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| 2. |
- de las Fuentes, Lisa, et al.
(författare)
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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| 3. |
- Cheng, Shi-Ping, et al.
(författare)
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Haplotype-resolved genome assembly and allele-specific gene expression in cultivated ginger
- 2021
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Ingår i: Horticulture Research. - : Springer Nature. - 2052-7276. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger.
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| 4. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 5. |
- Fang, Liang, et al.
(författare)
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Left ventricular pseudoaneurysm complicating a ruptured isolated congenital diverticulum
- 2020
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Ingår i: Echocardiography. - : John Wiley & Sons. - 0742-2822 .- 1540-8175. ; 37:6, s. 926-927
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Tidskriftsartikel (refereegranskat)abstract
- We report a case of 41-year-old woman who presented with chest tightness and shortness of breath. Transthoracic echocardiogram (TTE) showed left ventricular (LV) pseudoaneurysm of the inferior wall with preserved LV systolic function. Coronary angiogram was normal. Surgical repair of the pseudoaneurysm with a pericardial patch was performed, and pathological results confirmed rupture of an isolated congenital LV diverticulum, as the most likely etiology.
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| 6. |
- Jia, Kai-Hua, et al.
(författare)
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Chromosome-scale assembly and evolution of the tetraploid Salvia splendens (Lamiaceae) genome
- 2021
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Ingår i: Horticulture Research. - : Oxford University Press (OUP). - 2052-7276 .- 2662-6810. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Polyploidization plays a key role in plant evolution, but the forces driving the fate of homoeologs in polyploid genomes, i.e., paralogs resulting from a whole-genome duplication (WGD) event, remain to be elucidated. Here, we present a chromosome-scale genome assembly of tetraploid scarlet sage (Salvia splendens), one of the most diverse ornamental plants. We found evidence for three WGD events following an older WGD event shared by most eudicots (the γ event). A comprehensive, spatiotemporal, genome-wide analysis of homoeologs from the most recent WGD unveiled expression asymmetries, which could be associated with genomic rearrangements, transposable element proximity discrepancies, coding sequence variation, selection pressure, and transcription factor binding site differences. The observed differences between homoeologs may reflect the first step toward sub- and/or neofunctionalization. This assembly provides a powerful tool for understanding WGD and gene and genome evolution and is useful in developing functional genomics and genetic engineering strategies for scarlet sage and other Lamiaceae species.
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| 7. |
- Li, Fang-Yi, et al.
(författare)
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Inhibition of K-Ras4B-plasma membrane association with a membrane microdomain-targeting peptide
- 2020
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Ingår i: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 11:3, s. 826-832
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Tidskriftsartikel (refereegranskat)abstract
- The association of K-Ras4B protein with plasma membrane (PM) is required for its signaling activity. Thus, direct inhibition of K-Ras4B-PM interaction could be a potential anti-Ras therapeutic strategy. However, it remains challenging to modulate such protein-PM interaction. Based on Ras isoform-specific PM microdomain localization patterns, we have developed a potent and isoform-selective peptide inhibitor, Memrasin, for detachment of K-Ras4B from the PM. Memrasin is one of the first direct inhibitors of K-Ras4B-PM interaction, and consists of a membrane l(d) region-binding sequence derived from the C-terminal region of K-Ras4B and an endosome-escape enhancing motif that can aggregate on membrane. It forms peptide-enriched domains in the l(d) region, abrogates the tethering of K-Ras4B to the PM and accordingly impairs Ras signaling activity, thereby efficiently decreasing the viability of several human lung cancer cells in a dose-responsive and K-Ras dependent manner. Memrasin provides a useful tool for exploring the biological function of K-Ras4B on or off the PM and a potential starting point for further development into anti-Ras therapeutics.
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| 8. |
- Wang, Yuwen, et al.
