Unraveling the impact of iron oxides-organic matter complexes on iodine mobilization in alluvial-lacustrine aquifers from central Yangtze River Basin.

The biodegradation of organic matter triggers the reductive dissolution of iron oxides with the transformation among iodine species has been mostly accepted as the key iodine mobilization process in groundwater system. However, molecular characteristics of natural organic matter (NOM) and their interaction with iron oxides on geogenic iodine enrichment remain unclear. We used Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to characterize the molecular composition of both dissolved organic matter (DOM) in groundwater and water-soluble organic matter (WSOM) in aquifer sediments being depth-matched with groundwater from monitoring wells in typical iodine-affected aquifers within the central Yangtze River Basin. The results show that WSOM in high-iodine sediments contains more high molecular weight (HMW) organic compounds with higher aromaticity and nominal oxidation state of carbon (NOSC), including polycyclic aromatics, polyphenols and highly unsaturated compounds. These compounds are mostly positively associated with amorphous iron oxides (Feox1) in aquifer sediments. The association between iodine and WSOM is highly consistent with that between amorphous Feox1 and WSOM, but is contrary to that between crystalline iron oxides (Feox2) and WSOM. DOM in groundwater with higher iodine concentration contains more aliphatic compounds and less polyphenols. The complexation of HMW organic compounds of WSOM to iodine-bearing amorphous Feox1 plays an important role in iodine mobilization, which could inhibit the amorphous Feox1 transformation to crystalline Feox2. These observations indicate the biodegradation of HMW organic matter (polycyclic aromatics, polyphenols and highly unsaturated compounds) in WSOM fueling the reductive dissolution of amorphous Feox1 predominantly promotes the release of iodine from aquifer sediments into groundwater. This research provides new insights into the mobilization mechanisms of iodine in alluvial-lacustrine groundwater system controlled by the Fe-OM complexation at the molecular level.

LIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease.

Activating mutations in the tyrosine kinase Janus kinase 2 (JAK2) cause myeloproliferative neoplasms, clonal blood stem cell disorders with a propensity for leukaemic transformation. Leukaemia inhibitory factor (LIF) signalling through the JAK-signal transducer and activator of transcription (STAT) pathway enables self-renewal of embryonic stem (ES) cells. Here we show that mouse ES cells carrying the human JAK2V617F mutation were able to self-renew in chemically defined conditions without cytokines or small-molecule inhibitors, independently of JAK signalling through the STAT3 or phosphatidylinositol-3-OH kinase pathways. Phosphorylation of histone H3 tyrosine 41 (H3Y41) by JAK2 was recently shown to interfere with binding of heterochromatin protein 1α (HP1α). Levels of chromatin-bound HP1α were lower in JAK2V617F ES cells but increased following inhibition of JAK2, coincident with a global reduction in histone H3Y41 phosphorylation. JAK2 inhibition reduced levels of the pluripotency regulator Nanog, with a reduction in H3Y41 phosphorylation and concomitant increase in HP1α levels at the Nanog promoter. Furthermore, Nanog was required for factor independence of JAK2V617F ES cells. Taken together, these results uncover a previously unrecognized role for direct signalling to chromatin by JAK2 as an important mediator of ES cell self-renewal.

Gfi1 expression is controlled by five distinct regulatory regions spread over 100 kilobases, with Scl/Tal1, Gata2, PU.1, Erg, Meis1, and Runx1 acting as upstream regulators in early hematopoietic cells.

The growth factor independence 1 (Gfi1) gene was originally discovered in the hematopoietic system, where it functions as a key regulator of stem cell homeostasis, as well as neutrophil and T-cell development. Outside the blood system, Gfi1 is essential for inner-ear hair and intestinal secretory cell differentiation. To understand the regulatory hierarchies within which Gfi1 operates to control these diverse biological functions, we used a combination of comparative genomics, locus-wide chromatin immunoprecipitation assays, functional validation in cell lines, and extensive transgenic mouse assays to identify and characterize the complete ensemble of Gfi1 regulatory elements. This concerted effort identified five distinct regulatory elements spread over 100kb each driving expression in transgenic mice to a subdomain of endogenous Gfi1. Detailed characterization of an enhancer 35 kb upstream of Gfi1 demonstrated activity in the dorsal aorta region and fetal liver in transgenic mice, which was bound by key stem cell transcription factors Scl/Tal1, PU.1/Sfpi1, Runx1, Erg, Meis1, and Gata2. Taken together, our results reveal the regulatory regions responsible for Gfi1 expression and importantly establish that Gfi1 expression at the sites of hematopoietic stem cell (HSC) emergence is controlled by key HSC regulators, thus integrating Gfi1 into the wider HSC regulatory networks.