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Mathematical model for understanding the relationship between diabetes and novel coronavirus 用于理解糖尿病与新型冠状病毒之间关系的数学模型。
IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2024-09-30 DOI: 10.1016/j.gene.2024.148970
Preety Kumari , Harendra Pal Singh , Swarn Singh
A new model is proposed to explore interactions between diabetes and novel coronavirus. The model accounted for both the omicron variant and variants varying from omicron. The model investigated compartments such as hospitalization, diabetes, co-infection, omicron variant, and quarantine. Additionally, the impact of different vaccination doses is assessed. Sensitivity analysis is carried out to determine disease prevalence and control options, emphasizing the significance of knowing epidemics and their characteristics. The model is validated using actual data from Japan. The parameters are fitted with the help of ”Least Square Curve Fitting” method to describe the dynamic behavior of the proposed model. Simulation results and theoretical findings demonstrate the dynamic behavior of novel coronavirus and diabetes mellitus (DM). Biological illustrations that illustrate impact of model parameters are evaluated. Furthermore, effect of vaccine efficacy and vaccination rates for the vaccine’s first, second, and booster doses is conducted. The impact of various preventive measures, such as hospitalization rate, quarantine or self-isolation rate, vaccine dose-1, dose-2, and booster dose, is considered for diabetic individuals in contact with symptomatic or asymptomatic COVID-19 infectious people in the proposed model. The findings demonstrate the significance of vaccine doses on people with diabetes and individuals infectious with omicron variant. The proposed work helps with subsequent prevention efforts and the design of a vaccination policy to mitigate the effect of the novel coronavirus.
为探索糖尿病与新型冠状病毒之间的相互作用提出了一个新模型。该模型既考虑了奥米克龙变体,也考虑了与奥米克龙不同的变体。该模型研究了住院、糖尿病、合并感染、奥米克隆变种和检疫等方面。此外,还评估了不同接种剂量的影响。进行了敏感性分析,以确定疾病流行率和控制方案,强调了解流行病及其特征的重要性。利用日本的实际数据对模型进行了验证。利用 "最小平方曲线拟合 "方法对参数进行拟合,以描述拟议模型的动态行为。模拟结果和理论研究结果证明了新型冠状病毒和糖尿病(DM)的动态行为。评估了说明模型参数影响的生物学图解。此外,还研究了疫苗效力和疫苗第一、第二和加强剂量接种率的影响。在提议的模型中,考虑了各种预防措施的影响,如住院率、隔离或自我隔离率、疫苗剂量-1、剂量-2 和加强剂量,适用于接触有症状或无症状 COVID-19 感染者的糖尿病患者。研究结果表明,疫苗剂量对糖尿病患者和感染欧米茄变异体的个体具有重要意义。拟议的工作有助于后续的预防工作和疫苗接种政策的设计,以减轻新型冠状病毒的影响。
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引用次数: 0
An overview of lncRNA NEAT1 contribution in the pathogenesis of female cancers; from diagnosis to therapy resistance 综述lncRNA NEAT1在女性癌症发病机制中的贡献;从诊断到治疗耐药性。
IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2024-09-29 DOI: 10.1016/j.gene.2024.148975
Sulieman Ibraheem Shelash Al-Hawari , Saade Abdalkareem Jasim , Farag M. A. Altalbawy , Pooja Bansal , Harpreet Kaur , Ahmed Hjazi , Jaafaru Sani Mohammed , Mahamedha Deorari , Salim B. Alsaadi , Ahmed Hussein Zwamel
Despite the ongoing progress in detecting and treating cancer, there is still a need for extensive research into the molecular mechanisms involved in the emergence, progression, and resistance to recurrence of female reproductive tissue-specific cancers such as ovarian, breast, cervical, and endometrial cancers. The nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) that exhibits increased expression in female tumors. Moreover, elevated levels of NEAT1 have been associated with poorer survival outcomes in cancer patients. NEAT1 plays a pivotal role in driving tumor initiation through modulating the expression of genes involved in various aspects of tumor cell proliferation, epithelial-to-mesenchymal transition (EMT), metastasis, chemoresistance, and radio-resistance. Mechanistically, NEAT1 acts as a scaffold RNA molecule via interacting with EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit), thereby influencing the expression of downstream effectors of EZH2. Additionally, NEAT1 functions as a competing endogenous RNA (ceRNA) by microRNAs (miRNAs) sponging, consequently altering the expression levels of their target genes during the development of female cancers. This comprehensive review aims to shed light on the latest insights regarding the expression pattern, biological functions, and underlying mechanisms governing the function and regulation of NEAT1 in tumors. Furthermore, particular emphasis is placed on its clinical significance as a novel diagnostic biomarker and a promising therapeutic target for female cancers.
