Divergent wiring of repressive and active chromatin interactions between mouse embryonic and trophoblast lineages.

The establishment of the embryonic and trophoblast lineages is a developmental decision underpinned by dramatic differences in the epigenetic landscape of the two compartments. However, it remains unknown how epigenetic information and transcription factor networks map to the 3D arrangement of the genome, which in turn may mediate transcriptional divergence between the two cell lineages. Here, we perform promoter capture Hi-C experiments in mouse trophoblast (TSC) and embryonic (ESC) stem cells to understand how chromatin conformation relates to cell-specific transcriptional programmes. We find that key TSC genes that are kept repressed in ESCs exhibit interactions between H3K27me3-marked regions in ESCs that depend on Polycomb repressive complex 1. Interactions that are prominent in TSCs are enriched for enhancer-gene contacts involving key TSC transcription factors, as well as TET1, which helps to maintain the expression of TSC-relevant genes. Our work shows that the first developmental cell fate decision results in distinct chromatin conformation patterns establishing lineage-specific contexts involving both repressive and active interactions

Identification of the domains of cauliflower mosaic virus protein P6 responsible for suppression of RNA silencing and salicylic acid signalling

Cauliflower mosaic virus (CaMV) encodes a 520 aa polypeptide, P6, which participates in several essential activities in the virus life cycle including suppressing RNA silencing and salicylic acid-responsive defence signalling. We infected Arabidopsis with CaMV mutants containing short in-frame deletions within the P6 ORF. A deletion in the distal end of domain D-I (the N-terminal 112 aa) of P6 did not affect virus replication but compromised symptom development and curtailed the ability to restore GFP fluorescence in a GFP-silenced transgenic Arabidopsis line. A deletion in the minimum transactivator domain was defective in virus replication but retained the capacity to suppress RNA silencing locally. Symptom expression in CaMV-infected plants is apparently linked to the ability to suppress RNA silencing. When transiently co-expressed with tomato bushy stunt virus P19, an elicitor of programmed cell death in Nicotiana tabacum, WT P6 suppressed the hypersensitive response, but three mutants, two with deletions within the distal end of domain D-I and one involving the N-terminal nuclear export signal (NES), were unable to do so. Deleting the N-terminal 20 aa also abolished the suppression of pathogen-associated molecular pattern-dependent PR1a expression following agroinfiltration. However, the two other deletions in domain D-I retained this activity, evidence that the mechanisms underlying these functions are not identical. The D-I domain of P6 when expressed alone failed to suppress either cell death or PR1a expression and is therefore necessary but not sufficient for all three defence suppression activities. Consequently, concerns about the biosafety of genetically modified crops carrying truncated ORFVI sequences appear unfounded

A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells.

The ten-eleven translocation (TET) proteins are well known for their role in maintaining naive pluripotency of embryonic stem cells. Here, we demonstrate that, jointly, TET1 and TET2 also safeguard the self-renewal potential of trophoblast stem cells (TSCs) and have partially redundant roles in maintaining the epithelial integrity of TSCs. For the more abundantly expressed TET1, we show that this is achieved by binding to critical epithelial genes, notably E-cadherin, which becomes hyper-methylated and downregulated in the absence of TET1. The epithelial-to-mesenchymal transition phenotype of mutant TSCs is accompanied by centrosome duplication and separation defects. Moreover, we identify a role of TET1 in maintaining cyclin B1 stability, thereby acting as facilitator of mitotic cell-cycle progression. As a result, Tet1/2 mutant TSCs are prone to undergo endoreduplicative cell cycles leading to the formation of polyploid trophoblast giant cells. Taken together, our data reveal essential functions of TET proteins in the trophoblast lineage

The effect of atmospheric nudging on the stratospheric residual circulation in chemistry–climate models

