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Comparative RNA-seq analysis reveals transposable element-mediated transcriptional reprogramming under phosphorus-starvation stress in rice (Oryza sativa L.) RNA-seq比较分析揭示磷饥饿胁迫下水稻(Oryza sativa L.)转录重编程的转座元件介导机制
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-11-01 DOI: 10.1016/j.genrep.2024.102077
Simardeep Kaur , Karishma Seem , K.K. Vinod , Dwijesh Chandra Mishra , Suresh Kumar , Trilochan Mohapatra
Phosphorus (P) deficiency hinders crop productivity of 50 % of the rice grown in Asia, Africa, and South America. About 90 % of the phosphate in fertilizers applied to the crops gets fixed in the soil, reducing its availability to plants. This necessitates increased use of phosphatic fertilizers leading to higher cost of cultivation and environmental pollution. Although molecular mechanisms of P-deficiency tolerance in rice are being deciphered, the role of transposable elements (TEs) in transcriptional reprogramming under P-starvation/deficiency stress has not yet been reported. To investigate the role of Pup1 QTL in controlling TE-mediated reprogramming of gene expression, a pair of contrasting rice [Pusa-44 and its Near-Isogenic Line (NIL)-23] genotypes were grown hydroponically under control and stressed (0 ppm Pi) conditions. Comparative RNA-seq analysis of root and shoot tissues from 45-day-old plants of the rice genotypes revealed TE-mediated transcriptional reprogramming affecting biological processes and cellular components. Significantly up-regulated expression of several TEs under P-starvation stress, controlled by Pup1 QTL, particularly in shoots of NIL-23 indicates their crucial role in P homeostasis. Moreover, comparative physio-biochemical analyses confirmed the stress tolerance of NIL-23. Several biological processes including DNA replication/repair, metabolism, signaling, and phosphorylation were modulated through differential (mainly up-regulated) expression of TEs (controlled by Pup1 QTL) in shoots of NIL-23 under P-starvation. To the best of our knowledge, this is a pioneer study on the role of TEs in reprogramming biological processes/molecular functions/cellular components involved in P-use efficiency in rice under stress. The findings advance our understanding of the functions of Pup1 to improve the P-use efficiency/productivity of rice in P-deficient soils.
在亚洲、非洲和南美洲,50% 的水稻因缺磷而无法提高产量。施用于作物的肥料中约有 90% 的磷酸盐被固定在土壤中,减少了植物对磷的利用。这就需要增加磷肥的使用量,从而导致种植成本增加和环境污染。虽然水稻耐缺磷(P-deficiency)的分子机制正在被破解,但转座元件(TE)在 P-饥饿/缺磷胁迫下的转录重编程中的作用尚未见报道。为了研究 Pup1 QTL 在控制 TE 介导的基因表达重编程中的作用,在对照和胁迫(0 ppm Pi)条件下水培了一对对比水稻基因型[Pusa-44 及其近交系(NIL)-23]。对水稻基因型 45 天植株根部和芽组织的 RNA-seq 比较分析表明,TE 介导的转录重编程影响了生物过程和细胞成分。在 P-饥饿胁迫下,由 Pup1 QTL 控制的几个 TEs 的表达显著上调,尤其是在 NIL-23 的芽中,这表明它们在 P 平衡中起着关键作用。此外,比较生理生化分析证实了 NIL-23 的抗逆性。在P-饥饿条件下,NIL-23嫩枝中的TEs(由Pup1 QTL控制)通过差异表达(主要是上调)调节了DNA复制/修复、新陈代谢、信号转导和磷酸化等多个生物过程。据我们所知,这是一项关于逆境下 TEs 在重编程水稻 P 利用效率相关生物过程/分子功能/细胞组分中的作用的开创性研究。这些发现加深了我们对 Pup1 在缺钾土壤中提高水稻钾利用效率/生产力的功能的理解。
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引用次数: 0
Genomic characterization and comparative genomics of Chlorella sp. CH2018 from Musi River water, India 印度穆西河水中小球藻 CH2018 的基因组特征和比较基因组学
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-10-31 DOI: 10.1016/j.genrep.2024.102076
Rajender Goud Arolla , K. Srinivas Naik
