Artemisinin derivative SM934, influences the activation, proliferation, differentiation and antibody-secreting capacity of β-cells in systemic lupus erythematosus mice via inhibition of TLR7/9 signaling pathway

Purpose: To study the influence of artemisinin derivative, SM934 on activation, proliferation, differentiation and antibody-secreting capacity of B cells of systemic lupus erythematosus (SLE) mice, and the underlying mechanism. Methods: Female MRL/lpr mice (n = 60) were randomly assigned to four groups of 15 mice each: SLE, 2.5 mg/kg SM934; 5 mg/kg SM934, and 10 mg/kg SM934 groups. Serum levels of interleukins 6, 10, 17 and 21 (IL-6, IL-17, IL-10 and IL-21) were determined. The secretions of immunoglobulins G and M (IgG and IgM) by B cells were determined. The population of B lymphocyte subtypes was determined flow cytometrically. The expressions of Blimp-1 and Bcl-6, Toll-like receptors 7 and 9 (TLR7 and TLR9) mRNAs were determined. Results: SLE-induced upregulation of serum IL-10, IL-6, IL-17 and IL-21 was significantly and dosedependently reduced following a 2-month treatment with SM934 (p < 0.01). Treatment with SM934 significantly and dose-dependently accentuated B cell germinal center B cell populations, but significantly and dose-dependently decreased the populations of plasma and activated B cells (p < 0.01). The splenic levels of IgG and IgM were decreased in a dose-dependent fashion after 8 weeks of treatment (p < 0.01). Artemisinin derivative SM934 decreased the expression of Blimp-1, and upregulated the expression of Bcl-6, both in a dose-dependent manner (p < 0.01). Moreover, SM934 decreased the mRNA expressions of TLR7 and TLR9 in a dose-based manner (p < 0.01). Conclusion: Artemisinin derivative SM934 mitigates LSE syndromes by suppressing the TLR-induced B-cell stimulation and plasma cell generatio

Genome‑wide association analyses of leaf rust resistance in cultivated emmer wheat

Leaf rust, caused by Puccinia triticina (Pt), constantly threatens durum (Triticum turgidum ssp. durum) and bread wheat (Triticum aestivum) production worldwide. A Pt race BBBQD detected in California in 2009 poses a potential threat to durum production in North America because resistance source to this race is rare in durum germplasm. To find new resistance sources, we assessed a panel of 180 cultivated emmer wheat (Triticum turgidum ssp. dicoccum) accessions for seedling resistance to BBBQD and for adult resistance to a mixture of durum-specific races BBBQJ, CCMSS, and MCDSS in the field, and genotyped the panel using genotype-by-sequencing (GBS) and the 9 K SNP (Single Nucleotide Polymorphism) Infinium array. The results showed 24 and nine accessions consistently exhibited seedling and adult resistance, respectively, with two accessions providing resistance at both stages. We performed genome-wide association studies using 46,383 GBS and 4,331 9 K SNP markers and identified 15 quantitative trait loci (QTL) for seedling resistance located mostly on chromosomes 2B and 6B, and 11 QTL for adult resistance on 2B, 3B and 6A. Of these QTL, one might be associated with leaf rust resistance (Lr) gene Lr53, and two with the QTL previously reported in durum or hexaploid wheat. The remaining QTL are potentially associated with new Lr genes. Further linkage analysis and gene cloning are necessary to identify the causal genes underlying these QTL. The emmer accessions with high levels of resistance will be useful for developing mapping populations and adapted durum germplasm and varieties with resistance to the durum-specific races

Molecular dynamics modeling of mechanical and tribological properties of additively manufactured AlCoCrFe high entropy alloy coating on aluminum substrate

In this work, an improved molecular dynamics (MD) model is developed to simulate the nanoindentation and tribological tests of additively manufactured high entropy alloys (HEA) AlCoCrFe coated on an aluminum substrate. The model shows that in the interface region between the HEA coating and Al substrate, as the laser heating temperature increases during the HEA coating additive manufacturing process, more Al in the substrate is melted to react with other elements in the coating layer, which is qualitatively in agreement with experiment in literature. Using the simulated nanoindentation tests, the calculated Young's modulus of pure Al and Al with HEA coating is 79.93 GPa and 119.30 GPa, respectively. In both our simulations and the experimental results in the literature, the hardness of Al with the HEA coating layer is about 10 times higher than the Al hardness, indicating that HEA can significantly improve the hardness of the metallic substrate. Using the simulated tribological scratch tests, the computed wear tracks are qualitatively in agreement with experimental images in literature. Both our model and experiment show that the Al with HEA coating has a much smaller wear track than that of Al, due to less plastic deformation, confirmed by a dislocation analysis. The computed average coefficient of friction of Al is 0.62 and Al with HEA coating is 0.14. This work demonstrates that the HEA coating significantly improves the mechanical and tribology properties, which are in excellent agreement with the experiments reported in the literature

