47 research outputs found

    N6-methyladenosine (m<sup>6</sup>A) depletion regulates pluripotency exit by activating signaling pathways in embryonic stem cells.

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    N6-methyladenosine (m6A) deposition on messenger RNA (mRNA) controls embryonic stem cell (ESC) fate by regulating the mRNA stabilities of pluripotency and lineage transcription factors (TFs) [P. J. Batista et&nbsp;al., Cell Stem Cell 15, 707-719 (2014); Y. Wang et&nbsp;al., Nat. Cell Biol. 16, 191-198 (2014); and S. Geula et&nbsp;al., Science 347, 1002-1006 (2015)]. If the mRNAs of these two TF groups become stabilized, it remains unclear how the pluripotency or lineage commitment decision is implemented. We performed noninvasive quantification of Nanog and Oct4 TF protein levels in reporter ESCs to define cell-state dynamics at single-cell resolution. Long-term single-cell tracking shows that immediate m6A depletion by Mettl3 knock-down in serum/leukemia inhibitory factor supports both pluripotency maintenance and its departure. This is mediated by differential and opposing signaling pathways. Increased FGF5 mRNA stability activates pErk, leading to Nanog down-regulation. FGF5-mediated coactivation of pAkt reenforces Nanog expression. In formative stem cells poised toward differentiation, m6A depletion activates both pErk and pAkt, increasing the propensity for mesendodermal lineage induction. Stable m6A depletion by Mettl3 knock-out also promotes pErk activation. Higher pErk counteracts the pluripotency exit delay exhibited by stably m6A-depleted cells upon differentiation. At single-cell resolution, we illustrate that decreasing m6A abundances activates pErk and pAkt-signaling, regulating pluripotency departure

    Cyclic electron flow around photosystem I is required for adaptation to high temperature in a subtropical forest tree, Ficus concinna *

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    Dissipation mechanisms of excess photon energy under high-temperature stress were studied in a subtropical forest tree seedling, Ficus concinna. Net CO2 assimilation rate decreased to 16% of the control after 20 d high-temperature stress, and thus the absorption of photon energy exceeded the energy required for CO2 assimilation. The efficiency of excitation energy capture by open photosystem II (PSII) reaction centres (F v′/F m′) at moderate irradiance, photochemical quenching (q P), and the quantum yield of PSII electron transport (Φ PSII) were significantly lower after high-temperature stress. Nevertheless, non-photochemical quenching (q NP) and energy-dependent quenching (q E) were significantly higher under such conditions. The post-irradiation transient of chlorophyll (Chl) fluorescence significantly increased after the turnoff of the actinic light (AL), and this increase was considerably higher in the 39 °C-grown seedlings than in the 30 °C-grown ones. The increased post-irradiation fluorescence points to enhanced cyclic electron transport around PSI under high growth temperature conditions, thus helping to dissipate excess photon energy non-radiatively

    Engineering of a genome-reduced host:practical application of synthetic biology in the overproduction of desired secondary metabolites

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    Synthetic biology aims to design and build new biological systems with desirable properties, providing the foundation for the biosynthesis of secondary metabolites. The most prominent representation of synthetic biology has been used in microbial engineering by recombinant DNA technology. However, there are advantages of using a deleted host, and therefore an increasing number of biotechnology studies follow similar strategies to dissect cellular networks and construct genomereduced microbes. This review will give an overview of the strategies used for constructing and engineering reduced-genome factories by synthetic biology to improve production of secondary metabolites

    Study progress in therapeutic effects of traditional Chinese medicine monomer in severe acute pancreatitis

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    Severe acute pancreatitis (SAP) is a common acute abdomen clinical problem characterized by high mortality, multiple complications, complicated pathogenesis and difficult treatment. Recent studies found traditional Chinese medicine (TCM) monomers have markedly good effect for treating SAP. Many TCM monomers can inhibit pancreatin, resist inflammation, improve microcirculation and immunoloregulation, etc. to block the pathological progress of SAP in multiple ways, reduce complications and lower mortality with rapid effects. It is significant for enhancing SAP treatment to deeply understand the current situation in TCM monomers for treating SAP and take precious references therein. This article summarizes the treating effects and mechanisms of TCM monomers for SAP in recent years
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