Microalgae, a diverse class of photosynthetic eukaryote, can provide food and energy sustainably. Selecting productive strains is crucial for commercial viability. Here, we isolated an axenic microalgal species from Musi River water, and based on its morphology, molecular makeup, and cell wall composition identified it as Chlorella sp. CH2018. Scanning electron microscopy was used to measure the size of cells, which were found to be 3-, 4-, or 5-μm in diameter with a discernible thick outer cell wall. The characterization of algal genomes is imperative for comprehending species, studying metabolic pathways, and modifying genetics. In this study, we sequenced the entire genome of Chlorella sp. CH2018, yielded genome size of 56.83 Mb with 11,143 functionally annotated protein-coding gene models. The Gene Ontology (GO) analysis revealed that Chlorella's predominant metabolic pathway is carbohydrate metabolism. Ortholog comparative analysis of species of phylum Chlorophyta with Chlorella sp. CH2018 showed that the isolated species possesses unique protein families with a maximum number of 6292 ortholog groups with Chlorella sorokiniana. The phylogenetic tree created by concatenating single-copy ortholog sequences demonstrates the uniqueness of Chlorella sp. CH2018, and its genome sequence serves as a genetic resource for future research.
微藻类是一类种类繁多的光合真核生物,可持续提供食物和能源。选择高产菌株对商业可行性至关重要。在此,我们从穆西河水中分离出一种轴生微藻,并根据其形态、分子组成和细胞壁成分确定其为小球藻 CH2018。利用扫描电子显微镜测量了细胞的大小,发现其直径为 3、4 或 5 微米,细胞外壁很厚。藻类基因组的特征对于了解物种、研究代谢途径和修改遗传学至关重要。在这项研究中,我们对小球藻 CH2018 的全基因组进行了测序,获得了 56.83 Mb 的基因组大小和 11,143 个功能注释的蛋白编码基因模型。基因本体(GO)分析表明,小球藻的主要代谢途径是碳水化合物代谢。叶绿藻门物种与 Chlorella sp. CH2018 的同源物比较分析表明,该分离物种拥有独特的蛋白质家族,与 Chlorella sorokiniana 的同源物组数最多,达 6292 个。通过串联单拷贝直向同源物序列建立的系统发生树证明了 CH2018 小球藻的独特性,其基因组序列可作为未来研究的遗传资源。
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引用次数: 0
A case report on genetic variants in CHD8, KMT2C, EP300, and TCF4 associated with autism spectrum disorder 与自闭症谱系障碍相关的 CHD8、KMT2C、EP300 和 TCF4 基因变异病例报告
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-10-30 DOI: 10.1016/j.genrep.2024.102074
Hima J. Challa, Kalyan Ram Uppaluri, A.Sai. Rishika Gopikar, Rebecca Chalcedony, Srinivas Kethavath, K. Sri Manjari, K. Krishna Vardhani, Kalyani Palasamudram, Natya Kanuri, Aswini Korivepi
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition influenced by several environmental and genetic factors. We present a case of a 7-year-old male with ASD, neurogenic voiding dysfunction (NVD), speech and developmental delays, and hyperactivity, and current treatment includes speech, occupational, and behavioral therapy. Family history includes consanguinity and maternal intellectual disability. Whole-exome sequencing (WES) identified maternally inherited variants in CHD8 (benign), KMT2C (likely pathogenic), and EP300 and TCF4 (uncertain significance). Despite the benign classification of the CHD8 variant, its association with ASD highlights the complexity of genotype-phenotype correlations. The likely pathogenic KMT2C frameshift mutation and deletions in EP300 and TCF4 suggest a multifactorial genetic basis for ASD in this patient. These findings highlight the importance of integrating clinical and genetic data for accurate diagnosis and personalized treatment. Whole Exome Sequencing (WES) analysis revealed these variants in the child's mother, uncle, and maternal grandfather, with the maternal uncle unaffected by ASD, ID, or ADHD, indicating potential variant interplay in disease manifestation. This case emphasizes the need for further research to elucidate the combined effects of these variants, enhancing our understanding of ASD's genetic landscape and improving clinical outcomes.
