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Novel function of single-target regulator NorR involved in swarming motility and biofilm formation revealed in Vibrio alginolyticus. 揭示了藻溶弧菌中参与蜂拥运动和生物膜形成的单目标调节器 NorR 的新功能。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-06 DOI: 10.1186/s12915-024-02057-y
Tongxian Chen, Xiaoling Zhou, Ruonan Feng, Shuhao Shi, Xiyu Chen, Bingqi Wei, Zhong Hu, Tao Peng

NorR, as a single-target regulator, has been demonstrated to be involved in NO detoxification in bacteria under anaerobic conditions. Here, the norR gene was identified and deleted in the genome of Vibrio alginolyticus. The results showed that deletion of norR in Vibrio alginolyticus led to lower swarming motility and more biofilm formation on aerobic condition. Moreover, we proved that NorR from E. coli had a similar function in controlling motility. NorR overexpression led to increased resistance to oxidative stress and tetracycline. We also observed a reduced ability of the NorR-overexpressing strain to adapt to iron limitation condition. Transcriptome analysis showed that the genes responsible for bacterial motility and biofilm formation were affected by NorR. The expressions of several sigma factors (RpoS, RpoN, and RpoH) and response regulators (LuxR and MarR) were also controlled by NorR. Furthermore, Chip-qPCR showed that there is a direct binding between NorR and the promoter of rpoS. Based on these results, NorR appears to be a central regulator involved in biofilm formation and swarming motility in Vibrio alginolyticus.

NorR 作为一种单目标调控因子,已被证明参与了厌氧条件下细菌的 NO 解毒过程。研究人员在藻溶弧菌的基因组中发现并删除了 norR 基因。结果表明,在有氧条件下,删除藻溶弧菌中的 norR 基因会导致藻溶弧菌蜂拥运动能力降低,生物膜形成增多。此外,我们还证明大肠杆菌中的 NorR 也具有类似的控制运动的功能。过表达 NorR 可增强对氧化应激和四环素的抵抗力。我们还观察到,NorR过表达菌株适应铁限制条件的能力下降。转录组分析表明,负责细菌运动和生物膜形成的基因受到了 NorR 的影响。一些σ因子(RpoS、RpoN 和 RpoH)和反应调节因子(LuxR 和 MarR)的表达也受 NorR 控制。此外,芯片-qPCR 显示,NorR 与 rpoS 的启动子之间存在直接结合。根据这些结果,NorR 似乎是参与藻溶弧菌生物膜形成和蜂拥运动的中心调节因子。
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引用次数: 0
Hibernation reduces GABA signaling in the brainstem to enhance motor activity of breathing at cool temperatures. 冬眠会减少脑干中的 GABA 信号,从而在低温条件下增强呼吸运动。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-04 DOI: 10.1186/s12915-024-02050-5
Sandy E Saunders, Joseph M Santin

Background: Neural circuits produce reliable activity patterns despite disturbances in the environment. For this to occur, neurons elicit synaptic plasticity during perturbations. However, recent work suggests that plasticity not only regulates circuit activity during disturbances, but these modifications may also linger to stabilize circuits during future perturbations. The implementation of such a regulation scheme for real-life environmental challenges of animals remains unclear. Amphibians provide insight into this problem in a rather extreme way, as circuits that generate breathing are inactive for several months during underwater hibernation and use compensatory plasticity to promote ventilation upon emergence.

Results: Using ex vivo brainstem preparations and electrophysiology, we find that hibernation in American bullfrogs reduces GABAA receptor (GABAAR) inhibition in respiratory rhythm generating circuits and motor neurons, consistent with a compensatory response to chronic inactivity. Although GABAARs are normally critical for breathing, baseline network output at warm temperatures was not affected. However, when assessed across a range of temperatures, hibernators with reduced GABAAR signaling had greater activity at cooler temperatures, enhancing respiratory motor output under conditions that otherwise strongly depress breathing.

Conclusions: Hibernation reduces GABAAR signaling to promote robust respiratory output only at cooler temperatures. Although frogs do not ventilate lungs during underwater hibernation, we suggest this would be beneficial for stabilizing breathing when the animal passes through a large temperature range during emergence in the spring. More broadly, these results demonstrate that compensatory synaptic plasticity can increase the operating range of circuits in harsh environments, thereby promoting adaptive behavior in conditions that suppress activity.

