the emergence of Miocene reefs in South china Sea and its resilient adaptability under varying eustatic, climatic and oceanographic conditions

International audienceDuring the Miocene, extensive carbonate deposition thrived over wide latitudinal ranges in Southeast Asia despite perturbations of the global climate and thermohaline circulation that affected the Asian continent. Nevertheless, the mechanisms of its emergence, adaptability in siliciclastic-dominated margins and demise, especially in southern South China Sea (SCS), are largely speculative and remains enigmatic along with a scarcity of constraints on paleoclimatic and palaeoceanographic conditions. Here we show, through newly acquired high-resolution geophysical data and accurate stratigraphic records based on strontium isotopic dating, the evolution of these platforms from ~15.5–9.5 Ma is initially tied to tectonics and eustasy, and ultimately, after ~9.5 Ma, to changes in the global climate patterns and consequent palaeoceanographic conditions. Our results demonstrate at least two paleodeltas that provided favourable substratum of elevated sand bars, which conditioning the emergence of the buildups that inadvertently mirrored the underlying strata. We show unprecedented evidences for ocean current fluctuations linked to the intensification of the Asian summer monsoon winds resulting in the formation of drifts and moats, which extirpated the platforms through sediment removal and starvation. This work highlights the imperative role of palaeoceanography in creating favourable niches for reefal development that can be applicable to carbonate platforms elsewhere

MS4A3 Promotes Differentiation in Chronic Myeloid Leukemia by Enhancing Common β Chain Cytokine Receptor Endocytosis

The chronic phase of chronic myeloid leukemia (CP-CML) is characterized by excessive production of maturating myeloid cells. As CML stem/progenitor cells (LSPCs) are poised to cycle and differentiate, LSPCs must balance conservation and differentiation to avoid exhaustion, similar to normal hematopoiesis under stress. Since BCR-ABL1 tyrosine kinase inhibitors (TKIs) eliminate differentiating cells, but spare BCR-ABL1-independent LSPCs, understanding the mechanisms that regulate LSPC differentiation may inform strategies to eliminate LSPCs. Upon performing a meta-analysis of published CML transcriptomes, we discovered that low expression of the MS4A3 transmembrane protein is a universal characteristic of LSPC quiescence, BCR-ABL1 independence, and transformation to blast phase. Several mechanisms are involved in suppressing MS4A3, including aberrant methylation and a MECOM-C/EBPε axis. Contrary to previous reports, we find that MS4A3 does not function as a G1/S phase inhibitor, but promotes endocytosis of common β chain (βc) cytokine receptors upon GM-CSF/IL-3 stimulation, enhancing downstream signaling and cellular differentiation. This suggests that LSPCs downregulate MS4A3 to evade βc cytokine-induced differentiation and maintain a more primitive, TKI-insensitive state. Accordingly, knockdown or deletion of MS4A3/Ms4a3 promotes TKI resistance and survival of CML cells ex vivo and enhance leukemogenesis in vivo, while targeted delivery of exogenous MS4A3 protein promotes differentiation. These data support a model in which MS4A3 governs response to differentiating myeloid cytokines, providing a unifying mechanism for the differentiation block characteristic of CML quiescence and blast phase CML. Promoting MS4A3 re-expression or delivery of ectopic MS4A3 may help eliminating LSPCs in vivo

Massive dolomitization of a Messinian reef in the Great Bahama Bank: a numerical modelling evaluation of Kohout geothermal convection

The hypothesis that Kohout thermal convection may have induced the massive dolomitization of the 60 m thick lowest more reefal unit in well Unda [top of Great Bahama Bank (GBB)] is evaluated through numerical modelling. A two‐dimensional (2‐D) section, including lithological and petrophysical data, together with datings for the sediments of the GBB, was used in the basin model TEMISPACK to reconstruct the history of the whole platform, with a focus on the reef unit. Simulations showed that during high sea‐level periods, Kohout convection is a valid mechanism in the settings of the GBB, although the convection cell remains flat in most cases because of high permeability anisotropy. This mechanism induces rapid fluid flow in the superficial as well as in the deeper parts of the platform, with velocities of at least two orders of magnitude higher than with compaction alone. Lithology appears as a strong control of fluid circulations at the margin scale through the permeability anisotropy, for which a critical value lies between values of 10 and 100. The reefal unit in Unda is part of a larger area determined by the lithologic distribution, in which flow velocities are significantly higher than in the rest of the platform. These velocities are high enough to bring the magnesium necessary to precipitate the observed amounts of dolomite, within durations in agreement with the available time of post‐reef deposition high sea level(s). However, neither fluid flow pattern nor flow velocities are able to explain the preferential massive dolomitization of the lower reef unit and the complete absence of dolomite in the upper one