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Abnormal larval neuromuscular junction morphology and physiology in Drosophila prickle isoform mutants with known axonal transport defects and adult seizure behavior. 棘果蝇异型突变体的异常幼体神经肌肉连接形态和生理,已知轴突运输缺陷和成年癫痫行为。
IF 1.9 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-03-01 DOI: 10.1080/01677063.2022.2093353
Atsushi Ueda, Tristan C D G O'Harrow, Xiaomin Xing, Salleh Ehaideb, J Robert Manak, Chun-Fang Wu

Previous studies have demonstrated the striking mutational effects of the Drosophila planar cell polarity gene prickle (pk) on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the prickle-prickle (pkpk) and prickle-spiny-legs (pksple) isoforms (hereafter referred to as pk and sple alleles, respectively) exhibit differential phenotypes. While both pk and sple affect larval motor axon transport, only sple confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic pkpk/pksple flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both pk and sple alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in pk/pk larvae, i.e. increased excitatory junctional potential (EJP) amplitude in pk/pk but not in pk/+ or sple/sple. Interestingly, for motor terminal excitability sustained by presynaptic Ca2+ channels, both pk and sple exerted strong effects to produce prolonged depolarization. Notably, only sple acted dominantly whereas pk/+ appeared normal, but was able to suppress the sple phenotypes, i.e. pk/sple appeared normal. Our observations contrast the differential roles of the pk and sple isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ.

先前的研究表明,果蝇平面细胞极性基因prickle (pk)对幼虫运动轴突微管介导的囊泡运输和与神经元回路高兴奋性相关的成人癫痫行为具有显著的突变作用。刺-刺(pkpk)和刺-刺-腿(pksple)同型突变等位基因(以下分别称为pk和单等位基因)表现出不同的表型。虽然pk和simple都影响幼虫的运动轴突运输,但只有simple会导致运动回路和行为亢奋。然而,在异等位基因pkpk/ pkple果蝇中,两种同工异构体的突变明显抵消了成年运动回路和行为过度兴奋性的改善。我们进一步研究了轴突运输改变对幼虫神经肌肉连接(NMJ)发育和功能的影响。我们发现pk等位基因和单一等位基因都存在强大的显性表型,包括突触末端过度生长(通过抗hrp和-Dlg免疫染色显示)和囊泡释放同步性差(通过突触扣点记录显示)。然而,我们仅在pk/pk幼虫中观察到突触传递的隐性改变,即pk/pk中兴奋性连接电位(EJP)振幅增加,而pk/+或单/单中没有。有趣的是,对于由突触前Ca2+通道维持的运动终端兴奋性,pk和simple都发挥了强大的作用,产生了延长的去极化。值得注意的是,只有sple起主导作用,而pk/+表现正常,但能够抑制sple表型,即pk/sple表现正常。我们的观察对比了pk和简单同种异构体的不同作用,并强调了它们在幼虫NMJ的各种结构和功能方面的不同,可变的表型表达。
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引用次数: 0
Abnormalities of neural stem cells in Lesch-Nyhan disease. 莱希-尼汉病的神经干细胞异常。
IF 1.9 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-03-01 Epub Date: 2022-10-13 DOI: 10.1080/01677063.2022.2129632
Ashok R Dinasarapu, Diane J Sutcliffe, Fatemeh Seifar, Jasper E Visser, H A Jinnah

Lesch-Nyhan disease (LND) is a neurodevelopmental disorder caused by variants in the HPRT1 gene, which encodes the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGprt). HGprt deficiency provokes numerous metabolic changes which vary among different cell types, making it unclear which changes are most relevant for abnormal neural development. To begin to elucidate the consequences of HGprt deficiency for developing human neurons, neural stem cells (NSCs) were prepared from 6 induced pluripotent stem cell (iPSC) lines from individuals with LND and compared to 6 normal healthy controls. For all 12 lines, gene expression profiles were determined by RNA-seq and protein expression profiles were determined by shotgun proteomics. The LND lines revealed significant changes in expression of multiple genes and proteins. There was little overlap in findings between iPSCs and NSCs, confirming the impact of HGprt deficiency depends on cell type. For NSCs, gene expression studies pointed towards abnormalities in WNT signaling, which is known to play a role in neural development. Protein expression studies pointed to abnormalities in the mitochondrial F0F1 ATPase, which plays a role in maintaining cellular energy. These studies point to some mechanisms that may be responsible for abnormal neural development in LND.