尽管在检测和治疗癌症方面不断取得进展,但仍需要对卵巢癌、乳腺癌、宫颈癌和子宫内膜癌等女性生殖组织特异性癌症的出现、发展和抗复发的分子机制进行广泛研究。核壳旁组装转录本 1(NEAT1)是一种长非编码 RNA(lncRNA),在女性肿瘤中的表达量增加。此外,NEAT1 水平的升高与癌症患者较差的生存结果有关。NEAT1 通过调节参与肿瘤细胞增殖、上皮细胞向间质转化(EMT)、转移、化疗抗药性和放射抗药性等各方面的基因表达,在驱动肿瘤发生方面发挥着关键作用。从机理上讲,NEAT1 通过与 EZH2(Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit,泽斯特增强子 2 多聚核抑制复合体 2 亚基)相互作用,起到支架 RNA 分子的作用,从而影响 EZH2 下游效应物的表达。此外,NEAT1 还通过微 RNA(miRNA)的海绵作用充当竞争性内源性 RNA(ceRNA),从而在女性癌症的发展过程中改变其靶基因的表达水平。本综述旨在阐明有关 NEAT1 在肿瘤中的表达模式、生物学功能以及功能和调控机制的最新见解。此外,本文还特别强调了 NEAT1 作为一种新型诊断生物标志物和女性癌症治疗靶点的临床意义。
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引用次数: 0
RFWD2 increases proliferation and CDDP resistance of osteosarcoma cells RFWD2 可增加骨肉瘤细胞的增殖和 CDDP 抗性。
IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2024-09-28 DOI: 10.1016/j.gene.2024.148973
Pingting Liu , Na Xie
P53, a key tumor suppressor gene, usually produces mtp53 proteins with oncogenic functions due to missense mutations in the DNA-binding domain. P53 is the most commonly mutated gene in osteosarcoma and plays an important role in the development and metastasis of osteosarcoma. The ubiquitin proteasome system is an evolutionarily conserved post-translational modification that regulates a variety of disease processes, including tumors. Researches have shown that RFWD2, as a function of an E3 ubiquitin ligase, plays an important role in regulating tumor progression. However, the biological function of RFWD2 in osteosarcoma cells with different p53 status remains to be clarified. Initially, we found that sarcoma patients with high levels of RFWD2 expression tended to have shorter overall survival time by analyzing UALCAN-TCGA data. Subsequently, we used CCK-8, colony formation, Transwell, and xenograft methods to confirm that RFWD2 acts as an oncogene, regulating the proliferation and invasion of osteosarcoma cells (HOS(p53mut/-), U2OS(p53wt/wt) and Saos-2(p53-/-) cells) with different p53 status. Further co-IP experiments showed that in HOS(p53mut/-) and U2OS(p53wt/wt) cells, RFWD2 binds to p53 and participate in tumor progression. In addition, we demonstrated through both in vitro and in vivo experiments that RFWD2 regulates the sensitivity of osteosarcoma cells to CDDP. In conclusion, our study demonstrates that RFWD2 acts as an oncogene regulating osteosarcoma cell proliferation and sensitivity to CDDP. Our findings provide a new perspective and potential therapeutic target for the treatment of osteosarcoma.
P53是一种关键的肿瘤抑制基因,通常由于DNA结合域的错义突变而产生具有致癌功能的mtp53蛋白。P53 是骨肉瘤中最常见的突变基因,在骨肉瘤的发生和转移过程中发挥着重要作用。泛素蛋白酶体系统是一种进化保守的翻译后修饰,它调控着包括肿瘤在内的多种疾病过程。研究表明,RFWD2 作为一种 E3 泛素连接酶,在调控肿瘤进展方面发挥着重要作用。然而,RFWD2 在不同 p53 状态的骨肉瘤细胞中的生物学功能仍有待明确。最初,我们通过分析 UALCAN-TCGA 数据发现,RFWD2 高水平表达的肉瘤患者总生存时间往往较短。随后,我们使用 CCK-8、集落形成、Transwell 和异种移植等方法证实 RFWD2 是一种致癌基因,能调节不同 p53 状态的骨肉瘤细胞(HOS(p53mut/-)、U2OS(p53wt/wt) 和 Saos-2(p53-/-) 细胞)的增殖和侵袭。进一步的co-IP实验表明,在HOS(p53mut/-)和U2OS(p53wt/wt)细胞中,RFWD2与p53结合并参与肿瘤的进展。此外,我们还通过体外和体内实验证明,RFWD2 可调节骨肉瘤细胞对 CDDP 的敏感性。总之,我们的研究证明 RFWD2 是一种调节骨肉瘤细胞增殖和对 CDDP 敏感性的癌基因。我们的研究结果为骨肉瘤的治疗提供了一个新的视角和潜在的治疗靶点。
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引用次数: 0
Integration of bioinformatics and multi-layered experimental validation reveals novel functions of acetylation-related genes in intervertebral disc degeneration 生物信息学与多层实验验证的整合揭示了乙酰化相关基因在椎间盘退变中的新功能。
IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2024-09-28 DOI: 10.1016/j.gene.2024.148974
Jun Zhu , Tongqu Song , Zheng Li , Wei Zheng , Yong Liu , Hao Li , Song Wang , Jinlong Tang , Shuo Feng , Lei Wang , Xiaoqing Lu , Feng Yuan , Zhengya Zhu
<div><h3>Background</h3><div>The molecular mechanisms underlying intervertebral disc degeneration (IDD) remain poorly understood. The purpose of this work is to elucidate key molecules and investigate the roles of acetylation-related RNAs and their associated pathways in IDD.</div></div><div><h3>Method</h3><div>Datasets GSE70362 and GSE124272 were obtained from the Gene Expression Omnibus (GEO) and combined to investigate differentially expressed genes (DEGs) associated with acetylation in IDD patients compared to healthy controls. Critical genes were pinpointed by integrating GO, KEGG and PPI networks. Furthermore, CIBERSORTx analysis was used to investigate the differences in immune cell infiltration between different groups and the biological processes (BP), cellular components (CC) and molecular functions (MF) were calculated by GSEA and GSVA. In addition, The single-cell database GSE165722 was incorporated to validate the specific expression patterns of hub genes in cells and identify distinct cell subtypes. This provides a theoretical basis for a more in-depth understanding of the roles played by critical cell subtypes in the process of IDD. Subsequently, tissues from IVD with varying degrees of degeneration were collected to corroborate the key DEGs using western blot, RT-qPCR, and immunofluorescence staining.