Resultados de investigación

Mitochondria play a crucial role in cellular energy production, signaling and homeostasis. Respiratory supercomplexes represent evolutionary well-conserved, stable associations between membrane complexes and molecules, including proteins and lipids, within the inner mitochondrial membrane. They dynamically respond to metabolic demands and enhance the electron transfer rate, thereby reducing the production of ROS. Recent research has unveiled cytochrome c, a mobile electron carrier between complexes III and IV, as a potential key player in orchestrating the formation of these supra-associations. This study centers on elucidating the role of cytochrome c in modulating the assembly of supercomplexes, using the Saccharomyces cerevisiae yeast as a model system for mitochondrial metabolism. BN-PAGE and mass spectrometry-based proteomic analysis were employed to examine supercomplex organization in yeast strains expressing different cytochrome c isoforms, grown under fermentative and respiratory conditions. Our results demonstrate that both isoforms of cytochrome c contribute to supercomplex assembly, with isoform-2 significantly improving electron transfer and lowering ROS levels. We propose a model in which cytochrome c acts as a scaffold for the recruitment of assembly factors, facilitating the formation of higher order supercomplexes such as III2IV2. This model highlights cytochrome c's role beyond electron transfer, as it regulates supercomplex assembly and mitochondrial homeostasis., File name: Otras-figuras_Ms_IJBM.docx Description: A Word file with the figure images File name: Raw_data.zip Description: .nox files with the raw data of voltammetry File name: Fig_2+S5+S6+S7.jnb Description: A sigmaplot file with figures 2+S5+S6+S7

Post-translational modifications (PTMs) of proteins are ubiquitous processes present in all life kingdoms, involved in the regulation of protein stability, subcellular location and activity. In this context, cytochrome c (Cc) is an excellent case study to analyze the structural and functional changes induced by PTMS as Cc is a small, moonlighting protein playing different roles in different cell compartments at different cell-cycle stages. Cc is actually a key component of the mitochondrial electron transport chain (ETC) under homeostatic conditions but is translocated to the cytoplasm and even the nucleus under apoptotic conditions and/or DNA damage. Phosphorylation does specifically alter the Cc redox activity in the mitochondria and the Cc non-redox interaction with apoptosis-related targets in the cytoplasm. However, little is known on how phosphorylation alters the interaction of Cc with histone chaperones in the nucleus. Here, we report the effect of Cc Tyr48 phosphorylation by examining the protein interaction with SET/TAF-Iβ in the nuclear compartment using a combination of molecular dynamics simulations, biophysical and structural approaches such as isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) and in cell proximity ligation assays. From these experiments, we infer that Tyr48 phosphorylation allows a fine-tuning of the Cc-mediated inhibition of SET/TAF-Iβ histone chaperone activity in vitro. Our findings likewise reveal that phosphorylation impacts the nuclear, stress-responsive functions of Cc, and provide an experimental framework to explore novel aspects of Cc post-translational regulation in the nucleus., File name: Figuras_Ms_Protein_science.docx Description: A Word file with the figure images File name: Figure_S6a,b,c.jnb Description: A sigmaplot file with figures S6 File name: Raw_data_061023.zip Description: .nox files with the raw data

The dataset contains the results from transmission electron microscopy, particle size distribution, Raman spectroscopy and optical absorbance of Boron nitride nanosheet (BNNS) suspensions obtained by kitchen blender exfoliation at three rotor velocities. It also contains the results of the microstructural chracterization by scanning electron microscopy of spark plasma sintered ceramic composites with 3 mol% yttria tetragonal zirconia policrystal (3YTZP) matrix and different BNNS contents (1, 2.5 and 5 vol%), and their low temperature hydrothermal degradation study., Absorbance spectra Particle size distributions Raman spectra Scanning electron microscopy images from the fracture surfaces and polished cross section surfaces of the analyzed composites Hydrothermal ageing data

The dataset contains the results from X-ray diffraction, Raman spectroscopy and impedance spectroscopy studies of ceramic composites with 8 mol% yttria cubic stabilized zirconia (8YCSZ) matrix and different contents of reduced graphene oxide (rGO, 1, 2.5, 5 and 10 vol%). The composites were spark plasma sintered at 1300 and 1350 ºC. The dataset also includes scanning electron microscopy images of the sintered composites., Difractogramas de rayos X Espectros Raman Diagramas Nyquist Curvas Arrhenius de conductividad Imágenes de microscopía electrónica de barrido de las superficies de fractura, y de las superficies pulidas, de los compuestos analizados.

