Genetic mechanism

  • 文章类型: Journal Article
    由雄性森林麝香鹿(FMD;Moschusberezovskii)的麝香腺分泌的麝香因其制药和香水应用而受到高度重视。然而,麝香分泌的调节机制尚不清楚。本研究旨在研究不同时期和年龄的麝香分泌相关基因和转录因子。我们分析了成年男性口蹄疫在非分泌期和分泌期的麝香腺,以及分泌期的青少年和成年男性口蹄疫,采用单细胞多体ATAC+基因表达技术。我们的分析确定了13种细胞类型,包括1型和2型的腺泡细胞。染色质可及性分析和基因表达数据证实,基因Map3k2,Hsd17b12和Jun对于麝香分泌至关重要。此外,EHF,NR4A2和FOXO1蛋白起着重要的调控作用。加权基因共表达网络分析(WGCNA)强调了GnRH信号通路在麝香分泌中的重要性。基因集富集分析(GSEA)表明,类固醇激素生物合成途径在腺泡细胞中明显富集。此外,细胞间通讯似乎会影响麝香分泌的启动和维持。这些发现为口蹄疫中麝香分泌的分子途径提供了有价值的见解,提供增加麝香产量和开发治疗炎症和肿瘤的潜在途径。
    Musk secreted by the musk glands in male forest musk deer (FMD; Moschus berezovskii) is highly valued for its pharmaceutical and perfumery applications. However, the regulatory mechanisms underlying musk secretion are not well understood. This study aimed to investigate the genes and transcription factors involved in musk secretion across different periods and ages. We analyzed the musk glands of adult male FMD during the non-secretory and secretory periods, as well as juvenile and adult male FMD during the secretory period, using single-cell multiome ATAC+gene expression technique. Our analysis identified 13 cell types, including acinar cells of Types 1 and 2. Chromatin accessibility analysis and gene expression data confirmed that the genes Map3k2, Hsd17b12, and Jun are critical for musk secretion. Additionally, EHF, NR4A2, and FOXO1 proteins play crucial regulatory roles. Weighted gene co-expression network analysis (WGCNA) highlighted the importance of GnRH signaling pathway in musk secretion. Gene set enrichment analysis (GSEA) showed that the steroid hormone biosynthesis pathway is notably enriched in acinar cells. Furthermore, intercellular communication appears to influence both the initiation and maintenance of musk secretion. These findings provide valuable insights into the molecular pathways of musk secretion in FMD, offering potential avenues for increasing musk production and developing treatment for inflammation and tumors.
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  • 文章类型: Journal Article
    背景:先前的研究表明,炎症性肠病(IBD)与骨质疏松症(OP)和骨密度(BMD)有关,但潜在的遗传机制尚不清楚。我们的研究旨在探索IBD和OP之间的遗传和因果关系。
    方法:基于大规模全基因组关联汇总统计和个体水平数据集(即,英国生物银行),本研究进行了连锁不平衡评分回归(LDSC),复合零假设(PLACO)下的多效性分析,和孟德尔随机化(MR)分析以探索遗传关联,多效性基因与IBD和BMD之间的因果关系。
    结果:LDSC揭示了IBD和BMD之间的显着遗传相关性(例如,前臂BMD(rg=-0.3479,P=0.019)和股骨颈BMD(rg=-0.1335,P=0.0307)。PLACO确定了14个重叠的多效性基因座,1个共有风险基因(CDYL),和多个共享路径,揭示IBD和OP的可能机制。MR分析显示IBD和BMD之间存在因果关系。
    结论:我们的研究表明,IBD可能会增加OP的风险,并揭示了将IBD与骨质疏松症风险联系起来的复杂遗传机制,这对IBD和OP的诊断和治疗具有重要意义。
    BACKGROUND: Previous studies have shown that inflammatory bowel disease (IBD) is associated with osteoporosis (OP) and bone mineral density (BMD), but the underlying genetic mechanisms are unclear. Our study wanted to explore the genetic and causal relationship between IBD and OP.
