The Arabidopsis MATERNAL EFFECT EMBRYO ARREST45 protein modulates maternal auxin biosynthesis and controls seed size by inducing AINTEGUMENTA.

Seed size is a major factor determining crop yields that is controlled through the coordinated development of maternal and zygotic tissues. Here, we identified Arabidopsis MATERNAL EFFECT EMBRYO ARREST45 (MEE45) as a B3 transcription factor that controls cell proliferation and maternally regulates seed size through its transcriptional activation of AINTEGUMENTA (ANT) and its downstream control of auxin biosynthesis in the ovule integument. After characterizing reduced seed and organ size phenotypes in mee45 mutants and finding that overexpression of MEE45 causes oversized seeds, we discovered that the MEE45 protein can bind to the promoter region of the ANT locus and positively regulate its transcription. ANT in-turn activates the expression of auxin biosynthetic genes (e.g. YUCCA4) in the ovule integument. Our results thus illustrate mechanisms underlying maternal tissue-mediated regulation of seed size and suggest that MEE45 and its downstream components can be harnessed to develop higher-yielding crop varieties.

Integration of pluripotency pathways regulates stem cell maintenance in the Arabidopsis shoot meristem.

In the shoot meristem, both WUSCHEL (WUS) and SHOOT MERISTEMLESS (STM), two transcription factors with overlapping spatiotemporal expression patterns, are essential for maintaining stem cells in an undifferentiated state. Despite their importance, it remains unclear how these two pathways are integrated to coordinate stem cell development. Here, we show that the WUS and STM pathways in Arabidopsis thaliana converge through direct interaction between the WUS and STM proteins. STM binds to the promoter of CLAVATA3 (CLV3) and enhances the binding of WUS to the same promoter through the WUS-STM interaction. Both the heterodimerization and simultaneous binding of WUS and STM at two sites on the CLV3 promoter are required to regulate CLV3 expression, which in turn maintains a constant number of stem cells. Furthermore, the expression of STM depends on WUS, and this WUS-activated STM expression enhances the WUS-mediated stem cell activity. Our data provide a framework for understanding how spatial expression patterns within the shoot meristem are translated into regulatory units of stem cell homeostasis.

Genome wide analyses uncover allele-specific RNA editing in human and mouse.

RNA editing is one of the most common RNA level modifications that potentially generate amino acid changes similar to those resulting from genomic nonsynonymous mutations. However, unlike DNA level allele-specific modifications such as DNA methylation, it is currently unknown whether RNA editing displays allele-specificity across tissues and species. Here, we analyzed allele-specific RNA editing in human tissues and from brain tissues of heterozygous mice generated by crosses between divergent mouse strains and found a high proportion of overlap of allele-specific RNA editing sites between different samples. We identified three allele-specific RNA editing sites cause amino acid changes in coding regions of human and mouse genes, whereas their associated SNPs yielded synonymous differences. In vitro cellular experiments confirmed that sequences differing at a synonymous SNP can have differences in a linked allele-specific RNA editing site with nonsynonymous implications. Further, we demonstrate that allele-specific RNA editing is influenced by differences in local RNA secondary structure generated by SNPs. Our study provides new insights towards a better comprehension of the molecular mechanism that link SNPs with human diseases and traits.

Genome-wide identification of imprinted genes in pigs and their different imprinting status compared with other mammals.

Genomic imprinting often results in parent-of-origin specific differential expression of maternally and paternally inherited alleles and plays an essential role in mammalian development and growth. Mammalian genomic imprinting has primarily been studied in mice and humans, with only limited information available for pigs. To systematically characterize this phenomenon and evaluate imprinting status between different species, we investigated imprinted genes on a genome-wide scale in pig brain tissues. Specifically, we performed bioinformatics analysis of high-throughput sequencing results from parental genomes and offspring transcriptomes of hybrid crosses between Duroc and Diannan small-ear pigs. We identified 11 paternally and five maternally expressed imprinted genes in pigs with highly stringent selection criteria. Additionally, we found that the KCNQ1 and IGF2R genes, which are related to development, displayed a different imprinting status in pigs compared with that in mice and humans. This comprehensive research should help improve our knowledge on genomic imprinting in pigs and highlight the potential use of imprinted genes in the pig breeding field.

Determining population stratification and subgroup effects in association studies of rare genetic variants for nicotine dependence.

BACKGROUND: Rare variants (minor allele frequency < 1% or 5 %) can help researchers to deal with the confounding issue of 'missing heritability' and have a proven role in dissecting the etiology for human diseases and complex traits. METHODS: We extended the combined multivariate and collapsing (CMC) and weighted sum statistic (WSS) methods and accounted for the effects of population stratification and subgroup effects using stratified analyses by the principal component analysis, named here as 'str-CMC' and 'str-WSS'. To evaluate the validity of the extended methods, we analyzed the Genetic Architecture of Smoking and Smoking Cessation database, which includes African Americans and European Americans genotyped on Illumina Human Omni2.5, and we compared the results with those obtained with the sequence kernel association test (SKAT) and its modification, SKAT-O that included population stratification and subgroup effect as covariates. We utilized the Cochran-Mantel-Haenszel test to check for possible differences in single nucleotide polymorphism allele frequency between subgroups within a gene. We aimed to detect rare variants and considered population stratification and subgroup effects in the genomic region containing 39 acetylcholine receptor-related genes. RESULTS: The Cochran-Mantel-Haenszel test as applied to GABRG2 (P = 0.001) was significant. However, GABRG2 was detected both by str-CMC (P= 8.04E-06) and str-WSS (P= 0.046) in African Americans but not by SKAT or SKAT-O. CONCLUSIONS: Our results imply that if associated rare variants are only specific to a subgroup, a stratified analysis might be a better approach than a combined analysis.

