Rice CRYPTOCHROME-INTERACTING BASIC HELIX-LOOP-HELIX 1-LIKE interacts with OsCRY2 and promotes flowering by upregulating Early heading date 1.

Flowering time is a crucial adaptive response to seasonal variation in plants and is regulated by environmental cues such as photoperiod and temperature. In this study, we demonstrated the regulatory function of rice CRYPTOCHROME-INTERACTING BASIC HELIX-LOOP-HELIX 1-LIKE (OsCIBL1) in flowering time. Overexpression of OsCIB1L promoted flowering, whereas the oscib1l knockout mutation did not alter flowering time independent of photoperiodic conditions. Cryptochromes (CRYs) are blue light photoreceptors that enable plants to sense photoperiodic changes. OsCIBL1 interacted with OsCRY2, a member of the rice CRY family (OsCRY1a, OsCRY1b, and OsCRY2), and bound to the Early heading date 1 (Ehd1) promoter, activating the rice-specific Ehd1-Heading date 3a/RICE FLOWERING LOCUS T 1 pathway for flowering induction. Dual-luciferase reporter assays showed that the OsCIBL1-OsCRY2 complex required blue light to induce Ehd1 transcription. Natural alleles resulting from nonsynonymous single nucleotide polymorphisms in OsCIB1L and OsCRY2 may contribute to the adaptive expansion of rice cultivation areas. These results expand our understanding of the molecular mechanisms controlling rice flowering and highlight the importance of blue light-responsive genes in the geographic distribution of rice.

Notch-mediated hepatocyte MCP-1 secretion causes liver fibrosis.

Patients with nonalcoholic steatohepatitis (NASH) have increased expression of liver monocyte chemoattractant protein-1 (MCP-1), but its cellular source and contribution to various aspects of NASH pathophysiology remain debated. We demonstrated increased liver CCL2 (which encodes MCP-1) expression in patients with NASH, and commensurately, a 100-fold increase in hepatocyte Ccl2 expression in a mouse model of NASH, accompanied by increased liver monocyte-derived macrophage (MoMF) infiltrate and liver fibrosis. To test repercussions of increased hepatocyte-derived MCP-1, we generated hepatocyte-specific Ccl2-knockout mice, which showed reduced liver MoMF infiltrate as well as decreased liver fibrosis. Forced hepatocyte MCP-1 expression provoked the opposite phenotype in chow-fed wild-type mice. Consistent with increased hepatocyte Notch signaling in NASH, we observed a close correlation between markers of Notch activation and CCL2 expression in patients with NASH. We found that an evolutionarily conserved Notch/recombination signal binding protein for immunoglobulin kappa J region binding site in the Ccl2 promoter mediated transactivation of the Ccl2 promoter in NASH diet-fed mice. Increased liver MoMF infiltrate and liver fibrosis seen in opposite gain-of-function mice was ameliorated with concomitant hepatocyte Ccl2 knockout or CCR2 inhibitor treatment. Hepatocyte Notch activation prompts MCP-1-dependent increase in liver MoMF infiltration and fibrosis.

High-phytate/low-calcium diet is a risk factor for crystal nephropathies, renal phosphate wasting, and bone loss.

Phosphate overload contributes to mineral bone disorders that are associated with crystal nephropathies. Phytate, the major form of phosphorus in plant seeds, is known as an indigestible and of negligible nutritional value in humans. However, the mechanism and adverse effects of high-phytate intake on Ca2+ and phosphate absorption and homeostasis are unknown. Here, we show that excessive intake of phytate along with a low-Ca2+ diet fed to rats contributed to the development of crystal nephropathies, renal phosphate wasting, and bone loss through tubular dysfunction secondary to dysregulation of intestinal calcium and phosphate absorption. Moreover, Ca2+ supplementation alleviated the detrimental effects of excess dietary phytate on bone and kidney through excretion of undigested Ca2+-phytate, which prevented a vicious cycle of intestinal phosphate overload and renal phosphate wasting while improving intestinal Ca2+ bioavailability. Thus, we demonstrate that phytate is digestible without a high-Ca2+ diet and is a risk factor for phosphate overloading and for the development of crystal nephropathies and bone disease.

Impaired phagocytosis of apoptotic cells causes accumulation of bone marrow-derived macrophages in aged mice.

Accumulation of tissue macrophages is a significant characteristic of disease-associated chronic inflammation, and facilitates the progression of disease pathology. However, the functional roles of these bone marrow-derived macrophages (BMDMs) in aging are unclear. Here, we identified agedependent macrophage accumulation in the bone marrow, showing that aging significantly increases the number of M1 macrophages and impairs polarization of BMDMs. We found that age-related dysregulation of BMDMs is associated with abnormal overexpression of the anti-inflammatory interleukin-10. BMDM dysregulation in aging impairs the expression levels of pro-inflammatory cytokines and genes involved in B-cell maturation and activation. Phagocytosis of apoptotic Jurkat cells by BMDMs was reduced because of low expression of phagocytic receptor CD14, indicating that increased apoptotic cells may result from defective phagocytosis of apoptotic cells in the BM of aged mice. Therefore, CD14 may represent a promising target for preventing BMDM dysregulation, and macrophage accumulation may provide diagnostic and therapeutic clues. [BMB Reports 2017; 50(1): 43-48].

Molecular and biochemical characteristics of ß-propeller phytase from marine Pseudomonas sp. BS10-3 and its potential application for animal feed additives.

Phytate is an antinutritional factor that impacts the bioavailability of essential minerals such as Ca(2+), Mg(2+), Mn(2+), Zn(2+), and Fe(2+) by forming insoluble mineral-phytate salts. These insoluble mineral-phytate salts are hydrolyzed rarely by monogastric animals, because they lack the hydrolyzing phytases and thus excrete the majority of them. The ß-propeller phytases (BPPs) hydrolyze these insoluble mineral-phytate salts efficiently. In this study, we cloned a novel BPP gene from a marine Pseudomonas sp. This Pseudomonas BPP gene (PsBPP) had low sequence identity with other known phytases and contained an extra internal repeat domain (residues 24-279) and a typical BPP domain (residues 280-634) at the C-terminus. Structurebased sequence alignment suggested that the N-terminal repeat domain did not possess the active-site residues, whereas the C-terminal BPP domain contained multiple calcium-binding sites, which provide a favorable electrostatic environment for substrate binding and catalytic activity. Thus, we overexpressed the BPP domain from Pseudomonas sp. to potentially hydrolyze insoluble mineral-phytate salts. Purified recombinant PsBPP required Ca(2+) or Fe(2+) for phytase activity, indicating that PsBPP hydrolyzes insoluble Fe(2+)-phytate or Ca2+-phytate salts. The optimal temperature and pH for the hydrolysis of Ca(2+)-phytate by PsBPP were 50°C and 6.0, respectively. Biochemical and kinetic studies clearly showed that PsBPP efficiently hydrolyzed Ca(2+)-phytate salts and yielded myo-inositol 2,4,6-trisphosphate and three phosphate groups as final products. Finally, we showed that PsBPP was highly effective for hydrolyzing rice bran with high phytate content. Taken together, our results suggest that PsBPP has great potential in the animal feed industry for reducing phytates.