</div></div><div><h3>Results</h3><div>By integrating various datasets and references, we identified a total of 1620 acetylation-related genes. These genes were subjected to a combined analysis with the DEGs from the databases included in this study, resulting in the discovery of 358 acetylation-related differentially expressed genes (ARDEGs). A comparative analysis with differentially expressed genes obtained from three databases yielded 19 ARDEGs. The PPI network highlighted the top 10 genes (<em>IL1B, LAMP1, PPIA, SOD2, LAMP2, FBL, MBP, SELL, IRF1</em> and <em>KHDRBS1</em>) based on their protein interaction relationships. CIBERSORTx immune infiltration analysis revealed a moderate positive correlation between the gene <em>IL1β</em> and Mast.cells.activated, as well as a similar correlation between the gene <em>IRF1</em> and Mast.cells.activated. Single-cell dataset was used to identify cell types and illustrate the distribution of hub genes in different cell types. The two cell types with the highest AUCell scores (Neutrophils and Monocytes) were further explored, leading to the subdivision of Neutrophils into two new cell subtypes: S100A9-type Neutrophils and MARCKS-type Neutrophils. Monocytes were labeled as HLA-DRA9-type Monocytes and IGHG3-type Monocytes. Finally, molecular biology techniques were employed to validate the expression of the top 10 hub genes. Among them, four genes (<em>IL1β, SOD2, LAMP2, and IRF1</em>) were confirmed at the gene level, while two (<em>IL1β and SOD2</em>) were validated at the protein level.</div></div><div><h3>Conclusion</h3><div>In this study, we carried out a thorough analysis across three data
背景:椎间盘变性(IDD)的分子机制仍然鲜为人知。这项工作的目的是阐明关键分子并研究乙酰化相关 RNA 及其相关通路在 IDD 中的作用:方法:从基因表达总库(Gene Expression Omnibus,GEO)中获取数据集 GSE70362 和 GSE124272,并将其合并以研究与健康对照组相比,IDD 患者中与乙酰化相关的差异表达基因(DEGs)。通过整合 GO、KEGG 和 PPI 网络,确定了关键基因。此外,还利用 IBERSORTx 分析法研究了不同组间免疫细胞浸润的差异,并通过 GSEA 和 GSVA 计算了生物过程(BP)、细胞成分(CC)和分子功能(MF)。此外,还纳入了单细胞数据库 GSE165722,以验证细胞中枢基因的特定表达模式,并确定不同的细胞亚型。这为更深入地了解关键细胞亚型在 IDD 过程中所起的作用提供了理论基础。随后,研究人员收集了不同变性程度的 IVD 组织,利用 Western 印迹、RT-qPCR 和免疫荧光染色等方法证实了关键 DEGs:结果:通过整合各种数据集和参考文献,我们共发现了 1620 个乙酰化相关基因。我们将这些基因与本研究数据库中的 DEGs 进行了综合分析,发现了 358 个乙酰化相关差异表达基因(ARDEGs)。通过与三个数据库中的差异表达基因进行比较分析,发现了 19 个 ARDEGs。根据蛋白质相互作用关系,PPI 网络突出显示了前 10 个基因(IL1B、LAMP1、PPIA、SOD2、LAMP2、FBL、MBP、SELL、IRF1 和 KHDRBS1)。CIBERSORTx 免疫浸润分析表明,基因 IL1β 与肥大细胞活化(Mast.cell.activated)之间存在中度正相关,基因 IRF1 与肥大细胞活化(Mast.cell.activated)之间也存在类似的相关性。单细胞数据集用于识别细胞类型,并说明枢纽基因在不同细胞类型中的分布情况。对 AUCell 得分最高的两种细胞类型(中性粒细胞和单核细胞)进行了进一步探索,从而将中性粒细胞细分为两种新的细胞亚型:S100A9型中性粒细胞和MARCKS型中性粒细胞。单核细胞被标记为 HLA-DRA9 型单核细胞和 IGHG3 型单核细胞。最后,采用分子生物学技术验证了前 10 个中心基因的表达。其中,4 个基因(IL1β、SOD2、LAMP2 和 IRF1)在基因水平上得到证实,2 个基因(IL1β 和 SOD2)在蛋白质水平上得到验证:在这项研究中,我们对三个数据库进行了全面分析,以确定并比较 IDD 患者与健康人之间的 ARDEGs。此外,我们还利用分子生物学技术在临床样本中验证了这些基因的子集。这些不同表达基因的鉴定有可能为诊断和治疗 IDD 提供新的见解。
{"title":"Integration of bioinformatics and multi-layered experimental validation reveals novel functions of acetylation-related genes in intervertebral disc degeneration","authors":"Jun Zhu ,&nbsp;Tongqu Song ,&nbsp;Zheng Li ,&nbsp;Wei Zheng ,&nbsp;Yong Liu ,&nbsp;Hao Li ,&nbsp;Song Wang ,&nbsp;Jinlong Tang ,&nbsp;Shuo Feng ,&nbsp;Lei Wang ,&nbsp;Xiaoqing Lu ,&nbsp;Feng Yuan ,&nbsp;Zhengya Zhu","doi":"10.1016/j.gene.2024.148974","DOIUrl":"10.1016/j.gene.2024.148974","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The molecular mechanisms underlying intervertebral disc degeneration (IDD) remain poorly understood. The purpose of this work is to elucidate key molecules and investigate the roles of acetylation-related RNAs and their associated pathways in IDD.