莱希-尼汉病(LND)是一种由编码次黄嘌呤鸟嘌呤磷酸核糖转移酶(HGprt)的HPRT1基因变异引起的神经发育障碍。HGprt缺乏会引发许多不同细胞类型的代谢变化,因此尚不清楚哪些变化与异常神经发育最相关。为了开始阐明HGprt缺乏对发育中的人类神经元的影响,从患有LND的个体的6个诱导多能干细胞(iPSC)系制备神经干细胞(NSCs),并与6个正常健康对照进行比较。对于所有12个品系,通过RNA-seq测定基因表达谱,通过鸟枪蛋白质组学测定蛋白质表达谱。LND系揭示了多种基因和蛋白质表达的显著变化。iPSC和NSCs之间的发现几乎没有重叠,证实HGprt缺乏的影响取决于细胞类型。对于神经干细胞,基因表达研究指出WNT信号异常,已知WNT信号在神经发育中发挥作用。蛋白质表达研究指出线粒体F0F1-ATP酶异常,该酶在维持细胞能量方面发挥作用。这些研究指出了一些可能导致LND神经发育异常的机制。
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引用次数: 0
The origins of the force-from-lipid principle and the founding member of the TRP channel superfamily. 脂质力原理的起源和TRP通道超家族的创始成员。
IF 1.9 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-03-01 DOI: 10.1080/01677063.2022.2132104
Chun-Fang Wu
The 2021 Nobel Prize in Medicine and Physiology recognized the seminal work of David Julius, who established the temperature and pain sensory mechanisms based on the TRPV channel, and Ardem Patapoutian, who resolved the stretch activation mechanism for touch and proprietary sensation via Piezo channels. We are fortunate and proud to publish a special section on the force-from-lipid principle underlining Piezo channel activation and the origin of the first TRP channel, prepared by the pioneers who initiated the early work that led to the discoveries (Martinac & Kung, 2022; Minke & Pak, 2022). Professors Baruch Minke and William Pak recount the story of their early endeavor to reveal the phototransduction process mediated by the TRP channel in the fruit fly Drosophila. This light-sensitive TRP channel is now recognized as the founding member of the TRP channel superfamily, which encompasses a large category of channels underpinning different sensory mechanisms, including visual, auditory, thermal, and mechanosensory transduction. The functioning of Piezo channels turns out to be based on the same force-from-lipid principle, originating from lipid membrane lateral force without involving any cytoskeletal or cell adhesion molecules. As professors Ching Kung and Boris Martinac recount in their article, the initial finding actually originated from studies on a special strain of giant E. coli. Indeed, ‘what is true for E. coli is true for the elephant’.
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引用次数: 0
lncRNA XIST induces Aβ accumulation and neuroinflammation by the epigenetic repression of NEP in Alzheimer's disease. lncRNA XIST通过NEP在阿尔茨海默病中的表观遗传抑制诱导Aβ积累和神经炎症。
IF 1.9 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-03-01 Epub Date: 2022-01-31 DOI: 10.1080/01677063.2022.2028784
Xi-Wu Yan, Huai-Jun Liu, Yu-Xing Hong, Ting Meng, Jun Du, Cheng Chang

Alzheimer's disease (AD) is the leading cause of dementia globally, but effective treatment is lacking. We aimed to explore lncRNA XIST role in AD and the mechanisms involved in the effect of changes in lncRNA XIST on the expression of Aβ-degrading enzymes. The mouse model of AD and the cell model induced by Aβ were established. LncRNA XIST, IDE, NEP, Plasmin, ACE, EZH2 expressions and distribution of XIST in the nucleus and cytoplasm were detected by qRT-PCR. Inflammatory cytokines IL-6, IL-1β, TNFα, IL-8, and Aβ42 levels were detected by ELISA. TUNEL was used to measure brain tissue damage. Cell proliferation was detected by CCK-8 assay. Flow cytometry detected cell apoptosis. RIP validated the combination of XIST and EZH2. ChIP verified that XIST recruits EZH2 to mediate enrichment of HEK27me3 in the NEP promoter region. The protein expression in brain tissues and cells was detected by Western blot. The expression of lncRNA XIST was increased in AD mice and cell models. Inflammation and injury of nerve cells occurred in AD mice and cell models. The knockdown of lncRNA XIST alleviated Aβ-induced neuronal inflammation and damage. LncRNA XIST affected the expression of Aβ-degrading enzyme NEP, and lncRNA XIST was negatively correlated with NEP expression in AD mice. LncRNA XIST regulated NEP expression partly through epigenetic regulation by binding with EZH2. LncRNA XIST mediated neuronal inflammation and injury through epigenetic regulation of NEP. Overall, our study found that lncRNA XIST induced Aβ accumulation and neuroinflammation by the epigenetic repression of NEP in AD.