We perform the first multi-model intercomparison of the impact of nudged meteorology on the stratospheric residual circulation using hindcast simulations from the Chemistry–Climate Model Initiative (CCMI). We examine simulations over the period 1980–2009 from seven models in which the meteorological fields are nudged towards a reanalysis dataset and compare these with their equivalent free-running simulations and the reanalyses themselves. We show that for the current implementations, nudging meteorology does not constrain the mean strength of the stratospheric residual circulation and that the inter-model spread is similar, or even larger, than in the free-running simulations. The nudged models generally show slightly stronger upwelling in the tropical lower stratosphere compared to the free-running versions and exhibit marked differences compared to the directly estimated residual circulation from the reanalysis dataset they are nudged towards. Downward control calculations applied to the nudged simulations reveal substantial differences between the climatological lower-stratospheric tropical upward mass flux (TUMF) computed from the modelled wave forcing and that calculated directly from the residual circulation. This explicitly shows that nudging decouples the wave forcing and the residual circulation so that the divergence of the angular momentum flux due to the mean motion is not balanced by eddy motions, as would typically be expected in the time mean. Overall, nudging meteorological fields leads to increased inter-model spread for most of the measures of the mean climatological stratospheric residual circulation assessed in this study. In contrast, the nudged simulations show a high degree of consistency in the inter-annual variability in the TUMF in the lower stratosphere, which is primarily related to the contribution to variability from the resolved wave forcing. The more consistent inter-annual variability in TUMF in the nudged models also compares more closely with the variability found in the reanalyses, particularly in boreal winter. We apply a multiple linear regression (MLR) model to separate the drivers of inter-annual and long-term variations in the simulated TUMF; this explains up to ∼75 % of the variance in TUMF in the nudged simulations. The MLR model reveals a statistically significant positive trend in TUMF for most models over the period 1980–2009. The TUMF trend magnitude is generally larger in the nudged models compared to their free-running counterparts, but the intermodel range of trends doubles from around a factor of 2 to a factor of 4 due to nudging. Furthermore, the nudged models generally do not match the TUMF trends in the reanalysis they are nudged towards for trends over different periods in the interval 1980–2009. Hence, we conclude that nudging does not strongly constrain long-term trends simulated by the chemistry–climate model (CCM) in the residual circulation. Our findings show that while nudged simulations may, by construction, produce accurate temperatures and realistic representations of fast horizontal transport, this is not typically the case for the slower zonal mean vertical transport in the stratosphere. Consequently, caution is required when using nudged simulations to interpret the behaviour of stratospheric tracers that are affected by the residual circulation

Glass-ceramic sealant for solid oxide fuel cells application: Characterization and performance in dual atmosphere

This document is the Accepted Manuscript version of the following article: A. G. Sabato, G. Tempura, D. Montinaro, A. Chysanthou, M. Salvo, E. Bernardo, M. Secco, F. Meacetto, ‘Glass-ceramic sealant for solid oxide fuel cells application: characterization and performance in dual atmosphere’, Journal of Power Sources, Vol. 328:262-270, October 2016, doi: http://dx.doi.org/10.1016/j.jpowsour.2016.08.010. Published by Elsevier. This manuscript version is distributed distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License CC BY NC-ND 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Glass-ceramic composition was designed and tested for use as a sealant in solid oxide fuel cell (SOFC) planar stack design. The crystallization behaviour was investigated by calculating the Avrami parameter (n) and the activation energy for crystallization (Ec) was obtained. The calculated values for n and Ec were 3 and 413.5 kJ/mol respectively. The results of thermal analyses indicate that this composition shows no overlap between the sintering and crystallization stages and thus an almost pore-free sealant can be deposited and sintered at 850 °C in air for 30 min. A gas tightness test has been carried out at 800 °C for 1100 h in dual atmosphere (Ar-H2 and air) without recording any leakage. Morphological and crystalline phase analyses were conducted prior and following tests in dual atmospheres in order to assess the compatibility of the proposed sealant with the metallic interconnect.Peer reviewe

Loss of ancestral function in duckweed roots is accompanied by progressive anatomical reduction and a re-distribution of nutrient transporters

