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Abstract Cell cycle checkpoints, activated by stressful events, halt the cell cycle progression, and prevent the transmission of damaged DNA. These checkpoints prompt cell repair but also trigger cell death if damage persists. Decision-making between these responses is multifactorial and context-dependent, with the tumor suppressor p53 playing a central role. In many tumor cells, p53 alterations lead to G1/S checkpoint loss and the weakening of the G2 checkpoint, rendering cell viability dependent on the strength of the latter through mechanisms not fully characterized. Cells with a strong pro-survival drive can evade cell death despite substantial DNA lesions. Deciphering the integration of survival pathways with p53-dependent and -independent mechanisms governing the G2/M transition is crucial for understanding G2 arrest functionality and predicting tumor cell response to chemotherapy. The serine/threonine kinase GRK2 emerges as a signaling node in cell cycle modulation. In cycling cells, but not in G2 checkpoint-arrested cells, GRK2 protein levels decline during G2/M transition through a process triggered by CDK2-dependent phosphorylation of GRK2 at the S670 residue and Mdm2 ubiquitination. We report now that this downmodulation in G2 prevents the unscheduled activation of the PI3K/AKT pathway, allowing cells to progress into mitosis. Conversely, higher GRK2 levels lead to tyrosine phosphorylation by the kinase c-Abl, promoting the direct association of GRK2 with the p85 regulatory subunit of PI3K and AKT activation in a GRK2 catalytic-independent manner. Hyperactivation of AKT is conditioned by p53’s scaffolding function, triggering FOXO3a phosphorylation, impaired Cyclin B1 accumulation, and CDK1 activation, causing a G2/M transition delay. Upon G2 checkpoint activation, GRK2 potentiates early arrest independently of p53 through AKT activation. However, its ability to overcome the G2 checkpoint in viable conditions depends on p53. Our results suggest that integrating the GRK2/PI3K/AKT axis with non-canonical functions of p53 might confer a survival advantage to tumor cells.

Since 2017, targeted therapies combined with conventional intensive chemotherapy have started to improve outcome of patients with acute myeloid leukemia (AML). However, even before these innovations outcomes with intensive chemotherapy have improved, which has not yet been extensively studied. Thus, we used a large pan-European multicenter dataset of the HARMONY Alliance to evaluate treatment-time dependent outcomes over two decades. In 5359 AML patients, we compared the impact of intensive induction therapy on outcome over four consecutive 5-year calendar periods from 1997 to 2016. During that time, the 5- year survival of AML patients improved significantly, also across different genetic risk groups. In particular, the 60-day mortality rate has dropped from 13.0% to 4.7% over time. The independent effect of calendar periods on outcome was confirmed in multivariate models. Improvements were documented both for patients

Objective To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients.Methods Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3).Results Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p

Introducción: La Neuroartropatía de Charcot puede ser mal diagnosticada. Objetivo: Describir los elementos básicos para el diagnóstico de la Neuroartropatía de Charcot en personas con Diabetes mellitus. Material y Métodos: Se realizó una revisión bibliográfica descriptiva. Se utilizó como motor de búsqueda a Google Académico. Se empleo información de diferentes bases de datos. Las palabras clave utilizadas fueron: Diabetes mellitus; neuropatía diabética; neuroartropatía de Charcot; artropatía neuropática; pie de Charcot; pie diabético (en inglés y español). Se evaluaron artículos, que en general tenían menos de 10 años de publicados, en los idiomas referidos y que por el título trataban el tema de estudio. Fueron excluidos los que no abordaran la relación entre Diabetes mellitus y la neuroartropatía de Charcot. Se referenciaron 50 artículos. Desarrollo: La hiperglucemia persistente es causa de alteraciones neurotróficas, vasculares, inflamatorias e inmunológicas, que contribuyen a la aparición de la Neuroartropatía de Charcot, la cual se debe sospechar en personas con factores de riesgo que condicionan su aparición. Su diagnóstico es eminentemente clínico y puede evolucionar desde un estadio agudo (activo) a su etapa crónica (menos activa o inactiva). Las imágenes de Rx convencional y resonancia magnética de la zona afectada, pueden ayudar al diagnóstico positivo y diferencial. Conclusiones: El diagnóstico de la Neuroartropatía de Charcot, se realiza a través de la verificación de la existencia de factores de riesgo que condicionan su aparición en una persona con Diabetes mellitus. Su diagnóstico es predominantemente clínico y la imagenología, pueden ayudar al diagnóstico positivo y diferencial.