阿尔茨海默病(AD)是全球痴呆症的主要原因,但缺乏有效的治疗方法。我们旨在探讨lncRNA XIST在AD中的作用,以及lncRNA XIST改变对a β-降解酶表达影响的机制。建立小鼠AD模型和Aβ诱导的细胞模型。采用qRT-PCR检测LncRNA XIST、IDE、NEP、Plasmin、ACE、EZH2在细胞核和细胞质中的表达和分布。ELISA法检测各组炎症因子IL-6、IL-1β、TNFα、IL-8、a - β42水平。TUNEL用于测量脑组织损伤。CCK-8法检测细胞增殖。流式细胞术检测细胞凋亡。RIP验证了XIST和EZH2的结合。ChIP证实XIST招募EZH2介导NEP启动子区域HEK27me3的富集。Western blot检测脑组织及细胞蛋白表达。lncRNA XIST在AD小鼠和细胞模型中表达升高。AD小鼠和细胞模型均出现神经细胞炎症和损伤。lncRNA XIST的下调可减轻a β诱导的神经元炎症和损伤。LncRNA XIST影响a β-降解酶NEP的表达,且LncRNA XIST与AD小鼠NEP表达呈负相关。LncRNA XIST部分通过与EZH2结合的表观遗传调控调控NEP的表达。LncRNA XIST通过NEP的表观遗传调控介导神经元炎症和损伤。总的来说,我们的研究发现lncRNA XIST通过表观遗传抑制NEP在AD中诱导Aβ积累和神经炎症。
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引用次数: 14
Reduction of the α-synuclein expression promotes slowing down early neuropathology development in the Drosophila model of Parkinson’s disease α-突触核蛋白表达的降低促进帕金森病果蝇模型早期神经病理发展的减缓
IF 1.9 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-02 DOI: 10.1080/01677063.2022.2064462
Ilia M Golomidov, Evgenia M. Latypova, E. Ryabova, O. Bolshakova, A. Komissarov, S. Sarantseva
Abstract Parkinson’s disease (PD) is a neurodegenerative disease characterised by the formation of Lewy bodies and progressive loss of dopaminergic (DA) neurons in the substantia nigra. Lewy bodies mainly consist of α-synuclein, which plays a critical role in the pathophysiology of PD. The α-synuclein is encoded by the SNCA gene and is the first identified gene associated with hereditary PD. Currently, there are at least six disease-associated mutations in α-synuclein that cause dominantly inherited familial forms of PD. Targeted expression of human SNCA.WT/SNCA.A30P/SNCA.A53T gene in Drosophila melanogaster over specific times employing a temperature-dependent UAS/GAL4 – GAL80 system allows for the evaluation of neurodegenerative processes. In this study, SNCA was expressed only in the adult stage of Drosophila development for 1 or 2 weeks, followed by repression of gene expression for the rest of the fly’s life. It was demonstrated that the level of pathology significantly depends on the duration of α-synuclein expression. SNCA gene expression over a longer period of time caused the death of DA neurons, decreased levels of dopamine and locomotor ability. In this case, the observed neurodegenerative processes correlated with the accumulation of α-synuclein in the Drosophila brain. Importantly, repression of α-synuclein expression led to elimination of the soluble protein fraction, in contrast to the insoluble fraction. No further significant development of characteristic signs of pathology was observed after the α-synuclein expression was blocked. Thus, we suggest that reduction of α-synuclein expression alone contributes to slowing down the development of PD-like symptoms.