    METHODS: Based on large-scale genome-wide association summary statistics and individual-level datasets (i.e., the UK Biobank), this study performed linkage disequilibrium score regression (LDSC), pleiotropic analysis under the composite null hypothesis (PLACO), and Mendelian randomization (MR) analyses to explore the genetic association, the pleiotropic genes and the causal relationship between IBD and BMD.
    RESULTS: LDSC revealed significant genetic correlations between IBD and BMD (e.g., forearm BMD (rg = -0.3479, P = 0.019) and femoral neck BMD (rg = -0.1335, P = 0.0307). PLACO identified 14 overlapping pleiotropic loci, 1 shared risk gene (CDYL), and multiple shared pathways, revealing possible mechanisms for IBD and OP. MR analysis demonstrated a causal association between IBD and BMD.
    CONCLUSIONS: Our study indicates that IBD may increase the risk of OP and reveals a complex genetic mechanism linking IBD and the risk of osteoporosis, which has important implications for diagnosing and treating IBD and OP.
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  • 文章类型: Journal Article
    肝细胞癌(HCC)是全球最常见的癌症之一,在东亚很普遍。虽然肝癌的全基因组关联研究(GWAS)已经确定了23个风险区域,这些关联背后的易感基因在很大程度上仍不清楚.确定肝癌的新候选基因,我们在两个东亚人群中进行了肝脏单组织和跨组织全转录组关联研究(TWASs).
    使用来自中国启东队列的2,514名受试者(1,161例HCC病例和1,353例对照)和来自BioBank日本项目的161,323名受试者(2,122例HCC病例和159,201例对照)的GWAS汇总统计数据进行TWAS分析。单组织和跨组织TWAS方法均用于检测易感基因与HCC风险之间的关联。TWAS鉴定的基因通过Metascape进一步注释,UALCAN,GEPIA2和DepMap。
    我们在Bonferroni校正后,在16个独立位点鉴定出22个新基因与HCC风险显著相关。其中,13个基因位于新区域。此外,我们发现中国和日本队列中有83个基因重叠,P<0.05,通过单组织和跨组织TWAS方法可识别三个基因(NUAK2,HLA-DQA1和ATP6V1G2).在通过TWAS鉴定的基因中,其中很大一部分在肝癌生物学中表现出可信的作用,例如FAM96B,HSPA5、POLRMT、MPHOSPH10和RABL2A。HLA-DQA1,NUAK2和HSPA5与先前报道的HCC癌变过程相关。
    我们的发现强调了利用基因表达数据来识别超出GWAS关联的新候选基因的价值,并可以进一步为HCC的生物学提供遗传见解。
    UNASSIGNED: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is prevalent in East Asia. Although genome-wide association studies (GWASs) of HCC have identified 23 risk regions, the susceptibility genes underlying these associations largely remain unclear. To identify novel candidate genes for HCC, we conducted liver single-tissue and cross-tissue transcriptome-wide association studies (TWASs) in two populations of East Asia.
    UNASSIGNED: GWAS summary statistics of 2,514 subjects (1,161 HCC cases and 1,353 controls) from the Chinese Qidong cohort and 161,323 subjects (2,122 HCC cases and 159,201 controls) from the BioBank Japan project were used to conduct TWAS analysis. The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC. TWAS identified genes were further annotated by Metascape, UALCAN, GEPIA2, and DepMap.
    UNASSIGNED: We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction. Of these, 13 genes were located in novel regions. Besides, we found 83 genes overlapped in the Chinese and Japanese cohorts with P < 0.05, of which, three genes (NUAK2, HLA-DQA1, and ATP6V1G2) were discerned by both single-tissue and cross-tissue TWAS approaches. Among the genes identified through TWAS, a significant proportion of them exhibit a credible role in HCC biology, such as FAM96B, HSPA5, POLRMT, MPHOSPH10, and RABL2A. HLA-DQA1, NUAK2, and HSPA5 associated with the process of carcinogenesis in HCC as previously reported.
    UNASSIGNED: Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.