背景:尽管环境受到干扰,神经回路仍能产生可靠的活动模式。为了实现这一点,神经元在受到干扰时会产生突触可塑性。然而,最近的研究表明,可塑性不仅能在干扰期间调节神经回路的活动,而且在未来的干扰期间,这些可塑性还能稳定神经回路。针对动物在现实生活中面临的环境挑战,如何实施这种调节方案仍不清楚。两栖动物以一种相当极端的方式深入探讨了这一问题,因为在水下冬眠期间,产生呼吸的回路在几个月内都处于不活跃状态,而在出现时,它们会利用补偿可塑性来促进通气:通过体外脑干制备和电生理学研究,我们发现美国牛蛙冬眠会降低呼吸节律产生回路和运动神经元中的 GABAA 受体(GABAAR)抑制作用,这与长期不活动的代偿反应一致。虽然 GABAAR 通常对呼吸至关重要,但在温暖温度下,基线网络输出不受影响。然而,当在一定温度范围内进行评估时,GABAAR信号减少的冬眠者在较低温度下有更大的活动,从而在原本强烈抑制呼吸的条件下增强了呼吸运动输出:结论:冬眠减少了 GABAAR 信号传导,只有在温度较低时才能促进呼吸输出。虽然青蛙在水下冬眠期间不会对肺部进行换气,但我们认为,当动物在春季萌发时经过较大的温度范围时,这将有利于稳定呼吸。更广泛地说,这些结果表明,补偿性突触可塑性可以增加电路在恶劣环境中的工作范围,从而促进在抑制活动的条件下的适应行为。
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引用次数: 0
A powerful and versatile new fixation protocol for immunostaining and in situ hybridization that preserves delicate tissues. 用于免疫染色和原位杂交的功能强大、用途广泛的新固定方案,可保护脆弱的组织。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-04 DOI: 10.1186/s12915-024-02052-3
Carlos Guerrero-Hernández, Viraj Doddihal, Frederick G Mann, Alejandro Sánchez Alvarado

Background: Understanding how genes function to heal wounds and restore lost tissue is essential for studying regeneration. Whole-mount in situ hybridization (WISH) is a powerful and widely used technique to visualize the expression patterns of genes in different biological systems. Yet, existing methods to permeabilize samples for WISH can damage or destroy fragile regenerating tissues, thereby preventing such experiments.

Results: Here, we describe a new protocol for in situ hybridization (ISH) and immunostaining in the highly regenerative planarian Schmidtea mediterranea. This new Nitric Acid/Formic Acid (NAFA) protocol is compatible with both the assays and prevents degradation of the epidermis and regeneration blastema. The NAFA protocol achieves this without the use of proteinase K digestion which likely leads to better preservation of antigen epitopes. We show that the NAFA protocol successfully permits development of chromogenic and fluorescent signals in situ, while preserving the anatomy of the animal. Furthermore, the immunostaining of different proteins was compatible with the NAFA protocol following fluorescent in situ hybridization. Additionally, the tissue fixation protocol was easily adapted for regenerating killifish tail fin, which yielded better ISH signal with minimal background.

Conclusions: Thus, the NAFA protocol robustly preserves the delicate wounded tissues while also facilitating probe and antibody penetration into internal tissues. Furthermore, the fixation protocol is compatible for WISH on regenerating teleost fins suggesting that it will be a valuable technique for studying the processes of wounding response and regeneration in multiple species.

背景:了解基因如何发挥愈合伤口和恢复失去的组织的功能对研究再生至关重要。整装原位杂交(WISH)是一种功能强大、应用广泛的技术,可用于观察不同生物系统中基因的表达模式。然而,用于 WISH 的现有透化样本方法会损伤或破坏脆弱的再生组织,从而阻碍此类实验的进行:结果:在此,我们介绍了一种在再生能力极强的刨叶虫 Schmidtea mediterranea 中进行原位杂交(ISH)和免疫染色的新方案。这种新的硝酸/甲酸(NAFA)方案与这两种检测方法兼容,并能防止表皮和再生胚泡退化。NAFA方案无需使用蛋白酶K消化就能实现这一目的,这可能会更好地保存抗原表位。我们的研究表明,NAFA 方案成功地在原位形成了色原和荧光信号,同时保留了动物的解剖结构。此外,在进行荧光原位杂交后,不同蛋白质的免疫染色与 NAFA 方案兼容。此外,该组织固定方案很容易适用于再生鳉鱼尾鳍,能产生更好的 ISH 信号,且背景极低:因此,NAFA 方案既能有效保护脆弱的受伤组织,又能促进探针和抗体穿透内部组织。此外,该固定方案还可用于再生鳍鱼的 WISH,这表明它将成为研究多种鱼类创伤反应和再生过程的重要技术。
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引用次数: 0
Evolutionary divergent clusters of transcribed extinct truncated retroposons drive low mRNA expression and developmental regulation in the protozoan Leishmania. 原生动物利什曼原虫中转录已灭绝的截短反转录子的进化分化群驱动低 mRNA 表达和发育调控。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-29 DOI: 10.1186/s12915-024-02051-4
Gabriel Reis Ferreira, Jean-Guillaume Emond-Rheault, Lysangela Alves, Philippe Leprohon, Martin A Smith, Barbara Papadopoulou

Background: The Leishmania genome harbors formerly active short interspersed degenerated retroposons (SIDERs) representing the largest family of repetitive elements among trypanosomatids. Their substantial expansion in Leishmania is a strong predictor of important biological functions. In this study, we combined multilevel bioinformatic predictions with high-throughput genomic and transcriptomic analyses to gain novel insights into the diversified roles retroposons of the SIDER2 subfamily play in Leishmania genome evolution and expression.

