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GATA3 is as a lineage-specific transcription factor that drives the differentiation of CD4 + T helper 2 (Th2) cells, but is also involved in a variety of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. Here we show a mechanism utilised by CD4 + T cells to increase mitochondrial mass in response to DNA damage through the actions of GATA3 and AMPK. Activated AMPK increases expression of PPARG coactivator 1 alpha ( PPARGC1A or PGC1α protein) at the level of transcription and GATA3 at the level of translation, while DNA damage enhances expression of nuclear factor erythroid 2-related factor 2 ( NFE2L2 or NRF2). PGC1α, GATA3 and NRF2 complex together with the ATR to promote mitochondrial biogenesis. These findings extend the pleotropic interactions of GATA3 and highlight the potential for GATA3-targeted cell manipulation for intervention in CD4 + T cell viability and function after DNA damage. GATA3 has been considered to be primarily associated with CD4 + Th2 cell function. Using CD4 + effector memory that re-express CD45RA (EMRA) T cells the authors show that in response to DNA damage GATA3 can regulate increase of mitochondrial mass and biogenesis involving AMPK.

In women with late preterm pre-eclampsia, the optimal time to initiate delivery is unclear because limitation of maternal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of neonatal or infant outcomes, compared with expectant management (usual care) in women with late preterm pre-eclampsia. In this parallel-group, non-masked, multicentre, randomised controlled trial done in 46 maternity units across England and Wales, we compared planned delivery versus expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia from 34 to less than 37 weeks' gestation and a singleton or dichorionic diamniotic twin pregnancy. The co-primary maternal outcome was a composite of maternal morbidity or recorded systolic blood pressure of at least 160 mm Hg with a superiority hypothesis. The co-primary perinatal outcome was a composite of perinatal deaths or neonatal unit admission up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were by intention to treat, together with a per-protocol analysis for the perinatal outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN01879376. The trial is closed to recruitment but follow-up is ongoing. Between Sept 29, 2014, and Dec 10, 2018, 901 women were recruited. 450 women (448 women and 471 infants analysed) were allocated to planned delivery and 451 women (451 women and 475 infants analysed) to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group (289 [65%] women) compared with the expectant management group (338 [75%] women; adjusted relative risk 0·86, 95% CI 0·79–0·94; p=0·0005). The incidence of the co-primary perinatal outcome by intention to treat was significantly higher in the planned delivery group (196 [42%] infants) compared with the expectant management group (159 [34%] infants; 1·26, 1·08–1·47; p=0·0034). The results from the per-protocol analysis were similar. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group. There is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery. National Institute for Health Research Health Technology Assessment Programme.

Loss-of-function mutations in genes encoding lysine demethylases specific for trimethylated lysine 4 of histone 3 (H3K4me3) are associated with neurodevelopmental conditions, including autism spectrum disorder (ASD) and intellectual disability. To study the role of KDM5B (Lysine DeMethylase-5B)-mediated H3K4me3 demethylation, we investigated neurodevelopmental phenotypes in mice without KDM5B demethylase activity. These mice exhibited autism-like behaviours and increased brain size. H3K4me3 levels and the expression of neurodevelopmental genes were increased in the developing Kdm5b mutant neocortex. Increased H3K4me3 levels at the promoter and associated expression of the Grin2d gene was associated with increased levels of NMDAR2D protein in synaptosomes isolated from the early postnatal Kdm5b-deficient neocortex. Treating mice with the NMDAR antagonist memantine rescued deficits in ultrasonic vocalizations. These findings suggest that increased H3K4me3 levels and associated Grin2d gene upregulation disrupt brain development and function, leading to socio-communication deficits and identify a potential therapeutic target for neurodevelopmental disorders associated with KDM5B deficiency.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Revrt to previous version as per journal submission rulesFunder Information DeclaredMedical Research Council, https://ror.org/03x94j517, MR/V013173/1, MR/Y008170/1, MR/X010481/1, MR/W017156/1

GATA binding protein 3 (GATA3) has traditionally been regarded as a lineage-specific transcription factor that drives the differentiation of CD4+ T helper (Th) 2 cells. However, increasing evidence shows that GATA3 is involved in a myriad of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. We show here a previously unknown mechanism utilized by CD4+ T cells to increase mitochondrial mass in response to DNA damage through the binding of GATA3, AMP-activated protein kinase (AMPK), peroxisome-proliferator-activated receptor γ co-activator-1α (PGC1α), nuclear factor erythroid 2-related factor 2 (NRF2) and superoxide dismutase 3 (SOD3) to the DNA damage repair (DDR) component ATR. These findings extend the pleotropic nature of GATA3 and highlight the potential for GATA3-targeted cell manipulation for clinical interventions. Competing Interest Statement The authors have declared no competing interest. Footnotes * Included extra data that probes the structural nature of the interaction between GATA3 and PGC1a.

Nearshore reefs, at the interface of land-sea interactions, provide essential ecosystem services, but are susceptible to multiple global and local stressors. These stressors can detrimentally impact coral growth and the continuity of the reef framework. Here, we analyse coral growth records (1998 – 2016) of massive Porites spp. colonies from nearshore reefs in Fiji. Our aim is to assess the role of thermal stress and turbidity on coral growth across a range of environments. Our findings reveal a negative linear relationship between linear extension and seawater turbidity across locations (GLM, R 2  = 0.42, p  < 0.001), indicating that average coral growth is significantly influenced by local environmental conditions. On interannual timescales, all locations experienced a 14% to 30% decrease in linear extension in response to acute thermal stress during the 2013 – 2016 period. This finding highlights the existence of compounding effects between water quality and thermal stress. We suggest that inshore, long-lived massive hard corals in areas of high turbidity are more vulnerable to increasing SSTs due to an already reduced mean growth. Integrated management strategies in these regions that considers managing for multiple, interacting local stressors are warranted to enhance resilience.