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The initial years of the Cold Spring Harbor Laboratory summer course on the neurobiology of Drosophila. 冷泉港实验室果蝇神经生物学暑期课程的最初几年。
IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2024-11-04 DOI: 10.1080/01677063.2024.2393315
W L Pak
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引用次数: 0
Clinical potential of epigenetic and microRNA biomarkers in PTSD. 创伤后应激障碍的表观遗传学和微RNA生物标记的临床潜力。
IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2024-10-29 DOI: 10.1080/01677063.2024.2419098
Nathan J Wellington, Ana P Boucas, Jim Lagopoulos, Anna V Kuballa

Molecular studies identifying alterations associated with PTSD have predominantly focused on candidate genes or conducted genome-wide analyses, often encountering issues with replicability. This review aims to identify robust bi-directional epigenetic and microRNA (miRNA) regulators focusing on their functional impacts on post-traumatic stress disorder (PTSD) and their utility in clinical diagnosis, whilst examining knowledge gaps in the existing research. A systematic search was conducted across multiple databases, including Web of Science, Scopus, Global Health (CABI), and PubMed, augmented by grey literature, yielding 3465 potential articles. Ultimately, 92 studies met the inclusion criteria and were analysed to pinpoint significant epigenetic changes with clinically relevant potential in PTSD. The selected studies explored histone modifications, CpG sites, single nucleotide polymorphisms (SNPs), and miRNA biomarkers. Specifically, nine studies examined epigenetic markers, detailing the influence of methylation on chromatin accessibility at histone positions H3K4, H3K9, and H3K36 within a PTSD context. Seventy-three studies investigated DNA methylation, identifying 20 hypermethylated and five hypomethylated CpG islands consistently observed in PTSD participants. Nineteen studies linked 88 SNPs to PTSD, with only one SNP replicated within these studies. Furthermore, sixteen studies focused on miRNAs, with findings indicating 194 downregulated and 24 upregulated miRNAs were associated with PTSD. Although there are epigenetic mechanisms that are significantly affected by PTSD, a granular deconstruction of these mechanisms elucidates the need to incorporate more nuanced approaches to identifying the factors that contribute to PTSD. Technological advances in diagnostic tools are driving the need to integrate detailed participant characteristics, trauma type, genetic susceptibilities, and best practices for robust reporting. This comprehensive approach will be crucial for enhancing the translational potential of PTSD research for clinical application.

确定创伤后应激障碍相关改变的分子研究主要集中于候选基因或进行全基因组分析,经常遇到可复制性问题。本综述旨在确定稳健的双向表观遗传和微RNA(miRNA)调控因子,重点关注它们对创伤后应激障碍(PTSD)的功能影响及其在临床诊断中的作用,同时检查现有研究中的知识空白。我们在多个数据库(包括 Web of Science、Scopus、Global Health (CABI) 和 PubMed)中进行了系统性检索,并对灰色文献进行了补充,共检索到 3465 篇潜在文章。最终,有 92 项研究符合纳入标准,经分析后确定了创伤后应激障碍中具有临床相关潜力的重要表观遗传变化。所选研究探讨了组蛋白修饰、CpG 位点、单核苷酸多态性 (SNP) 和 miRNA 生物标记物。具体来说,九项研究考察了表观遗传标记,详细研究了在创伤后应激障碍的背景下,甲基化对组蛋白位置 H3K4、H3K9 和 H3K36 的染色质可及性的影响。73 项研究对 DNA 甲基化进行了调查,在创伤后应激障碍患者中发现了 20 个高甲基化和 5 个低甲基化的 CpG 岛。有 19 项研究将 88 个 SNP 与创伤后应激障碍联系起来,其中只有一个 SNP 在这些研究中得到了重复。此外,有 16 项研究关注 miRNA,结果表明有 194 个下调和 24 个上调的 miRNA 与创伤后应激障碍有关。尽管创伤后应激障碍对表观遗传机制有显著影响,但对这些机制的细化解构阐明,需要采用更细致的方法来确定导致创伤后应激障碍的因素。诊断工具的技术进步促使人们需要整合详细的参与者特征、创伤类型、遗传易感性和健全报告的最佳实践。这种综合方法对于提高创伤后应激障碍研究在临床应用中的转化潜力至关重要。
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引用次数: 0
Molecular analysis of SMN2, NAIP, and GTF2H2 gene deletions and relationships with clinical subtypes of spinal muscular atrophy. SMN2、NAIP 和 GTF2H2 基因缺失的分子分析以及与脊髓性肌萎缩症临床亚型的关系。
IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2024-09-25 DOI: 10.1080/01677063.2024.2407332
Nilgun Karasu, Hamit Acer, Hilal Akalin, Burcu Turkgenc, Mikail Demir, Izem Olcay Sahin, Nuriye Gokce, Ayten Gulec, Asli Ciplakligil, Ayse Caglar Sarilar, Isa Cuce, Hakan Gumus, Huseyin Per, Mehmet Canpolat, Munis Dundar