The bioactive potential of phenolic extracts derived from olive mill solid by-product (OMSbP), also called alperujo, and olive mill water (OMW), remains a topic of significant interest due to the amount of these, especially in Mediterranean regions, and their potential health benefits. In this study, the antioxidant and immunomodulatory properties of phenolic extracts obtained from OMSbP and OMW (OMSbP-P and OMW-P, respectively) in intestinal cells were evaluated. Initially, phenol-rich extracts were prepared by ethanol/ethyl acetate extraction and were characterized by HPLC-DAD analyses. The in vitro antioxidant activity showed potent bioactivities for all extracts evaluated. Toxicity assays did not reveal adverse effects on Caco-2 cell viability at concentrations relevant to immunomodulatory activity. Subsequently, the immunomodulatory effects of these extracts were assessed by measuring gene expression of pro- and anti-inflammatory cytokines. The results demonstrate that both OMSbP-P and OMW-P exhibit significant immunomodulatory activities, as evidenced by modulated cytokine gene expression in intestinal cells. Furthermore, molecular docking analyses of the identified phenols with the TLR4/MD2 receptor showed binding affinity, increasing the evidence that these extracts could exert immunomodulatory activity. Overall, our findings suggest that OMSbP-P and OMW-P possess promising immunomodulatory properties in intestinal cells, thus emphasizing their potential as natural therapeutic agents for managing immune-related disorders and promoting gut health. Further elucidation of the molecular mechanisms underlying these effects and in vivo studies are warranted to fully exploit the therapeutic potential of these extracts.

Not available.

Objectives To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD).Design Prospective population-based cohort study.Setting 10 primary healthcare centres in the north of the city of Madrid (Spain).Participants A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose

An ageing workforce and the coexistence of different generations in the same work environment has garnered the interest of practitioners and theoreticians with regard to the climate and interactions that occur between these generations. Although there are various instruments that attempt to measure the intergenerational climate in organizations, there are no studies that demonstrate the effectiveness of such instruments in the Spanish university context. This article presents the analysis of the psychometric properties of the Spanish version of the Workplace Intergenerational Climate Scale (WICS) adjusted to the specific context of higher education institutions and administered to a sample of 1,116 university teachers. After the analyses were carried out, an instrument with 16 items was obtained (4 less than the original questionnaire), and we can affirm that the resulting questionnaire is appropriate to measure the intergenerational climate among university teachers in the fields of teaching, research and management in the Spanish university context. However, more detailed, and individual analysis of each of the areas (i.e., teaching, research and management) would likely yield slightly different models but a better fit.

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Abstract Electrodes with nanostructured surface have emerged as promising low-impedance neural interfaces that can avoid the charge‐injection restrictions typically associated to microelectrodes. In this work, we propose a novel approximation, based on a two-step template assisted electrodeposition technique, to obtain flexible nanostructured electrodes coated with core–shell Ni–Au vertical nanowires. These nanowires benefit from biocompatibility of the Au shell exposed to the environment and the mechanical properties of Ni that allow for nanowires longer and more homogeneous in length than their only-Au counterparts. The nanostructured electrodes show impedance values, measured by electrochemical impedance spectroscopy (EIS), at least 9 times lower than those of flat reference electrodes. This ratio is in good accordance with the increased effective surface area determined both from SEM images and cyclic voltammetry measurements, evidencing that only Au is exposed to the medium. The observed EIS profile evolution of Ni–Au electrodes over 7 days were very close to those of Au electrodes and differently from Ni ones. Finally, the morphology, viability and neuronal differentiation of rat embryonic cortical cells cultured on Ni–Au NW electrodes were found to be similar to those on control (glass) substrates and Au NW electrodes, accompanied by a lower glial cell differentiation. This positive in-vitro neural cell behavior encourages further investigation to explore the tissue responses that the implantation of these nanostructured electrodes might elicit in healthy (damaged) neural tissues in vivo, with special emphasis on eventual tissue encapsulation.

