Genome-wide redistribution of MeCP2 in dorsal root ganglia after peripheral nerve injury.

BACKGROUND: Methyl-CpG-binding protein 2 (MeCP2), a protein with affinity for methylated cytosines, is crucial for neuronal development and function. MeCP2 regulates gene expression through activation, repression and chromatin remodeling. Mutations in MeCP2 cause Rett syndrome, and these patients display impaired nociception. We observed an increase in MeCP2 expression in mouse dorsal root ganglia (DRG) after peripheral nerve injury. The functional implication of increased MeCP2 is largely unknown. To identify regions of the genome bound by MeCP2 in the DRG and the changes induced by nerve injury, a chromatin immunoprecipitation of MeCP2 followed by sequencing (ChIP-seq) was performed 4 weeks after spared nerve injury (SNI). RESULTS: While the number of binding sites across the genome remained similar in the SNI model and sham control, SNI induced the redistribution of MeCP2 to transcriptionally relevant regions. To determine how differential binding of MeCP2 can affect gene expression in the DRG, we investigated mmu-miR-126, a microRNA locus that had enriched MeCP2 binding in the SNI model. Enriched MeCP2 binding to miR-126 locus after nerve injury repressed miR-126 expression, and this was not mediated by alterations in methylation pattern at the miR-126 locus. Downregulation of miR-126 resulted in the upregulation of its two target genes Dnmt1 and Vegfa in Neuro 2A cells and in SNI model compared to control. These target genes were significantly downregulated in Mecp2-null mice compared to wild-type littermates, indicating a regulatory role for MeCP2 in activating Dnmt1 and Vegfa expression. Intrathecal delivery of miR-126 was not sufficient to reverse nerve injury-induced mechanical and thermal hypersensitivity, but decreased Dnmt1 and Vegfa expression in the DRG. CONCLUSIONS: Our study shows a regulatory role for MeCP2 in that changes in global redistribution can result in direct and indirect modulation of gene expression in the DRG. Alterations in genome-wide binding of MeCP2 therefore provide a molecular basis for a better understanding of epigenetic regulation-induced molecular changes underlying nerve injury

Dynamics of sediment flux to a bathyal continental margin section through the Paleocene–Eocene Thermal Maximum

The response of the Earth system to greenhouse-gas-driven warming is of critical importance for the future trajectory of our planetary environment. Hyperthermal events – past climate transients with global-scale warming significantly above background climate variability – can provide insights into the nature and magnitude of these responses. The largest hyperthermal of the Cenozoic was the Paleocene–Eocene Thermal Maximum (PETM ∼ 56 Ma). Here we present new high-resolution bulk sediment stable isotope and major element data for the classic PETM section at Zumaia, Spain. With these data we provide a new detailed stratigraphic correlation to other key deep-ocean and terrestrial PETM reference sections. With this new correlation and age model we are able to demonstrate that detrital sediment accumulation rates within the Zumaia continental margin section increased more than 4-fold during the PETM, representing a radical change in regional hydrology that drove dramatic increases in terrestrial-to-marine sediment flux. Most remarkable is that detrital accumulation rates remain high throughout the body of the PETM, and even reach peak values during the recovery phase of the characteristic PETM carbon isotope excursion (CIE). Using a series of Earth system model inversions, driven by the new Zumaia carbon isotope record, we demonstrate that the silicate weathering feedback alone is insufficient to recover the PETM CIE, and that active organic carbon burial is required to match the observed dynamics of the CIE. Further, we demonstrate that the period of maximum organic carbon sequestration coincides with the peak in detrital accumulation rates observed at Zumaia. Based on these results, we hypothesise that orbital-scale variations in subtropical hydro-climates, and their subsequent impact on sediment dynamics, may contribute to the rapid climate and CIE recovery from peak-PETM conditions

Homo- and heterodehydrocoupling of phosphines mediated by alkali metal catalysts

Catalytic chemistry that involves the activation and transformation of main group substrates is relatively undeveloped and current examples are generally mediated by expensive transition metal species. Herein, we describe the use of inexpensive and readily available tBuOK as a catalyst for P–P and P–E (E = O, S, or N) bond formation. Catalytic quantities of tBuOK in the presence of imine, azobenzene hydrogen acceptors, or a stoichiometric amount of tBuOK with hydrazobenzene, allow efficient homodehydrocoupling of phosphines under mild conditions (e.g. 25 °C and < 5 min). Further studies demonstrate that the hydrogen acceptors play an intimate mechanistic role. We also show that our tBuOK catalysed methodology is general for the heterodehydrocoupling of phosphines with alcohols, thiols and amines to generate a range of potentially useful products containing P–O, P–S, or P–N bonds

Overcast on Osiris: 3D radiative-hydrodynamical simulations of a cloudy hot Jupiter using the parametrized, phase-equilibrium cloud formation code EDDYSED (article)