SMA (spinal muscular atrophy) is an autosomal recessive neuromuscular disease that causes muscle atrophy and weakness. SMA is diagnosed by a homozygous deletion in exon 7 of the SMN1 gene. However, mutations in genes located in the SMA region, such as SMN2, NAIP, SERF1, and GTF2H2, may also contribute to the severity of the disease. Within our study's scope, 58 SMA patients who applied in 2018-2021 and 40 healthy controls were analyzed. The study retrospectively included the SMN1 and SMN2 copy numbers previously determined by the MLPA method. Then, NAIP gene analyses with the multiplex PCR method and GTF2H2 gene analyses with the RFLP method were performed. There was a significant correlation (p = 0.00001) between SMN2 copy numbers and SMA subtypes. Also, the NAIP gene (p = 0.01) and the GTF2H2 gene (p = 0.0049) revealed a significant difference between healthy and SMA subjects, whereas the SMA subtypes indicated no significant differences. We detected a significant correlation between clinical subtypes and HFMSE scores in 32 pediatric SMA patients compared (p = 0.01). While pediatric patients with GTF2H2 deletions demonstrated higher motor functions, and those with NAIP deletions demonstrated lower motor functions. In this study, we examined the relationship between NAIP and GTF2H2, called SMN region modifier genes, and the clinical severity of the disease in Turkish SMA patients. Despite its small scale, this research will benefit future investigations into the pathogenesis of SMA disease.

SMA(脊髓性肌萎缩症)是一种常染色体隐性神经肌肉疾病,会导致肌肉萎缩和无力。SMA 的诊断依据是 SMN1 基因第 7 外显子的同源染色体缺失。然而,位于 SMA 区域的基因(如 SMN2、NAIP、SERF1 和 GTF2H2)的突变也可能导致该病的严重程度。在我们的研究范围内,对2018-2021年申请的58名SMA患者和40名健康对照者进行了分析。研究回顾性地纳入了之前通过MLPA方法确定的SMN1和SMN2拷贝数。然后,用多重 PCR 方法对 NAIP 基因进行分析,用 RFLP 方法对 GTF2H2 基因进行分析。SMN2拷贝数与SMA亚型之间存在明显的相关性(p = 0.00001)。此外,NAIP基因(p = 0.01)和GTF2H2基因(p = 0.0049)在健康受试者和SMA受试者之间存在显著差异,而SMA亚型则无显著差异。我们发现,32 名小儿 SMA 患者的临床亚型与 HFMSE 评分之间存在明显的相关性(p = 0.01)。GTF2H2缺失的小儿患者运动功能较高,而NAIP缺失的患者运动功能较低。在这项研究中,我们考察了被称为SMN区域修饰基因的NAIP和GTF2H2与土耳其SMA患者疾病临床严重程度之间的关系。尽管研究规模较小,但这项研究将有助于今后对SMA疾病发病机制的研究。
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引用次数: 0
Neurobiology of egg-laying behavior in Drosophila: neural control of the female reproductive system. 果蝇产卵行为的神经生物学:雌性生殖系统的神经控制。
IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2024-09-09 DOI: 10.1080/01677063.2024.2396352
Mehrnaz Afkhami

