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Influence of developmental diet on adult energy reserves in Drosophila. 发育期饮食对果蝇成虫能量储备的影响。
IF 4.5 1区 生物学 Q1 BIOLOGY Pub Date : 2025-12-07 DOI: 10.1186/s12915-025-02486-3
Emanuel Manfred Makwisa, Emanuel Procházka, Martina Gáliková, Peter Klepsatel

Background: Nutrition during early life often has lasting consequences for adult physiology. However, it remains unclear how developmental diet shapes both the initial energetic state and subsequent change of energy stores. To address this, we systematically varied yeast and sugar concentrations in the developmental diet of Drosophila melanogaster and quantified energy reserves (in joules, derived from fat, glycogen, trehalose, and glucose) at eclosion and after 10 days of adulthood on a standardized diet. Comparing these time points allowed estimation of net change in energy reserves. Additionally, we examined how these effects depend on sex, population, and reproductive status.

Results: Developmental diet strongly influenced initial energy reserves. Higher sugar concentrations increased energy stores at eclosion. However, the subsequent net change in energy was inversely related to these starting conditions. Flies reared on high-sugar larval diets, which emerged with the most energy, exhibited the smallest net change during early adulthood. In contrast, flies from low-sugar diets emerged leaner and subsequently showed the largest net increase. These patterns were modulated by sex and reproductive status. In males, energy stores more closely reflected the larval nutritional background, whereas in females this relationship was weaker-likely due to the energetic demands of oogenesis. Mating was generally associated with lower energy reserves across groups.

Conclusions: Early-life diet affects both the starting point and early-adult change in energy reserves in Drosophila. These findings outline a framework in which developmental history and adult conditions jointly shape energetic trajectories.

背景:生命早期的营养通常对成年后的生理机能有持久的影响。然而,尚不清楚发育饮食如何影响初始能量状态和随后能量储存的变化。为了解决这个问题,我们系统地改变了黑腹果蝇发育饮食中的酵母和糖浓度,并量化了羽化时和成年后10天标准化饮食中的能量储备(以焦耳为单位,来自脂肪、糖原、海藻糖和葡萄糖)。比较这些时间点可以估计能源储备的净变化。此外,我们还研究了这些影响如何取决于性别、人口和生殖状况。结果:发育期饮食对初始能量储备有显著影响。较高的糖浓度增加了羽化时的能量储存。然而,随后的净能量变化与这些起始条件成反比。以高糖幼虫为食的果蝇能量最大,在成年早期表现出最小的净变化。相比之下,低糖饮食的果蝇变得更瘦,随后表现出最大的净增长。这些模式受到性别和生殖状况的调节。在雄性中,能量储存更密切地反映了幼虫的营养背景,而在雌性中,这种关系较弱——可能是由于产卵的能量需求。交配通常与群体中较低的能量储备有关。结论:早期饮食影响果蝇能量储备的起点和成年早期的变化。这些发现勾勒出一个框架,在这个框架中,发育历史和成人条件共同塑造了能量轨迹。
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引用次数: 0
Nictation behavior in nematodes. 线虫的引诱行为。
IF 4.5 1区 生物学 Q1 BIOLOGY Pub Date : 2025-12-05 DOI: 10.1186/s12915-025-02443-0
Tuan Anh Le, Liesbet Temmerman, Charline Roy

Nictation is a dispersal behavior in nematodes, aiding movement and host-finding under stress. This review explores its diversity, genetic and neuronal basis, regulation, and ecological relevance. Nictation involves sensory integration, plasticity, and inter-organismal communication. Though its neural circuitry and molecular pathways remain partly understood, recent findings highlight roles for dauer signaling, neurotransmitters, and neuropeptides. Advances in scoring methods and genetic tools, including of parasitic species, now enable deeper study of its environmental triggers, evolutionary context, and impact on nematode virulence, with key knowledge gaps identified for future research.

叮咬是线虫的一种扩散行为,在逆境中帮助运动和寻找寄主。本文就其多样性、遗传和神经基础、调控及其生态学意义作一综述。尼古丁包括感觉整合、可塑性和生物间的交流。尽管其神经回路和分子通路仍部分被理解,但最近的研究结果强调了能量信号、神经递质和神经肽的作用。包括寄生物种在内的评分方法和遗传工具的进步,现在能够更深入地研究其环境触发因素、进化背景和对线虫毒力的影响,并为未来的研究确定了关键的知识空白。
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引用次数: 0
Genetic differentiation in domesticated black soldier fly (Hermetia illucens) populations. 驯化黑兵蝇居群的遗传分化。
IF 4.5 1区 生物学 Q1 BIOLOGY Pub Date : 2025-12-05 DOI: 10.1186/s12915-025-02480-9
Shaktheeshwari Silvaraju, Rebecca Ker Loh, Sandra Kittelmann, Nalini Puniamoorthy