摘要帕金森病(PD)是一种神经退行性疾病,其特征是黑质中路易体的形成和多巴胺能(DA)神经元的逐渐丧失。路易体主要由α-突触核蛋白组成,在帕金森病的病理生理学中起着至关重要的作用。使用温度依赖性UAS/GAL4–GAL80系统在特定时间内在黑腹果蝇中靶向表达人SNCA.WT/SNCA.A30P/SNCA.A53T基因,可以评估神经退行性过程。在这项研究中,SNCA仅在果蝇发育的成年阶段表达1或2 数周,然后在苍蝇的余生中抑制基因表达。研究表明,病理水平显著依赖于α-突触核蛋白表达的持续时间。SNCA基因长时间表达导致DA神经元死亡,多巴胺水平下降,运动能力下降。在这种情况下,观察到的神经退行性过程与果蝇大脑中α-突触核蛋白的积累有关。重要的是,α-突触核蛋白表达的抑制导致可溶性蛋白部分的消除,而不溶性部分则相反。α-突触核蛋白表达被阻断后,没有观察到病理学特征性体征的进一步显著发展。因此,我们认为,α-突触核蛋白表达的减少单独有助于减缓PD样症状的发展。
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引用次数: 0
LncRNA GAS5 promotes epilepsy progression through the epigenetic repression of miR-219, in turn affecting CaMKIIγ/NMDAR pathway LncRNA GAS5通过miR-219的表观遗传学抑制促进癫痫进展,进而影响CaMKIIγ/NDAR通路
IF 1.9 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-02 DOI: 10.1080/01677063.2022.2067536
Chen-sheng Zhao, Dong-xing Liu, Yanping Fan, Jian-kun Wu
Abstract It has been widely reported that dysregulated long-chain noncoding RNAs (lncRNAs) are closely associated with epilepsy. This study aimed to probe the function of lncRNA growth arrest-specific 5 (GAS5), microRNA (miR)-219 and Calmodulin-dependent protein kinase II (CaMKII)γ/N-methyl-D-aspartate receptor (NMDAR) pathway in epilepsy. Epileptic cell and animal models were constructed using magnesium deficiency treatment and diazepam injection, respectively. GAS5 and miR-219 expressions in epileptic cell and animal models were determined using qRT-PCR assay. The protein levels of CaMKIIγ, NMDAR and apoptosis-related proteins levels were assessed by western blot. Cell counting kit-8 (CCK-8) assay was employed to determine cell proliferation. Besides, TNFα, IL-1β, IL-6 and IL-8 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Furthermore, cell apoptosis was evaluated using TUNEL staining and flow cytometric analysis. Finally, the binding relationship between GAS5 and EZH2 was verified using RIP and ChIP assay. Our results revealed that GAS5 was markedly upregulated in epileptic cell and animal models, while miR-219 was down-regulated. GAS5 knockdown dramatically increased cell proliferation of epileptic cells, whereas suppressed inflammation and the apoptosis. Furthermore, our results showed that GAS5 epigenetically suppressed transcriptional miR-219 expression via binding to EZH2. miR-219 mimics significantly enhanced cell proliferation of epileptic cells, while inhibited inflammation and the apoptosis, which was neutralized by CaMKIIγ overexpression. Finally, miR-219 inhibition reversed the effects of GAS5 silence on epileptic cells, which was eliminated by CaMKIIγ inhibition. In conclusion, GAS5 affected inflammatory response and cell apoptosis of epilepsy via inhibiting miR-219 and further regulating CaMKIIγ/NMDAR pathway (See graphic summary in Supplementary Material).
