Chloro­bis­(naphthalen-1-yl)phosphane

In the title compound, C20H14ClP, the dihedral angle between the naphthyl rings is 81.77 (6)°. The crystal packing suggests weak π–π stacking inter­actions between the naphthyl rings in adjacent units [minimum ring centroid separation 3.7625 (13) Å]

Demographics and clinical characteristics of a new population of Centenarians in Colombia. The COOLCEN cohort

Objetivo: los centenarios representan un modelo exitoso de envejecimiento biológico que se está volviendo cada vez más Común pero aún en gran medida desconocido. Los datos sobre centenarios en Colombia son escasos. El objetivo de esto El estudio fue para proporcionar una descripción de las características demográficas y clínicas de una nueva cohorte de centenarios en Colombia. Métodos: se realizó un estudio de cohorte retrospectivo y basado en la población, empleando un Registro validado proporcionado por una compañía de seguros de salud. Información demográfica y Se evaluaron las tasas de prevalencia de enfermedades crónicas significativas. La distribución geográfica de Los centenarios a nivel nacional fueron mapeados. Luego se compararon los datos con otros grupos de edad. (> 18-59 y 60-99 años), y con descripciones previas de centenarios. Resultados: Entre las 2.362.436 personas incluidas en el estudio, una prevalencia de 0.12% centenarios se observó, de los cuales 50.7% eran mujeres y la mayoría reside en las áreas urbanas (64.9%). Se observaron enfermedades crónicas en 275 (9.27%) centenarios, de los cuales 113 (3.81%) revelaron uno Enfermedad crónica y 162 (5.46%) revelada multimorbilidad. Las enfermedades crónicas más frecuentes eran hipertensión esencial (8,6%) y enfermedad renal crónica (4.4%), que fueron significativamente inferior en comparación con otros grupos de edad. Los centenarios estaban libres de hematológicos, inflamatorios Artritis, tuberculosis e infecciones por virus de inmunodeficiencia humana. Covid-19 se observó en 2% de los casos. Se observaron diferencias significativas en los resultados de salud evaluados al comparar nuestro Resultados con centenarios de zonas azules descritas anteriormente. Conclusiones: la cohorte Coolcen revela una baja prevalencia de enfermedades crónicas relacionadas con la edad, bajo Estado económico y sin diferencia en la distribución de género. El estudio proporcionará ideas valiosas en envejecimiento saludable, prevención de enfermedades y mejora del bienestar de los adultos mayores. Palabras clave: centenarios, envejecimiento, envejecimiento saludable, Colombia, multimorbilidad.Aim: Centenarians represent a successful model of biological aging that is becoming increasingly common but still largely unknown. Data about centenarians in Colombia is scarce. The aim of this study was to provide a description of the demographic and clinical characteristics of a new cohort of centenarians in Colombia. Methods: A retrospective, population-based cohort study was undertaken, employing a nationally validated registry provided by a health insurance company. Demographic information and prevalence rates of significant chronic diseases were evaluated. The geographical distribution of centenarians at the national level was mapped. Data were then compared with other age groups (>18-59 and 60-99 years-old), and with previous descriptions of centenarians. Results: Among the 2,362,436 persons included in the study, a prevalence of 0.12% centenarians was observed, of which 50.7% were female and the majority resides in urban areas (64.9%). Chronic diseases were observed in 275 (9.27%) centenarians, of whom 113 (3.81%) disclosed one chronic disease and 162 (5.46%) disclosed multimorbidity. The most prevalent chronic diseases were essential hypertension (8.6%), and chronic kidney disease (4.4%), which were significantly lower compared to others age groups. Centenarians were free of hematological, inflammatory arthritis, tuberculosis and human immunodeficiency virus infections. COVID-19 was observed in 2% of cases. Significant differences in health outcomes assessed were seen when comparing our results with centenarians from previously described blue zones. Conclusions: The COOLCEN cohort discloses a low prevalence of age-related chronic diseases, low economic status and no difference in gender distribution. The study will provide valuable insights into healthy aging, disease prevention, and improving the well-being of older adults. Key words: Centenarians, Aging, Healthy Aging, Colombia, Multimorbidity.https://orcid.org/0000-0003-0368-0577https://scholar.google.com/citations?user=hG_TD_sAAAAJ&hl=es&oi=aohttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000175361Revista Internacional - No indexadaS

