385 research outputs found
Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iß by cytochrome c
Chromatin is pivotal for regulation of the DNA damage process insofar as it influences access to DNA and serves as a DNA repair docking site. Recent works identify histone chaperones as key re- gulators of damaged chromatin’s transcriptional activity. However, understanding how chaperones are modulated during DNA damage response is still challenging. This study reveals that the histone chap- erone SET/TAF-Iß interacts with cytochrome c following DNA damage. Specifically, cytochrome c is shown to be translocated into cell nuclei upon induction of DNA damage, but not upon stimulation of the death receptor or stress-induced pathways. Cytochrome c was found to competitively hinder binding of SET/TAF-Iß to core histones, thereby locking its histone-binding domains and inhibiting its nucle- osome assembly activity. In addition, we have used NMR spectros- copy, calorimetry, mutagenesis, and molecular docking to provide an insight into the structural features of the formation of the complex between cytochrome c and SET/TAF-Iß. Overall, these findings estab- lish a framework for understanding the molecular basis of cyto- chrome c-mediated blocking of SET/TAF-Iß, which subsequently may facilitate the development of new drugs to silence the oncogenic effect of SET/TAF-Iß’s histone chaperone activity
Annual dune plant communities in the Southwest coast of Europe
This study presents an updated sintaxonomic review of the annual communities from coastal dunes in the Southwest coast of
Europe, specifically in the Iberian Peninsula, including both types: directly influenced by the sea salt spray and not affected
by this influence. The floristic segregation of the different plant associations was obtained by statistical agglomerative
processes (UPGMA, Unweighted Pair Group Method with Arithmetic Mean) plus principal coordinate analysis (PCoA) and
discussed based on the interpretation of phytosociological tables. Three new communities in central western Portugal were
found and are described: Pseudorlayo minusculae-Polycarpietum alsinifoli, Cerastio diffusae-Vulpietum fontqueranae and
Omphalodo kunzinskyanae-Evacietum ramosissimae
Implications of the Molybdenum Coordination Environment in MFI Zeolites on Methane Dehydroaromatisation Performance
The structure and activity of Mo/Silicalite‐1 (MFI, Si/Al=∞) were compared to Mo/H‐ZSM‐5 (MFI, Si/Al=15), a widely studied catalyst for methane dehydroaromatisation (MDA). The anchoring mode of Mo was evaluated by in situ X‐ray absorption spectroscopy (XAS) and density functional theory (DFT). The results showed that in Mo/Silicalite‐1, calcination leads to dispersion of MoO3 precursor into tetrahedral Mo‐oxo species in close proximity to the microporous framework. A weaker interaction of the Mo‐oxo species with the Silicalite‐1 was determined by XAS and DFT. While both catalysts are active for MDA, Mo/Silicalite‐1 undergoes rapid deactivation which was attributed to a faster sintering of Mo species leading to the accumulation of carbon deposits on the zeolite outer surface. The results shed light onto the nature of the Mo structure(s) while evidencing the importance of framework Al in stabilising active Mo species under MDA conditions
Structure of the Collision Zone Between the Nazca Ridge and the Peruvian Convergent Margin: Geodynamic and Seismotectonic Implications
We study the structure and tectonics of the collision zone between the Nazca Ridge (NR) and the Peruvian margin constrained by seismic, gravimetric, bathymetric, and natural seismological data. The NR was formed in an on-ridge setting, and it is characterized by a smooth and broad shallow seafloor (swell) with an estimated buoyancy flux of ~7 Mg/s. The seismic results show that the NR hosts an oceanic lower crust 10–14 km thick with velocities of 7.2–7.5 km/s suggesting intrusion of magmatic material from the hot spot plume to the oceanic plate. Our results show evidence for subduction erosion in the frontal part of the margin likely enhanced by the collision of the NR. The ridge-trench collision zone correlates with the presence of a prominent normal scarp, a narrow continental slope, and (uplifted) shelf. In contrast, adjacent of the collision zone, the slope does not present a topographic scarp and the continental slope and shelf become wider and deeper. Geophysical and geodetic evidence indicate that the collision zone is characterized by low seismic coupling at the plate interface. This is consistent with vigorous subduction erosion enhanced by the subducting NR causing abrasion and increase of fluid pore pressure at the interplate contact. Furthermore, the NR has behaved as a barrier for rupture propagation of megathrust earthquakes (e.g., 1746 Mw 8.6 and 1942 Mw 8.1 events). In contrast, for moderate earthquakes (e.g., 1996 Mw 7.7 and 2011 Mw 6.9 events), the NR has behaved as a seismic asperity nucleating at depths >20 km
Calibration methodology for air pollutants dispersion models. Case Study: PM10 dispersion in the surroundings of Havana.