自闭症谱系障碍(ASD)是一种复杂的神经发育疾病,受多种环境和遗传因素的影响。我们为您介绍一例患有自闭症谱系障碍、神经源性排尿功能障碍(NVD)、言语和发育迟缓以及多动的 7 岁男性患者。家族史包括近亲结婚和母亲智力残疾。全外显子组测序(WES)发现了CHD8(良性)、KMT2C(可能致病)以及EP300和TCF4(意义不确定)的母体遗传变异。尽管 CHD8 变异属于良性,但它与 ASD 的关联凸显了基因型与表型相关性的复杂性。可能致病的 KMT2C 框移突变以及 EP300 和 TCF4 的缺失表明,该患者的 ASD 具有多因素遗传基础。这些发现凸显了整合临床和基因数据对于准确诊断和个性化治疗的重要性。全外显子组测序(WES)分析显示,该患儿的母亲、舅舅和外祖父存在这些变异,其中舅舅未受ASD、ID或ADHD影响,这表明变异在疾病表现中可能存在相互作用。该病例强调了进一步研究的必要性,以阐明这些变异的综合效应,从而加深我们对 ASD 遗传结构的了解并改善临床结果。
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引用次数: 0
Unveiling the genotypic diversity of Candida albicans and Candida dubliniensis in the oral cavities of drug abusers in Ahvaz, Iran 揭示伊朗阿瓦士吸毒者口腔中白色念珠菌和杜布林念珠菌的基因型多样性
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-10-30 DOI: 10.1016/j.genrep.2024.102073
Aynaz Ghojoghi , Ali Zarei Mahmoudabadi , Sadegh Khodavaisy , Eisa Nazar , Mahnaz Fatahinia
Candida albicans is a diploid yeast that, under certain conditions, can cause oral or oropharyngeal infections, particularly in immunocompromised individuals. Recent molecular investigations have classified genotypes A, B, and C for Candida albicans, along with genotype D for Candida dubliniensis. This study aimed to identify the different genotypes of the C. albicans complex in drug abusers in Iran. Oral swabs were collected from drug abusers and cultured on CHROMagar Candida. A 21-plex PCR method was employed for the detection of isolates, and the Candida 25S rDNA gene was amplified using primer pairs CA-INT-L and CA-INT-R for ABC genotyping of C. albicans. Out of the 245 substance abusers screened, 151 individuals (61.63 %) were found to harbor the C. albicans complex. The most common genotype among patients was genotype D (39.1 %), followed by genotype A (31.12 %), genotype B (9.93 %), and genotype C (5.29 %). Additionally, 14.56 % of patients had a mixed genotype. Notably, significant differences in genotype distribution were observed in relation to age, underlying diseases, and marital status (P < 0.05). This study highlights the significance of molecular genotyping in understanding the epidemiology of C. albicans and C. dubliniensis in at-risk groups.
白色念珠菌是一种二倍体酵母菌,在某些条件下可引起口腔或口咽感染,尤其是免疫力低下的人。最近的分子研究已将白色念珠菌的基因型分为 A、B 和 C 三类,并将杜布林念珠菌的基因型分为 D 类。本研究旨在确定伊朗吸毒者中白念珠菌复合体的不同基因型。研究人员采集了吸毒者的口腔拭子,并在 CHROMagar 念珠菌培养基上进行培养。采用 21-plex PCR 方法检测分离物,并使用引物对 CA-INT-L 和 CA-INT-R 扩增白色念珠菌 25S rDNA 基因,对白色念珠菌进行 ABC 基因分型。在筛查的 245 名药物滥用者中,发现 151 人(61.63%)携带白念珠菌复合体。患者中最常见的基因型是基因型 D(39.1%),其次是基因型 A(31.12%)、基因型 B(9.93%)和基因型 C(5.29%)。此外,14.56%的患者具有混合基因型。值得注意的是,基因型分布与年龄、基础疾病和婚姻状况有明显差异(P < 0.05)。这项研究强调了分子基因分型在了解高危人群中白僵菌和杜布林杆菌流行病学方面的重要意义。
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引用次数: 0
Comparing liver RNA-seq analysis of human, rhesus monkey, mouse and rat 比较人、恒河猴、小鼠和大鼠的肝脏 RNA-seq 分析
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-10-30 DOI: 10.1016/j.genrep.2024.102075
Anqi Chen , Chaoneng Ji , Chengtao Li , Suhua Zhang

