetric wavelengths using OVRO. In the near and mid-IR, its morphology is similar to that expected for a jet driven outflow, where the leading bow shocks entrain and accelerate the surrounding molecular gas. As expected, fine structure atomic/ionic emission lines arise from the bow shocks, at both the Mach Disk and the stagnation tip, where J-shocks are dominant
Infrared and Millimetric Study of the Young Outflow Cepheus E
The Cepheus E outflow has been studied in the mid- and far-IR using the ISOCAM and Long Wavelength Spectrometer (LWS) instruments and at millimetric wavelengths using the Owens Valley Radio Observatory (OVRO). In the near- and mid-IR, its morphology is similar to that expected for a jet-driven outflow, where the leading bow shocks entrain and accelerate the surrounding molecular gas. As expected, fine-structure atomic/ionic emission lines arise from the bow shocks, at both the Mach disk and the stagnation tip, where J-shocks are dominant. The H2, H2O, and CO molecular emission could arise farther ``downstream'' at the bow shock wings where the shocks (v=8-35 km s-1) are oblique and more likely to be C-type. The 13CO emission arises from entrained molecular gas, and a compact high-velocity emission is observed, together with an extended low-velocity component that almost coincides spatially with the H2 near-IR emission. The millimetric continuum emission shows two sources. We identify one of them with IRAS 23011+6126, postulating that it is the driver of the Cepheus E outflow; the other, also an embedded source, is likely to be driving one of the other outflows observed in the region. Finally, we suggest that the strong [C II] 158 μm emission must originate from an extended photodissociation region, very likely excited by the nearby Cepheus OB3 association
Promoter analysis of the DHCR24 (3β-hydroxysterol Δ24-reductase) gene: characterization of SREBP (sterol-regulatoryelement-binding protein)-mediated activation
DHCR24 (3β-hydroxysterol Δ24-reductase) catalyses the reduction of the C-24 double bond of sterol intermediates during cholesterol biosynthesis. DHCR24 has also been involved in cell growth, senescence and cellular response to oncogenic and oxidative stress. Despite its important roles, little is known about the transcriptional mechanisms controlling DHCR24 gene expression. We analysed the proximal promoter region and the cholesterol-mediated regulation of DHCR24. A putative SRE (sterol-regulatory element) at −98/−90 bp of the transcription start site was identified. Other putative regulatory elements commonly found in SREBP (SRE-binding protein)-targeted genes were also identified. Sterol responsiveness was analysed by luciferase reporter assays of approximately 1 kb 5′-flanking region of the human DHCR24 gene in HepG2 and SK-N-MC cells. EMSAs (electrophoretic mobility-shift assays) and ChIP (chromatin immunoprecipitation) assays demonstrated cholesterol-dependent recruitment and binding of SREBPs to the putative SRE. Given the presence of several CACCC-boxes in the DHCR24 proximal promoter, we assessed the role of KLF5 (Krüppel-like factor 5) in androgen-regulated DHCR24 expression. DHT (dihydrotestosterone) increased DHCR24 expression synergistically with lovastatin. However, DHT was unable to activate the DHCR24 proximal promoter, whereas KLF5 did, indicating that this mechanism is not involved in the androgen-induced stimulation of DHCR24 expression. The results of the present study allow the elucidation of the mechanism of regulation of the DHCR24 gene by cholesterol availability and identification of other putative cis-acting elements which may be relevant for the regulation of DHCR24 expression
Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N
Mycobacterium tuberculosis, the causative agent of human tuberculosis, is forced into latency by nitric oxide produced by macrophages during infection. In response to nitrosative stress M. tuberculosis has evolved a defense mechanism that relies on the oxygenated form of "truncated hemoglobin" N (trHbN), formally acting as NO-dioxygenase, yielding the harmless nitrate ion. X-ray crystal structures have shown that trHbN hosts a two-branched protein matrix tunnel system, proposed to control diatomic ligand migration to the heme, as the rate-limiting step in NO conversion to nitrate. Extended molecular dynamics simulations (0.1 mu s), employed here to characterize the factors controlling diatomic ligand diffusion through the apolar tunnel system, suggest that O-2 migration in deoxy-trHbN is restricted to a short branch of the tunnel, and that O-2 binding to the heme drives conformational and dynamical fluctuations promoting NO migration through the long tunnel branch. The simulation results suggest that trHbN has evolved a dual-path mechanism for migration of O-2 and NO to the heme, to achieve the most efficient NO detoxification
Occurrence of South American fur seals Arctocephalus australis (Zimmermann, 1783) in San Mat\uedas Gulf, Patagonia, Argentina
The South American fur seal, Arctocephalus australis (SAFS) population suffered a drastic reduction due to commercial exploitation during the eighteenth and nineteenth centuries. In the last decades a population recovery was detected on the Atlantic region. However, in this region, many aspects of the ecology of the SAFS, such as the post-reproductive dispersal of individuals, the location of feeding areas, and the migration routes between colonies in the southern border of its distribution. are still unknown. Here, we report for the first time the occupation of San Matías Gulf (SMG, Northern Patagonia, Argentina) by this species. We found that more than 1,600 SAFS used SMG between May and October (post-reproductive season) and detected a non-reproductive colony on Lobos Islet (41°24´S, 65°03´W). The presence of SAFS in SMG is recent and would be associated with an increase of the population. The importance of SMG in the ecology of SAFS seems to lie on three factors: the strategic location in the geographic context of its potential migration routes, the physical environment suitable for coastal settlements, and the availability of food resources.La población del lobo marino de dos pelos sudamericano Arctocephalus australis (SAFS) sufrió
una drástica reducción durante los siglos XVIII y XIX. En las últimas décadas se observó la recuperación poblacional en su distribución en la región Atlántica. Sin embargo, en esta región todavía se desconocen muchos aspectos sobre la ecología de los SAFS tales como la distribución post-reproductiva de los individuos, ubicación de las zonas de alimentación y desplazamientos de individuos entre los apostaderos que se ubican en los límites de su distribución geográfica. En este trabajo se registra por primera vez la presencia de esta especie en el golfo San Matías (SMG, norte de Patagonia, Argentina). Se encontró que al menos 1.600 SAFS utilizan el SMG entre mayo y octubre (temporada post-reproductiva) y se detectó un apostadero no reproductivo en el Islote Lobos (41°24'S, 65°03'W). La presencia de los SAFS en el SMG es reciente y la misma estaría asociada al incremento de la población en la región Atlántica. La importancia del SMG en la ecología de los SAFS se debería a tres factores: ubicación estratégica en el contexto geográfico de potenciales movimientos de individuos entre apostaderos distantes, disponibilidad de ambiente físico apropiado para el asentamiento en tierra, y disponibilidad de recursos alimenticios.Fil: Svendsen, Guillermo. Universidad Nacional del Comahue. Instituto de Biologia Marina y Pesquera Almirante Storni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dans, Silvana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: González, Raul Alberto Candido. Universidad Nacional del Comahue. Instituto de Biologia Marina y Pesquera Almirante Storni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Romero, Maria Alejandra. Universidad Nacional del Comahue. Instituto de Biologia Marina y Pesquera Almirante Storni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Crespo, Enrique Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentin
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