Results: We show that SIDER2 retroposons form various evolutionary divergent clusters, each harboring homologous SIDER2 sequences usually located nearby in the linear sequence of chromosomes. This intriguing genomic organization underscores the importance of SIDER2 proximity in shaping chromosome dynamics and co-regulation. Accordingly, we show that transcripts belonging to the same SIDER2 cluster can display similar levels of expression. SIDER2 retroposons are mostly transcribed as part of 3'UTRs and account for 13% of the Leishmania transcriptome. Genome-wide expression profiling studies underscore SIDER2 association generally with low mRNA expression. The remarkable link of SIDER2 retroposons with downregulation of gene expression supports their co-option as major regulators of mRNA abundance. SIDER2 sequences also add to the diversification of the Leishmania gene expression repertoire since ~ 35% of SIDER2-containing transcripts can be differentially regulated throughout the parasite development, with a few encoding key virulence factors. In addition, we provide evidence for a functional bias of SIDER2-containing transcripts with protein kinase and transmembrane transporter activities being most represented.

Conclusions: Altogether, these findings provide important conceptual advances into evolutionary innovations of transcribed extinct retroposons acting as major RNA cis-regulators.

背景:利什曼原虫基因组中以前存在着活跃的短穿插变性逆转录子(SIDERs),是锥虫中最大的重复元件家族。它们在利什曼原虫中的大量扩增是重要生物学功能的有力预测。在这项研究中,我们将多层次生物信息学预测与高通量基因组和转录组分析相结合,对 SIDER2 亚家族的逆转录子在利什曼原虫基因组进化和表达中发挥的多样化作用有了新的认识:结果:我们发现SIDER2逆回子形成了各种进化分化的簇,每个簇都包含同源的SIDER2序列,这些序列通常位于染色体线性序列的附近。这种耐人寻味的基因组组织凸显了 SIDER2 邻近性在形成染色体动态和协同调控方面的重要性。因此,我们发现属于同一 SIDER2 簇的转录本可以表现出相似的表达水平。SIDER2 反转录子大多作为 3'UTR 的一部分被转录,占利什曼原虫转录组的 13%。全基因组表达谱分析研究强调了 SIDER2 通常与低 mRNA 表达有关。SIDER2 反转录子与基因表达下调的显著联系支持了它们作为 mRNA 丰度主要调节因子的共同作用。SIDER2 序列还增加了利什曼原虫基因表达库的多样性,因为约 35% 含 SIDER2 的转录本可在寄生虫的整个发育过程中受到不同的调控,其中一些编码关键的毒力因子。此外,我们还提供了含 SIDER2 转录本功能偏倚的证据,其中蛋白激酶和跨膜转运活性的转录本最多:总之,这些发现为转录灭绝的逆转录子作为主要 RNA 顺式调控因子的进化创新提供了重要的概念性进展。
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引用次数: 0
Cold snaps lead to a 5-fold increase or a 3-fold decrease in disease proliferation depending on the baseline temperature. 根据基线温度的不同,寒流会导致病害扩散增加 5 倍或减少 3 倍。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-29 DOI: 10.1186/s12915-024-02041-6
Niamh McCartan, Jeremy Piggott, Sadie DiCarlo, Pepijn Luijckx

Background: Climate change is driving increased extreme weather events that can impact ecology by moderating host-pathogen interactions. To date, few studies have explored how cold snaps affect disease prevalence and proliferation. Using the Daphnia magna-Ordospora colligata host-parasite system, a popular model system for environmentally transmitted diseases, the amplitude and duration of cold snaps were manipulated at four baseline temperatures, 10 days post-exposure, with O. colligata fitness recorded at the individual level.

Results: Cold snaps induced a fivefold increase or a threefold decrease in parasite burden relative to baseline temperature, with complex nuances and varied outcomes resulting from different treatment combinations. Both amplitude and duration can interact with the baseline temperature highlighting the complexity and baseline dependence of cold snaps. Furthermore, parasite fitness, i.e., infection prevalence and burden, were simultaneously altered in opposite directions in the same cold snap treatment.

Conclusions: We found that cold snaps can yield complicated outcomes that are unique from other types of temperature variation (for example, heatwaves). These results underpin the challenges and complexity in understanding and predicting how climate and extreme weather may alter disease under global change.