Background

Animal models are commonly utilized by the pharmaceutical industry to evaluate new drugs; however, the results of these studies are not always applicable to humans due to differences between the genetic backgrounds.

Methods

Since liver plays a prominent role in drug metabolism, we evaluated the expression profiles of human, mouse, rat, and rhesus monkey liver tissues. The differentially expressed genes were identified in different genders, strains, and species.

Results

The primates had fewer differences compared to the rodents, suggesting rhesus monkey could be a preferred model organism. Although the human HGFR (MET), a putative AAV3 receptor, together with its ligand HGF, showed no significant expression differences to the mammal models, the ligand-receptor (HGF/MET) ratio difference between the human (HGF/MET = 0.56) and the mice (HGF/MET = 0.12) might result in the transduction failure of murine hepatocytes using the AAV3 vectors. Our results also showed ACE2 expression was not detected in the human liver, while low expression levels were observed in other species, suggesting that the liver might not be the main target of SARS-CoV2.

Conclusion

In summary, even though all model organisms have limitations, non-human primates or humanized animals are indispensable during drug development before proceeding to clinical trials.
背景制药业通常利用动物模型来评估新药;然而,由于遗传背景的差异,这些研究的结果并不总是适用于人类。方法由于肝脏在药物代谢中起着重要作用,我们评估了人、小鼠、大鼠和恒河猴肝脏组织的表达谱。结果灵长类动物与啮齿类动物相比差异较小,这表明恒河猴可能是首选的模式生物。虽然人的 HGFR (MET)(一种推定的 AAV3 受体)及其配体 HGF 的表达与哺乳动物模型无显著差异,但人(HGF/MET = 0.56)与小鼠(HGF/MET = 0.12)之间配体-受体(HGF/MET)比值的差异可能导致使用 AAV3 载体转导小鼠肝细胞失败。我们的结果还显示,在人类肝脏中未检测到 ACE2 的表达,而在其他物种中也观察到较低的表达水平,这表明肝脏可能不是 SARS-CoV2 的主要靶标。
{"title":"Comparing liver RNA-seq analysis of human, rhesus monkey, mouse and rat","authors":"Anqi Chen ,&nbsp;Chaoneng Ji ,&nbsp;Chengtao Li ,&nbsp;Suhua Zhang","doi":"10.1016/j.genrep.2024.102075","DOIUrl":"10.1016/j.genrep.2024.102075","url":null,"abstract":"<div><h3>Background</h3><div>Animal models are commonly utilized by the pharmaceutical industry to evaluate new drugs; however, the results of these studies are not always applicable to humans due to differences between the genetic backgrounds.</div></div><div><h3>Methods</h3><div>Since liver plays a prominent role in drug metabolism, we evaluated the expression profiles of human, mouse, rat, and rhesus monkey liver tissues. The differentially expressed genes were identified in different genders, strains, and species.</div></div><div><h3>Results</h3><div>The primates had fewer differences compared to the rodents, suggesting rhesus monkey could be a preferred model organism. Although the human HGFR (MET), a putative AAV3 receptor, together with its ligand HGF, showed no significant expression differences to the mammal models, the ligand-receptor (HGF/MET) ratio difference between the human (HGF/MET = 0.56) and the mice (HGF/MET = 0.12) might result in the transduction failure of murine hepatocytes using the AAV3 vectors. Our results also showed ACE2 expression was not detected in the human liver, while low expression levels were observed in other species, suggesting that the liver might not be the main target of SARS-CoV2.</div></div><div><h3>Conclusion</h3><div>In summary, even though all model organisms have limitations, non-human primates or humanized animals are indispensable during drug development before proceeding to clinical trials.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102075"},"PeriodicalIF":1.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification and molecular modelling of potential drugs targeting the genes involved in the progression of lung cancer in patients with idiopathic pulmonary fibrosis 鉴定针对特发性肺纤维化患者肺癌进展相关基因的潜在药物并建立分子模型
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-10-29 DOI: 10.1016/j.genrep.2024.102067
Sanjukta Dasgupta

Background

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrosis in the lung parenchyma. Given the fact that IPF patients are at significant risk of developing lung cancer (LC), the overlapping gene signatures between IPF and LC need to be explored.

Methods

Two datasets (GSE79544 and GSE103888) were procured from the Gene Expression Omnibus repository and used to determine the overlapping genes between IPF and LC. Next, the prediction ability of these genes in differentiating the diseased group from controls was explored using two machine learning (ML) models (random forest and k-nearest neighbor). Potential drugs targeting the candidate genes were identified, and advanced structural analysis was conducted to determine the binding affinity between the candidate drug and target receptor.

Result

A total of ten common genes (CCL13, CXCL2, MALT1, MARCKS, PLA2G7, SEMA6B, SFTPB, SPARC, SPP1, and TLCD2) are differentially expressed in IPF and LC as compared to the controls. PLA2G7 demonstrated promising potential in differentiating between IPF, LC, and controls. The increased expression correlated with poor survival in patients with LC. The expression of PLA2G7 indicated a similar trend in the validation dataset. Darapladib, a selective inhibitor that belongs to toxicity class 4 and lethal dose50 value of 800 mg/kg exhibited maximum potential in targeting PLA2G7 with a binding affinity score of −9.2 kcal/mol (chain A) and −9.3 kcal/mol (chain B), respectively.