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  • 文章类型: Journal Article
    背景:松材线虫(PWN;松材线虫)是松材枯萎病(PWD)的病原体,这被认为是全球针叶树最危险的生物危害。PWN的传播依赖于昆虫媒介,特别是日本松树锯片(JPS;Monochamusalternatus)。然而,PWN-JPS组装的分子机制在很大程度上仍然未知。
    结果:这里,我们发现,地域和性别都会显著影响JPS的PCA(PWN携带量);因此,关于PWN负荷,探索了来自不同位置和性别的JPS转录组。由于基因组的短缺,我们开发了用于分析下一代测序数据的全长参考转录组.进行了比较基因组研究,通过使用报告的PWN和非PWN携带者昆虫物种的基因组,在JPS中提名了11248个潜在的携带PWN的相关基因(β)。然后,151个差异表达转录本(DES),其中28个与β重叠,与JPS的PCA相关的是由RNA-Seq提名的,发现脂肪酸β-氧化可能是影响JPSPCA的关键因素。此外,使用抑制剂Etomoxir实验降低了JPS脂肪酸β-氧化速率,导致JPS的PCA增加。同时,通过RNA干扰沉默JPS中的MaCPT1导致脂肪酸β-氧化速率降低和JPS的PCA增加。
    结论:结论:MaCPT1能够通过JPS的脂肪酸β-氧化减少PWN-JPS组装体的形成。这些结果为探索PWN入侵对JPS的影响提供了新的见解。©2024化学工业学会。
    BACKGROUND: Pine wood nematode (PWN; Bursaphelenchus xylophilus) is the causative agent of pine wilt disease (PWD), which is considered the most dangerous biohazard to conifer trees globally. The transmission of PWN relies on insect vectors, particularly the Japanese pine sawyer (JPS; Monochamus alternatus). However, the molecular mechanism underlying PWN-JPS assembly remains largely unknown.
    RESULTS: Here, we found that both geographical and gender could significantly affect the PCA (PWN carrying amount) of JPS; thus, JPS transcriptomes from diverse locations and genders were explored regard to PWN loading. Due to the shortage of genomes, we developed a full-length reference transcriptome for analyzing next-generation sequencing data. A comparative genomic study was performed, and 11 248 potential PWN-carrying associate genes (β) were nominated in JPS by using the reported genomes of PWN and non-PWN carrier insect species. Then, 151 differentially expressed transcripts (DETs), 28 of them overlapped with β, correlated with the PCA of JPS were nominated by RNA-Seq, and found that fatty acid β-oxidation might be the key factor that affected the PCA of JPS. Furthermore, JPS fatty acid β-oxidation rates were experimentally decreased using the inhibitor Etomoxir, leading to an increased PCA of JPS. Meanwhile, silencing MaCPT1 in JPS by RNA interference led to a decreased fatty acid β-oxidation rate and increased PCA of JPS.
    CONCLUSIONS: In conclusion, MaCPT1 was able to decrease the PWN-JPS assembly formation through the fatty acid β-oxidation of JPS. These results provide new insights for exploring the impact of PWN invasion on JPS. © 2024 Society of Chemical Industry.
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  • 文章类型: Journal Article
    块茎植物作为人类食粮作物在世界上具有主要意义。多糖,块茎植物中的重要代谢产物,也可以作为具有显着药理作用的创新药物的来源。这些药物因其免疫调节和抗肿瘤特性而特别为人所知。充分挖掘块茎植物多糖的潜在价值,建立其靶向合成的合成体系,解剖它们的代谢过程和遗传调控机制至关重要。在这篇文章中,我们全面总结了各种块茎植物多糖合成的基本途径。我们还概述了近年来在该领域取得的关键研究进展。我们对块茎植物多糖的主要类型和功能进行了分类,并分析了参与淀粉代谢途径的关键酶的生物合成过程和遗传调控机制。纤维素,果胶,块茎植物中的果聚糖。我们已经确定己糖激酶和糖基转移酶是参与多糖合成过程的关键酶。通过阐明块茎植物中多糖的合成途径,并了解代谢途径中关键酶的潜在作用机制,我们可以为提高植物培养细胞中多糖和其他代谢产物的产量提供理论框架。这将最终提高生产效率。
    Tuber plants are of great significance in the world as human food crops. Polysaccharides, important metabolites in tuber plants, also serve as a source of innovative drugs with significant pharmacological effects. These drugs are particularly known for their immunomodulation and antitumor properties. To fully exploit the potential value of tuber plant polysaccharides and establish a synthetic system for their targeted synthesis, it is crucial to dissect their metabolic processes and genetic regulatory mechanisms. In this article, we provide a comprehensive summary of the basic pathways involved in the synthesis of various types of tuber plant polysaccharides. We also outline the key research progress that has been made in this area in recent years. We classify the main types and functions of tuber plant polysaccharides and analyze the biosynthetic processes and genetic regulation mechanisms of key enzymes involved in the metabolic pathways of starch, cellulose, pectin, and fructan in tuber plants. We have identified hexokinase and glycosyltransferase as the key enzymes involved in the polysaccharide synthesis process. By elucidating the synthesis pathway of polysaccharides in tuber plants and understanding the underlying mechanism of action of key enzymes in the metabolic pathway, we can provide a theoretical framework for enhancing the yield of polysaccharides and other metabolites in plant culture cells. This will ultimately lead to increased production efficiency.
