Rachel Jones

Messenger RNA (mRNA) export adaptors play an important role in the transport of mRNA from the nucleus to the cytoplasm. They couple early mRNA processing events such as 5′ capping and 3′ end formation with loading of the TAP/NXF1 export receptor onto mRNA. The canonical adaptor REF/ALY/Yra1 is recruited to mRNA via UAP56 and subsequently delivers the mRNA to NXF1 [1Carmody S.R. Wente S.R. mRNA nuclear export at a glance.J. Cell Sci. 2009; 122: 1933-1937Crossref PubMed Scopus (181) Google Scholar]. Knockdown of UAP56 [2MacMorris M. Brocker C. Blumenthal T. UAP56 levels affect viability and mRNA export in Caenorhabditis elegans.RNA. 2003; 9: 847-857Crossref PubMed Scopus (77) Google Scholar, 3Gatfield D. Le Hir H. Schmitt C. Braun I.C. Kocher T. Wilm M. Izaurralde E. The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila.Curr. Biol. 2001; 11: 1716-1721Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar] and NXF1 [4Herold A. Klymenko T. Izaurralde E. NXF1/p15 heterodimers are essential for mRNA nuclear export in Drosophila.RNA. 2001; 7: 1768-1780PubMed Google Scholar, 5Wilkie G.S. Zimyanin V. Kirby R. Korey C. Francis-Lang H. Van Vactor D. Davis I. Small bristles, the Drosophila ortholog of NXF-1, is essential for mRNA export throughout development.RNA. 2001; 7: 1781-1792PubMed Google Scholar, 6Herold A. Teixeira L. Izaurralde E. Genome-wide analysis of nuclear mRNA export pathways in Drosophila.EMBO J. 2003; 22: 2472-2483Crossref PubMed Scopus (134) Google Scholar, 7Williams B.J. Boyne J.R. Goodwin D.J. Roaden L. Hautbergue G.M. Wilson S.A. Whitehouse A. The prototype gamma-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA via the cellular mRNA export pathway.Biochem. J. 2005; 387: 295-308Crossref PubMed Scopus (62) Google Scholar] in higher eukaryotes efficiently blocks mRNA export, whereas knockdown of REF only causes a modest reduction, suggesting the existence of additional adaptors [8Gatfield D. Izaurralde E. REF1/Aly and the additional exon junction complex proteins are dispensable for nuclear mRNA export.J. Cell Biol. 2002; 159: 579-588Crossref PubMed Scopus (170) Google Scholar, 9Longman D. Johnstone I.L. Caceres J.F. The Ref/Aly proteins are dispensable for mRNA export and development in Caenorhabditis elegans.RNA. 2003; 9: 881-891Crossref PubMed Scopus (87) Google Scholar, 10Katahira J. Inoue H. Hurt E. Yoneda Y. Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA.EMBO J. 2009; 28: 556-567Crossref PubMed Scopus (109) Google Scholar]. Here we identify a new UAP56-interacting factor, UIF, which functions as an export adaptor, binding NXF1 and delivering mRNA to the nuclear pore. REF and UIF are simultaneously found on the same mRNA molecules, and both proteins are required for efficient export of mRNA. We show that the histone chaperone FACT specifically binds UIF, but not REF, via the SSRP1 subunit, and this interaction is required for recruitment of UIF to mRNA. Together the results indicate that REF and UIF represent key human adaptors for the export of cellular mRNAs via the UAP56-NXF1 pathway.

AIMS: Non-invasive imaging is routinely used to estimate left ventricular (LV) filling pressure (LVFP) in heart failure (HF). Cardiovascular magnetic resonance (CMR) is emerging as an important imaging tool for sub-phenotyping HF. However, currently, LVFP cannot be estimated from CMR. This study sought to investigate (i) if CMR can estimate LVFP in patients with suspected HF and (ii) if CMR-modelled LVFP has prognostic power. METHODS AND RESULTS: Suspected HF patients underwent right heart catheterization (RHC), CMR and transthoracic echocardiography (TTE) (validation cohort only) within 24 h of each other. Right heart catheterization measured pulmonary capillary wedge pressure (PCWP) was used as a reference for LVFP. At follow-up, death was considered as the primary endpoint. We enrolled 835 patients (mean age: 65 ± 13 years, 40% male). In the derivation cohort (n = 708, 85%), two CMR metrics were associated with RHC PCWP:LV mass and left atrial volume. When applied to the validation cohort (n = 127, 15%), the correlation coefficient between RHC PCWP and CMR-modelled PCWP was 0.55 (95% confidence interval: 0.41-0.66, P < 0.0001). Cardiovascular magnetic resonance-modelled PCWP was superior to TTE in classifying patients as normal or raised filling pressures (76 vs. 25%). Cardiovascular magnetic resonance-modelled PCWP was associated with an increased risk of death (hazard ratio: 1.77, P < 0.001). At Kaplan-Meier analysis, CMR-modelled PCWP was comparable to RHC PCWP (≥15 mmHg) to predict survival at 7-year follow-up (35 vs. 37%, χ2 = 0.41, P = 0.52). CONCLUSION: A physiological CMR model can estimate LVFP in patients with suspected HF. In addition, CMR-modelled LVFP has a prognostic role.