Conclusion

The present study is the first of its kind that combines in-silico and ML algorithms to identify the gene signatures and promising drugs for treating the progression of LC in patients with IPF.
背景特发性肺纤维化(IPF)的特点是肺实质进行性纤维化。方法从基因表达总库中获取两个数据集(GSE79544 和 GSE103888),用于确定 IPF 和 LC 之间的重叠基因。然后,使用两种机器学习(ML)模型(随机森林和k-近邻)探讨了这些基因在区分患病组和对照组方面的预测能力。结果与对照组相比,共有十个常见基因(CCL13、CXCL2、MALT1、MARCKS、PLA2G7、SEMA6B、SFTPB、SPARC、SPP1 和 TLCD2)在 IPF 和 LC 中有差异表达。PLA2G7 在区分 IPF、LC 和对照组方面表现出良好的潜力。PLA2G7 的表达增加与 LC 患者的生存率较低有关。在验证数据集中,PLA2G7的表达也显示出类似的趋势。Darapladib是一种选择性抑制剂,属于毒性4级,致死剂量50值为800 mg/kg,在靶向PLA2G7方面表现出最大的潜力,其结合亲和力得分分别为-9.2 kcal/mol(链A)和-9.3 kcal/mol(链B)。
{"title":"Identification and molecular modelling of potential drugs targeting the genes involved in the progression of lung cancer in patients with idiopathic pulmonary fibrosis","authors":"Sanjukta Dasgupta","doi":"10.1016/j.genrep.2024.102067","DOIUrl":"10.1016/j.genrep.2024.102067","url":null,"abstract":"<div><h3>Background</h3><div>Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrosis in the lung parenchyma. Given the fact that IPF patients are at significant risk of developing lung cancer (LC), the overlapping gene signatures between IPF and LC need to be explored.</div></div><div><h3>Methods</h3><div>Two datasets (GSE79544 and GSE103888) were procured from the Gene Expression Omnibus repository and used to determine the overlapping genes between IPF and LC. Next, the prediction ability of these genes in differentiating the diseased group from controls was explored using two machine learning (ML) models (random forest and k-nearest neighbor). Potential drugs targeting the candidate genes were identified, and advanced structural analysis was conducted to determine the binding affinity between the candidate drug and target receptor.</div></div><div><h3>Result</h3><div>A total of ten common genes (<em>CCL13</em>, <em>CXCL2</em>, <em>MALT1</em>, <em>MARCKS</em>, <em>PLA2G7</em>, <em>SEMA6B</em>, <em>SFTPB</em>, <em>SPARC</em>, <em>SPP1</em>, and <em>TLCD2</em>) are differentially expressed in IPF and LC as compared to the controls. <em>PLA2G7</em> demonstrated promising potential in differentiating between IPF, LC, and controls. The increased expression correlated with poor survival in patients with LC. The expression of <em>PLA2G7</em> indicated a similar trend in the validation dataset. Darapladib, a selective inhibitor that belongs to toxicity class 4 and lethal dose50 value of 800 mg/kg exhibited maximum potential in targeting <em>PLA2G7</em> with a binding affinity score of −9.2 kcal/mol (chain A) and −9.3 kcal/mol (chain B), respectively.</div></div><div><h3>Conclusion</h3><div>The present study is the first of its kind that combines in-silico and ML algorithms to identify the gene signatures and promising drugs for treating the progression of LC in patients with IPF.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102067"},"PeriodicalIF":1.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic variants in ghrelin (rs27647, rs696217) and leptin (rs7799039) are not associated with body composition parameters but are related to appetitive traits in Mexican young adults 在墨西哥青壮年中,胃泌素(rs27647、rs696217)和瘦素(rs7799039)的基因变异与身体成分参数无关,但与食欲特征有关
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-10-29 DOI: 10.1016/j.genrep.2024.102071
Astrid S. Espinoza García , Rosa L. Díaz Chávez , Elia H. Valdés Miramontes , Isela Parra Rojas , Zyanya Reyes Castillo

Purpose

Obesity develops as a result of the interplay between obesogenic environment and the individual's eating behaviors. Genetic variants in genes coding for neuropeptides involved in metabolic regulation, such as ghrelin (GHRL) and leptin (LEP) have been associated to development of obesity and its role on appetite regulation has also been suggested. The purpose of this exploratory study was to evaluate the association of genetic variants at GHRL (rs27647, rs696217) and LEP (rs7799039) with body composition parameters as well as food approach and food avoidance appetitive traits in young adults from western Mexico.

Methods

255 young adults were included. Body composition parameters were measured by bioelectrical bioimpedance, and appetitive traits were assessed via Adult Eating Behavior Questionnaire (AEBQ). Genotyping of rs27647, rs696217 and rs7799039 variants was performed using PCR-RFLP techniques.