Literacy research from a neo-materialist and post-human perspective attends to the relations and affects among human and non-human bodies, in which the label "more-than-human" appeals to a non-hierarchical view of matter, whether it is of human or non-human origin. Such relationships are materialised in childhood, among other ways, in movements, gestures, linguistic and non-linguistic sounds. However, educational research tends to be based primarily on visual or audiovisual data, with a clear tendency towards occulocentrism. In this paper we propose an analysis and reflection based on strictly auditory data, and we explore the implications that the absence of image has on the elaboration, presentation and analysis. To this aim we focus on an event in an early childhood education classroom, in which different layers of linguistic and non-linguistic sounds overlay without any visual support, and we show the strategies implemented by the researchers to construct the data from a post-qualitative approach. The conclusions of this analysis lead us not only to reformulate the way in which children relate to sound, listening and time, but also the implications for the adult conception of these dimensions in educational settings., La investigación sobre alfabetización desde una perspectiva neomaterialista y posthumana atiende las relaciones y afectos que se establecen entre los cuerpos humanos y no humanos, en los que la etiqueta de “más-que-humanos" apela a una visión no jerárquica de la materia, sea esta de origen humano o no. Dichas relaciones se materializan en la infancia, entre otros, en movimientos, gestos, sonidos lingüísticos y no lingüísticos. Sin embargo, la investigación educativa suele basarse en datos visuales o audiovisuales, con una clara tendencia al oculocentrismo. En esta comunicación proponemos un análisis y reflexión partiendo de datos estrictamente auditivos, y exploramos las implicaciones que la ausencia de imagen tiene en la elaboración, presentación y análisis. Para ello, nos centramos en un evento generado el 10/03/2023 en un aula de Educación Infantil del CEIP Almutamid en el que se superponen diferentes sonidos lingüísticos y no lingüísticos sin soporte visual, y mostramos cuáles son las estrategias implementadas por las investigadoras para construir el dato desde un enfoque postcualitativo. Nuestras conclusiones nos llevan no solo a reformular la manera en la que los niños se relacionan con el sonido, con el acto de escuchar y con el tiempo sino también las implicaciones en la concepción adulta de estas dimensiones en entornos educativos., En este marco se sitúan nuestros datos: la transcripción de la grabación de los datos sonoros generados por los niños, la maestra y la investigadora, además del podcast emitido por Radio Nacional de España (RNE).

Nuclear Magnetic Resonance Spectra of proton and carbon, High Resolution Mass Spectra and X-rays of the synthesized compounds named as EBIs. Biological Assays and Docking., Espectros de Resonancia Magnética Nuclear de protón y carbono, Espectros de Masas de Alta Resolución, Rayos X, Caracterización de compuestos, datos de ensayos de actividad biológica, solubilidad, reglas de lipinski, HPLC/Masas y bibliografía., Resonancia Magnética Nuclear; Espectrometría de masas; Rayos X; Caracterización química; Ensayos biológicos; Solubilidad; Reglas de Lipinski; HPLC/MS; Bibliografía.

Datos de monitorización de viviendas en Burkina Faso.

Response determinants to immunotherapy in metastatic pancreatic ductal adenocarcinoma (mPDAC) remain unclear, limiting treatment advancements. We report a single-arm phase 1b/2 study (OPTIMIZE-1) evaluating the safety and efficacy of the cluster of differentiation 40 (CD40) agonist mitazalimab combined with modified FOLFIRINOX (mFOLFIRINOX), in chemotherapy-naive patients with mPDAC. Patients receive an initial dose of mitazalimab one week before starting biweekly cycles of mFOLFIRINOX plus mitazalimab. The study meets its pre-specified primary endpoint, achieving a confirmed objective response rate (ORR) of 42.1%. Median duration of response, progression-free survival, and overall survival was 12.6 months, 7.7 months, and 14.9 months, respectively. Multi-omic analyses of tumor and blood specimens identify a baseline tumor-intrinsic gene signature related to fibrosis associated with improved survival. Additionally, mitazalimab-induced increases in activated circulating myeloid, B cell, and T cell frequencies correlate with better outcomes. These results may inform future patient stratification strategies supporting a planned randomized confirmatory trial of mitazalimab with mFOLFIRINOX in mPDAC. This study was registered at ClinicalTrials.gov (NCT04888312)., Si