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  • 文章类型: Journal Article
    多孔砂岩地热水是一种重要的地热资源,这是一种低碳清洁的资源,但缺乏区域范围内的系统研究。济南市北部地热资源丰富,特别是多孔砂岩热储层。然而,关于多孔砂岩中地热成因机制和地热水水化学特征的研究还不完全。本研究旨在通过收集济南北部的21个地下水样品,并比较其常规离子和同位素特征,研究地热水形成过程中的水化学特征,揭示多孔砂岩地热水的成因机制。结果表明,地热水分为Na-Cl型和Na-SO4-Cl型。地热水的水化学特征主要受水-岩相互作用和地下水混合的影响。水源主要来自太一山的大气降水,海拔910.75-1542.2m.s.a.l..储热器的估计温度范围为51至78°C,地热水循环深度估计在1316至2216m之间。根据地热田的特征,包括“盖帽岩”,水源,热源,水库,和频道,“提出了多孔砂岩地热水流动系统的概念模型。该模型为类似地质条件下地热水的成因机制提供了新的见解。
    Porous sandstone geothermal water is an important geothermal resource, which is a low-carbon and clean resource, but lacks systematic research on a regional scale. The northern part of Jinan City is rich in geothermal resources, specifically porous sandstone thermal reservoirs. However, there is still incomplete research on the mechanism of geothermal genesis and the hydrochemical characteristics of geothermal water in porous sandstone. This study aims to address this gap by collecting 21 groundwater samples from northern Jinan and comparing their conventional ion and isotope characteristics to investigate the hydrochemical characteristics during the formation of geothermal water and uncover the genesis mechanism of porous sandstone geothermal water. The results indicate that the geothermal water is classified as Na-Cl type and Na-SO4-Cl type. The hydrochemical characteristics of geothermal water are primarily influenced by water-rock interaction and groundwater mixing. The water source primarily comes from the atmospheric precipitation in the Taiyi mountains, with an altitude of 910.75-1542.2 m.s.a.l.. The estimated temperature of the thermal reservoir ranges from 51 to 78 °C, and the depth of geothermal water circulation is estimated to be between 1316 and 2216 m. Based on the characteristics of the geothermal field, including the \"cap rock, water source, heat source, reservoir, and channel,\" a conceptual model of the porous sandstone geothermal water flow system is proposed. This model offers novel insights into the genesis mechanism of geothermal water under similar geological conditions.