Background: The black soldier fly (BSF, Hermetia illucens) is widely used for waste bioconversion and sustainable protein production. However, domestication and prolonged captive rearing can rapidly alter genetic diversity and population structure. This study investigated how selective breeding, genetic drift, and relaxed selection have shaped genomic variation and effective population size in multiple BSF populations. Using genome-wide restriction site-associated DNA sequencing, we analysed population structure, heterozygosity, and selection signatures across 11 BSF populations, including 1 long-term domesticated line, 5 selectively bred lines (Line A to Line E), 3 wild-derived populations, and 2 commercial strains.

Results: Despite shared origins, lines LA to LE diverged rapidly within 6 years. Principal component analysis and ADMIXTURE clustering (K = 11) revealed that LC to LE retained close genetic affinity, while LA and LB diverged markedly from each other and LC-LE. Demographic reconstructions using Stairway Plot showed that effective population sizes increased during the initial homogenized selective breeding phase (2018-2019) but declined after 2022, consistent with bottlenecks and relaxed selection. Wild-derived populations maintained higher heterozygosity and lower inbreeding coefficients than domesticated lines. Finally, genome-wide analyses identified 133 candidate genes under selection, including signatures of balancing selection and selective sweeps, reflecting divergent evolution under domestication.

Conclusions: These findings demonstrate that genetic differentiation occurs rapidly in BSF populations under domestication, driven by artificial selection, relaxation, genetic drift, and environmental adaptation. These results highlight the need for genetic monitoring in breeding programmes, including maintenance of large founder populations, periodic genetic assessment, and genetic rescue to preserve adaptive potential and reduce inbreeding risks.

背景:黑兵蝇(Hermetia illucens, BSF)被广泛用于废物生物转化和可持续蛋白质生产。然而,驯化和长期圈养可以迅速改变遗传多样性和种群结构。本研究探讨了选择育种、遗传漂变和宽松选择如何影响多个牛sf群体的基因组变异和有效群体规模。利用全基因组限制性内切位点相关DNA测序,研究人员分析了11个BSF群体的群体结构、杂合度和选择特征,包括1个长期驯化系、5个选择性育种系(A系至E系)、3个野生衍生群体和2个商业品系。结果:尽管有共同的起源,LA系到LE系在6年内迅速分化。主成分分析和ADMIXTURE聚类分析(K = 11)表明,LC与LE的遗传亲和性较强,而LA与LB的遗传亲和性较差,LC-LE的遗传亲和性较差。利用阶梯图进行的种群重建显示,有效种群规模在初始同质化选育阶段(2018-2019)有所增加,但在2022年之后有所下降,与瓶颈和宽松选择相一致。野生种群保持较高的杂合度和较低的近交系系数。最后,全基因组分析确定了133个候选基因,包括平衡选择和选择性扫描的特征,反映了驯化下的分化进化。结论:驯化过程中,在人工选择、放松、遗传漂变和环境适应的驱动下,BSF群体发生了快速的遗传分化。这些结果强调了在育种计划中进行遗传监测的必要性,包括维持大量创始种群、定期遗传评估和遗传救援,以保持适应潜力并降低近交风险。
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引用次数: 0
Signals of corresponding genetic diversity loss in four warbler species exhibiting regional or range-wide declines. 相应的遗传多样性丧失的信号在四种莺显示区域或范围内的下降。
IF 4.5 1区 生物学 Q1 BIOLOGY Pub Date : 2025-12-05 DOI: 10.1186/s12915-025-02478-3
Madelyn J Ore, Bronwyn G Butcher, Michael E Akresh, Jeremy J Kirchman, Joel Ralston, Patrick J Ruhl, David P L Toews, Irby J Lovette, Jennifer Walsh

Background: Anthropogenic forces have resulted in staggering losses of biodiversity and population declines in many species over the past two centuries. Associated with these declines are potential adverse effects linked to small population sizes, including loss of genetic diversity and increased levels of inbreeding. Here, we leverage DNA sequencing from museum specimens to examine genetic variation between historic and contemporary populations of four species of warblers (Aves, Setophaga) that vary with respect to degree of population changes over this period. To explore the genetic impacts of varying population declines, we gathered polymorphism data at 157 PCR-amplified loci in 341 individuals sampled in two time periods-historic (1789-1955) vs contemporary (2001-2020).