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;Datasets GSE70362 and GSE124272 were obtained from the Gene Expression Omnibus (GEO) and combined to investigate differentially expressed genes (DEGs) associated with acetylation in IDD patients compared to healthy controls. Critical genes were pinpointed by integrating GO, KEGG and PPI networks. Furthermore, CIBERSORTx analysis was used to investigate the differences in immune cell infiltration between different groups and the biological processes (BP), cellular components (CC) and molecular functions (MF) were calculated by GSEA and GSVA. In addition, The single-cell database GSE165722 was incorporated to validate the specific expression patterns of hub genes in cells and identify distinct cell subtypes. This provides a theoretical basis for a more in-depth understanding of the roles played by critical cell subtypes in the process of IDD. Subsequently, tissues from IVD with varying degrees of degeneration were collected to corroborate the key DEGs using western blot, RT-qPCR, and immunofluorescence staining.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;By integrating various datasets and references, we identified a total of 1620 acetylation-related genes. These genes were subjected to a combined analysis with the DEGs from the databases included in this study, resulting in the discovery of 358 acetylation-related differentially expressed genes (ARDEGs). A comparative analysis with differentially expressed genes obtained from three databases yielded 19 ARDEGs. The PPI network highlighted the top 10 genes (&lt;em&gt;IL1B, LAMP1, PPIA, SOD2, LAMP2, FBL, MBP, SELL, IRF1&lt;/em&gt; and &lt;em&gt;KHDRBS1&lt;/em&gt;) based on their protein interaction relationships. CIBERSORTx immune infiltration analysis revealed a moderate positive correlation between the gene &lt;em&gt;IL1β&lt;/em&gt; and Mast.cells.activated, as well as a similar correlation between the gene &lt;em&gt;IRF1&lt;/em&gt; and Mast.cells.activated. Single-cell dataset was used to identify cell types and illustrate the distribution of hub genes in different cell types. The two cell types with the highest AUCell scores (Neutrophils and Monocytes) were further explored, leading to the subdivision of Neutrophils into two new cell subtypes: S100A9-type Neutrophils and MARCKS-type Neutrophils. Monocytes were labeled as HLA-DRA9-type Monocytes and IGHG3-type Monocytes. Finally, molecular biology techniques were employed to validate the expression of the top 10 hub genes. Among them, four genes (&lt;em&gt;IL1β, SOD2, LAMP2, and IRF1&lt;/em&gt;) were confirmed at the gene level, while two (&lt;em&gt;IL1β and SOD2&lt;/em&gt;) were validated at the protein level.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In this study, we carried out a thorough analysis across three data","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Full-length nanopore sequencing of circular RNA landscape in peripheral blood cells following sequential BNT162b2 mRNA vaccination 对连续接种 BNT162b2 mRNA 疫苗后外周血细胞中的环状 RNA 图谱进行全长纳米孔测序。
IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2024-09-27 DOI: 10.1016/j.gene.2024.148971
Yu-Chen Liu , Masakazu Ishikawa , Shuhei Sakakibara , Mohamad Al Kadi , Daisuke Motooka , Yoko Naito , Shingo Ito , Yuko Imamura , Hisatake Matsumoto , Fuminori Sugihara , Haruhiko Hirata , Hiroshi Ogura , Daisuke Okuzaki
Circular RNAs (circRNA) lack 5′ or 3′ ends; their unique covalently closed structures prevent RNA degradation by exonucleases. These characteristics provide circRNAs with high pharmaceutical stability and biostability relative to current standard-of-care linear mRNAs. CircRNA levels are reportedly associated with certain human diseases, making them novel disease biomarkers and a noncanonical class of therapeutic targets. In this study, the endogenous circRNAs underlying the response to BNT162b2 mRNA vaccination were evaluated. To this end, peripheral blood samples were subjected to full-length sequencing of circRNAs via nanopore sequencing and transcriptome sequencing. Fifteen samples, comprising pre-, first, and second vaccination cohorts, were obtained from five healthcare workers with no history of SARS-CoV-2 infection or previous vaccination. A total of 4706 circRNAs were detected; following full-length sequencing, 4217 novel circRNAs were identified as being specifically expressed during vaccination. These circRNAs were enriched in the binding motifs of stress granule assemblies and SARS-CoV-2 RNA binding proteins, namely poly(A) binding protein cytoplasmic 1 (PABPC1), pumilio RNA binding family member 1 (PUM1), and Y box binding protein 1 (YBX1). Moreover, 489 circRNAs were identified as previously reported miRNA sponges. The differentially expressed circRNAs putatively originated from plasma B cells compared to circRNAs reported in human blood single-cell RNA sequencing datasets. The pre- and post-vaccination differences observed in the circRNA expression landscape in response to the SARS-CoV-2 BNT162b2 mRNA vaccine.