Results and conclusion

Median age for both sexes were 20 (19–21) years, mean body fat percentage was 36.1 ± 7.8 for women, and for men 23.7 ± 7.4. The evaluated genetic variants were not associated to body composition parameters, however GG genotype of the rs696217 variant in GHRL was associated to higher scores on food approach appetitive traits (enjoyment of food p < 0.01 and food responsiveness p < 0.0009). In addition, the GG genotype of rs7799039 variant in LEP was associated to higher scores in food avoidance appetitive traits (emotional undereating p < 0.004 and food fussiness p < 0.001). Our results suggest an association between genetic variants in GHRL and LEP genes with appetitive traits in Mexican young adults, showing an indirect genetic link with obesity, through eating behaviors modulation.
目的肥胖的形成是肥胖环境与个人饮食行为相互作用的结果。参与代谢调节的神经肽(如胃泌素(GHRL)和瘦素(LEP))编码基因的遗传变异与肥胖的发生有关,其对食欲调节的作用也被认为与肥胖有关。这项探索性研究的目的是评估 GHRL(rs27647、rs696217)和 LEP(rs7799039)基因变异与墨西哥西部青壮年身体成分参数以及食物接近和食物回避食欲特征的关系。身体成分参数通过生物电生物阻抗测量,食欲特质通过成人进食行为问卷(AEBQ)评估。采用 PCR-RFLP 技术对 rs27647、rs696217 和 rs7799039 变体进行了基因分型。结果和结论男女平均年龄为 20(19-21)岁,女性平均体脂率为 36.1 ± 7.8,男性为 23.7 ± 7.4。所评估的基因变异与身体成分参数无关,但GHRL中rs696217变异的GG基因型与较高的食物接近性食欲特征得分有关(食物享受性p < 0.01,食物反应性p < 0.0009)。此外,LEP 中 rs7799039 变体的 GG 基因型与较高的食物回避食欲特质得分相关(情绪性不节食 p < 0.004 和食物烦躁 p < 0.001)。我们的研究结果表明,GHRL 和 LEP 基因的遗传变异与墨西哥年轻人的食欲特质有关,这表明通过饮食行为的调节与肥胖有间接的遗传联系。
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引用次数: 0
The expression of CCL-3, FGF2, TPO and CTGF in newly diagnosed acute myeloblastic leukemia (AML) 新诊断的急性髓细胞白血病(AML)中 CCL-3、FGF2、TPO 和 CTGF 的表达
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-10-28 DOI: 10.1016/j.genrep.2024.102068
Razieh Farkhondeh , Seyedeh Zahra Hasanpour , Mohsen Hamidpour , Mehdi Allah Bakhshian , Seyedeh Ommolbanin Ghasemian , Majid Gholami-Ahangaran

Introduction

The interaction between Bone marrow (BM) microenvironment and acute myeloblastic leukemia (AML) cells is an essential event in the development of leukemia.

Material and methods

In this study investigated the expression of fibroblastic growth factor 2 (FGF2), chemokine (CC motif) ligand 3 (CCL-3), thrombopoietin (TPO) and connective tissue growth factor (CTGF) in 60 newly diagnosed AML patients and 60 healthy volunteers. BM and peripheral blood samples were collected from patients and healthy individuals and the expression of genes was assessed using qRT-PCR. The obtained data were analyzed using t-test, one-way ANOVA and Pearson correlation coefficient.

Results

The results showed that while the expression of CCL-3 and FGF2 was upregulated, the expression of TPO was downregulated in AML patients as compared with the control group. We also failed to find any difference in the expression of CTGF between patients and healthy individuals. Moreover, we found that there was no association between gene expression and the age and gender of AML patients. Only the expression of CTGF had a negative correlation with the percentage of blasts in AML patients. A positive significant correlation between FGF2 and CCL-3, FGF2 and TPO, FGF2 and CTGF as well as CCL-3 and TPO were detected.