The tryptophan-kynurenine pathway is linked to inflammation. We hypothesize that metabolites implicated in this pathway may be associated with the risk of heart failure (HF) or atrial fibrillation (AF) in a population at high risk of cardiovascular disease. We aimed to prospectively analyze the associations of kynurenine-related metabolites with the risk of HF and AF and to analyze a potential effect modification by the randomized interventions of the PREDIMED (Prevención con Dieta Mediterránea) trial with Mediterranean diet (MedDiet). Two case-control studies nested within the PREDIMED trial were designed. We selected 324 incident HF cases and 502 incident AF cases individually matched with ≤3 controls. Conditional logistic regression models were fitted. Interactions with the intervention were tested for each of the baseline plasma metabolites measured by LC-tandem MS. Higher baseline kynurenine:tryptophan ratio (OR for 1 SD: 1.20; 95% CI: 1.01, 1.43) and higher levels of kynurenic acid (OR: 1.19; 95% CI: 1.01, 1.40) were associated with HF. Quinolinic acid was associated with AF (OR: 1.15; 95% CI: 1.01, 1.32) and HF (OR: 1.25; 95% CI: 1.04, 1.49). The MedDiet intervention modified the positive associations of kynurenine (Pinteraction = 0.006), kynurenic acid (Pinteraction = 0.008), and quinolinic acid (Pinteraction = 0.033) with HF and the association between kynurenic acid and AF (Pinteraction = 0.02). We found that tryptophan-kynurenine pathway metabolites were prospectively associated with higher HF risk and to a lesser extent with AF risk. Moreover, an effect modification by MedDiet was observed for the association between plasma baseline kynurenine-related metabolites and the risk of HF, showing that the positive association of increased levels of these metabolites and HF was restricted to the control group., Sí

Background: Consumption of a Mediterranean diet, adequate levels of physical activity, and energy-restricted lifestyle interventions have been individually associated with improvements in HDL functions. Evidence of intensive interventions with calorie restriction and physical activity is, however, scarce. Objectives: To determine whether an intensive lifestyle intervention with an energy-restricted Mediterranean diet plus physical activity enhanced HDL function compared to a non-hypocaloric Mediterranean eating pattern without physical activity. Methods: In 391 older adults with metabolic syndrome (mean age, 65 years; mean BMI, 33.3 kg/m2) from 1 of the Prevención con Dieta Mediterránea-Plus trial centers, we evaluated the impact of a 6-month intervention with an energy-restricted Mediterranean diet plus physical activity (intensive lifestyle; n = 190) relative to a nonrestrictive Mediterranean diet without physical activity (control; n = 201) on a set of HDL functional traits. These included cholesterol efflux capacity, HDL oxidative/inflammatory index, HDL oxidation, and levels of complement component 3, serum amyloid A, sphingosine-1-phosphate, triglycerides, and apolipoproteins A-I, A-IV, C-III, and E in apoB-depleted plasma. Results: The intensive-lifestyle intervention participants displayed greater 6-month weight reductions (-3.83 kg; 95% CI: -4.57 to -3.09 kg) but no changes in HDL cholesterol compared with control-diet participants. Regarding HDL functional traits, the intensive lifestyle decreased triglyceride levels (-0.15 mg/g protein; 95% CI: -0.29 to -0.014 mg/g protein) and apoC-III (-0.11 mg/g protein; 95% CI: -0.18 to -0.026 mg/g protein) compared to the control diet, with weight loss being the essential mediator (proportions of mediation were 77.4% and 72.1% for triglycerides and apoC-III levels in HDL, respectively). Conclusions: In older adults with metabolic syndrome, an energy-restricted Mediterranean diet plus physical activity improved the HDL triglyceride metabolism compared with a nonrestrictive Mediterranean diet without physical activity. This trial is registered at isrctn.com as ISRCTN89898870., This work was supported by the Instituto de Salud Carlos III (grant numbers: CB06/03/0028, CD17/00122, IFI16/00012, PI15/00047, PI18/00020, and P19/00017), Fundació La Marató de TV3 (grant number: 201512.31), Agència de Gestió d’Ajuts Universitaris i de Recerca (grant number: 2017 BP 00021, 2017 SGR 222, SLT002/16/00088), and the European Regional Development Fund., Sí