Smooth Muscle miRNAs Are Critical for Post-Natal Regulation of Blood Pressure and Vascular Function

Phenotypic modulation of smooth muscle cells (SMCs) plays a key role in vascular disease, including atherosclerosis. Several transcription factors have been suggested to regulate phenotypic modulation of SMCs but the decisive mechanisms remain unknown. Recent reports suggest that specific microRNAs (miRNAs) are involved in SMC differentiation and vascular disease but the global role of miRNAs in postnatal vascular SMC has not been elucidated. Thus, the objective of this study was to identify the role of Dicer-dependent miRNAs for blood pressure regulation and vascular SMC contractile function and differentiation in vivo. Tamoxifen-inducible and SMC specific deletion of Dicer was achieved by Cre-Lox recombination. Deletion of Dicer resulted in a global loss of miRNAs in aortic SMC. Furthermore, Dicer-deficient mice exhibited a dramatic reduction in blood pressure due to significant loss of vascular contractile function and SMC contractile differentiation as well as vascular remodeling. Several of these results are consistent with our previous observations in SM-Dicer deficient embryos. Therefore, miRNAs are essential for maintaining blood pressure and contractile function in resistance vessels. Although the phenotype of miR-143/145 deficient mice resembles the loss of Dicer, the phenotypes of SM-Dicer KO mice were far more severe suggesting that additional miRNAs are involved in maintaining postnatal SMC differentiation

Epigenetically controlled tumor antigens derived from splice junctions between exons and transposable elements

Oncogenesis often implicates epigenetic alterations, including derepression of transposable elements (TEs) and defects in alternative splicing. Here, we explore the possibility that noncanonical splice junctions between exons and TEs represent a source of tumor-specific antigens. We show that mouse normal tissues and tumor cell lines express wide but distinct ranges of mRNA junctions between exons and TEs, some of which are tumor specific. Immunopeptidome analyses in tumor cell lines identified peptides derived from exon-TE splicing junctions associated to MHC-I molecules. Exon-TE junction-derived peptides were immunogenic in tumor-bearing mice. Both prophylactic and therapeutic vaccinations with junction-derived peptides delayed tumor growth in vivo. Inactivation of the TE-silencing histone 3-lysine 9 methyltransferase Setdb1 caused overexpression of new immunogenic junctions in tumor cells. Our results identify exon-TE splicing junctions as epigenetically controlled, immunogenic, and protective tumor antigens in mice, opening possibilities for tumor targeting and vaccination in patients with cancer

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Influence of Short-Term Glucocorticoid Therapy on Regulatory T Cells In Vivo

Background: Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(Treg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs). Objective: We readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and naı¨ve mice. Methods: Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and Treg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood Treg cells were analyzed prior and after a 14 day GC therapy based on different markers. Results: Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.861.86104 cells/ml vs. 336116104 in control mice) and spleen (dexamethasone: 2.861.96105/spleen vs. 956226105/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3+ Treg cells amongst the CD4+ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of Treg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating Treg cells in a relevant manner, although there was some variation depending on the definition of the Treg cells (FOXP3+: 4.061.5% vs 3.461.5%*; AITR+: 0.660.4 vs 0.560.3%, CD127low: 4.061.3 vs 5.063.0%* and CTLA4+: 13.8611.5 vs 15.6612.5%; * p,0.05). Conclusion: Short-term GC therapy does not induce the hitherto supposed increase in circulating Treg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating Treg cell numbers