[EN] This paper describes a general methodology for calibration of air pollutants dispersion models. Numerical simulation of this phenomenon is a complex process due to it depends on many factors. Main contribution of this paper is to consider in a unique calibration methodology of uncertainty and sensitivity analysis. Furthermore, the methodology is applied successfully in the calibration process gaussian dispersion model ISCST3 applied in a densely populated area, the Higher Polytechnic Institute José Antonio Echeverría (CUJAE) in Havana.[ES] El presente documento describe una metodología general para la calibración de modelos de dispersión de contaminantes atmosféricos. La simulación numérica de este fenómeno es un proceso complejo debido a la cantidad de factores de los que depende. La principal contribución de este trabajo es la consideración conjunta en una única metodología del análisis de incertidumbre y el de sensibilidad. Asimismo, se aplica con gran éxito en el proceso de calibración del modelo gaussiano de dispersión ISCST3, implementado en un área densamente poblada, el Instituto Superior Politécnico José Antonio Echeverría (CUJAE) ubicado en La Habana.González Cruz, MB.; Pire Rivas, S.; Cuesta Zedeño, LF.; López Jiménez, PA. (2013). Metodología para la calibración de modelos de dispersión de contaminantes atmosféricos. Caso de estudio: dispersión de PM10 en el entorno de La Habana. Revista Facultad de Ingeniería Universidad de Antioquia. (69):274-288. http://hdl.handle.net/10251/113269S2742886
Exciton and multiexciton optical properties of single InAs/GaAs site-controlled quantum dots
[EN] We have studied the optical properties of InAs site-controlled quantum dots (SCQDs) grown on pre-patterned GaAs substrates. Since InAs nucleates preferentially on the lithography motifs, the location of the resulting QDs is determined by the pattern, which is fabricated by local oxidation nanolithography. Optical characterization has been performed on such SCQDs to study the fundamental and excited states. At the ground state different exciton complex transitions of about 500 μeV linewidth have been identified and the fine structure splitting of the neutral exciton has been determined (≈65 μeV). The observed electronic structure covers the demands of future quantum information technologiesThe authors want to acknowledge the financial support from Spanish government through grants QD-NANOTICS: TEC2011-29120-C05-01, EPIC-NANOTICS: TEC2011-29120-C05-04, PROMESA: ENE2012-37804-C02-02, and Q&C Light: S2009ESP-1503. We also thank the support from the PROMETEO2009/74 project (Generalitat Valenciana). J.C.-F. thanks the Spanish MCI for his FPI grant (No. BES-2006-12300) and J.H. acknowledges to the JAE program for the funds.Canet-Ferrer, J.; Muñoz Matutano, G.; Herranz, J.; Rivas, D.; Alén, B.; González, Y.; Fuster, D.... (2013). Exciton and multiexciton optical properties of single InAs/GaAs site-controlled quantum dots. Applied Physics Letters. 103(18). https://doi.org/10.1063/1.4828352S1031
Reseñas
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Dissecting the role of TP53 alterations in del(11q) chronic lymphocytic leukemia
© 2021 The Authors.[Background]: Several genetic alterations have been identified as driver events in chronic lymphocytic leukemia (CLL) pathogenesis and oncogenic evolution. Concurrent driver alterations usually coexist within the same tumoral clone, but how the cooperation of multiple genomic abnormalities contributes to disease progression remains poorly understood. Specifically, the biological and clinical consequences of concurrent high-risk alterations such as del(11q)/ATM-mutations and del(17p)/TP53-mutations have not been established.[Methods]: We integrated next-generation sequencing (NGS) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques to characterize the in vitro and in vivo effects of concurrent monoallelic or biallelic ATM and/or TP53 alterations in CLL prognosis, clonal evolution, and therapy response.[Results]: Targeted sequencing analysis of the co-occurrence of high-risk alterations in 271 CLLs revealed that biallelic inactivation of both ATM and TP53 was mutually exclusive, whereas monoallelic del(11q) and TP53 alterations significantly co-occurred in a subset of CLL patients with a highly adverse clinical outcome. We determined the biological effects of combined del(11q), ATM and/or TP53 mutations in CRISPR/Cas9-edited CLL cell lines. Our results showed that the combination of monoallelic del(11q) and TP53 mutations in CLL cells led to a clonal advantage in vitro and in in vivo clonal competition experiments, whereas CLL cells harboring biallelic ATM and TP53 loss failed to compete in in vivo xenotransplants. Furthermore, we demonstrated that CLL cell lines harboring del(11q) and TP53 mutations show only partial responses to B cell receptor signaling inhibitors, but may potentially benefit from ATR inhibition.[Conclusions]: Our work highlights that combined monoallelic del(11q) and TP53 alterations coordinately contribute to clonal advantage and shorter overall survival in CLL.Spanish Fondo de Investigaciones Sanitarias, Grant/Award Numbers: PI15/01471, PI18/01500); Fundación Memoria Don Samuel Solórzano Barruso, Grant/Award Number: RD12/0036/006
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