背景:气候变化导致极端天气事件增多,这些事件会通过调节宿主与病原体之间的相互作用来影响生态。迄今为止,很少有研究探讨寒流如何影响疾病的流行和扩散。通过使用大型水蚤-Ordospora colligata 宿主-寄生虫系统(一种流行的环境传播疾病模型系统),在四种基线温度下操纵寒流的幅度和持续时间,在暴露后 10 天记录 O. colligata 在个体水平上的适应性:结果:相对于基线温度,寒流会导致寄生虫数量增加五倍或减少三倍,不同的处理组合会产生复杂的细微差别和不同的结果。振幅和持续时间都会与基线温度相互作用,这凸显了寒流的复杂性和基线依赖性。此外,寄生虫的适应性,即感染率和负担,在相同的冷冻处理中同时发生相反方向的改变:我们发现,寒流会产生复杂的结果,与其他类型的温度变化(如热浪)截然不同。这些结果凸显了理解和预测全球变化下气候和极端天气如何改变疾病所面临的挑战和复杂性。
{"title":"Cold snaps lead to a 5-fold increase or a 3-fold decrease in disease proliferation depending on the baseline temperature.","authors":"Niamh McCartan, Jeremy Piggott, Sadie DiCarlo, Pepijn Luijckx","doi":"10.1186/s12915-024-02041-6","DOIUrl":"10.1186/s12915-024-02041-6","url":null,"abstract":"<p><strong>Background: </strong>Climate change is driving increased extreme weather events that can impact ecology by moderating host-pathogen interactions. To date, few studies have explored how cold snaps affect disease prevalence and proliferation. Using the Daphnia magna-Ordospora colligata host-parasite system, a popular model system for environmentally transmitted diseases, the amplitude and duration of cold snaps were manipulated at four baseline temperatures, 10 days post-exposure, with O. colligata fitness recorded at the individual level.</p><p><strong>Results: </strong>Cold snaps induced a fivefold increase or a threefold decrease in parasite burden relative to baseline temperature, with complex nuances and varied outcomes resulting from different treatment combinations. Both amplitude and duration can interact with the baseline temperature highlighting the complexity and baseline dependence of cold snaps. Furthermore, parasite fitness, i.e., infection prevalence and burden, were simultaneously altered in opposite directions in the same cold snap treatment.</p><p><strong>Conclusions: </strong>We found that cold snaps can yield complicated outcomes that are unique from other types of temperature variation (for example, heatwaves). These results underpin the challenges and complexity in understanding and predicting how climate and extreme weather may alter disease under global change.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"250"},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bridging chemical structure and conceptual knowledge enables accurate prediction of compound-protein interaction. 在化学结构和概念知识之间架起桥梁,可以准确预测化合物与蛋白质之间的相互作用。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-29 DOI: 10.1186/s12915-024-02049-y
Wen Tao, Xuan Lin, Yuansheng Liu, Li Zeng, Tengfei Ma, Ning Cheng, Jing Jiang, Xiangxiang Zeng, Sisi Yuan

Background: Accurate prediction of compound-protein interaction (CPI) plays a crucial role in drug discovery. Existing data-driven methods aim to learn from the chemical structures of compounds and proteins yet ignore the conceptual knowledge that is the interrelationships among the fundamental elements in the biomedical knowledge graph (KG). Knowledge graphs provide a comprehensive view of entities and relationships beyond individual compounds and proteins. They encompass a wealth of information like pathways, diseases, and biological processes, offering a richer context for CPI prediction. This contextual information can be used to identify indirect interactions, infer potential relationships, and improve prediction accuracy. In real-world applications, the prevalence of knowledge-missing compounds and proteins is a critical barrier for injecting knowledge into data-driven models.

Results: Here, we propose BEACON, a data and knowledge dual-driven framework that bridges chemical structure and conceptual knowledge for CPI prediction. The proposed BEACON learns the consistent representations by maximizing the mutual information between chemical structure and conceptual knowledge and predicts the missing representations by minimizing their conditional entropy. BEACON achieves state-of-the-art performance on multiple datasets compared to competing methods, notably with 5.1% and 6.6% performance gain on the BIOSNAP and DrugBank datasets, respectively. Moreover, BEACON is the only approach capable of effectively predicting knowledge representations for knowledge-lacking compounds and proteins.

Conclusions: Overall, our work provides a general approach for directly injecting conceptual knowledge to enhance the performance of CPI prediction.

背景:准确预测化合物-蛋白质相互作用(CPI)在药物发现中起着至关重要的作用。现有的数据驱动方法旨在从化合物和蛋白质的化学结构中学习,但忽略了概念知识,即生物医学知识图谱(KG)中基本元素之间的相互关系。知识图谱提供了超越单个化合物和蛋白质的实体和关系的综合视图。知识图谱涵盖了大量信息,如路径、疾病和生物过程,为 CPI 预测提供了更丰富的背景信息。这种上下文信息可用于识别间接相互作用、推断潜在关系并提高预测准确性。在实际应用中,知识缺失化合物和蛋白质的普遍存在是将知识注入数据驱动模型的关键障碍:在此,我们提出了一个数据和知识双驱动框架--BEACON,它将化学结构和概念知识连接起来,用于 CPI 预测。所提出的 BEACON 通过最大化化学结构与概念知识之间的互信息来学习一致的表征,并通过最小化其条件熵来预测缺失的表征。与其他竞争方法相比,BEACON 在多个数据集上取得了最先进的性能,特别是在 BIOSNAP 和 DrugBank 数据集上分别提高了 5.1% 和 6.6%。此外,BEACON 是唯一一种能够有效预测缺乏知识的化合物和蛋白质的知识表征的方法:总之,我们的工作提供了一种直接注入概念知识以提高 CPI 预测性能的通用方法。
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引用次数: 0
Hoxa5 alleviates adipose tissue metabolic distortions in high-fat diet mice associated with a reduction in MERC. Hoxa5 可减轻高脂饮食小鼠脂肪组织代谢的扭曲,这与 MERC 的减少有关。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-29 DOI: 10.1186/s12915-024-02047-0
Qi Chen, Zeyu Ren, Liping Dang, Zunhai Liu, Simeng Wang, Xinhao Chen, Guiping Qiu, Chao Sun