Conclusions

This study proposed that the expression of growth factors and cytokines could be used as a prognostic factor. However, to gain better insight into the precise role of these factors, further studies at larger statistical population are required.
材料与方法 本研究调查了 60 名新诊断的急性髓细胞性白血病(AML)患者和 60 名健康志愿者的成纤维细胞生长因子 2(FGF2)、趋化因子(CC motif)配体 3(CCL-3)、血小板生成素(TPO)和结缔组织生长因子(CTGF)的表达情况。收集患者和健康人的骨髓和外周血样本,并使用 qRT-PCR 评估基因的表达。结果表明,与对照组相比,AML 患者的 CCL-3 和 FGF2 表达上调,而 TPO 表达下调。我们也没有发现 CTGF 的表达在患者和健康人之间有任何差异。此外,我们还发现基因表达与急性髓细胞性白血病患者的年龄和性别没有关联。只有 CTGF 的表达与急性髓细胞性白血病患者的囊泡百分比呈负相关。结论本研究提出,生长因子和细胞因子的表达可作为预后因素。然而,要更好地了解这些因子的确切作用,还需要在更大的统计人群中开展进一步的研究。
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引用次数: 0
CRISPR/Cas mediated disruption of the Porcine Circovirus-1 gene present in PK-15 cells using sgRNA cocktail 使用 sgRNA 鸡尾酒,以 CRISPR/Cas 为介导,破坏 PK-15 细胞中的猪圆环病毒-1 基因
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-10-28 DOI: 10.1016/j.genrep.2024.102070
Chayna Singha Mahapatra , Aruna Kuniyal , Gaurav Sharma , Shyma K. Latheef , Amit Kumar , Pronab Dhar
Porcine circovirus 1(PCV-1) is an inherent contaminant in all cells of porcine origin, including cell lines. Porcine Kidney 15 (PK-15) cells are one such cell line which are widely being used for the propagation of different porcine viruses and development of cell culture vaccines for pigs. PCV1 is a single-stranded DNA virus that remain in circular form with a high copy number inside the host cell. The presence of PCV1virus in PK-15 cells may affect the yield of porcine viruses and other vaccine strains like Classical Swine Fever Virus (CSFV) propagated in these cells. Hence the present study was conducted to explore the promising CRISPR/Cas9 tool in cleaving PCV-1 DNA from PK-15 cells, followed by the evaluation of these cells for producing CSF vaccine virus with better yield. PK-15 cells were subjected to CRISPR/Cas9 mediated cleavage with a cocktail of guide RNAs (sgRNAs) to cleave PCV-1 DNA. A significant reduction of PCV-1 DNA in the transfected cells was observed in droplet digital PCR and real-time PCR; indicating successful targeting of PCV-1 DNA by the chosen sgRNAs. Further, the PCV-1 cleaved PK-15 cells were infected with CSFV and found to have a better yield of harvested virus. Based on the present study, it can be suggested that knocking out of PCV-1 DNA from PK-15 cells offers a promising platform for generating contaminant free cell lines and vaccine development with higher yield.
猪圆环病毒 1(PCV-1)是包括细胞系在内的所有猪源细胞的固有污染物。猪肾 15(PK-15)细胞就是这样一种细胞系,被广泛用于繁殖不同的猪病毒和开发猪用细胞培养疫苗。PCV1 是一种单链 DNA 病毒,在宿主细胞内呈环状,拷贝数较高。PK-15 细胞中 PCV1 病毒的存在可能会影响猪病毒和其他疫苗株(如经典猪瘟病毒(CSFV))的产量。因此,本研究旨在探索 CRISPR/Cas9 工具在切割 PK-15 细胞中的 PCV-1 DNA 方面的前景,然后评估这些细胞在生产 CSF 疫苗病毒方面的产量。PK-15 细胞在 CRISPR/Cas9 的介导下,使用鸡尾酒引导 RNA(sgRNA)裂解 PCV-1 DNA。在液滴数字 PCR 和实时 PCR 中观察到转染细胞中 PCV-1 DNA 明显减少,这表明所选 sgRNA 成功靶向了 PCV-1 DNA。此外,用 CSFV 感染 PCV-1 被裂解的 PK-15 细胞,发现收获的病毒产量更高。根据本研究,可以认为从 PK-15 细胞中敲除 PCV-1 DNA 为生成无污染细胞系和开发产量更高的疫苗提供了一个前景广阔的平台。
{"title":"CRISPR/Cas mediated disruption of the Porcine Circovirus-1 gene present in PK-15 cells using sgRNA cocktail","authors":"Chayna Singha Mahapatra ,&nbsp;Aruna Kuniyal ,&nbsp;Gaurav Sharma ,&nbsp;Shyma K. Latheef ,&nbsp;Amit Kumar ,&nbsp;Pronab Dhar","doi":"10.1016/j.genrep.2024.102070","DOIUrl":"10.1016/j.genrep.2024.102070","url":null,"abstract":"<div><div>Porcine circovirus 1(PCV-1) is an inherent contaminant in all cells of porcine origin, including cell lines. Porcine Kidney 15 (PK-15) cells are one such cell line which are widely being used for the propagation of different porcine viruses and development of cell culture vaccines for pigs. PCV1 is a single-stranded DNA virus that remain in circular form with a high copy number inside the host cell. The presence of PCV1virus in PK-15 cells may affect the yield of porcine viruses and other vaccine strains like Classical Swine Fever Virus (CSFV) propagated in these cells. Hence the present study was conducted to explore the promising CRISPR/Cas9 tool in cleaving PCV-1 DNA from PK-15 cells, followed by the evaluation of these cells for producing CSF vaccine virus with better yield. PK-15 cells were subjected to CRISPR/Cas9 mediated cleavage with a cocktail of guide RNAs (sgRNAs) to cleave PCV-1 DNA. A significant reduction of PCV-1 DNA in the transfected cells was observed in droplet digital PCR and real-time PCR; indicating successful targeting of PCV-1 DNA by the chosen sgRNAs. Further, the PCV-1 cleaved PK-15 cells were infected with CSFV and found to have a better yield of harvested virus. Based on the present study, it can be suggested that knocking out of PCV-1 DNA from PK-15 cells offers a promising platform for generating contaminant free cell lines and vaccine development with higher yield.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102070"},"PeriodicalIF":1.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetical and cellular induction of interferon genes via the treatment with (Allium sativum) garlic extract against recombinant influenza A/Puerto Rico/8/34 H1N PR8 infection 用(薤白)大蒜提取物处理重组甲型/波多黎各/8/34 H1N PR8 流感感染,从基因和细胞方面诱导干扰素基因
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-10-28 DOI: 10.1016/j.genrep.2024.102069
Omer Abid Kathum , Saafa Abd.Al-kahdum , Umniah Abd-Al-Naser Saleh Hadi , Sarah Kamil Abood , Shaimaa Y. Abdulfattah