环状 RNA(circRNA)没有 5' 或 3' 末端;其独特的共价封闭结构可防止 RNA 被外切酶降解。与目前的标准线性 mRNA 相比,这些特点使 circRNA 具有较高的药物稳定性和生物稳定性。据报道,circRNA 的水平与某些人类疾病相关,使其成为新型疾病生物标志物和一类非经典的治疗靶标。本研究评估了 BNT162b2 mRNA 疫苗接种反应所依赖的内源性 circRNA。为此,通过纳米孔测序和转录组测序对外周血样本进行了 circRNAs 全长测序。研究人员从五名没有 SARS-CoV-2 感染史或接种过疫苗的医护人员身上采集了 15 份样本,包括接种前、第一批和第二批样本。共检测到 4706 个 circRNA;经过全长测序,确定 4217 个新型 circRNA 在接种疫苗期间特异性表达。这些 circRNA 富含应激颗粒集合体和 SARS-CoV-2 RNA 结合蛋白的结合基序,即细胞质多聚(A)结合蛋白 1 (PABPC1)、Pumilio RNA 结合家族成员 1 (PUM1) 和 Y 盒结合蛋白 1 (YBX1)。此外,489 个 circRNA 被鉴定为以前报道过的 miRNA 海绵。与人类血液单细胞 RNA 测序数据集中报道的 circRNA 相比,这些差异表达的 circRNA 可能来自血浆 B 细胞。在接种 SARS-CoV-2 BNT162b2 mRNA 疫苗前后观察到的 circRNA 表达差异。
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引用次数: 0
Analysis of chicken LGALSL (galectin-related protein) gene’s proximal promoter and its control by Krüppel-like factors 3 and 7 分析鸡 LGALSL(galectin 相关蛋白)基因的近端启动子及其受 Krüppel 样因子 3 和 7 的控制。
IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2024-09-27 DOI: 10.1016/j.gene.2024.148972
Herbert Kaltner, Gabriel García Caballero, Sebastian Schmidt
The Galectin-Related Protein (GRP), encoded by the LGALSL gene, assigned to the protein family of β-galactoside-binding Galectins, has lost carbohydrate-binding abilities. Its chicken homolog (C-GRP) occurs in the bursa of Fabricius’ epithelial and B cells. Our study investigates the unknown regulatory mechanisms controlling its expression by analyzing the promoter region of the chicken (C-)LGALSL gene in chicken cells. We aimed to identify the sequence elements of the C-LGALSL gene promoter responsible for maximum activity and transcription factors (TFs) that can modulate this activity. Using luciferase reporter assays, we investigated deletion variants of the 5′ region (−2480 bp to +26 bp). Through in silico analyses and site-directed mutagenesis, we explored potential transcription factor binding sites, identified crucial transcription factors through transient overexpression and tested its direct binding by ChIP. Our findings highlight that the region from −274 to −75 bp, conserved among bird species, is crucial for promoter regulation. Among other tested factors, only the chicken (ch) Krüppel-like factors, chKLF3 and chKLF7, modulate the promoter’s activity. The TFs chKLF3 acts as a repressor, and chKLF7 as an activator, although direct binding could not be confirmed. In conclusion, chKLF3 and chKLF7 contribute, in contrast to other factors with binding sites in the region from −274 to −75 bp, to C-LGALSL gene promoter regulation with a balanced impact on activity.
