Despite its importance in drug metabolism and disease susceptibility, CYP2D6 activity and genetic polymorphism have rarely been investigated in African-American populations. In order to bridge this gap, we examined the genotype and phenotype of the enzyme in 154 African-American (AA) and 143 Caucasian (C) normal volunteers. AAs are significantly more likely to possess *17 and *5, but less likely to have *4. Overall, the two groups were similar in their CYP2D6 activity as measured with dextromethorphan as the probe (metabolic ratio 2.21 +/- 0.78 for AAs; 2.11 +/- 0.86 for Cs; t = 1.02, NS). Two of four AAs and six of seven Cs were classified as poor metabolizers and have two nonfunctioning alleles. CYP2D6 activity is determined by *17, *4, *5 and age in AAs (r2 = 0.33, f = 18.8, P < 0.001) and by *4 and *XN in Cs (r2 = 0.14, f = 10.8, P < 0.001). These results support previous findings demonstrating the importance of *17 in determining CYP2D6 activity in AAs.

The mechanisms associated with the regulation of iron (Fe) homeostasis have been extensively examined, however, epigenetic regulation of these processes remains largely unknown. Here, we report that a naturally occurring epigenetic mutant, Colorless non-ripening (Cnr), displayed increased Fe-deficiency responses compared to its wild-type Ailsa Craig (AC). RNA-sequencing revealed that a total of 947 and 1,432 genes were up-regulated by Fe deficiency in AC and Cnr roots, respectively, while 923 and 1,432 genes were, respectively, down-regulated. Gene ontology analysis of differentially expressed genes showed that genes encoding enzymes, transporters, and transcription factors were preferentially affected by Fe deficiency. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed differential metabolic responses to Fe deficiency between AC and Cnr. Based on comparative transcriptomic analyses, 24 genes were identified as potential targets of Cnr epimutation, and many of them were found to be implicated in Fe homeostasis. By developing CRISPR/Cas9 genome editing SlSPL-CNR knockout (KO) lines, we found that some Cnr-mediated Fe-deficiency responsive genes showed similar expression patterns between SlSPL-CNR KO plants and the Cnr epimutant. Moreover, both two KO lines displayed Fe-deficiency-induced chlorosis more severe than AC plants. Additionally, the Cnr mutant displayed hypermethylation in the 286-bp epi-mutated region on the SlSPL-CNR promoter, which contributes to repressed expression of SlSPL-CNR when compared with AC plants. However, Fe-deficiency induced no change in DNA methylation both at the 286-bp epi-allele region and the entire region of SlSPL-CNR gene. Taken together, using RNA-sequencing and genetic approaches, we identified Fe-deficiency responsive genes in tomato roots, and demonstrated that SlSPL-CNR is a novel regulator of Fe-deficiency responses in tomato, thereby, paving the way for further functional characterization and regulatory network dissection.

Cadmium (Cd) toxicity severely limits plant growth and development. Moreover, Cd accumulation in vegetables, fruits, and food crops poses health risks to animals and humans. Although the root cell wall has been implicated in Cd stress in plants, whether Cd binding by cell wall polysaccharides contributes to tolerance remains controversial, and the mechanism underlying transcriptional regulation of cell wall polysaccharide biosynthesis in response to Cd stress is unknown. Here, we functionally characterized an Arabidopsis thaliana NAC‐type transcription factor, NAC102, revealing its role in Cd stress responses. Cd stress rapidly induced accumulation of NAC102.1, the major transcript encoding functional NAC102, especially in the root apex. Compared to wild‐type plants, a nac102 mutant exhibited enhanced Cd sensitivity, whereas NAC102.1‐overexpressing plants displayed the opposite phenotype. Furthermore, NAC102 localizes to the nucleus, binds directly to the promoter of WALL‐ASSOCIATED KINASE‐LIKE PROTEIN11 (WAKL11), and induces transcription, thereby facilitating pectin degradation and decreasing Cd binding by pectin. Moreover, WAKL11 overexpression restored Cd tolerance in nac102 mutants to the wild‐type levels, which was correlated with a lower pectin content and lower levels of pectin‐bound Cd. Taken together, our work shows that the NAC102−WAKL11 module regulates cell wall pectin metabolism and Cd binding, thus conferring Cd tolerance in Arabidopsis.This article is protected by copyright. All rights reserved.

Deoxyribonucleic acid (DNA) methylation is an important epigenetic mark involved in diverse biological processes. Here, we report the critical function of tomato (Solanum lycopersicum) Domains Rearranged Methyltransferase7 (SlDRM7) in plant growth and development, especially in leaf interveinal chlorosis and senescence. Using a hairpin RNA-mediated RNA interference (RNAi), we generated SlDRM7-RNAi lines and observed pleiotropic developmental defects including small and interveinal chlorosis leaves. Combined analyses of whole genome bisulfite sequence (WGBS) and RNA-seq revealed that silencing of SlDRM7 caused alterations in both methylation levels and transcript levels of 289 genes, which are involved in chlorophyll synthesis, photosynthesis, and starch degradation. Furthermore, the photosynthetic capacity decreased in SlDRM7-RNAi lines, consistent with the reduced chlorophyll content and repression of genes involved in chlorophyll biosynthesis, photosystem, and photosynthesis. In contrast, starch granules were highly accumulated in chloroplasts of SlDRM7-RNAi lines and associated with lowered expression of genes in the starch degradation pathway. In addition, SlDRM7 was activated by aging- and dark-induced senescence. Collectively, these results demonstrate that SlDRM7 acts as an epi-regulator to modulate the expression of genes related to starch and chlorophyll metabolism, thereby affecting leaf chlorosis and senescence in tomatoes.

Objective: Curcumin possesses extensive therapeutic effects on several diseases and tumor cells, which has inhibitory effects on mammalian target of rapamycin (mTOR)-STAT3 signaling. Our study aims to explore the influences of curcumin on promoting the recovery of motor function after spinal cord injury (SCI) in rats through the mTOR-STAT3 signaling pathway. Methods : SCI rats were treated with rapamycin and curcumin followed by establishing rat models of SCI. The influences of rapamycin and curcumin on the protein expressions of PTEN, Akt, phosphorylated S6 and chondroitin sulphate proteoglycans (CSPGs) were measured by western blot. Means of Basso, Beattie and Bresnahan (BBB) locomotor rating scale was used to assess motor function. Results: After SCI, curcumin promoted the expression of PTEN, reduced the proliferation of neuroglia cells, affected the expressions of CSPGs and improved the motor function. Conclusion: Curcumin can promote motor function recovery after SCI which is possibly by up-regulating the PTEN expression via the mTOR-STAT3 signaling pathway.