Starch composition and the amount in endosperm, both of which contribute dramatically to seed yield, cooking quality, and taste in cereals, are determined by a series of complex biochemical reactions. However, the mechanism regulating starch biosynthesis in cereal seeds is not well understood. This study showed that OsbZIP58, a bZIP transcription factor, is a key transcriptional regulator controlling starch synthesis in rice endosperm. OsbZIP58 was expressed mainly in endosperm during active starch synthesis. osbzip58 null mutants displayed abnormal seed morphology with altered starch accumulation in the white belly region and decreased amounts of total starch and amylose. Moreover, osbzip58 had a higher proportion of short chains and a lower proportion of intermediate chains of amylopectin. Furthermore, OsbZIP58 was shown to bind directly to the promoters of six starch-synthesizing genes, OsAGPL3, Wx, OsSSIIa, SBE1, OsBEIIb, and ISA2, and to regulate their expression. These findings indicate that OsbZIP58 functions as a key regulator of starch synthesis in rice seeds and provide new insights into seed quality control.
Despite an estimated twin heritability of ~50%, genome-wide association studies (GWAS) of opioid use disorder (OUD) have revealed few genome-wide signi cant (GWS) loci, with replicated ndings only in European-ancestry individuals. To identify novel loci, including those in non-European ancestries, and improve our understanding of the biology of OUD, we conducted a cross-ancestry meta-analysis using the Million Veteran Program (MVP). OUD cases in MVP had at least 1 International Classi cation of Diseases (ICD)-9 or ICD-10 code for opioid abuse or dependence (N=31,473). Opioid-exposed controls (N=394,471) had one or more outpatient opioid prescription lls. We conducted GWAS for each major ancestral group in MVP: African Americans (AAs; N=88,498), European Americans (EAs; N=302,585), and Hispanic Americans (HAs; N=34,861), followed by a cross-ancestry meta-analysis. Ten loci were GWS in the cross-ancestry meta-analysis, 8 of them novel. In addition to the known coding variant rs1799971 in OPRM1, which was the lead SNP genome-wide (p=6.78x10 −10 ), and a recently reported exonic variant in FURIN, we identi ed intronic variants in RABEPK, FBXW4, NCAM1, and KCNN1. Ancestry-speci c analyses identi ed an additional novel locus for each of the 3 ancestry groups. A supplementary meta-analysis within EAs that included MVP and other samples identi ed a locus in TSNARE1, which was also GWS in the cross-ancestry meta-analysis of all datasets. Gene-based association analyses identi ed 1 gene in AAs (CHRM2) and 3 in EAs (OPRM1, DRD2, and FTO). Signi cant genetic correlations (r g 's) were identi ed for 127 traits, including positive correlations with schizophrenia, problematic alcohol use, and major depressive disorder. The most signi cantly enriched cell type group was the central nervous system with gene-expression enrichment identi ed in brain regions previously associated with substance use disorders. With a case sample 50% larger than that of the previous largest GWAS, we identi ed 14 loci for OUD, including 12 novel loci, some of which were ancestry speci c. These ndings increase our understanding of the biological pathways involved in OUD, which can inform preventive, diagnostic, and therapeutic efforts and thereby help to address the opioid epidemic. Revision (ICD-10) diagnosis of OUD and control subjects were opioid exposed. Further details on phenotyping are described below. This GWAS was used for all subsequent downstream analyses.In a supplementary analysis, we performed within-ancestry meta-analyses for AAs and EAs from the MVP, Yale-Penn
Flavonoids, also called vitamin P, are widely distributed in plants fulfilling many functions. Yeast α-glucosidase (YAGH; EC 3.2.1.20), as extensively used target protein for screening bioactive compounds from medicine plants, was selected to explore the possible mechanisms of multiple biological function of flavonoids. The results in this study indicated that flavonoids, as mixed-type inhibitors, quenched the intrinsic fluorescence of YAGH by a mixed fluorescence quenching mechanism. The interaction information between flavonoids and YAGH was analyzed using a flexible docking method (AutoDock) and showed that 3', 4' dihydroxyl groups of B ring and 3-OH of C ring played a more important role in the inhibition activity than other hydroxyl groups, because the 3', 4' dihydroxyl groups of B ring directly interacted with the active-site residues of YAGH to inhibit enzyme activity and 3-OH of C ring seemed to be necessary to maintain the proper binding orientation of flavonoid molecules, thereby making the hydroxyl groups of B ring interact with active-site residues tightly in the hydrophobic pocket of YAGH. The results supply a basis for understanding the mechanisms of multiple biological functions of flavonoids.
High temperature (HT) has an adverse effect on rice grain filling by inhibiting the accumulation of storage materials. However, the regulatory mechanism of this inhibition remains unknown. Here, we report that Opaque2 like transcription factor OsbZIP58 is a key factor regulating storage material accumulation under HT. The OsbZIP58 gene promotes expression of many seed storage protein genes and starch synthesis genes while inhibits expression of some starch hydrolyzing α‐amylase genes under HT. The loss of OsbZIP58 function leads to floury and shrunken endosperms and dramatically reduced storage materials in the seeds under HT. HT is found to affect alternative splicing of OsbZIP58, promoting the formation of the truncated OsbZIP58β protein form over the full‐length OsbZIP58α protein form. The OsbZIP58β form has a lower transcriptional activity than the OsbZIP58α form, especially under HT condition. Interestingly, rice varieties with less heat sensitivity have reduced alternative splicing of OsbZIP58. Therefore, OsbZIP58 is a crucial gene in regulating storage material accumulation under HT and lower alternative splicing of OsbZIP58 may contribute to heat tolerance during grain filling.
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