• Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders

      Gerrard, Dave T.; orcid: 0000-0001-6890-7213; Berry, Andrew A.; Jennings, Rachel E.; Birket, Matthew J.; orcid: 0000-0002-5985-6626; Zarrineh, Peyman; Garstang, Myles G.; Withey, Sarah L.; Short, Patrick; orcid: 0000-0002-7626-6177; Jiménez-Gancedo, Sandra; Firbas, Panos N.; et al. (Nature Publishing Group UK, 2020-08-06)
      Abstract: How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we study histone modifications across thirteen tissues during human organogenesis. We integrate the data with transcription to build an overview of how the human genome differentially regulates alternative organ fates including by repression. Promoters from nearly 20,000 genes partition into discrete states. Key developmental gene sets are actively repressed outside of the appropriate organ without obvious bivalency. Candidate enhancers, functional in zebrafish, allow imputation of tissue-specific and shared patterns of transcription factor binding. Overlaying more than 700 noncoding mutations from patients with developmental disorders allows correlation to unanticipated target genes. Taken together, the data provide a comprehensive genomic framework for investigating normal and abnormal human development.
    • Evidence for ligand- and solvent-induced disproportionation of uranium(IV)

      Du, Jingzhen; orcid: 0000-0003-4037-9281; Douair, Iskander; orcid: 0000-0002-7482-5510; Lu, Erli; orcid: 0000-0002-0619-5967; Seed, John A.; orcid: 0000-0002-3751-0325; Tuna, Floriana; orcid: 0000-0002-5541-1750; Wooles, Ashley J.; Maron, Laurent; orcid: 0000-0003-2653-8557; email: laurent.maron@irsamc.ups-tlse.fr; Liddle, Stephen T.; orcid: 0000-0001-9911-8778; email: steve.liddle@manchester.ac.uk (Nature Publishing Group UK, 2021-08-10)
      Abstract: Disproportionation, where a chemical element converts its oxidation state to two different ones, one higher and one lower, underpins the fundamental chemistry of metal ions. The overwhelming majority of uranium disproportionations involve uranium(III) and (V), with a singular example of uranium(IV) to uranium(V/III) disproportionation known, involving a nitride to imido/triflate transformation. Here, we report a conceptually opposite disproportionation of uranium(IV)-imido complexes to uranium(V)-nitride/uranium(III)-amide mixtures. This is facilitated by benzene, but not toluene, since benzene engages in a redox reaction with the uranium(III)-amide product to give uranium(IV)-amide and reduced arene. These disproportionations occur with potassium, rubidium, and cesium counter cations, but not lithium or sodium, reflecting the stability of the corresponding alkali metal-arene by-products. This reveals an exceptional level of ligand- and solvent-control over a key thermodynamic property of uranium, and is complementary to isolobal uranium(V)-oxo disproportionations, suggesting a potentially wider prevalence possibly with broad implications for the chemistry of uranium.
    • Exceptional uranium(VI)-nitride triple bond covalency from 15 N nuclear magnetic resonance spectroscopy and quantum chemical analysis

      Du, Jingzhen; orcid: 0000-0003-4037-9281; Seed, John A.; orcid: 0000-0002-3751-0325; Berryman, Victoria E. J.; Kaltsoyannis, Nikolas; Adams, Ralph W.; orcid: 0000-0001-8009-5334; email: ralph.adams@manchester.ac.uk; Lee, Daniel; orcid: 0000-0002-1015-0980; email: daniel.lee@manchester.ac.uk; Liddle, Stephen T.; orcid: 0000-0001-9911-8778; email: steve.liddle@manchester.ac.uk (Nature Publishing Group UK, 2021-09-24)
      Abstract: Determining the nature and extent of covalency of early actinide chemical bonding is a fundamentally important challenge. Recently, X-ray absorption, electron paramagnetic, and nuclear magnetic resonance spectroscopic studies have probed actinide-ligand covalency, largely confirming the paradigm of early actinide bonding varying from ionic to polarised-covalent, with this range sitting on the continuum between ionic lanthanide and more covalent d transition metal analogues. Here, we report measurement of the covalency of a terminal uranium(VI)-nitride by 15N nuclear magnetic resonance spectroscopy, and find an exceptional nitride chemical shift and chemical shift anisotropy. This redefines the 15N nuclear magnetic resonance spectroscopy parameter space, and experimentally confirms a prior computational prediction that the uranium(VI)-nitride triple bond is not only highly covalent, but, more so than d transition metal analogues. These results enable construction of general, predictive metal-ligand 15N chemical shift-bond order correlations, and reframe our understanding of actinide chemical bonding to guide future studies.
    • Global predictions of primary soil salinization under changing climate in the 21st century

      Hassani, Amirhossein; orcid: 0000-0002-6470-0490; email: ahas@nilu.no; Azapagic, Adisa; orcid: 0000-0003-2380-918X; email: adisa.azapagic@manchester.ac.uk; Shokri, Nima; orcid: 0000-0001-6799-4888; email: nima.shokri@tuhh.de (Nature Publishing Group UK, 2021-11-18)
      Abstract: Soil salinization has become one of the major environmental and socioeconomic issues globally and this is expected to be exacerbated further with projected climatic change. Determining how climate change influences the dynamics of naturally-occurring soil salinization has scarcely been addressed due to highly complex processes influencing salinization. This paper sets out to address this long-standing challenge by developing data-driven models capable of predicting primary (naturally-occurring) soil salinity and its variations in the world’s drylands up to the year 2100 under changing climate. Analysis of the future predictions made here identifies the dryland areas of South America, southern and western Australia, Mexico, southwest United States, and South Africa as the salinization hotspots. Conversely, we project a decrease in the soil salinity of the drylands in the northwest United States, the Horn of Africa, Eastern Europe, Turkmenistan, and west Kazakhstan in response to climate change over the same period.