RESUMEN
Unveiling the molecular mechanisms of tissue remodelling following injury is imperative to elucidate its regenerative capacity and aberrant repair in disease. Using different omics approaches, we identified enhancer of zester homolog 2 (EZH2) as a key regulator of fibrosis in injured lung epithelium. Epithelial injury drives an enrichment of nuclear transforming growth factor-ß-activated kinase 1 (TAK1) that mediates EZH2 phosphorylation to facilitate its liberation from polycomb repressive complex 2 (PRC2). This process results in the establishment of a transcriptional complex of EZH2, RNA-polymerase II (POL2) and nuclear actin, which orchestrates aberrant epithelial repair programmes. The liberation of EZH2 from PRC2 is accompanied by an EZH2-EZH1 switch to preserve H3K27me3 deposition at non-target genes. Loss of epithelial TAK1, EZH2 or blocking nuclear actin influx attenuates the fibrotic cascade and restores respiratory homeostasis. Accordingly, EZH2 inhibition significantly improves outcomes in a pulmonary fibrosis mouse model. Our results reveal an important non-canonical function of EZH2, paving the way for new therapeutic interventions in fibrotic lung diseases.
Asunto(s)
Proteína Potenciadora del Homólogo Zeste 2 , Histonas , Animales , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Fibrosis , Histonas/metabolismo , Ratones , Fosforilación , Complejo Represivo Polycomb 2/metabolismoRESUMEN
BACKGROUND: Paramedics experience post-traumatic stress in their work, and many paramedics turn to their intimate partner for support. However, exposure to traumatic event details can leave partners vulnerable to secondary traumatic stress. Despite substantial research into reducing stress and improving support for paramedics, few studies have investigated their partners' trauma experiences and support needs. This scoping review aimed to examine evidence regarding secondary traumatic stress in paramedic partners. METHODS: The MEDLINE, PsychINFO, CINAHL, EMCare, and Sociology Source Ultimate databases were searched up to November 9, 2022. The results sections of studies published in English involving a sample of paramedic partners that examined the impact of paramedics' work-related exposure to trauma on their intimate partner were extracted for analysis. This scoping review was guided by the Joanna Briggs Institute methodology. Key themes were generated using a framework synthesis approach. RESULTS: Five qualitative studies and one quantitative study were included, indicating a paucity of literature regarding secondary traumatic stress in paramedic partners. Post-traumatic stress experienced by paramedics can crossover to paramedic partners in the form of secondary traumatic stress; furthermore, it can have widespread effects on couple functioning. While paramedic partners appear to recognise the need for effective coping strategies, they perceive that little support is available to them. Notably, effective strategies aimed at reducing secondary traumatic stress in paramedic partners are limited. CONCLUSION: Further research is required to quantify secondary traumatic stress severity in paramedic partners and explore relationships between post-traumatic stress, secondary traumatic stress, and couple functioning. Further, evaluation of partner support needs and barriers to accessing support is warranted.
Asunto(s)
Desgaste por Empatía , Auxiliares de Urgencia , Humanos , Paramédico , Investigación CualitativaRESUMEN
We present a checklist of the large branchiopod crustaceans of Idaho, Oregon and Washington, USA. New distributional records are presented for most species, including the first records of Branchinecta constricta Rogers, 2006 and Lepidurus cryptus Rogers, 2001 from Idaho, the first record of B. oriena Belk & Rogers 2002 from Oregon, the first record of B. mackini Dexter, 1956 and Artemiafranciscana Kellogg, 1906 co-occurring, and the first record of L. cryptus from Washington. Furthermore, we present the first record of Eulimnadia diversa Mattox, 1937 from west of the continental divide, which we interpret as an accidental introduction. In 1959, Lynch collected a new fairy shrimp species from Washington, deposited that material in the US National Museum, labeled "muddy fairy shrimp, Branchinecta lutulenta", but never described it. Numerous efforts have been made to rediscover extant populations since 1999. We rediscovered this species in 2011, from two small pools from the vicinity of Lynch's original collection site, which appears to have been destroyed. Branchinecta lutulenta sp. nov. is most closely related to B. lindahli Packard, 1883 and B. oterosanvicentei Obregón-Barboza et al., 2002. Branchinecta lutulenta sp. nov. is readily separable from all other Branchinecta species by the form of the male second antennal distal antennomere and the ornamentation of the female dorsum.