Egg-laying is one of the key aspects of female reproductive behavior in insects. Egg-laying has been studied since the dawn of Drosophila melanogaster as a model organism. The female's internal state, hormones, and external factors, such as nutrition, light, and social environment, affect egg-laying output. However, only recently, neurobiological features of egg-laying behavior have been studied in detail. fruitless and doublesex, two key players in the sex determination pathway, have become focal points in identifying neurons of reproductive significance in both central and peripheral nervous systems. The reproductive tract and external terminalia house sensory neurons that carry the sensory information of egg maturation, mating and egg-laying. These sensory signals include the presence of male accessory gland products and mechanical stimuli. The abdominal neuromere houses neurons that receive information from the reproductive tract, including sex peptide abdominal ganglion neurons (SAGs), and send their information to the brain. In the brain, neuronal groups like aDNs and pC1 clusters modulate egg-laying decision-making, and other neurons like oviINs and oviDNs are necessary for egg-laying itself. Lastly, motor neurons involved in egg-laying, which are mostly octopaminergic, reside in the abdominal neuromere and orchestrate the muscle movements required for laying the egg. Egg-laying neuronal control is important in various evolutionary processes like cryptic female choice, and using different Drosophila species can provide intriguing avenues for the future of the field.

产卵是昆虫雌性生殖行为的关键环节之一。自黑腹果蝇成为模式生物以来,人们一直在研究产卵行为。雌性的内部状态、激素以及营养、光照和社会环境等外部因素都会影响产卵量。Fruitless和doublesex是性别决定途径中的两个关键角色,它们已成为鉴定中枢和外周神经系统中具有生殖意义的神经元的焦点。生殖道和外末梢神经中的感觉神经元传递着卵成熟、交配和产卵的感觉信息。这些感觉信号包括雄性附属腺产品的存在和机械刺激。腹部神经丘中的神经元接收来自生殖道的信息,包括性肽腹神经节神经元(SAGs),并将信息发送到大脑。在大脑中,aDNs 和 pC1 簇等神经元群调节产卵决策,而 oviINs 和 oviDNs 等其他神经元则是产卵本身所必需的。最后,参与产卵的运动神经元主要是章胺能神经元,它们位于腹部神经节,协调产卵所需的肌肉运动。产卵神经元控制在隐性雌性选择等各种进化过程中都很重要,利用不同果蝇物种可以为该领域的未来发展提供有趣的途径。
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引用次数: 0
Memoir of the early years of the CSHL summer Drosophila neurobiology course: 1984-1985. CSHL 夏季果蝇神经生物学课程早年回忆录:1984-1985 年。
IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2024-09-02 DOI: 10.1080/01677063.2024.2393884
Ralph J Greenspan
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引用次数: 0
Oncogenic roles of long non-coding RNAs in essential glioblastoma signaling pathways. 长非编码 RNA 在胶质母细胞瘤重要信号通路中的致癌作用。
IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2024-08-22 DOI: 10.1080/01677063.2024.2390403
Mina Lashkarboloki, Amin Jahanbakhshi, Seyed Javad Mowla, Hassan Bjeije, Bahram M Soltani

Glioblastoma multiforme (GBM) is an aggressive and diffuse type of glioma with the lowest survival rate in patients. The recent failure of multiple treatments suggests that targeting several targets at once may be a different strategy to overcome GBM carcinogenesis. Normal function of oncogenes and tumor suppressor genes need for the preservation of regular cellular processes, so any defects in these genes' activity, operate the corresponding signaling pathways, which initiate carcinogenic processes. Long non-coding RNAs (lncRNAs) that can be found in the cytoplasm or nucleus of the cells, control the transcription and translation of genes. LncRNAs perform a variety of functions, including epigenetic alteration, protein modification and stability, transcriptional regulation, and competition for miRNA that regulate mRNA translation through sponging miRNAs. Identification of various oncogenic lncRNAs and their multiple roles in brain cancers making them potential candidates for use as glioma diagnostic, prognostic, and therapeutic targets in the future. This study highlighted multiple oncogenic lncRNAs and classified them into different signaling pathways based on the regulated target genes in glioblastoma.