BACKGROUND: A recent dialogue in the field of play, learn, and teach outdoors (referred to as "PLaTO" hereafter) demonstrated the need for developing harmonized and consensus-based terminology, taxonomy, and ontology for PLaTO. This is important as the field evolves and diversifies in its approaches, contents, and contexts over time and in different countries, cultures, and settings. Within this paper, we report the systematic and iterative processes undertaken to achieve this objective, which has built on the creation of the global PLaTO-Network (PLaTO-Net). METHODS: This project comprised of four major methodological phases. First, a systematic scoping review was conducted to identify common terms and definitions used pertaining to PLaTO. Second, based on the results of the scoping review, a draft set of key terms, taxonomy, and ontology were developed, and shared with PLaTO members, who provided feedback via four rounds of consultation. Third, PLaTO terminology, taxonomy, and ontology were then finalized based on the feedback received from 50 international PLaTO member participants who responded to ≥ 3 rounds of the consultation survey and dialogue. Finally, efforts to share and disseminate project outcomes were made through different online platforms. RESULTS: This paper presents the final definitions and taxonomy of 31 PLaTO terms along with the PLaTO-Net ontology model. The model incorporates other relevant concepts in recognition that all the aspects of the model are interrelated and interconnected. The final terminology, taxonomy, and ontology are intended to be applicable to, and relevant for, all people encompassing various identities (e.g., age, gender, culture, ethnicity, ability). CONCLUSIONS: This project contributes to advancing PLaTO-based research and facilitating intersectoral and interdisciplinary collaboration, with the long-term goal of fostering and strengthening PLaTO's synergistic linkages with healthy living, environmental stewardship, climate action, and planetary health agendas. Notably, PLaTO terminology, taxonomy and ontology will continue to evolve, and PLaTO-Net is committed to advancing and periodically updating harmonized knowledge and understanding in the vast and interrelated areas of PLaTO.

Cardiac magnetic resonance (CMR) is emerging as an important tool in the assessment of heart failure with preserved ejection fraction (HFpEF). This study sought to investigate the prognostic value of multiparametric CMR, including left and right heart volumetric assessment, native T1-mapping and LGE in HFpEF. In this retrospective study, we identified patients with HFpEF who have undergone CMR. CMR protocol included: cines, native T1-mapping and late gadolinium enhancement (LGE). The mean follow-up period was 3.2 ± 2.4 years. We identified 86 patients with HFpEF who had CMR. Of the 86 patients (85% hypertensive; 61% males; 14% cardiac amyloidosis), 27 (31%) patients died during the follow up period. From all the CMR metrics, LV mass (area under curve [AUC] 0.66, SE 0.07, 95% CI 0.54-0.76, p = 0.02), LGE fibrosis (AUC 0.59, SE 0.15, 95% CI 0.41-0.75, p = 0.03) and native T1-values (AUC 0.76, SE 0.09, 95% CI 0.58-0.88, p < 0.01) were the strongest predictors of all-cause mortality. The optimum thresholds for these were: LV mass > 133.24 g (hazard ratio [HR] 1.58, 95% CI 1.1-2.2, p < 0.01); LGE-fibrosis > 34.86% (HR 1.77, 95% CI 1.1-2.8, p = 0.01) and native T1 > 1056.42 ms (HR 2.36, 95% CI 0.9-6.4, p = 0.07). In multivariate cox regression, CMR score model comprising these three variables independently predicted mortality in HFpEF when compared to NTproBNP (HR 4 vs HR 1.65). In non-amyloid HFpEF cases, only native T1 > 1056.42 ms demonstrated higher mortality (AUC 0.833, p < 0.01). In patients with HFpEF, multiparametric CMR aids prognostication. Our results show that left ventricular fibrosis and hypertrophy quantified by CMR are associated with all-cause mortality in patients with HFpEF.