由 LGALSL 基因编码的半乳肽酶相关蛋白(GRP)隶属于 β-半乳糖苷结合型半乳肽酶蛋白家族,但已丧失了与碳水化合物结合的能力。它的鸡同源物(C-GRP)存在于法氏囊上皮细胞和 B 细胞中。我们的研究通过分析鸡细胞中鸡(C-)LGALSL 基因的启动子区域,研究了控制其表达的未知调控机制。我们的目的是确定C-LGALSL基因启动子中负责最大活性的序列元件以及能调节该活性的转录因子(TFs)。通过荧光素酶报告实验,我们研究了5'区(-2480 bp至+26 bp)的缺失变体。通过硅分析和定点突变,我们探索了潜在的转录因子结合位点,通过瞬时过表达确定了关键的转录因子,并通过 ChIP 测试了其直接结合情况。我们的研究结果表明,从-274到-75 bp的区域在鸟类物种中是保守的,是启动子调控的关键。在其他测试因子中,只有鸡(ch)类克鲁珀尔因子(chKLF3和chKLF7)能调节启动子的活性。尽管不能确认直接结合,但chKLF3和chKLF7分别作为抑制因子和激活因子发挥作用。总之,chKLF3和chKLF7与其他结合位点位于-274至-75 bp区域的因子不同,它们对C-LGALSL基因启动子的调控对活性的影响是均衡的。
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引用次数: 0
Peripherally-restricted recurrent infection by engineered E. coli strain modulates hippocampal proteome promoting memory impairments in a rat model 大肠杆菌工程菌株的外周限制性复发性感染可调节海马蛋白质组,从而促进大鼠模型的记忆损伤。
IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2024-09-26 DOI: 10.1016/j.gene.2024.148969
Anam Abdullah , Anuranjani Kumar , Ayesha Zainab Beg , Anupam Chawla , Sudeshna Kar , Surajit Ganguly , Asad U Khan
Commensal bacteria that breach endothelial barrier has been reported to induce low grade chronic inflammation producing disease symptoms in major peripheral tissues. In this study, we investigated the role of genetically modified cellular invasive form of commensal E. coli K12 (SK3842) in cognitive impairment. Low-grade systemic infection model was developed using recurring peripheral inoculation of live bacteria in Wistar rats. To examine memory parameters, Novel object recognition test and Radial arm maze test were performed. Differential protein expression profiling of rat hippocampus was carried out using LC-MS/MS and subsequently quantified using SWATH. HBA1/2, NEFH, PFN1 and ATP5d were chosen for validation using quantitative RT-PCR. Results showed drastic decline in Recognition memory of the SK3842 infected rats. Reference and Working Memory of the infected group were also significantly reduced in comparison to control group. Proteome analysis using LC-MS/MS coupled with SWATH revealed differential expression of key proteins that are crucial for the maintenance of various neurological functions. Moreover, expression of NEFH and PFN1transcripts were found to be in line with the proteomics data. Protein interaction network of these validated proteins generated by STRING database converged to RhoA protein. Thus, the present study establishes an association between peripheral infection of a hippocampal protein network dysregulation and overall memory decline.
据报道,突破内皮屏障的共生细菌可诱发低度慢性炎症,在主要外周组织中产生疾病症状。在本研究中,我们调查了经过基因改造的细胞侵袭型共生大肠杆菌 K12(SK3842)在认知障碍中的作用。我们在 Wistar 大鼠的外周反复接种活细菌,建立了低度全身感染模型。为了检测记忆参数,对大鼠进行了新颖物体识别测试和径向臂迷宫测试。使用 LC-MS/MS 对大鼠海马进行了差异蛋白表达谱分析,随后使用 SWATH 进行了量化。选择 HBA1/2、NEFH、PFN1 和 ATP5d 进行定量 RT-PCR 验证。结果显示,SK3842感染组大鼠的识别记忆力急剧下降。与对照组相比,感染组的参考记忆和工作记忆也明显下降。利用 LC-MS/MS 和 SWATH 进行的蛋白质组分析显示,对维持各种神经功能至关重要的关键蛋白质的表达存在差异。此外,还发现 NEFH 和 PFN1transcripts 的表达与蛋白质组学数据一致。由 STRING 数据库生成的这些验证蛋白的蛋白质相互作用网络与 RhoA 蛋白趋同。因此,本研究确定了外周感染海马蛋白网络失调与整体记忆力衰退之间的关联。
{"title":"Peripherally-restricted recurrent infection by engineered E. coli strain modulates hippocampal proteome promoting memory impairments in a rat model","authors":"Anam Abdullah ,&nbsp;Anuranjani Kumar ,&nbsp;Ayesha Zainab Beg ,&nbsp;Anupam Chawla ,&nbsp;Sudeshna Kar ,&nbsp;Surajit Ganguly ,&nbsp;Asad U Khan","doi":"10.1016/j.gene.2024.148969","DOIUrl":"10.1016/j.gene.2024.148969","url":null,"abstract":"<div><div>Commensal bacteria that breach endothelial barrier has been reported to induce low grade chronic inflammation producing disease symptoms in major peripheral tissues. In this study, we investigated the role of genetically modified cellular invasive form of commensal <em>E. coli</em> K12 (SK3842) in cognitive impairment. Low-grade systemic infection model was developed using recurring peripheral inoculation of live bacteria in Wistar rats. To examine memory parameters, Novel object recognition test and Radial arm maze test were performed. Differential protein expression profiling of rat hippocampus was carried out using LC-MS/MS and subsequently quantified using SWATH. HBA1/2, NEFH, PFN1 and ATP5d were chosen for validation using quantitative RT-PCR. Results