Background: Mitochondria-endoplasmic reticulum membrane contact (MERC) is an important mode of intercellular organelle communication and plays a crucial role in adipose tissue metabolism. Functionality of Hoxa5 is an important transcription factor involved in adipose tissue fate determination and metabolic regulation, but the relationship between Hoxa5 and MERC is not well understood.

Results: In our study, we established an obesity model mouse by high-fat diet (HFD), induced the alteration of Hoxa5 expression by adenoviral transfection, and explored the effect of Hoxa5 on MERC dysfunction and metabolic distortions of adipose tissue with the help of transmission electron microscopy, calcium ion probe staining, and other detection means. The results showed Hoxa5 was able to reduce MERC production, alleviate endoplasmic reticulum stress (ERS) and calcium over-transport, and affect cGAS-STING-mediated innate immune response affecting adipose tissue energy metabolism, as well as affect the AKT-IP3R pathway to alleviate insulin resistance and ameliorate metabolic distortions in adipose tissue of mice.

Conclusions: Our results suggest that Hoxa5 can ameliorate high-fat diet-induced MERC overproduction and related functional abnormalities, in which finding is expected to provide new ideas for the improvement of obesity-related metabolic distortions.

背景:线粒体-内质网膜接触(MERC)是细胞器间通讯的重要方式,在脂肪组织代谢中起着至关重要的作用。Hoxa5是参与脂肪组织命运决定和代谢调控的重要转录因子,但Hoxa5与MERC之间的关系尚不十分清楚:结果:我们通过高脂饮食(HFD)建立了肥胖模型小鼠,通过腺病毒转染诱导Hoxa5表达改变,并借助透射电镜、钙离子探针染色等检测手段探讨了Hoxa5对MERC功能障碍和脂肪组织代谢畸变的影响。结果表明,Hoxa5能够减少MERC的产生,缓解内质网应激(ERS)和钙离子过度转运,影响cGAS-STING介导的影响脂肪组织能量代谢的先天性免疫反应,并影响AKT-IP3R通路,从而缓解胰岛素抵抗,改善小鼠脂肪组织的代谢扭曲:我们的研究结果表明,Hoxa5 可改善高脂饮食诱导的 MERC 过度分泌及相关功能异常,这一发现有望为改善肥胖相关的代谢扭曲提供新思路。
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引用次数: 0
Thymosin β4 promotes zebrafish Mauthner axon regeneration by facilitating actin polymerization through binding to G-actin. 胸腺肽β4通过与G-肌动蛋白结合促进肌动蛋白聚合,从而促进斑马鱼毛氏轴突再生。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-23 DOI: 10.1186/s12915-024-02045-2
Zheng Song, Along Han, Bing Hu

Background: Thymosin beta 4 (Tβ4) is a monomeric actin-binding protein that plays many roles in biological activities. However, some studies on the role of Tβ4 in central axon regeneration have yielded contradictory results. Previous research has focused primarily on cultured cells, leading to a deficiency in in vivo experimental evidence. Therefore, we used a single axon injury model of Mauthner cells in zebrafish larvae to investigate the role of Tβ4 in central axon regeneration in vivo.

Results: Our results demonstrated that knockout of Tβ4 impaired axon regeneration, whereas overexpression of Tβ4 promoted axon regeneration. Moreover, this promotion is mediated through the interaction between Tβ4 and G-actin. Furthermore, our results suggest that the binding of Tβ4 to G-actin promotes actin polymerization rather than depolymerization. In the rapid escape behavior test, larvae with damaged axons presented impaired tail muscle control, resulting in a lack of normal tail bending, termed the straight tail phenomenon. The proportion of straight tails was significantly negatively correlated with axon regeneration length, suggesting that it is a new indicator for assessing rapid escape behavior recovery. Finally, the results showed that the overexpression of Tβ4 effectively restored the functionality of rapid escape behaviors mediated by Mauthner cells.

Conclusions: Our results provide evidence that Tβ4 promotes central axon regeneration in vivo through binding to G-actin and suggest that Tβ4 could serve as a potential polypeptide drug for clinical therapy.