This is the final version. Available from OUP via the DOI in this recordThe dataset associated with this article is available in ORE: https://doi.org/10.24378/exe.1483We present results from 3D radiative-hydrodynamical simulations of HD 209458b with a fully coupled treatment of clouds using the EDDYSED code, critically, including cloud radiative feedback via absorption and scattering. We demonstrate that the thermal and optical structure of the simulated atmosphere is markedly different, for the majority of our simulations, when including cloud radiative effects, suggesting this important mechanism cannot be neglected. Additionally, we further demonstrate that the cloud structure is sensitive to not only the cloud sedimentation efficiency (termed fsed in EDDYSED), but also the temperature–pressure profile of the deeper atmosphere. We briefly discuss the large difference between the resolved cloud structures of this work, adopting a phase-equilibrium and parametrized cloud model, and our previous work incorporating a cloud microphysical model, although a fairer comparison where, for example, the same list of constituent condensates is included in both treatments is reserved for a future work. Our results underline the importance of further study into the potential condensate size distributions and vertical structures, as both strongly influence the radiative impact of clouds on the atmosphere. Finally, we present synthetic observations from our simulations reporting an improved match, over our previous cloud-free simulations, to the observed transmission, HST WFC3 emission, and 4.5 μm Spitzer phase curve of HD 209458b. Additionally, we find all our cloudy simulations have an apparent albedo consistent with observations.Leverhulme TrustScience and Technology Facilities Council (STFC

Tephra deposition and bonding with reactive oxides enhances burial of organic carbon in the Bering Sea

Preservation of organic carbon (OC) in marine sediments exerts a major control on the cycling of carbon in the Earth system. In these marine environments, OC preservation may be enhanced by diagenetic reactions in locations where deposition of fragmental volcanic material called tephra occurs. While the mechanisms by which this process occurs are well understood, site‐specific studies of this process are limited. Here, we report a study of sediments from the Bering Sea (IODP Site U1339D) to investigate the effects of marine tephra deposition on carbon cycling during the Pleistocene and Holocene. Our results suggest that tephra layers are loci of OC burial with distinct δ13C values, and that this process is primarily linked to bonding of OC with reactive metals, accounting for ∼80% of all OC within tephra layers. In addition, distribution of reactive metals from the tephra into non‐volcanic sediments above and below the tephra layers enhances OC preservation in these sediments, with ∼33% of OC bound to reactive phases. Importantly, OC‐Fe coupling is evident in sediments >700,000 years old. Thus, these interactions may help explain the observed preservation of OC in ancient marine sediments.Plain Language Summary: The burial of organic carbon (OC) in marine sediments is one of the major carbon sinks on Earth, meaning that it removes carbon dioxide from the ocean‐atmosphere system. However, the speed at which burial occurs varies across the globe, and is dependent on a range of factors, from the amount of nutrients in the water column, to the type of sediment. Despite evidence suggesting that when tephra is deposited to the seafloor carbon burial is enhanced, very little work has been done to investigate this process. We have therefore analyzed sediments from the Bering Sea, where volcanoes from the Aleutian Islands and Kamchatka regularly deposit tephra in the ocean. We found that OC burial is indeed associated with ash deposition, and importantly, that OC is preserved in the ash layers themselves. We show here that this carbon is preserved effectively because of chemical reactions between the OC and reactive iron, which is released by the ash, creating conditions which preserve carbon for hundreds of thousands of years.Key Points: Tephra layers are loci of marine organic carbon (OC) burial with distinct carbon isotopic compositions. Preservation primarily linked to association of OC with reactive iron phases, accounting for ∼80% of all OC in tephra layers. OC‐reactive Fe coupling is observed in sediments >700,000 years old, indicating long‐term persistence of these complexes.NER

The development of life-cycle and risk assessment methodology using data from AWE Aldermaston

The research described in this thesis further develops Life-Cycle Assessment (LCA) methodology to include radiological releases to air, water and as waste. A new methodology has been developed to characterise radioactive aspects based on known effects to man and behaviour in the environment. Equivalency factors have been developed for nine radioisotopes (24'Am, 137Cs56 0Co, 239Pu52 41Pu53 HI 234U, 235U and 238U). A new LCA valuation method is developed for weighting environmental impacts in an Environmental Management System (EMS). A detailed LCA inventory of environmental burdens has been compiled from data from AWE Aldermaston and used as a case study to develop and demonstrate the methodologies developed in this work. As part of the research, the links between environmental aspects and impacts has been investigated using LCA, based on the high hazard facilities at AWE Aldermaston, which is a major industrial site. The case study also includes the contribution from vehicle use in the impact assessment. The results of this work have clearly identified which facilities and hence which processes are causing the most damaging environmental impact. New risk assessment methods are developed to quantify environmental accidents, that include revised consequence definitions that can be applied without the need for modelling and thus offer an economical alternative to existing methods. A new six-step screening methodology is presented to identify potential major accidents to the environment (MATTE) and to comply with the COMAH Regulations 1999. A method to prioritise MATTE scenarios has also been developed. The research has revealed that the current approach to significance assessment does not provide enough sophistication for sites as complex as AWE Aldermaston. The impacts of most concern are environmental irradiation, the generation of all categories of waste and global warming. The impacts associated with radioactive discharges (to air, water and as waste) are given the highest weighting largely reflecting the concern of the major stakeholder groups (local community, regulatory bodies and pressure groups). The methods proposed can be readily applied to any nuclear or chemical site.EThOS - Electronic Theses Online ServiceAEA Technology plcAWE plcUKAEAGBUnited Kingdo