RESUMO
Darwin's assertion that "it is mere rubbish thinking, at present, of origin of life" is no longer valid. By synthesizing origin of life (OoL) research from its inception to recent findings, with a focus on (i) proof-of-principle prebiotically plausible syntheses and (ii) molecular relics of the ancient RNA World, we present a comprehensive up-to-date description of science's understanding of the OoL and the RNA World hypothesis. Based on these observations, we solidify the consensus that RNA evolved before coded proteins and DNA genomes, such that the biosphere began with an RNA core where much of the translation apparatus and related RNA architecture arose before RNA transcription and DNA replication. This supports the conclusion that the OoL was a gradual process of chemical evolution involving a series of transitional forms between prebiotic chemistry and the last universal common ancestor (LUCA) during which RNA played a central role, and that many of the events and their relative order of occurrence along this pathway are known. The integrative nature of this synthesis also extends previous descriptions and concepts and should help inform future questions and experiments about the ancient RNA World and the OoL.
Assuntos
Replicação do DNA , RNA , RNA/genética , RNA/química , DNA , Evolução Molecular , Origem da VidaRESUMO
Retinoblastoma-binding proteins 4 and 7 (RBBP4 and RBBP7) are two highly homologous human histone chaperones. They function in epigenetic regulation as subunits of multiple chromatin-related complexes and have been implicated in numerous cancers. Due to their overlapping functions, our understanding of RBBP4 and 7, particularly outside of Opisthokonts, has remained limited. Here, we report that in the ciliate protozoan Tetrahymena thermophila a single orthologue of human RBBP4 and 7 proteins, RebL1, physically interacts with histone H4 and functions in multiple epigenetic regulatory pathways. Functional proteomics identified conserved functional links for Tetrahymena RebL1 protein as well as human RBBP4 and 7. We found that putative subunits of multiple chromatin-related complexes including CAF1, Hat1, Rpd3, and MuvB, co-purified with RebL1 during Tetrahymena growth and conjugation. Iterative proteomics analyses revealed that the cell cycle regulatory MuvB-complex in Tetrahymena is composed of at least five subunits including evolutionarily conserved Lin54, Lin9 and RebL1 proteins. Genome-wide analyses indicated that RebL1 and Lin54 (Anqa1) bind within genic and intergenic regions. Moreover, Anqa1 targets primarily promoter regions suggesting a role for Tetrahymena MuvB in transcription regulation. RebL1 depletion inhibited cellular growth and reduced the expression levels of Anqa1 and Lin9. Consistent with observations in glioblastoma tumors, RebL1 depletion suppressed DNA repair protein Rad51 in Tetrahymena, thus underscoring the evolutionarily conserved functions of RBBP4/7 proteins. Our results suggest the essentiality of RebL1 functions in multiple epigenetic regulatory complexes in which it impacts transcription regulation and cellular viability.
Assuntos
Chaperonas de Histonas/metabolismo , Proteínas de Protozoários/metabolismo , Tetrahymena thermophila/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/metabolismo , Evolução Biológica , Sequência Conservada , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética , Expressão Gênica , Células HEK293 , Chaperonas de Histonas/química , Chaperonas de Histonas/fisiologia , Histonas/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/mortalidade , Oncogenes , Proteínas de Protozoários/química , Proteínas de Protozoários/fisiologia , Proteína 4 de Ligação ao Retinoblastoma/metabolismo , Proteína 7 de Ligação ao Retinoblastoma/metabolismo , Tetrahymena thermophila/genética , Tetrahymena thermophila/crescimento & desenvolvimentoRESUMO
PURPOSE: To examine surrogates' mental health, social support, and relationship with intended parents (IPs) during the COVID-19 pandemic from March 2020 to February 2022. METHODS: Data were collected between April 29, 2022 and July 31, 2022, at an academic IVF center in Canada using an 85-item online anonymous cross-sectional survey that included three standardized scales measuring mental health (PHQ-4), loneliness, and social support. Eligible surrogates actively involved in surrogacy during the study period received email invitations. RESULTS: The response rate was 50.3% (338/672); 320 submitted surveys were analyzed. Two-thirds (65%) of respondents experienced mental health concerns during the pandemic and were significantly less comfortable about seeking mental health support than those without concerns. Nonetheless, 64% were highly satisfied with their surrogacy experience; 80% received a high level of support from their IPs, and 90% reported a good relationship with them. The final hierarchical regression model identified five significant predictors, explaining 39.4% of the variance in PHQ-4 scores: a prior mental health history, COVID-19 impact on personal life, surrogacy satisfaction, loneliness, and social support. CONCLUSIONS: COVID-19 created an unprecedented challenge to surrogacy care, increasing surrogates' risk of experiencing mental health symptoms. Our data show that IP support and the surrogate-IP relationship were fundamentals to surrogacy satisfaction. The findings are relevant to fertility and mental health practitioners in identifying surrogates who are more susceptible to mental health challenges. Fertility clinics should ensure adequate psychological screening of surrogate candidates and proactively offer mental health support services.
Assuntos
COVID-19 , Pandemias , Gravidez , Feminino , Humanos , Saúde Mental , Estudos Transversais , Mães Substitutas/psicologia , Relações Interpessoais , COVID-19/epidemiologia , Apoio SocialRESUMO
OBJECTIVE: No empirical data are available on the healthcare experiences of surrogates during the COVID-19 pandemic. This study aimed to examine the impact of pandemic-control measures on surrogates' fertility, pregnancy and birthing experiences. METHODS: Sampling frame included eligible surrogates who were actively involved in a surrogacy process at an academic IVF centre during the pandemic (03/2020 to 02/2022). Data were collected between 29/04/2022 and 31/07/2022 using an anonymous 85-item online survey that included twelve open-ended questions. Free-text comments were analysed by thematic analysis. FINDINGS: The response rate was 50.7% (338/667). Of the 320 completed surveys used for analysis, 609 comments were collected from 206 respondents. Twelve main themes and thirty-six sub-themes grouped under 'vaccination', 'fertility treatment', 'pregnancy care', and 'surrogacy birth' were identified. Three in five surrogates found the control measures highly or moderately affected their surrogacy experiences. Themes involving loneliness and isolation frequently emerged when essential surrogacy support was restricted by the visitor protocols implemented at healthcare facilities. DISCUSSION: Our findings show that restricting or limiting intended parents' in-person involvement increased surrogates' feelings of isolation and made the overall surrogacy experience less rewarding and fulfilling. Furthermore, the childbirth experiences of surrogates were mostly negative, suggesting that hospitals were ill-equipped to manage all births, including surrogacy births, during the pandemic. IMPLICATIONS FOR PRACTICE: Our findings highlight the needs to rethink how surrogacy care and maternity services could be strengthened to better serve the needs of surrogates during times of public health crises, such as COVID-19, while still allowing for risk mitigation and maximising patient safety.