(författare)
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Fast room-temperature hydrogenation of nitroaromatics on Pd nanocrystal-boron cluster/graphene oxide nanosheets
- 2022
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Ingår i: Molecular Catalysis. - : Elsevier. - 2468-8231. ; 529
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Tidskriftsartikel (refereegranskat)abstract
- The reduction of nitroaromatics to aminoaromatics is essential for fine chemical production and effective sewage treatment. However, the activity of an external catalyst is essential for the reaction. In this study, Pd nanocrystals were anchored in situ on two-dimensional graphene oxide (GO), which acted as a catalyst support with high specific surface area. The oxygen-containing groups on the surface of GO bonded to the functionally rich boron clusters through hydrogen bonding interactions. A mildly reducible closed-dodecahydrododecaboric acid anion cluster (closo‑[B12H12]2–) was employed as the target site. The mild reducibility of closo‑[B12H12]2– resulted in a wide dispersion of ultrafine Pd nanocrystals on GO. Under ambient conditions, Pd/BGO rapidly hydrogenated nitroaromatics, such as 4-nitrophenol, to aminoaromatics with approximately 100% efficiency. Moreover, Pd/BGO retained its high catalytic activity for the hydrogenation/reduction of 4-nitrophenol after five catalytic cycles. Therefore, Pd/BGO could be a promising and economically viable candidate for various practical applications. The proposed innovative preparation strategy and highly efficient catalytic activity suggested the effective performance of closo‑[B12H12]2– as nanometal nucleation target sites. In addition to providing an alternate route for preparing supported nanometals, this study presents a stable and efficient catalyst for the hydrogenation of nitroaromatics.
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| 9. |
- Yang, Fu-Sheng, et al.
(författare)
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Chromosome-level genome assembly of a parent species of widely cultivated azaleas
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Azaleas (Ericaceae) comprise one of the most diverse ornamental plants, renowned for their cultural and economic importance. We present a chromosome-scale genome assembly for Rhododendron simsii, the primary ancestor of azalea cultivars. Genome analyses unveil the remnants of an ancient whole-genome duplication preceding the radiation of most Ericaceae, likely contributing to the genomic architecture of flowering time. Small-scale gene duplications contribute to the expansion of gene families involved in azalea pigment biosynthesis. We reconstruct entire metabolic pathways for anthocyanins and carotenoids and their potential regulatory networks by detailed analysis of time-ordered gene co-expression networks. MYB, bHLH, and WD40 transcription factors may collectively regulate anthocyanin accumulation in R. simsii, particularly at the initial stages of flower coloration, and with WRKY transcription factors controlling progressive flower coloring at later stages. This work provides a cornerstone for understanding the underlying genetics governing flower timing and coloration and could accelerate selective breeding in azalea. Azaleas are one of the most diverse ornamental plants and have cultural and economic importance. Here, the authors report a chromosome-scale genome assembly for the primary ancestor of the azalea cultivar Rhododendro simsi and identify transcription factors that may function in flower coloration at different stages.
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| 10. |
- Zhao, Hongxing, et al.
(författare)
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Detection of SARS-CoV-2 antibodies in serum and dried blood spot samples of vaccinated individuals using a sensitive homogeneous proximity extension assay.
- 2022
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Ingår i: New biotechnology. - : Elsevier BV. - 1871-6784 .- 1876-4347. ; 72, s. 139-148
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Tidskriftsartikel (refereegranskat)abstract
- A homogeneous PCR-based assay for sensitive and specific detection of antibodies in serum or dried blood spots (DBS) is presented and the method is used to monitor individuals infected with or vaccinated against SARS-CoV-2. Detection probes were prepared by conjugating the recombinant spike protein subunit 1 (S1), containing the receptor binding domain (RBD) of SARS-CoV-2, to each of a pair of specific oligonucleotides. The same was done for the nucleocapsid protein (NP). Upon incubation with serum or DBS samples, the bi- or multivalency of the antibodies (IgG, IgA or IgM) brings pairs of viral proteins with their conjugated oligonucleotides in proximity, allowing the antibodies to be detected by a modified proximity extension assay (PEA). Anti-S1 and anti-NP antibodies could be detected simultaneously from one incubation reaction. This Antibody PEA (AbPEA) test uses only 1µl of neat or up to 100,000-fold diluted serum or one ø1.2mm disc cut from a DBS. All 100 investigated sera and 21 DBS collected prior to the COVID-19 outbreak were negative, demonstrating a 100% specificity. The area under the curve, as evaluated by Receiver Operating Characteristic (ROC) analysis reached 0.998 (95%CI: 0.993-1) for samples taken from 11 days after symptoms onset. The kinetics of antibody responses were monitored after a first and second vaccination using serially collected DBS from 14 individuals. AbPEA offers highly specific and sensitive solution-phase antibody detection without requirement for secondary antibodies, no elution step when using DBS sample in a simple procedure that lends itself to multiplex survey of antibody responses.
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