Organ loss occurs frequently during plant and animal evolution. Sometimes, non-functional organs are retained through evolution. Vestigial organs are defined as genetically determined structures that have lost their ancestral (or salient) function. Duckweeds, an aquatic monocot family, exhibit both these characteristics. They possess a uniquely simple body plan, variably across five genera, two of which are rootless. Due to the existence of closely related species with a wide diversity in rooting strategies, duckweed roots represent a powerful system for investigating vestigiality. To explore this, we employed a panel of physiological, ionomic, and transcriptomic analyses, with the main goal of elucidating the extent of vestigiality in duckweed roots. We uncovered a progressive reduction in root anatomy as genera diverge and revealed that the root has lost its salient ancestral function as an organ required for supplying nutrients to the plant. Accompanying this, nutrient transporter expression patterns have lost the stereotypical root biased localization observed inother plant species. While other examples of organ loss such as limbs in reptiles or eyes in cavefish frequently display a binary of presence/absence, duckweeds provide a unique snapshot of an organ with varying degrees of vestigialization in closely related neighbors and thus provide a unique resource for exploration of how organs behave at different stages along the process of loss. [Abstract copyright: Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Revisiting the Mystery of Recent Stratospheric Temperature Trends

Simulated stratospheric temperatures over the period 1979–2016 in models from the Chemistry-Climate Model Initiative are compared with recently updated and extended satellite data sets. The multimodel mean global temperature trends over 1979–2005 are -0.88 ± 0.23, -0.70 ± 0.16, and -0.50 ± 0.12 K/decade for the Stratospheric Sounding Unit (SSU) channels 3 (~40–50 km), 2 (~35–45 km), and 1 (~25–35 km), respectively (with 95% confidence intervals). These are within the uncertainty bounds of the observed temperature trends from two reprocessed SSU data sets. In the lower stratosphere, the multimodel mean trend in global temperature for the Microwave Sounding Unit channel 4 (~13–22 km) is -0.25 ± 0.12 K/decade over 1979–2005, consistent with observed estimates from three versions of this satellite record. The models and an extended satellite data set comprised of SSU with the Advanced Microwave Sounding Unit-A show weaker global stratospheric cooling over 1998–2016 compared to the period of intensive ozone depletion (1979–1997). This is due to the reduction in ozone-induced cooling from the slowdown of ozone trends and the onset of ozone recovery since the late 1990s. In summary, the results show much better consistency between simulated and satellite-observed stratospheric temperature trends than was reported by Thompson et al. (2012, https://doi.org/10.1038/nature11579) for the previous versions of the SSU record and chemistry-climate models. The improved agreement mainly comes from updates to the satellite records; the range of stratospheric temperature trends over 1979–2005 simulated in Chemistry-Climate Model Initiative models is comparable to the previous generation of chemistry-climate models

Mechanisms of hypoxic up-regulation of versican gene expression in macrophages

Hypoxia is a hallmark of many pathological tissues. Macrophages accumulate in hypoxic sites and up-regulate a range of hypoxia-inducible genes. The matrix proteoglycan versican has been identified as one such gene, but the mechanisms responsible for hypoxic induction are not fully characterised. Here we investigate the up-regulation of versican by hypoxia in primary human monocyte-derived macrophages (HMDM), and, intriguingly, show that versican mRNA is up-regulated much more highly (>600 fold) by long term hypoxia (5 days) than by 1 day of hypoxia (48 fold). We report that versican mRNA decay rates are not affected by hypoxia, demonstrating that hypoxic induction of versican mRNA is mediated by increased transcription. Deletion analysis of the promoter identified two regions required for high level promoter activity of luciferase reporter constructs in human macrophages. The hypoxia-inducible transcription factor HIF-1 has previously been implicated as a key potential regulator of versican expression in hypoxia, however our data suggest that HIF-1 up-regulation is unlikely to be principally responsible for the high levels of induction observed in HMDM. Treatment of HMDM with two distinct specific inhibitors of Phosphoinositide 3-kinase (PI3K), LY290042 and wortmannin, significantly reduced induction of versican mRNA by hypoxia and provides evidence of a role for PI3K in hypoxic up-regulation of versican expression

Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.

Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.RCUK Cancer Research UK ERC H2020 Wellcome Trus