摘要广泛报道,失调的长链非编码RNA(lncRNA)与癫痫密切相关。本研究旨在探讨lncRNA生长停滞特异性5(GAS5)、微小RNA(miR)-219和钙调蛋白依赖性蛋白激酶II(CaMKII)γ/N-甲基-D-天冬氨酸受体(NMDAR)通路在癫痫中的作用。分别使用镁缺乏治疗和安定注射液构建癫痫细胞和动物模型。使用qRT-PCR测定癫痫细胞和动物模型中GAS5和miR-219的表达。免疫印迹法检测CaMKIIγ、NMDAR蛋白水平及细胞凋亡相关蛋白水平。细胞计数试剂盒-8(CCK-8)测定法用于测定细胞增殖。采用酶联免疫吸附试验(ELISA)测定TNFα、IL-1β、IL-6和IL-8水平。此外,使用TUNEL染色和流式细胞术分析来评估细胞凋亡。最后,使用RIP和ChIP分析验证了GAS5和EZH2之间的结合关系。我们的研究结果显示,GAS5在癫痫细胞和动物模型中显著上调,而miR-219则下调。GAS5基因敲除显著增加癫痫细胞的增殖,同时抑制炎症和细胞凋亡。此外,我们的研究结果表明,GAS5通过与EZH2结合,表观遗传学抑制转录miR-219的表达。miR-219模拟显著增强癫痫细胞的细胞增殖,同时抑制炎症和细胞凋亡,这被CaMKIIγ过表达所中和。最后,miR-219的抑制逆转了GAS5沉默对癫痫细胞的影响,这种影响被CaMKIIγ的抑制所消除。总之,GAS5通过抑制miR-219和进一步调节CaMKIIγ/NDAR途径影响癫痫的炎症反应和细胞凋亡(见补充材料中的图形摘要)。
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引用次数: 4
Novel insights into the genetic profile of hereditary spastic paraplegia in India 新见解遗传痉挛性截瘫在印度的遗传概况
IF 1.9 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-02 DOI: 10.1080/01677063.2022.2064463
Sundarapandian Narendiran, M. Debnath, S. Shivaram, Ramakrishnan Kannan, Shivani Sharma, R. Christopher, D. Seshagiri, S. Jain, M. Purushottam, Sandhya Mangalore, R. Bharath, P. Bindu, S. Sinha, A. Taly, M. Nagappa
Abstract The Hereditary Spastic Paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders characterized by length dependent degeneration of the corticospinal tracts. Genetic data related to HSPs are limited from India. We aimed to comprehensively analyse the phenotypic characteristics and genetic basis of a large cohort of HSP from India. Patients with HSP phenotype were evaluated for their clinical features, electrophysiological and radiological abnormalities. Genetic analyses were carried out by clinical exome sequencing (n = 52) and targeted sequencing (n = 5). The cohort comprised of 57 probands (M:F 40:17, age: 3.5–49 years). Based on the phenotype, the cohort could be categorized as ‘pure’ (n = 15, 26.3%) and ‘complicated’ (n = 42, 73.7%) HSP. Brain MRI showed thin corpus callosum (n = 10), periventricular hyperintensities (n = 20), cerebral atrophy (n = 3), cerebellar atrophy (n = 3) and diffuse atrophy (n = 4). Sixty-seven variants representing 40 genes were identified including 47 novel variants. Forty-eight patients (84.2%) had variants in genes previously implicated in HSP and other spastic paraplegia syndromes (SPG genes = 24, non-SPG genes = 24); among these 13 had variations in more than one gene and 12 patients (21.0%) had variations in genes implicated in potentially treatable/modifiable metabolic disorders (MTHFR = 8, MTRR = 1, ARG1 = 2 and ABCD1 = 1). In nine patients, no genetic variants implicated in spastic paraplegia phenotype were identified. Thus, the present study from India highlights the phenotypic complexities and spectrum of genetic variations in patients with HSP including those implicated in metabolically modifiable disorders. It sets a platform for carrying out functional studies to validate the causal role of the novel variants and variants of uncertain significance.
遗传性痉挛性截瘫(HSPs)是一组临床和遗传异质性疾病,其特征是皮质脊髓束的长度依赖性变性。印度与热休克蛋白相关的遗传数据有限。我们的目的是全面分析来自印度的一个大队列热休克综合征的表型特征和遗传基础。对HSP表型患者的临床特征、电生理和放射学异常进行评估。通过临床外显子组测序(n = 52)和靶向测序(n = 5)进行遗传分析。该队列由57个先证者组成(男:女40:17,年龄:3.5-49岁)。根据表型,该队列可分为“纯”(n = 15, 26.3%)和“复杂”(n = 42, 73.7%) HSP。脑MRI表现为胼胝体薄(10例),脑室周围高信号(20例),脑萎缩(3例),小脑萎缩(3例),弥漫性萎缩(4例)。共鉴定出40个基因的67个变异,其中包括47个新变异。48例患者(84.2%)具有先前与HSP和其他痉挛性截瘫综合征相关的基因变异(SPG基因= 24,非SPG基因= 24);在这些患者中,13名患者有一个以上的基因变异,12名患者(21.0%)有与潜在可治疗/可改变代谢疾病相关的基因变异(MTHFR = 8, MTRR = 1, ARG1 = 2和ABCD1 = 1)。在9例患者中,没有发现与痉挛性截瘫表型相关的遗传变异。因此,目前来自印度的研究强调了HSP患者的表型复杂性和遗传变异谱,包括那些与代谢可改变疾病有关的患者。它为开展功能研究提供了一个平台,以验证新变体和不确定意义变体的因果作用。
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引用次数: 1
Environmental influences on for-mediated oviposition decisions in Drosophila melanogaster. 环境对果蝇产卵决定的影响。