showed drastic decline in Recognition memory of the SK3842 infected rats. Reference and Working Memory of the infected group were also significantly reduced in comparison to control group. Proteome analysis using LC-MS/MS coupled with SWATH revealed differential expression of key proteins that are crucial for the maintenance of various neurological functions. Moreover, expression of NEFH and PFN1transcripts were found to be in line with the proteomics data. Protein interaction network of these validated proteins generated by STRING database converged to RhoA protein. Thus, the present study establishes an association between peripheral infection of a hippocampal protein network dysregulation and overall memory decline.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From sequence to significance: A thorough investigation of the distinctive genome features uncovered in C. Werkmanii strain NIB003 从序列到意义:对在 C. Werkmanii 菌株 NIB003 中发现的独特基因组特征的深入研究。
IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2024-09-26 DOI: 10.1016/j.gene.2024.148965
Mohammad Uzzal Hossain , Neyamat Khan Tanvir , A.B.Z. Naimur Rahman , Zeshan Mahmud Chowdhury , Md. Shahadat Hossain , Shajib Dey , Arittra Bhattacharjee , Ishtiaque Ahammad , Umme Salma Zohora , Abu Hashem , Keshob Chandra Das , Chaman Ara Keya , Md. Salimullah
Citrobacter werkmanii (C. werkmanii), an opportunistic urinary bacterium that causes diarrhea, is poorly understood. Our research focuses on genetic features that are crucial to disease development, such as pathogenic interactions, antibiotic resistance, virulence genes and genetic variation. Following its morphological, biochemical, and molecular identification, the whole genome of C. werkmanii strain NIB003 was sequenced in Bangladesh for the first time. Despite having around 80% whole genome conservation, the research shows that the Bangladeshi strain forms a separate phylogenetic cluster. This emphasises the genetic variability within C. werkmanii, resulting in particular modifications at the strain level and changes in its ability to cause disease. The results of the genetic diversity analysis indicate that the Bangladeshi sequenced genome is more diverse than the other strains due to the existence of unique features, such as the presence of t-RNA binding domain and N-6 adenine-specific DNA methylases.
韦克曼柠檬酸杆菌(C. werkmanii)是一种会导致腹泻的机会性泌尿细菌,但人们对它的了解甚少。我们的研究重点是对疾病发展至关重要的遗传特征,如致病相互作用、抗生素耐药性、毒力基因和遗传变异。继形态学、生物化学和分子鉴定之后,孟加拉国首次对 C. werkmanii 菌株 NIB003 进行了全基因组测序。尽管全基因组保存率约为 80%,但研究表明孟加拉国菌株形成了一个独立的系统发育群。这强调了 C. werkmanii 内部的遗传变异,导致了菌株水平上的特殊改变及其致病能力的变化。遗传多样性分析的结果表明,孟加拉国测序基因组比其他菌株更具多样性,因为它具有独特的特征,如存在 t-RNA 结合域和 N-6 腺嘌呤特异性 DNA 甲基化酶。
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引用次数: 0
Transcriptome sequencing and identification of full-length genes involved in the biosynthesis of anticancer compounds Oleanolic acid and Ursolic acid in Achyranthes aspera L. 转录组测序和鉴定牛膝中参与抗癌化合物齐墩果酸和熊果酸生物合成的全长基因
IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2024-09-26 DOI: 10.1016/j.gene.2024.148964
C.M. Jeevitha, Kumar Ravichandiran, Tanuja Tanuja, Madasamy Parani
Achyranthes aspera is renowned for its rich medicinal properties since the Ayurvedic era. This plant is known for the presence of experimentally validated anticancer compounds like oleanolic acid (OA) and ursolic acid (UA). Our study involved sequencing the RNA from the root tissue of A. aspera to elucidate the genes responsible for synthesizing these two critical secondary metabolites. Through RNA-Seq analysis, we assembled approximately 167,698 transcripts, averaging 847 base pairs in length, with an N50 value of 1509 bp. From this data, we mapped 604 sequences involved in the metabolism of terpenoids and polyketide pathways. Among them, 241 transcripts were mapped to the triterpenoid biosynthesis pathway, which included 127 transcripts involved in OA and UA biosynthesis. From these transcripts, we identified 22 full-length genes coding for all the 21 enzymes required for OA and UA biosynthesis. Identifying these full-length genes will lead to a better understanding of the pathway and adopting genetic engineering approaches.