A non-threshold region-specific method for detecting rare variants in complex diseases.

A region-specific method, NTR (non-threshold rare) variant detection method, was developed-it does not use the threshold for defining rare variants and accounts for directions of effects. NTR also considers linkage disequilibrium within the region and accommodates common and rare variants simultaneously. NTR weighs variants according to minor allele frequency and odds ratio to combine the effects of common and rare variants on disease occurrence into a single score and provides a test statistic to assess the significance of the score. In the simulations, under different effect sizes, the power of NTR increased as the effect size increased, and the type I error of our method was controlled well. Moreover, NTR was compared with several other existing methods, including the combined multivariate and collapsing method (CMC), weighted sum statistic method (WSS), sequence kernel association test (SKAT), and its modification, SKAT-O. NTR yields comparable or better power in simulations, especially when the effects of linkage disequilibrium between variants were at least moderate. In an analysis of diabetic nephropathy data, NTR detected more confirmed disease-related genes than the other aforementioned methods. NTR can thus be used as a complementary tool to help in dissecting the etiology of complex diseases.

[Chemical speciations of heavy metals and their risk assessment in agricultural soils in a coal mining area from Xingren County, Guizhou Province, China.] / è´µå·žå ´ä»ç ¤çŸ¿åŒºå†œç”°åœŸå£¤é‡é‡‘å±žåŒ–å­¦å½¢æ€åŠé£Žé™©è¯„ä¼°.

In this study, total concentrations and chemical speciations of heavy metals (As, Cr, Pb, Zn, Cd, Hg, Cu and Ni) in 64 agricultural soil samples were determined to evaluate the level of contamination from a coal mining area in Xingren County, Guizhou Province. The single factor index, the Hkanson potential ecological risk index and the risk assessment code (RAC) were used for the evaluation of potential ecological and environmental risks in four main utilized types of soils (paddy soil, Coix lacryma-jobi soil, tobacco-growing soil and vegetable soil). The results demonstrated that the concentrations of heavy metals were significantly higher than their soil background values in Guizhou Province, with the exception of Zn. According to the evaluation results of the single factor index method, the soils were severely contaminated with As, Pb, Hg and Cu. And the chemical speciations of heavy metals significantly varied among the different utilized types of soils. As and Cd mainly existed in acid soluble fraction. Cr, Zn, Cu and Ni mainly existed in residual fraction. The existence of Pb was mainly in reducible fraction and residual fraction. And the content of Hg was distributed mainly in acid soluble fraction, reducible fraction and oxidizable fraction which accounted for about 55% of the total concentration. The bioavailability of heavy metals was characterized by the order of As(63.6%) > Hg(57.3%) > Cd(56.4%) > Pb(52.5%) > Cu (45.7%) > Zn (32.8%) > Ni (26.2%) > Cr (13.2%). The Hkanson potential ecological risk index (RI) suggested that the heavy metals were at considerable ecological risk and the ranking order was vegetable soil (505.19) > C. lacryma-jobi soil (486.06) > tobacco-growing soil〖JP2〗(475.33) > paddy soil (446.86). The risk assessment code (RAC) indicated that As was at high risk in the paddy soils, C. lacryma-jobi soils and tobacco-growing soils, while As was at medium risk in the vegetable soils. Cd and Hg were at medium risk, Cr, Pb, Zn, Cu and Ni were at low risk. Therefore, management measures must be taken to control contamination of As, Cd and Hg in this area.

Hepatitis B virus induces expression of cholesterol metabolism-related genes via TLR2 in HepG2 cells.

AIM: To investigate whether hepatitis B virus (HBV) exacerbates hepatic cholesterol accumulation, and explore the underlying mechanisms. METHODS: HepG2 cells were infected with adenovirus (Ad) containing 1.3-fold overlength HBV genome. Real-time polymerase chain reaction and Western blotting were used to measure mRNA and protein expression of target genes. Cholesterol accumulation was measured by fluorescence microscopy. Cell toxicity due to Ad-HBV treatment was determined by the mitochondrial tetrazolium assay. The protein levels of toll-like receptors (TLRs) were determined by Western blotting. RESULTS: Ad-HBV increased hepatic cholesterol accumulation and enhanced the mRNA and protein levels of low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCoAr) mRNA and protein expression in HepG2 cells. In addition, these inductive effects were partly offset by suppressing TLR2 expression levels by small interfering RNA in HepG2 cells. CONCLUSION: Ad-HBV increases LDLR and HMGCoAr expression, resulting in exacerbated cholesterol accumulation in HepG2 cells, which was mediated via the TLR2 pathway.