| 1. |
- Ishigaki, Kazuyoshi, et al.
(författare)
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Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:11, s. 1640-1651
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10−8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.
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| 2. |
- Kang, Chengjun, et al.
(författare)
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Covalent organic framework atropisomers with multiple gas-triggered structural flexibilities
- 2023
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Ingår i: Nature Materials. - 1476-1122 .- 1476-4660. ; 22:5, s. 636-643
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Tidskriftsartikel (refereegranskat)abstract
- Covalent organic frameworks (COFs) are emerging crystalline porous polymers, showing great potential for applications but lacking gas-triggered flexibility. Atropisomerism was experimentally discovered in 1922 but has rarely been found in crystals with infinite framework structures. Here we report atropisomerism in COF single crystals. The obtained COF atropisomers, namely COF-320 and COF-320-A, have identical chemical and interpenetrated structures but differ in the spatial arrangement of repeating units. In contrast to the rigid COF-320 structure, its atropisomer (COF-320-A) exhibits unconventional gas sorption behaviours with one or more sorption steps in isotherms at different temperatures. Single-crystal structures determined from continuous rotation electron diffraction and in situ powder X-ray diffraction demonstrate that these adsorption steps originate from internal pore expansion with or without changing the crystal space group. COF-320-A recognizes different gases by expanding its internal pores continuously (crystal-to-amorphous transition) or discontinuously (crystal-to-crystal transition) or having mixed transition styles, distinguishing COF-320-A from existing soft/flexible porous crystals. These findings extend atropisomerism from molecules to crystals and propel COFs into the covalently linked soft porous crystal regime, further advancing applications of soft porous crystals in gas sorption, separation and storage.
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| 3. |
- Nagahage, Isura Sumeda Priyadarshana, et al.
(författare)
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NAC domain transcription factors VNI2 and ATAF2 form protein complexes and regulate leaf senescence
- 2023
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Ingår i: Plant Direct. - : John Wiley & Sons. - 2475-4455. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- The NAM, ATAF1/2, and CUC2 (NAC) domain transcription factor VND-INTERACTING2 (VNI2) negatively regulates xylem vessel formation by interacting with another NAC domain transcription factor, VASCULAR-RELATED NAC-DOMAIN7 (VND7), a master regulator of xylem vessel formation. Here, we screened interacting proteins with VNI2 using yeast two-hybrid assay and isolated two NAC domain transcription factors, Arabidopsis thaliana ACTIVATION FACTOR 2 (ATAF2) and NAC DOMAIN CONTAINING PROTEIN 102 (ANAC102). A transient gene expression assay showed that ATAF2 upregulates the expression of genes involved in leaf senescence, and VNI2 effectively inhibits the transcriptional activation activity of ATAF2. vni2 mutants accelerate leaf senescence, whereas ataf2 mutants delay leaf senescence. In addition, the accelerated leaf senescence phenotype of the vni2 mutant is recovered by simultaneous mutation of ATAF2. Our findings strongly suggest that VNI2 interacts with and inhibits ATAF2, resulting in negatively regulating leaf senescence.
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