早在阿育吠陀时代,牛膝就因其丰富的药用价值而闻名于世。这种植物因含有齐墩果酸(OA)和熊果酸(UA)等实验验证的抗癌化合物而闻名。我们的研究包括对 A. aspera 根组织的 RNA 进行测序,以阐明负责合成这两种重要次生代谢物的基因。通过 RNA-Seq 分析,我们收集了约 167,698 个转录本,平均长度为 847 个碱基对,N50 值为 1509 bp。根据这些数据,我们绘制了 604 个涉及萜类化合物和聚酮途径代谢的序列。其中,241 个转录本被映射到三萜类生物合成途径,包括 127 个参与 OA 和 UA 生物合成的转录本。从这些转录本中,我们确定了 22 个全长基因,它们编码 OA 和 UA 生物合成所需的全部 21 种酶。鉴定这些全长基因将有助于更好地了解该途径并采用基因工程方法。
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引用次数: 0
GefB, a GGDEF domain-containing protein, affects motility and biofilm formation of Vibrio parahaemolyticus and is regulated by quorum sensing regulators GefB是一种含GGDEF结构域的蛋白质,它影响副溶血性弧菌的运动能力和生物膜的形成,并受法定量感应调节因子的调控。
IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2024-09-26 DOI: 10.1016/j.gene.2024.148968
Yining Zhou , Jingyang Chang , Miaomiao Zhang , Xue Li , Xi Luo , Wanpeng Li , Zhukang Tian , Nan Zhang , Bin Ni , Yiquan Zhang , Renfei Lu
Vibrio parahaemolyticus (V. parahaemolyticus) stands as the predominant etiological agent responsible for gastroenteritis associated with the consumption of seafood. Cyclic di-guanosine monophosphate (c-di-GMP), a secondary messenger in bacteria, controls multiple bacterial behaviors including pathogenesis, the development of biofilms, and motility. The protein GefB (VPA1478), characterized by the presence of a GGDEF domain, inhibits the swarming motility of V. parahaemolyticus. In this study, we showed that deletion of gefB remarkably reduced cellular c-di-GMP level and biofilm formation by V. parahaemolyticus, but significantly enhanced the swimming and swarming motility. In addition, GefB inhibited the polar and lateral flagellar genes but activated genes associated with exopolysaccharide production of V. parahaemolyticus. The data also demonstrated that vpa1477 and gefB are co-transcribed as a single transcriptional unit, designated as vpa1477-gefB. Transcription of vpa1477-gefB was under the collective regulation of the master quorum sensing (QS) regulators AphA and OpaR, which function at low (LCD) and high cell density (HCD), respectively. AphA positively regulated vpa1477-gefB transcription at LCD, whereas OpaR negatively regulated its transcription at HCD. The findings significantly enhance our comprehension of the metabolism and regulatory mechanisms of c-di-GMP in V. parahaemolyticus.
副溶血性弧菌(V. parahaemolyticus)是与食用海鲜有关的肠胃炎的主要病原体。环状二鸟苷单磷酸(c-di-GMP)是细菌的次级信使,控制着细菌的多种行为,包括致病、生物膜的形成和运动。蛋白质 GefB(VPA1478)的特点是存在一个 GGDEF 结构域,它能抑制副溶血性弧菌的蜂拥运动。在这项研究中,我们发现删除gefB可显著降低细胞中c-di-GMP的水平,减少副溶血性弧菌生物膜的形成,但却能显著增强游动和蜂拥运动能力。此外,GefB 还抑制了副溶血性弧菌的极鞭毛和侧鞭毛基因,但激活了与外多糖生产相关的基因。数据还表明,vpa1477 和 gefB 作为一个转录单元共同转录,称为 vpa1477-gefB。vpa1477-gefB 的转录受法定量感应(QS)主调节因子 AphA 和 OpaR 的集体调控,它们分别在低细胞密度(LCD)和高细胞密度(HCD)时发挥作用。AphA 在 LCD 处对 vpa1477-gefB 的转录起正向调节作用,而 OpaR 则在 HCD 处对其转录起负向调节作用。这些发现大大加深了我们对副溶血弧菌中 c-di-GMP 代谢和调控机制的理解。
{"title":"GefB, a GGDEF domain-containing protein, affects motility and biofilm formation of Vibrio parahaemolyticus and is regulated by quorum sensing regulators","authors":"Yining Zhou ,&nbsp;Jingyang Chang ,&nbsp;Miaomiao Zhang ,&nbsp;Xue Li ,&nbsp;Xi Luo ,&nbsp;Wanpeng Li ,&nbsp;Zhukang Tian ,&nbsp;Nan Zhang ,&nbsp;Bin Ni ,&nbsp;Yiquan Zhang ,&nbsp;Renfei Lu","doi":"10.1016/j.gene.2024.148968","DOIUrl":"10.1016/j.gene.2024.148968","url":null,"abstract":"<div><div><em>Vibrio parahaemolyticus</em> (<em>V. parahaemolyticus</em>) stands as the predominant etiological agent responsible for gastroenteritis associated with the consumption of seafood. Cyclic di-guanosine monophosphate (c-di-GMP), a secondary messenger in bacteria, controls multiple bacterial behaviors including pathogenesis, the development of biofilms, and motility. The protein GefB (VPA1478), characterized by the presence of a GGDEF domain, inhibits the swarming motility of <em>V. parahaemolyticus</em>. In this study, we showed that deletion of <em>gefB</em> remarkably reduced cellular c-di-GMP level and biofilm formation by <em>V. parahaemolyticus</em>, but significantly enhanced the swimming and swarming motility. In addition, GefB inhibited the polar and lateral flagellar genes but activated genes associated with exopolysaccharide production of <em>V. parahaemolyticus</em>. The data also demonstrated that <em>vpa1477</em> and <em>gefB</em> are co-transcribed as a single transcriptional unit, designated as <em>vpa1477</em>-<em>gefB</em>. Transcription of <em>vpa1477</em>-<em>gefB</em> was under the collective regulation of the master quorum sensing (QS) regulators AphA and OpaR, which function at low (LCD) and high cell density (HCD), respectively. AphA positively regulated <em>vpa1477</em>-<em>gefB</em> transcription at LCD, whereas OpaR negatively regulated its transcription at HCD. The findings significantly enhance our comprehension of the metabolism and regulatory mechanisms of c-di-GMP in <em>V. parahaemolyticus</em>.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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