多形性胶质母细胞瘤(GBM)是一种侵袭性弥漫型胶质瘤,患者存活率最低。最近多种治疗方法的失败表明,同时针对多个靶点可能是克服多形性胶质母细胞瘤癌变的不同策略。致癌基因和抑癌基因的正常功能需要维持正常的细胞过程,因此这些基因活性的任何缺陷都会使相应的信号通路起作用,从而启动致癌过程。长非编码 RNA(lncRNA)存在于细胞的细胞质或细胞核中,控制着基因的转录和翻译。LncRNA 具有多种功能,包括表观遗传学改变、蛋白质修饰和稳定性、转录调控,以及通过海绵状 miRNA 与调控 mRNA 翻译的 miRNA 竞争。各种致癌lncRNA的鉴定及其在脑癌中的多重作用使它们成为未来胶质瘤诊断、预后和治疗靶点的潜在候选者。这项研究强调了多种致癌 lncRNA,并根据胶质母细胞瘤中受调控的靶基因将它们归类为不同的信号通路。
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引用次数: 0
A memorial piece of my experience with Bill Pak. 我与比尔-帕克的一段纪念经历。
IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2024-08-20 DOI: 10.1080/01677063.2024.2391887
Mamiko Ozaki
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引用次数: 0
A tribute to Bill Pak, unsung hero of neurogenetics. 向神经遗传学的无名英雄比尔-帕克致敬。
IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2024-07-22 DOI: 10.1080/01677063.2024.2380297
Barry Ganetzky
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引用次数: 0
Bill Pak: reflections on mentoring. Bill Pak:关于指导的思考。
IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2024-07-08 DOI: 10.1080/01677063.2024.2374054
Martin G Burg
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引用次数: 0
Personal essay of a rookie's journey with Bill Pak and his legacy: tales and perspectives on PI-PLC, NorpA and cyclophilin, NinaA - William L. Pak, PhD., 1932-2023: in memoriam. 白威廉博士(William L. Pak, PhD.,1932-2023:悼念)的个人随笔:一个菜鸟与比尔-白及其遗产的旅程:关于 PI-PLC、NorpA 和环嗜血素 NinaA 的故事和观点。
IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2024-06-24 DOI: 10.1080/01677063.2024.2366455
Paulo A Ferreira

The neurogenetics and vision community recently mourned William L. Pak, PhD, whose pioneering work spearheaded the genetic, electrophysiological, and molecular bases of biological processes underpinning vision. This essay provides a historical background to the daunting challenges and personal experiences that carved the path to seminal findings. It also reflects on the intellectual framework, mentoring philosophy, and inspirational legacy of Bill Pak's research. An emphasis and perspectives are placed on the discoveries and implications to date of the phosphatidylinositol-specific phospholipase C (PI-PLC), NorpA, and the cyclophilin, NinaA of the fruit fly, Drosophila melanogaster, and their respective mammalian homologues, PI-PLCβ4, and cyclophilin-related protein, Ran-binding protein 2 (Ranbp2) in critical biological processes and diseases of photoreceptors and other neurons.

神经遗传学和视觉学界最近悼念了威廉-L-帕克(William L. Pak)博士,他的开创性工作是视觉生物过程的遗传学、电生理学和分子基础的先驱。这篇文章介绍了白威廉在取得开创性发现的道路上所面临的艰巨挑战和个人经历的历史背景。文章还反思了比尔-帕克研究的知识框架、指导理念和鼓舞人心的遗产。文章重点论述了迄今为止发现的磷脂酰肌醇特异性磷脂酶 C(P IP LC)、NorpA 和环纤蛋白、果蝇的 NinaA 以及它们各自的哺乳动物同源物 P I-P LCβ4 和环纤蛋白相关蛋白 Ran 结合蛋白 2(Ranbp2)在感光器和其他神经元的关键生物过程和疾病中的作用和影响。
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引用次数: 0
期刊
Journal of neurogenetics
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