Background

It had been established that; influenza A viral infection is connected in a big range with stimulation of many cellular kinases which either being necessary for viral live cycle or as a kind of antagonistic response against this attack hoping to stop the viral invasion. This induction includes many cellular mediator's response. Among them; induction of Retinoic Inducible Genes I (RIG I) which is classified as the precursor of interferon β activation thereby the activation of another mediator like IRF3.
The objective of this study is to identify and establish a new and natural antiviral active compound which might help in enhancing the cellular immunity against influenza A virus thereby attenuating its ability to invade living cells.

Methods

In this work, variety of concentration of Alluim sativum (AS) or garlic plant extract; 12.5, 25, 50 μg/ml were tested on MDCKII or A549 cell as an in vitro experimental work to examine its ability to abort the replication of Influenza A/Puerto Rico/8/34 H1N1 (IAV PR8) strain depending on many techniques like, viral plaque assay, gene expression by real time PCR (rt PCR), luciferase assay and immunofluorescent stating.

Results

Our data explained that there was weak replication ability as explained in viral replication titer by plaque assay whether after 8 hours post infection using 0.1 MOI or even after 24 hours post infection using 0.01 MOI of influenza A PR8, this finding was propped with a prosaic expression of some viral protein genes like NS1, NP. the immunofluorescent staining also supported those data via the weak localization of NS1 protein during the treatment with garlic extract and that’s normally is connected with high induction of cellular gene expression representing by RIG I, IRF3 mediator and Interferon β genes necessary for induction of type I interferon caused by treatment with garlic extract.

Conclusion

Allium sativum plant extract sequestered influenza A virus PR8 replication significantly especially, at concentration of 50 μg/ ml which is the best concentration that can act against the virus due to acute induction of cellular proteins represented by RIG I pathogen recognizer and other proteins that interferes with activation of interferon then preventing the viral competition with cellular immunity to invade the cells.
In another word, the garlic extract is a direct inducer for RIG I and other mediators important for activation of type I interferon pathway as an immune response to prevent viral attack.
背景已经证实,甲型流感病毒感染在很大程度上与许多细胞激酶的刺激有关,这些激酶或者是病毒生命周期所必需的,或者是对这种攻击的一种拮抗反应,希望阻止病毒入侵。这种诱导包括许多细胞介质反应。本研究的目的是鉴定和建立一种新的天然抗病毒活性化合物,它可能有助于增强细胞对甲型流感病毒的免疫力,从而削弱其入侵活细胞的能力。5, 25, 50 μg/ml 在 MDCKII 或 A549 细胞上进行体外实验,通过病毒斑块检测、实时 PCR(rt PCR)基因表达、荧光素酶检测和免疫荧光检测等多种技术,检测其终止甲型流感/波多黎各/8/34 H1N1(IAV PR8)病毒株复制的能力。结果我们的数据表明,无论是在感染后 8 小时(使用 0.1 MOI),还是在感染后 24 小时(使用 0.01 MOI),病毒复制滴度的斑块检测都表明病毒复制能力很弱。免疫荧光染色也通过大蒜提取物处理过程中 NS1 蛋白的弱定位支持了这些数据,这通常与大蒜提取物处理过程中诱导 I 型干扰素所需的 RIG I、IRF3 mediator 和 Interferon β 基因对细胞基因表达的高诱导有关。结论大蒜提取物能显著抑制甲型流感病毒 PR8 的复制,特别是在 50 μg/ ml 的浓度下,该浓度是抗病毒的最佳浓度,这是因为大蒜提取物能急性诱导以 RIG I 病原体识别器为代表的细胞蛋白和其他蛋白,从而干扰干扰素的激活,阻止病毒与细胞免疫竞争入侵细胞。换句话说,大蒜提取物是 RIG I 和其他介质的直接诱导剂,这些介质对激活 I 型干扰素通路非常重要,是防止病毒攻击的一种免疫反应。
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引用次数: 0
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Gene Reports
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