HMGB1 A box protects neurons by potently inhibiting both microglia and T cell-mediated inflammation in a mouse Parkinson's disease model.

In the subacute Parkinson's disease (PD) mice model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), injection of HMGB1 competitive inhibitor protein HMGB1 A box and the ethyl pyruvate (EP) that inhibit the release of HMGB1 from cells restored the number of dopaminergic neurons and TH+ fibers in the SN and striatum. Our data show that A box up-regulated CD200-CD200R signal of microglia inhibited the activation of microglia mediated by HMGB1, and the production of TNF-α, IL-1ß and IL-6 in vivo and in vitro mixed culture system. Microglia overexpressing CD200R produced less inflammatory chemokines and reduced the loss of TH+ neurons. In addition, HMGB1 A box decreased the level of CCL5 and significantly inhibited the infiltration of almost all T cells including Th17 and the proportion of Th17 in CD4+ T cells. In vitro MPP+ induced model and HMGB1-stimulated mesencephalic cell system activated microglia induced the differentiation of naïve T cells to Th17, and A box significantly inhibited this process. To sum up, our results show that HMGB1 A box targeting HMGB1, which effectively reduces the activation of microglia in MPTP PD model by restoring CD200-CD200R signal inhibit microglia mediated neuroinflammation and the differentiation of T cells to Th17.

OsSPL13 controls grain size in cultivated rice.

Although genetic diversity has a cardinal role in domestication, abundant natural allelic variations across the rice genome that cause agronomically important differences between diverse varieties have not been fully explored. Here we implement an approach integrating genome-wide association testing with functional analysis on grain size in a diverse rice population. We report that a major quantitative trait locus, GLW7, encoding the plant-specific transcription factor OsSPL13, positively regulates cell size in the grain hull, resulting in enhanced rice grain length and yield. We determine that a tandem-repeat sequence in the 5' UTR of OsSPL13 alters its expression by affecting transcription and translation and that high expression of OsSPL13 is associated with large grains in tropical japonica rice. Further analysis indicates that the large-grain allele of GLW7 in tropical japonica rice was introgressed from indica varieties under artificial selection. Our study demonstrates that new genes can be effectively identified on the basis of genome-wide association data.

Genome-wide association study of flowering time and grain yield traits in a worldwide collection of rice germplasm.

A high-density haplotype map recently enabled a genome-wide association study (GWAS) in a population of indica subspecies of Chinese rice landraces. Here we extend this methodology to a larger and more diverse sample of 950 worldwide rice varieties, including the Oryza sativa indica and Oryza sativa japonica subspecies, to perform an additional GWAS. We identified a total of 32 new loci associated with flowering time and with ten grain-related traits, indicating that the larger sample increased the power to detect trait-associated variants using GWAS. To characterize various alleles and complex genetic variation, we developed an analytical framework for haplotype-based de novo assembly of the low-coverage sequencing data in rice. We identified candidate genes for 18 associated loci through detailed annotation. This study shows that the integrated approach of sequence-based GWAS and functional genome annotation has the potential to match complex traits to their causal polymorphisms in rice.

Genome-wide association studies of 14 agronomic traits in rice landraces.

Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified ∼ 3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained ∼ 36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice.