No abstract

Background: UHRF1 is an important epigenetic regulator connecting DNA methylation and histone methylations. Results: PHD-H3 interaction is independent of the TTD, whereas TTD-H3K9me3 interaction the PHD. Conclusion: Both TTD and PHD are essential for specific recognition of H3K9me3 by human UHRF1. Significance: This work reveals how UHRF1 recognizes H3K9me3, which is important for its cellular localization and DNA methylation.

Recently, an connection between Short-chain fatty acids (SCFAs) produced by intestinal microbiota and kidney has been revealed. The aim of this study was to explore whether SCFAs or their specific G protein-coupled receptors 43 (GPR43) agonist inhibit oxidative stress and inflammatory response in glomerular mesangial cells (GMCs) induced by high glucose and lipopolysaccharide (LPS). Our research showed that treatment with SCFAs, especially acetate and butyrate, or GPR43 agonist significantly inhibited GMCs proliferation induced by high glucose and LPS, and then reversed the production of reactive oxygen species (ROS) and malondialdehyde (MDA) but increased levels of antioxidant enzyme superoxide dismutase (SOD). Furthermore, SCFAs or GPR43 agonist obviously increased the protein expression of GPR43 induced by high glucose and LPS, but diminished the expression of adhesion molecule intercellular adhesion molecule-1 (ICAM-1), and then decreased the proinflammatory cytokine monocyte chemoattractant protein (MCP-1) and interleukin-1β (IL-1β) release from GMCs stimulated by the high glucose and LPS. These combined results support the hypothesis that SCFAs or GPR43 agonist can inhibit oxidative stress and inflammation of GMCs induced by high glucose and LPS, suggesting that SCFAs induced signaling pathway may act as new therapeutic targets of diabetic nephropathy (DN).

e To determine talin1's role in osteoclasts, we mated TLN1 fl/fl mice with those expressing cathepsin K-Cre (CtsK-TLN1) to delete the gene in mature osteoclasts or with lysozyme M-Cre (LysM-TLN1) mice to delete TLN1 in all osteoclast lineage cells. Absence of TLN1 impairs macrophage colony-stimulating factor (M-CSF)-stimulated inside-out integrin activation and cytoskeleton organization in mature osteoclasts. Talin1-deficient precursors normally express osteoclast differentiation markers when exposed to M-CSF and receptor activator of nuclear factor B (RANK) ligand but attach to substrate and migrate poorly, arresting their development into mature resorptive cells. In keeping with inhibited resorption, CtsK-TLN1 mice exhibit an ϳ5-fold increase in bone mass. Osteoclast-specific deletion of Rap1 (CtsK-Rap1), which promotes talin/␤ integrin recognition, yields similar osteopetrotic mice. The fact that the osteopetrosis of CtsK-TLN1 and CtsK-Rap1 mice is substantially more severe than that of those lacking ␣v␤3 is likely due to added failed activation of ␤1 integrins. In keeping with osteoclast dysfunction, mice in whom talin is deleted late in the course of osteoclastogenesis are substantially protected from ovariectomy-induced osteoporosis and the periarticular osteolysis attending inflammatory arthritis. Thus, talin1 and Rap1 are critical for resorptive function, and their selective inhibition in mature osteoclasts retards pathological bone loss.

Melatonin, an indoleamine widely found in animals and plants, is considered as a candidate phytohormone that affects responses to a variety of biotic and abiotic stresses. In plants, melatonin has a similar action to that of the auxin indole-3-acetic acid (IAA), and IAA and melatonin have the same biosynthetic precursor, tryptophan. Salt stress results in the rapid accumulation of melatonin in plants. Melatonin enhances plant resistance to salt stress in two ways: one is via direct pathways, such as the direct clearance of reactive oxygen species; the other is via an indirect pathway by enhancing antioxidant enzyme activity, photosynthetic efficiency, and metabolite content, and by regulating transcription factors associated with stress. In addition, melatonin can affect the performance of plants by affecting the expression of genes. Interestingly, other precursors and metabolite molecules associated with melatonin can also increase the tolerance of plants to salt stress. This paper explores the mechanisms by which melatonin alleviates salt stress by its actions on antioxidants, photosynthesis, ion regulation, and stress signaling.

Global soil salinization is increasingly a serious threat to agriculture worldwide. Therefore, it is imperative to improve crop salt tolerance as a means of adaptation to saline habitats. Some halophytes and most monocotyledonous crops are salt-excluders. Understanding the regulatory mechanisms of salt exclusion at the molecular level in salt-exclusion plants is critical for improving the salt tolerance of monocotyledonous crops such as maize, wheat, rice, and sorghum. In this review, we summarize recent research into salt-exclusion mechanisms and the genes that underlie them. Findings related to salt exclusion may accelerate the process of breeding tolerant cultivars by using genomic and molecular tools.

No abstract

Pyruvate kinase isoform M2 (PKM2) converts phosphoenolpyruvate (PEP) to pyruvate and plays an important role in cancer metabolism. Here, we show that post-translational modifications and a patient-derived mutation regulate pyruvate kinase activity of PKM2 through modulating the conformation of the PKM2 tetramer. We determined crystal structures of human PKM2 mutants and proposed a “seesaw” model to illustrate conformational changes between an inactive T-state and an active R-state tetramers of PKM2. Biochemical and structural analyses demonstrate that PKM2Y105E (phosphorylation mimic of Y105) decreases pyruvate kinase activity by inhibiting FBP (fructose 1,6-bisphosphate)-induced R-state formation, and PKM2K305Q (acetylation mimic of K305) abolishes the activity by hindering tetramer formation. K422R, a patient-derived mutation of PKM2, favors a stable, inactive T-state tetramer because of strong intermolecular interactions. Our study reveals the mechanism for dynamic regulation of PKM2 by post-translational modifications and a patient-derived mutation and provides a structural basis for further investigation of other modifications and mutations of PKM2 yet to be discovered.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-015-0132-x) contains supplementary material, which is available to authorized users.