Abstract Background The Peruvian ‘chanque’ or Chilean ‘loco’ Concholepas concholepas is an economically, ecologically, and culturally important muricid gastropod heavily exploited by artisanal fisheries in the temperate southeastern Pacific Ocean. In this study, we have profited from a set of bioinformatics tools to recover important biological information of C. concholepas from low-coverage short-read NGS datasets. Specifically, we calculated the size of the nuclear genome, ploidy, and estimated transposable elements content using an in silico k-mer approach, we discovered, annotated, and quantified those transposable elements, we assembled and annotated the 45S rDNA RNA operon and mitochondrial genome, and we confirmed the phylogenetic position of C. concholepas within the muricid subfamily Rapaninae based on translated protein coding genes. Results Using a k-mer approach, the haploid genome size estimated for the predicted diploid genome of C. concholepas varied between 1.83 Gbp (with kmer = 24) and 2.32 Gbp (with kmer = 36). Between half and two thirds of the nuclear genome of C. concholepas was composed of transposable elements. The most common transposable elements were classified as Long Interspersed Nuclear Elements and Short Interspersed Nuclear Elements, which were more abundant than DNA transposons, simple repeats, and Long Terminal Repeats. Less abundant repeat elements included Helitron mobile elements, 45S rRNA DNA, and Satellite DNA, among a few others.The 45S rRNA DNA operon of C. concholepas that encodes for the ssrRNA, 5.8S rRNA, and lsrRNA genes was assembled into a single contig 8,090 bp long. The assembled mitochondrial genome of C. concholepas is 15,449 bp long and encodes 13 protein coding genes, two ribosomal genes, and 22 transfer RNAs. Conclusion The information gained by this study will inform the assembly of a high quality nuclear genome for C. concholepas and will support bioprospecting and biomonitoring using environmental DNA to advance development of conservation and management plans in this overexploited marine snail.

The objective of this work was to assess the suitability of the Droplet-vitrification protocol previously developed with Agave peacockii shoot tips for the cryopreservation of six Agave species. Shoot tips were precultured for 1 day on a medium with 0.3 M sucrose in the dark, loaded in a solution with 1.6 M glycerol and 0.4 M sucrose for 20 min, and dehydrated by exposure to Plant Vitrification Solution 2 (PVS2) at 0 °C for 20 min. Complementary studies using histological analysis, Differential scanning calorimetry (DSC), and evaluation of morphological characteristics in cryo-derived plants were performed. Survival rates ranged from 84% to 100% and from 76% to 97% before and after cryopreservation regardless of the Agave species belonging to two taxonomic subgenera. Thermal analysis of shoot tips subjected to the successive steps of the Droplet-vitrification protocol identified ice crystal formation after loading treatment and glass transition after osmotic dehydration with PVS2. The average glass transition temperature (Tg) was −55.44 °C based on the results of four Agave species. The histological studies showed the anatomical differences that could be found in the meristematic structures depending on the loss of apical dominance. This is the most advanced research on cryopreservation of Agave shoot tips.

Metal pollution is a worldwide problem and one of the greatest threats to ecosystem integrity due to its toxicity, persistence, and bioaccumulation in biological systems. Anthropogenic pollution impacts marine organisms and host-parasite dynamics, with the northern Chilean coast experiencing elevated copper levels in marine waters and sediments due to mining activities. In this study, we assessed the effects of exposure to copper concentrations at low and high-water temperatures on the survival and longevity of the marine parasite Himasthla sp. cercariae (Trematoda: Digenea) using the snail Echinolittorina peruviana as its first intermediate host. Snails were collected from intertidal rocky pools in northern Chile (23°S). To assess parasite survival and longevity, cercariae were collected from a pool of infected snails, and their mortality was recorded every 6 hours until all cercariae were dead. In a preliminary experiment conducted at 19°C, cercariae were exposed to different copper concentrations (0.2, 1.5, 3.0, and 6.0 mg/L) for 78 hours. Cercariae showed tolerance to copper. However, at the higher copper concentration (6 mg/L), survival was negatively impacted (50%) at 54 hours. In contrast, at the lower concentration (0.2 mg/L) and in the control group, cercariae sustained a 73-90% survival rate even after 54 hours. Based on these findings, we conducted subsequent experiments involving two copper treatments (0.2 and 3.0 mg/L) and two temperatures (14 and 22°C). Survival and longevity were significantly higher at lower temperature and copper concentration (14°C and 0.2 mg/L). Conversely, at higher temperature and copper concentration (22°C and 3 mg/L), survival and longevity decreased to only 66 hours. Our results show that Himasthla sp. cercariae tolerated most copper concentrations, with vulnerability observed primarily in high water temperatures, indicating an adverse effect on cercariae performance. This study contributes valuable insights into how parasites respond to environmental pollution, in marine ecosystems influenced by anthropogenic activities.