Genomewide Expression Analysis in Zebrafish mind bomb Alleles with Pancreas Defects of Different Severity Identifies Putative Notch Responsive Genes

10.1371/journal.pone.0001479PLoS ONE3

The Oryza sativa Regulator HDR1 Associates with the Kinase OsK4 to Control Photoperiodic Flowering.

Rice is a facultative short-day plant (SDP), and the regulatory pathways for flowering time are conserved, but functionally modified, in Arabidopsis and rice. Heading date 1 (Hd1), an ortholog of Arabidopsis CONSTANS (CO), is a key regulator that suppresses flowering under long-day conditions (LDs), but promotes flowering under short-day conditions (SDs) by influencing the expression of the florigen gene Heading date 3a (Hd3a). Another key regulator, Early heading date 1 (Ehd1), is an evolutionarily unique gene with no orthologs in Arabidopsis, which acts as a flowering activator under both SD and LD by promoting the rice florigen genes Hd3a and RICE FLOWERING LOCUST 1 (RFT1). Here, we report the isolation and characterization of the flowering regulator Heading Date Repressor1 (HDR1) in rice. The hdr1 mutant exhibits an early flowering phenotype under natural LD in a paddy field in Beijing, China (39°54'N, 116°23'E), as well as under LD but not SD in a growth chamber, indicating that HDR1 may functionally regulate flowering time via the photoperiod-dependent pathway. HDR1 encodes a nuclear protein that is most active in leaves and floral organs and exhibits a typical diurnal expression pattern. We determined that HDR1 is a novel suppressor of flowering that upregulates Hd1 and downregulates Ehd1, leading to the downregulation of Hd3a and RFT1 under LDs. We have further identified an HDR1-interacting kinase, OsK4, another suppressor of rice flowering under LDs. OsK4 acts similarly to HDR1, suppressing flowering by upregulating Hd1 and downregulating Ehd1 under LDs, and OsK4 can phosphorylate HD1 with HDR1 presents. These results collectively reveal the transcriptional regulators of Hd1 for the day-length-dependent control of flowering time in rice

An-1 encodes a basic helix-loop-helix protein that regulates awn development, grain size, and grain number in rice

Long awns are important for seed dispersal in wild rice (Oryza rufipogon), but are absent in cultivated rice (Oryza sativa). The genetic mechanism involved in loss-of-awn in cultivated rice remains unknown. We report here the molecular cloning of a major quantitative trait locus, An-1, which regulates long awn formation in O. rufipogon. An-1 encodes a basic helix-loop-helix protein, which regulates cell division. The nearly-isogenic line (NIL-An-1) carrying a wild allele An-1 in the genetic background of the awnless indica Guangluai4 produces long awns and longer grains, but significantly fewer grains per panicle compared with Guangluai4. Transgenic studies confirmed that An-1 positively regulates awn elongation, but negatively regulates grain number per panicle. Genetic variations in the An-1 locus were found to be associated with awn loss in cultivated rice. Population genetic analysis of wild and cultivated rice showed a significant reduction in nucleotide diversity of the An-1 locus in rice cultivars, suggesting that the An-1 locus was a major target for artificial selection. Thus, we propose that awn loss was favored and strongly selected by humans, as genetic variations at the An-1 locus that cause awn loss would increase grain numbers and subsequently improve grain yield in cultivated rice

HDR1 interacts with OsK4.

<p>(A) HDR1 directly interacted with kinase OsK4 in the Y2H system. (B) Exon1 and Exon2 of HDR1, but not Exon3, directly interacted with OsK4 in yeast cells. (C) BiFC analyses of the interactions of HDR1 with OsK4 in <i>Arabidopsis</i> protoplast. YFP signals resulted from the physical association of HDR1 with OsK4 proteins, not negative pairs, in the nuclei. Scale bar = 10μm. (D) Co-immunoprecipitation of HDR1 with OsK4 in rice plant. Total protein extracted from the leaves expressing FLAG-HDR1 and WT, and then FLAG-HDR1 was immunoprecipitated with anti-FLAG, followed by western blotting to analyze the OsK4 with OsK4 antibody.</p