背景:胸腺肽β4(Tβ4)是一种单体肌动蛋白结合蛋白,在生物活动中发挥着多种作用。然而,关于 Tβ4 在中枢轴突再生中的作用的一些研究却得出了相互矛盾的结果。以往的研究主要集中在培养细胞上,导致缺乏体内实验证据。因此,我们利用斑马鱼幼体毛氏细胞单轴突损伤模型来研究Tβ4在体内中枢轴突再生中的作用:结果:我们的研究结果表明,敲除Tβ4会阻碍轴突再生,而过表达Tβ4会促进轴突再生。而且,这种促进作用是通过 Tβ4 和 G-actin 之间的相互作用介导的。此外,我们的研究结果表明,Tβ4与G-肌动蛋白的结合促进了肌动蛋白的聚合而非解聚。在快速逃逸行为测试中,轴突受损的幼虫对尾部肌肉的控制能力受损,导致尾部无法正常弯曲,这被称为直尾现象。直尾比例与轴突再生长度呈显著负相关,这表明它是评估快速逃逸行为恢复情况的一个新指标。最后,研究结果表明,过表达 Tβ4 能有效恢复毛特纳细胞介导的快速逃逸行为的功能:我们的研究结果提供了 Tβ4 通过与 G-actin 结合促进体内中枢轴突再生的证据,并表明 Tβ4 可作为一种潜在的多肽药物用于临床治疗。
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引用次数: 0
Breaking muscle: neurotoxic and myotoxic effects of Central American snake venoms and the relative efficacies of antivenom and varespladib. 破坏肌肉:中美洲蛇毒的神经毒性和肌毒性作用以及抗蛇毒血清和伐雷司他啶的相对疗效。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-23 DOI: 10.1186/s12915-024-02044-3
Lee Jones, Mimi Lay, Edgar Neri-Castro, Vanessa Zarzosa, Wayne C Hodgson, Matthew Lewin, Bryan G Fry

Background: The snake genera Atropoides, Cerrophidion, and Metlapilcoatlus form a clade of neotropical pit vipers distributed across Mexico and Central America. This study evaluated the myotoxic and neurotoxic effects of nine species of Atropoides, Cerrophidion, and Metlapilcoatlus, and the neutralising efficacy of the ICP antivenom from Costa Rica against these effects, in the chick biventer cervicis nerve-muscle preparation. Given the prominence of PLA2s within the venom proteomes of these species, we also aimed to determine the neutralising potency of the PLA2 inhibitor, varespladib.

Results: All venoms showed myotoxic and potential neurotoxic effects, with differential intra-genera and inter-genera potency. This variation was also seen in the antivenom ability to neutralise the muscle damaging pathophysiological effects observed. Variation was also seen in the relative response to the PLA2 inhibitor varespladib. While the myotoxic effects of M. mexicanus and M. nummifer venoms were effectively neutralised by varespladib, indicating myotoxicity is PLA2 mediated, those of C. godmani and M. olmec venoms were not, revealing that the myotoxicity is driven by non-PLA2 toxin types.

Conclusions: This study characterises the myotoxic and neurotoxic venom activity, as well as neutralisation of venom effects from the Atropoides, Cerrophidion, and Metlapilcoatlus clade of American crotalids. Our findings contribute significant clinical and evolutionary knowledge to a clade of poorly researched snakes. In addition, these results provide a platform for future research into the reciprocal interaction between ecological niche specialisation and venom evolution, as well as highlighting the need to test purified toxins to accurately evaluate the potential effects observed in these venoms.

