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BACKGROUND/OBJECTIVE: This study examined the role of different psychological coping mechanisms in mental and physical health during the initial phases of the COVID-19 crisis with an emphasis on meaning-centered coping. METHOD: A total of 11,227 people from 30 countries across all continents participated in the study and completed measures of psychological distress (depression, stress, and anxiety), loneliness, well-being, and physical health, together with measures of problem-focused and emotion-focused coping, and a measure called the Meaning-centered Coping Scale (MCCS) that was developed in the present study. Validation analyses of the MCCS were performed in all countries, and data were assessed by multilevel modeling (MLM). RESULTS: The MCCS showed a robust one-factor structure in 30 countries with good test-retest, concurrent and divergent validity results. MLM analyses showed mixed results regarding emotion and problem-focused coping strategies. However, the MCCS was the strongest positive predictor of physical and mental health among all coping strategies, independently of demographic characteristics and country-level variables. CONCLUSIONS: The findings suggest that the MCCS is a valid measure to assess meaning-centered coping. The results also call for policies promoting effective coping to mitigate collective suffering during the pandemic.
ANTECEDENTES/OBJETIVO: Este estudio examinó el papel de diferentes estrategias de afrontamiento psicológico en la salud mental y física durante las fases iniciales de la crisis de COVID-19. MÉTODO: 11,227 personas de 30 países representando todos los continentes participaron en el estudio y completaron medidas de malestar psicológico (depresión, estrés y ansiedad), soledad, bienestar, salud física, medidas de afrontamiento centrado en el problema y en la emoción, y una medida denominada Escala del Afrontamiento Centrado en el Sentido (MCCS) que fue desarrollada en este estudio. El análisis de validación de la MCCS se realizó en todos los países, y los datos se evaluaron mediante un modelo multinivel. RESULTADOS: La MCCS mostró una estructura unifactorial en 30 países con buenos resultados de validez test-retest, concurrente y divergente. Los análisis mostraron resultados mixtos en cuanto a las estrategias de afrontamiento centradas en la emoción y en el problema. La MCCS fue el predictor positivo más fuerte de salud física y mental, independientemente de las características demográficas y las variables a nivel de país. CONCLUSIONES: Los resultados sugieren que la MCCS es un insrumento fiable para medir afrontamiento centrado en el sentido. Estos resultados pueden servir para dirigir políticas que promuevan un afrontamiento eficaz con el fin de mitigar el sufrimiento colectivo durante la pandemia.
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BACKGROUND: The aim of this study was to analyze potential risk factors for early and late dental implant failure (DIF) in a clinical cohort trial. In a private practice, 9080 implants were inserted during a period of 10 years. In case of DIF, data were classified into early and late DIF and compared to each other in regard of gender, age, site of implantation, implant geometry, and patients' systemic diseases. RESULTS: Three hundred fifty-one implants failed within the observation period (survival rate: 96.13%). Early DIF occurred in 293 implants (83.48%) compared to late DIF in 58 implants (16.52%). Significant earlier DIF was seen in the mandible (OR = 3.729, p < 0.001)-especially in the posterior area-and in younger patients (p = 0.017), whereas an increased likelihood of late DIF was associated with maxillary implants (OR = 3.729, p < 0.001) and older patients. CONCLUSIONS: Early DIF is about twice as common as late DIF. Main risk factors for early DIF are implant location in the (posterior) mandible as well as younger age. On contrary, late DIF is rather associated with older patients, cancellous bone quality, and longer implants.
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Theories about the origin of life require chemical pathways that allow formation of life's key building blocks under prebiotically plausible conditions. Complex molecules like RNA must have originated from small molecules whose reactivity was guided by physico-chemical processes. RNA is constructed from purine and pyrimidine nucleosides, both of which are required for accurate information transfer, and thus Darwinian evolution. Separate pathways to purines and pyrimidines have been reported, but their concurrent syntheses remain a challenge. We report the synthesis of the pyrimidine nucleosides from small molecules and ribose, driven solely by wet-dry cycles. In the presence of phosphate-containing minerals, 5'-mono- and diphosphates also form selectively in one-pot reactions. The pathway is compatible with purine synthesis, allowing the concurrent formation of all Watson-Crick bases.