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    这项研究调查了水稻基因型\'9311\'对Cd胁迫的生理和分子响应以及二氧化硅纳米颗粒(SiONPs)的缓解作用。Cd暴露严重阻碍了植物生长,叶绿素含量,光合作用,和Cd积累。然而,SiONPs补充,特别是SiONP100处理,显著减轻Cd诱导的毒性,减轻对植物生长的不利影响,同时保持叶绿素含量和光合属性。SiONP100处理也减少了Cd的积累,表明基因型9311对Si摄取的偏好。Cd之间的复杂相互作用,Si,Mg,Ca,K被发现了,随着MDA和H2O2含量的波动。观察到气孔孔径和叶肉细胞结构的明显形态变化,包括淀粉颗粒的变化,花岗岩类囊体,和嗜卵性球蛋白。此外,补充SiONP100后,基因型9311增加了过氧化物酶,超氧化物歧化酶,过氧化氢酶活性降低了56%,44%,53%的芽和62%的芽,49%,65%的根,分别,表明了对Cd胁迫的强大防御机制。值得注意的是,OsNramp5,OsHMA3,OsSOD-Cu/Zn,OsCATA,OsCATB,和OsAPX1显示在SiONPs处理后显著表达,表明水稻组织内潜在的Cd易位。总的来说,SiONPs的补充有望增强水稻植物的Cd耐受性,同时保持基本的生理功能。
    This study investigated the physiological and molecular responses of rice genotype \'9311\' to Cd stress and the mitigating effects of silicon oxide nanoparticles (SiO NPs). Cd exposure severely hindered plant growth, chlorophyll content, photosynthesis, and Cd accumulation. However, SiO NPs supplementation, particularly the SiONP100 treatment, significantly alleviated Cd-induced toxicity, mitigating the adverse effects on plant growth while maintaining chlorophyll content and photosynthetic attributes. The SiONP100 treatment also reduced Cd accumulation, indicating a preference for Si uptake in genotype 9311. Complex interactions among Cd, Si, Mg, Ca, and K were uncovered, with fluctuations in MDA and H2O2 contents. Distinct morphological changes in stomatal aperture and mesophyll cell structures were observed, including changes in starch granules, grana thylakoids, and osmophilic plastoglobuli. Moreover, following SiONP100 supplementation, genotype 9311 increased peroxidase, superoxide dismutase, and catalase activities by 56%, 44%, and 53% in shoots and 62%, 49%, and 65% in roots, respectively, indicating a robust defense mechanism against Cd stress. Notably, OsNramp5, OsHMA3, OsSOD-Cu/Zn, OsCATA, OsCATB, and OsAPX1 showed significant expression after SiO NPs treatment, suggesting potential Cd translocation within rice tissues. Overall, SiO NPs supplementation holds promise for enhancing Cd tolerance in rice plants while maintaining essential physiological functions.
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    了解籽粒产量的遗传和分子基础对玉米改良具有重要意义。这里,我们使用QTL荟萃分析确定了控制玉米产量相关性状的49个共有数量性状位点(cQTL)。然后,我们收集了通过关联作图检测到的产量相关性状相关SNP,并确定了17个共有显著位点.将cQTL的物理位置与重要SNP的物理位置进行比较,发现47个重要SNP位于20个cQTL区域内。此外,对调节玉米产量相关性状的31个基因的深入评论发现,许多基因的功能在玉米和其他植物物种中是保守的。功能保守性表明,575个玉米基因中的一些基因(与其他植物物种中控制产量或种子性状的247个基因直系同源)可能与玉米产量相关性状在功能上相关,特别是cQTL区域的49个玉米直系同源基因,和41个直系同源基因接近显著SNP的物理位置。最后,对整合公共资源探索玉米产量相关性状的遗传和分子机制进行了展望,以及利用遗传和分子机制进行玉米改良。
    在线版本包含补充材料,可在10.1007/s11032-021-01214-3获得。
    Understanding the genetic and molecular basis of grain yield is important for maize improvement. Here, we identified 49 consensus quantitative trait loci (cQTL) controlling maize yield-related traits using QTL meta-analysis. Then, we collected yield-related traits associated SNPs detected by association mapping and identified 17 consensus significant loci. Comparing the physical positions of cQTL with those of significant SNPs revealed that 47 significant SNPs were located within 20 cQTL regions. Furthermore, intensive reviews of 31 genes regulating maize yield-related traits found that the functions of many genes were conservative in maize and other plant species. The functional conservation indicated that some of the 575 maize genes (orthologous to 247 genes controlling yield or seed traits in other plant species) might be functionally related to maize yield-related traits, especially the 49 maize orthologous genes in cQTL regions, and 41 orthologous genes close to the physical positions of significant SNPs. In the end, we prospected on the integration of the public sources for exploring the genetic and molecular mechanisms of maize yield-related traits, and on the utilization of genetic and molecular mechanisms for maize improvement.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s11032-021-01214-3.
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