背景:蛇属 Atropoides、Cerrophidion 和 Metlapilcoatlus 是分布于墨西哥和中美洲的新热带蝮蛇支系。本研究评估了九种 Atropoides、Cerrophidion 和 Metlapilcoatlus 的肌毒性和神经毒性效应,以及哥斯达黎加生产的 ICP 抗蛇毒血清对这些效应的中和效果。鉴于 PLA2 在这些物种的毒液蛋白质组中的显著地位,我们还旨在确定 PLA2 抑制剂 varespladib 的中和效力:结果:所有毒液都显示出肌毒性和潜在的神经毒性作用,不同毒液种内和种间的效力不同。抗蛇毒血清中和所观察到的肌肉损伤性病理生理效应的能力也存在这种差异。对 PLA2 抑制剂 varespladib 的相对反应也存在差异。虽然varespladib能有效中和M. mexicanus和M. nummifer毒液的肌毒性效应,表明肌毒性是由PLA2介导的,但C. godmani和M. olmec毒液的肌毒性效应却没有被中和,这表明肌毒性是由非PLA2毒素类型驱动的:本研究揭示了美洲黄鼠狼的肌毒性和神经毒性毒液活性以及Atropoides、Cerrophidion和Metlapilcoatlus支系毒液的中和效应。我们的研究结果为研究较少的蛇类支系提供了重要的临床和进化知识。此外,这些结果还为今后研究生态位特化与毒液进化之间的相互影响提供了一个平台,同时也强调了测试纯化毒素的必要性,以便准确评估在这些毒液中观察到的潜在影响。
{"title":"Breaking muscle: neurotoxic and myotoxic effects of Central American snake venoms and the relative efficacies of antivenom and varespladib.","authors":"Lee Jones, Mimi Lay, Edgar Neri-Castro, Vanessa Zarzosa, Wayne C Hodgson, Matthew Lewin, Bryan G Fry","doi":"10.1186/s12915-024-02044-3","DOIUrl":"10.1186/s12915-024-02044-3","url":null,"abstract":"<p><strong>Background: </strong>The snake genera Atropoides, Cerrophidion, and Metlapilcoatlus form a clade of neotropical pit vipers distributed across Mexico and Central America. This study evaluated the myotoxic and neurotoxic effects of nine species of Atropoides, Cerrophidion, and Metlapilcoatlus, and the neutralising efficacy of the ICP antivenom from Costa Rica against these effects, in the chick biventer cervicis nerve-muscle preparation. Given the prominence of PLA<sub>2</sub>s within the venom proteomes of these species, we also aimed to determine the neutralising potency of the PLA<sub>2</sub> inhibitor, varespladib.</p><p><strong>Results: </strong>All venoms showed myotoxic and potential neurotoxic effects, with differential intra-genera and inter-genera potency. This variation was also seen in the antivenom ability to neutralise the muscle damaging pathophysiological effects observed. Variation was also seen in the relative response to the PLA<sub>2</sub> inhibitor varespladib. While the myotoxic effects of M. mexicanus and M. nummifer venoms were effectively neutralised by varespladib, indicating myotoxicity is PLA<sub>2</sub> mediated, those of C. godmani and M. olmec venoms were not, revealing that the myotoxicity is driven by non-PLA<sub>2</sub> toxin types.</p><p><strong>Conclusions: </strong>This study characterises the myotoxic and neurotoxic venom activity, as well as neutralisation of venom effects from the Atropoides, Cerrophidion, and Metlapilcoatlus clade of American crotalids. Our findings contribute significant clinical and evolutionary knowledge to a clade of poorly researched snakes. In addition, these results provide a platform for future research into the reciprocal interaction between ecological niche specialisation and venom evolution, as well as highlighting the need to test purified toxins to accurately evaluate the potential effects observed in these venoms.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"243"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New insights into the phylogenetic relationships within the Lauraceae from mitogenomes. 从有丝分裂基因组看月桂科植物系统发育关系的新见解。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-23 DOI: 10.1186/s12915-024-02040-7
Yu Song, Qun-Fei Yu, Di Zhang, Li-Gang Chen, Yun-Hong Tan, Wen Zhu, Hua-Long Su, Xin Yao, Chao Liu, Richard T Corlett

Background: The family Lauraceae is subdivided into six main lineages: Caryodaphnopsideae, Cassytheae, Cryptocaryeae, Hypodaphnideae, Laureae, and Neocinnamomeae. However, phylogenetic relationships among these lineages have been debatable due to incongruence between trees constructed using nuclear ribosomal DNA (nrDNA) sequences and chloroplast (cp) genomes. As with cp DNA, the mitochondrial (mt) DNA of most flowering plants is maternally inherited, so the phylogenetic relationships recovered with mt genomes are expected to be consistent with that from cp genomes, rather than nrDNA sequences.

Results: The mitogenome of Machilus yunnanensis, with a length of 735,392 bp, has a very different genome size and gene linear order from previously published magnoliid mitogenomes. Phylogenomic reconstructions based on 41 mt genes from 92 Lauraceae mitogenomes resulted in highly supported relationships: sisterhood of the Laureae and a group containing Neocinnamomeae and Caryodaphnopsideae, with Cassytheae being the next sister group, followed by Cryptocaryeae. However, we found significant incongruence among the mitochondrial, chloroplast, and nuclear phylogenies, especially for the species within the Caryodaphnopsideae and Neocinnamomeae lineages. Time-calibrated phylogenetic analyses showed that the split between Caryodaphnopsideae and Neocinnamomeae dated to the later Eocene, around 38.5 Ma, Laureae originated in the Late Cretaceous, around 84.9 Ma, Cassytheae originated in the mid-Cretaceous around 102 Ma, and Cryptocaryeae originated in the Early Cretaceous around 116 Ma. From the Late Cretaceous to the Paleocene, net diversification rates significantly increased across extant clades of major lineages, and both speciation rates and net diversification rates continued steady growth towards the present.

Conclusions: The topology obtained here for the first time shows that mt genes can be used to support relationships among lineages of Lauraceae. Our results highlight that both Caryodaphnopsideae and Neocinnamomeae lineages are younger than previously thought, likely first diversifying in the Eocene, and species in the other extant lineages of Lauraceae dates in a long-time span from the Early Cretaceous to the Eocene, and the climate of a period of about 90 million years was relatively warm, while the extant species of Lauraceae then continuously diversified with global cooling from the Eocene to the present day.