IF 1.9 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-09-01 Epub Date: 2021-07-14 DOI: 10.1080/01677063.2021.1950713
Anders Vesterberg, Rudy Rizkalla, Mark J Fitzpatrick

Deciding whether or not to lay an egg on a given substrate is an important task undertaken by females of many arthropods. It involves perceiving the environment (e.g. quality of the substrate, temperature, and humidity), formulating a decision, and then conducting the appropriate behaviours to oviposit. This oviposition site selection (OSS) provides a useful system for studying simple decision-making. OSS in fruit flies, Drosophila melanogaster, is influenced by both genetic and environmental variation. Naturally occurring allelic variation in the foraging gene (for) is known to affect OSS. Given a choice of high- and low-nutrient oviposition substrates, groups of rovers (forR) are known to lay significantly more of their eggs on low-nutrient sites than sitters (fors) and sitter mutants (fors2). Here we ask three questions: (1) Is the role of for in OSS affected by the availability of alternate oviposition sites? (2) Is the role of for in OSS sensitive to the density of ovipositing females? and (3) Does the gustatory sensation of yeast play a role in for-mediated variation in OSS? We find a role of choice and female density in rover/sitter differences in OSS, as well as a role of for in response to glycerol, an indicator of yeast. The role of for in OSS decision-making is complex and multi-faceted and should prove fertile ground for further research into the factors affecting decision-making behaviours.

决定是否在给定的基质上产卵是许多节肢动物雌性承担的一项重要任务。它包括感知环境(例如基质的质量、温度和湿度),制定决策,然后对产卵进行适当的行为。这种产卵选址方法为简单决策研究提供了一个有用的系统。果蝇(Drosophila melanogaster)的OSS受到遗传和环境变异的影响。已知觅食基因(for)中自然发生的等位基因变异会影响OSS。假设有高营养和低营养的产卵基质可供选择,游览者群体(forR)在低营养地点产卵的几率明显高于静止者(fors)和静止突变者(fors2)。在这里,我们提出三个问题:(1)for在OSS中的作用是否受到替代产卵地点的可用性的影响?(2) for在OSS中的作用是否对雌性产卵密度敏感?(3)酵母的味觉感觉是否在for介导的OSS变异中起作用?我们发现选择和雌性密度在OSS的流浪者/保姆差异中的作用,以及对甘油(酵母的一种指标)的反应中的作用。for在OSS决策中的作用是复杂和多方面的,应该是进一步研究影响决策行为的因素的沃土。
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引用次数: 1
Spatiotemporal organization of enteroendocrine peptide expression in Drosophila. 果蝇肠内分泌肽表达的时空组织。
IF 1.9 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-09-01 Epub Date: 2021-10-20 DOI: 10.1080/01677063.2021.1989425
Sooin Jang, Ji Chen, Jaekyun Choi, Seung Yeon Lim, Hyejin Song, Hyungjun Choi, Hyung Wook Kwon, Min Sung Choi, Jae Young Kwon

The digestion of food and absorption of nutrients occurs in the gut. The nutritional value of food and its nutrients is detected by enteroendocrine cells, and peptide hormones produced by the enteroendocrine cells are thought to be involved in metabolic homeostasis, but the specific mechanisms are still elusive. The enteroendocrine cells are scattered over the entire gastrointestinal tract and can be classified according to the hormones they produce. We followed the changes in combinatorial expression of regulatory peptides in the enteroendocrine cells during metamorphosis from the larva to the adult fruit fly, and re-confirmed the diverse composition of enteroendocrine cell populations. Drosophila enteroendocrine cells appear to differentially regulate peptide expression spatially and temporally depending on midgut region and developmental stage. In the late pupa, Notch activity is known to determine which peptides are expressed in mature enteroendocrine cells of the posterior midgut, and we found that the loss of Notch activity in the anterior midgut results in classes of enteroendocrine cells distinct from the posterior midgut. These results suggest that enteroendocrine cells that populate the fly midgut can differentiate into distinct subtypes that express different combinations of peptides, which likely leads to functional variety depending on specific needs.