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Nucleósidos de Purina/síntesis química , Nucleósidos de Pirimidina/síntesis química , Ribonucleótidos/síntesis química , Fenómenos Químicos , Hidroxilamina/química , Nucleósidos de Purina/química , Nucleótidos de Purina/síntesis química , Nucleósidos de Pirimidina/química , Nucleótidos de Pirimidina/síntesis química , ARN/síntesis química , Ribosa/químicaRESUMEN
Multicellular organisms developed the concept of specialized cells that perform specific functions. Examples are neurons and fibroblast to name just two out of more than 200. These cellular differences are established based on the same sequence information stored in the cell nucleus of all cells of an organism. The sequence information needs consequently different interpretations by the different cell types. During cellular development this interpretation of the genetic code has to be tightly regulated in space and time. Interpretation of the sequence information involves the controlled activation and silencing of specific genes so that certain proteins are made in one cell type but not in others. This involves an additional regulatory information layer beyond the pure base sequence. One aspect of this regulatory information layer relies on functional groups that are attached to the C(5) position of the canonical base dC. Currently four regulatory, non-canonical bases with a methyl (CH3 )-, a hydroxymethyl (CH2 OH)-, a formyl (CHO)- and a carboxyl (COOH)- group are known. While 5-methyl-cytidine is long recognised to be a regulatory base in the genome, the other three bases and the enzymes responsible for generating them, were just recently discovered.
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Citidina/análogos & derivados , ADN/química , ADN/genética , Citidina/química , Citidina/genética , HumanosRESUMEN
Enzymatic oxidation of 5-methylcytosine (5-mC) in the CpG dinucleotides to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxycytosine (5-caC) has central role in the process of active DNA demethylation and epigenetic reprogramming in mammals. However, it is not known whether the 5-mC oxidation products have autonomous epigenetic or regulatory functions in the genome. We used an artificial upstream promoter constituted of one cAMP response element (CRE) to measure the impact of 5-mC in a hemi-methylated CpG on the promoter activity and further explored the consequences of 5-hmC, 5-fC, and 5-caC in the same system. All modifications induced mild impairment of the CREB transcription factor binding to the consensus 5'-TGACGTCA-3' CRE sequence. The decrease of the gene expression by 5-mC or 5-hmC was proportional to the impairment of CREB binding and had a steady character over at least 48 h. In contrast, promoters containing single 5-fC or 5-caC underwent further progressive loss of activity, up to an almost complete repression. This decline was dependent on the thymine-DNA glycosylase (TDG). The results thus indicate that 5-fC and 5-caC can provide a signal for perpetuation and enhancement of the repressed transcriptional state by a mechanism that requires base excision repair.
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Islas de CpG/genética , Metilación de ADN , Regiones Promotoras Genéticas/genética , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/química , 5-Metilcitosina/metabolismo , Animales , Secuencia de Bases , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Citosina/análogos & derivados , Citosina/química , Citosina/metabolismo , ADN/genética , ADN/metabolismo , Regulación de la Expresión Génica , Humanos , Unión Proteica , Timina ADN Glicosilasa/metabolismoRESUMEN
RNA modifications are integral to the regulation of RNA metabolism. One abundant mRNA modification is N6-methyladenosine (m6A), which affects various aspects of RNA metabolism, including splicing, translation and degradation. Current knowledge about the proteins recruited to m6A to carry out these molecular processes is still limited. Here we describe comprehensive and systematic mass-spectrometry-based screening of m6A interactors in various cell types and sequence contexts. Among the main findings, we identified G3BP1 as a protein that is repelled by m6A and positively regulates mRNA stability in an m6A-regulated manner. Furthermore, we identified FMR1 as a sequence-context-dependent m6A reader, thus revealing a connection between an mRNA modification and an autism spectrum disorder. Collectively, our data represent a rich resource and shed further light on the complex interplay among m6A, m6A interactors and mRNA homeostasis.