背景介绍月桂科细分为六个主要分支:Caryodaphnopsideae, Cassytheae, Cryptocaryeae, Hypodaphnideae, Laureae 和 Neocinnamomeae。然而,由于使用核核糖体 DNA(nrDNA)序列和叶绿体(cp)基因组构建的树之间不一致,这些世系之间的系统发育关系一直存在争议。与 cp DNA 一样,大多数有花植物的线粒体(mt)DNA 也是母系遗传的,因此利用 mt 基因组恢复的系统发生关系有望与 cp 基因组而非 nrDNA 序列恢复的系统发生关系保持一致:结果:长度为735,392 bp的云南马氏蛛有丝分裂基因组的基因组大小和基因线性顺序与之前发表的木兰科动物有丝分裂基因组截然不同。基于 92 个月桂科植物有丝分裂基因组中的 41 个 mt 基因进行的系统发生组重建得出了高度支持的关系:月桂科和包含新肉桂科(Neocinnamomeae)和莸科(Caryodaphnopsideae)的姊妹群,仙鹤草科(Cassytheae)是下一个姊妹群,其次是隐花植物科(Cryptocaryae)。然而,我们发现线粒体、叶绿体和核系统发生之间存在明显的不一致性,尤其是 Caryodaphnopsideae 和 Neocinnamomeae 系中的物种。时间校准系统发育分析表明,Caryodaphnopsideae 和 Neocinnamomeae 之间的分裂可追溯到始新世晚期(约 38.5 Ma),Laureae 起源于白垩纪晚期(约 84.9 Ma),Cassytheae 起源于白垩纪中期(约 102 Ma),而 Cryptocaryeae 起源于白垩纪早期(约 116 Ma)。从晚白垩世到古新世,现存各主要类群的净分化率显著增加,直到现在,物种分化率和净分化率仍在稳步增长:本文获得的拓扑结构首次表明,mt 基因可用于支持月桂科各系之间的关系。我们的研究结果突出表明,Caryodaphnopsideae和Neocinnamomeae两个品系都比以前认为的要年轻,很可能在始新世就已经开始分化,而其他现存的月桂科品系中的物种年代跨度很长,从早白垩世到始新世,约9000万年的气候相对温暖,而现存的月桂科物种则随着从始新世到现在的全球变冷而不断分化。
{"title":"New insights into the phylogenetic relationships within the Lauraceae from mitogenomes.","authors":"Yu Song, Qun-Fei Yu, Di Zhang, Li-Gang Chen, Yun-Hong Tan, Wen Zhu, Hua-Long Su, Xin Yao, Chao Liu, Richard T Corlett","doi":"10.1186/s12915-024-02040-7","DOIUrl":"10.1186/s12915-024-02040-7","url":null,"abstract":"<p><strong>Background: </strong>The family Lauraceae is subdivided into six main lineages: Caryodaphnopsideae, Cassytheae, Cryptocaryeae, Hypodaphnideae, Laureae, and Neocinnamomeae. However, phylogenetic relationships among these lineages have been debatable due to incongruence between trees constructed using nuclear ribosomal DNA (nrDNA) sequences and chloroplast (cp) genomes. As with cp DNA, the mitochondrial (mt) DNA of most flowering plants is maternally inherited, so the phylogenetic relationships recovered with mt genomes are expected to be consistent with that from cp genomes, rather than nrDNA sequences.</p><p><strong>Results: </strong>The mitogenome of Machilus yunnanensis, with a length of 735,392 bp, has a very different genome size and gene linear order from previously published magnoliid mitogenomes. Phylogenomic reconstructions based on 41 mt genes from 92 Lauraceae mitogenomes resulted in highly supported relationships: sisterhood of the Laureae and a group containing Neocinnamomeae and Caryodaphnopsideae, with Cassytheae being the next sister group, followed by Cryptocaryeae. However, we found significant incongruence among the mitochondrial, chloroplast, and nuclear phylogenies, especially for the species within the Caryodaphnopsideae and Neocinnamomeae lineages. Time-calibrated phylogenetic analyses showed that the split between Caryodaphnopsideae and Neocinnamomeae dated to the later Eocene, around 38.5 Ma, Laureae originated in the Late Cretaceous, around 84.9 Ma, Cassytheae originated in the mid-Cretaceous around 102 Ma, and Cryptocaryeae originated in the Early Cretaceous around 116 Ma. From the Late Cretaceous to the Paleocene, net diversification rates significantly increased across extant clades of major lineages, and both speciation rates and net diversification rates continued steady growth towards the present.</p><p><strong>Conclusions: </strong>The topology obtained here for the first time shows that mt genes can be used to support relationships among lineages of Lauraceae. Our results highlight that both Caryodaphnopsideae and Neocinnamomeae lineages are younger than previously thought, likely first diversifying in the Eocene, and species in the other extant lineages of Lauraceae dates in a long-time span from the Early Cretaceous to the Eocene, and the climate of a period of about 90 million years was relatively warm, while the extant species of Lauraceae then continuously diversified with global cooling from the Eocene to the present day.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"241"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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