食物的消化和营养的吸收发生在肠道。食物及其营养成分的营养价值是由肠内分泌细胞检测的,肠内分泌细胞产生的肽激素被认为与代谢稳态有关,但具体机制尚不清楚。肠内分泌细胞分布在整个胃肠道,可以根据它们产生的激素进行分类。我们跟踪了果蝇幼虫到成虫蜕变过程中肠内分泌细胞中调控肽的组合表达变化,再次证实了肠内分泌细胞群的多样性组成。果蝇肠内分泌细胞对肽表达的调节在时空上存在差异,这取决于中肠区域和发育阶段。在蛹后期,Notch活性决定了哪些肽在成熟的后中肠肠内分泌细胞中表达,我们发现前中肠Notch活性的丧失导致肠内分泌细胞与后中肠不同。这些结果表明,分布在果蝇中肠的肠内分泌细胞可以分化成不同的亚型,表达不同的肽组合,这可能导致根据特定需求的功能变化。
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引用次数: 5
A cGMP-dependent protein kinase, encoded by the Drosophila foraging gene, regulates neurotransmission through changes in synaptic structure and function. 一种由果蝇觅食基因编码的cgmp依赖性蛋白激酶,通过改变突触结构和功能来调节神经传递。
IF 1.9 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-09-01 Epub Date: 2021-05-16 DOI: 10.1080/01677063.2021.1905639
Jeffrey S Dason, Marla B Sokolowski

A cGMP-dependent protein kinase (PKG) encoded by the Drosophila foraging (for) gene regulates both synaptic structure (nerve terminal growth) and function (neurotransmission) through independent mechanisms at the Drosophila larval neuromuscular junction (nmj). Glial for is known to restrict nerve terminal growth, whereas presynaptic for inhibits synaptic vesicle (SV) exocytosis during low frequency stimulation. Presynaptic for also facilitates SV endocytosis during high frequency stimulation. for's effects on neurotransmission can occur independent of any changes in nerve terminal growth. However, it remains unclear if for's effects on neurotransmission affect nerve terminal growth. Furthermore, it's possible that for's effects on synaptic structure contribute to changes in neurotransmission. In the present study, we examined these questions using RNA interference to selectively knockdown for in presynaptic neurons or glia at the Drosophila larval nmj. Consistent with our previous findings, presynaptic knockdown of for impaired SV endocytosis, whereas knockdown of glial for had no effect on SV endocytosis. Surprisingly, we found that knockdown of either presynaptic or glial for increased neurotransmitter release in response to low frequency stimulation. Knockdown of presynaptic for did not affect nerve terminal growth, demonstrating that for's effects on neurotransmission does not alter nerve terminal growth. In contrast, knockdown of glial for enhanced nerve terminal growth. This enhanced nerve terminal growth was likely the cause of the enhanced neurotransmitter release seen following knockdown of glial for. Overall, we show that for can affect neurotransmitter release by regulating both synaptic structure and function.

果蝇觅食(for)基因编码的cgmp依赖性蛋白激酶(PKG)通过果蝇幼虫神经肌肉连接处(nmj)的独立机制调节突触结构(神经末梢生长)和功能(神经传递)。已知胶质细胞抑制神经末梢生长,而突触前细胞抑制突触囊泡(SV)在低频刺激下的胞吐。在高频刺激时,突触前受体也促进SV内吞作用。对于神经传递的影响可以独立于神经末梢生长的任何变化而发生。然而,对于神经传递的影响是否会影响神经末梢的生长,目前还不清楚。此外,它对突触结构的影响可能会导致神经传递的变化。在本研究中,我们使用RNA干扰来选择性地敲除果蝇幼虫nmj的突触前神经元或胶质细胞。与我们之前的研究结果一致,突触前敲低SV内吞作用,而敲低胶质细胞对SV内吞作用没有影响。令人惊讶的是,我们发现在低频刺激下突触前或胶质细胞的敲除增加了神经递质释放。突触前for的敲除不影响神经末梢的生长,表明for对神经传递的影响不改变神经末梢的生长。相反,敲除胶质细胞促进神经末梢生长。这种增强的神经末梢生长可能是神经递质释放增强的原因。总的来说,我们表明,它可以通过调节突触结构和功能来影响神经递质释放。
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引用次数: 7
期刊
Journal of neurogenetics
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