Results: For all four species, we observed decreases in nucleotide diversity and heterozygosity in contemporary data sets compared to historic data sets. In three species, this loss was accompanied by a corresponding increase in inbreeding coefficient FIS. We find that these genetic diversity declines correspond to declining contemporary effective population sizes (Ne) over deeper time scales, as well as fluctuations in contemporary estimates of Ne.

Conclusion: Our findings suggest that loss of genetic diversity resulting from historic population declines persists over time (50-100 years), even when population trajectories later stabilize. Our results highlight the utility of long-term genetic temporal comparisons to reveal hidden genetic diversity loss and reveal important considerations for managing genetic diversity loss.

背景:在过去的两个世纪里,人为的力量导致了生物多样性的惊人丧失和许多物种的数量下降。与这些下降相关的是与人口规模小有关的潜在不利影响,包括遗传多样性的丧失和近亲繁殖水平的提高。在这里,我们利用博物馆标本的DNA测序来检查历史和当代四种莺(鸟,Setophaga)种群之间的遗传变异,这些种群在这一时期的种群变化程度不同。为了探索不同种群数量下降的遗传影响,我们收集了341个个体在历史(1789-1955)和当代(2001-2020)两个时间段的157个pcr扩增位点的多态性数据。结果:对于所有四个物种,我们观察到与历史数据集相比,当代数据集的核苷酸多样性和杂合性都有所下降。在三个物种中,这种损失伴随着近交系数FIS的相应增加。我们发现,这些遗传多样性的下降对应于当代有效种群规模(Ne)在更深时间尺度上的下降,以及当代Ne估计的波动。结论:我们的研究结果表明,即使种群轨迹后来趋于稳定,由于历史种群数量下降而导致的遗传多样性丧失也会持续一段时间(50-100年)。我们的研究结果强调了长期遗传时间比较的效用,揭示了隐藏的遗传多样性丧失,并揭示了管理遗传多样性丧失的重要考虑因素。
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引用次数: 0
Loss of mitochondrial single stranded DNA-binding protein (mtSSB) gene is associated with mitochondrial genome fragmentation in Psocodea (bark lice, book lice, and parasitic lice). 线粒体单链dna结合蛋白(mtSSB)基因缺失与棘虱(树皮虱、书虱和寄生虱)线粒体基因组断裂有关。
IF 4.5 1区 生物学 Q1 BIOLOGY Pub Date : 2025-12-05 DOI: 10.1186/s12915-025-02479-2
Nan Song, Renfu Shao

Background: Organelle genome fragmentation is a drastic large-scale chromosomal mutation. Why and how organelle genomes become fragmented is still poorly understood. Two previous studies based on whole genome comparison between human louse and fruit fly proposed that the loss of mtSSB gene (for mitochondrial single-stranded DNA-binding protein) might be associated with mitochondrial (mt) genome fragmentation. Whether this association is valid has not been investigated due to the lack of mt genome fragmentation data.

Results: We investigated this association by exploring the genomic and transcriptomic data of 198 species of parasitic lice, book lice, bark lice, and other closely related hemipteroid insects accumulated in the past few decades. We show that the loss of mtSSB gene is correlated significantly with mt genome fragmentation in bark lice, book lice, and parasitic lice (Psocodea). The absence of mtSSB is more frequent than expected in the species with fragmented mt genomes whereas the presence of mtSSB is more frequent than expected in the species with single-chromosome mt genome organization. Nevertheless, our results reject a cause-and-effect relationship between the loss of mtSSB and mt genome fragmentation because mtSSB is present in 11 species of parasitic lice and one book louse species that have fragmented mt genomes.

Conclusions: The loss of mtSSB gene is correlated with mt genome fragmentation but is not the cause of mt genome fragmentation. Rather, it is plausible that fragmented mt genomes with multiple small-sized minichromosomes may make mtSSB gene and mtSSB protein less critical or unnecessary, leading to their loss eventually in the species with fragmented mt genomes.

背景:细胞器基因组断裂是一种剧烈的大规模染色体突变。细胞器基因组为何以及如何变得碎片化仍然知之甚少。先前两项基于人虱和果蝇全基因组比较的研究提出,线粒体单链dna结合蛋白(mtSSB)基因的缺失可能与线粒体(mt)基因组断裂有关。由于缺乏mt基因组片段数据,这种关联是否有效尚未进行调查。结果:通过对近几十年来积累的198种寄生虱、书虱、树皮虱和其他密切相关的半类昆虫的基因组和转录组学数据进行分析,研究了这种关联。我们发现树皮虱、书虱和寄生虱(Psocodea)的mtSSB基因缺失与mtSSB基因组断裂显著相关。mtSSB的缺失在mt基因组片段化的物种中比预期的更频繁,而mtSSB的存在在单染色体mt基因组组织的物种中比预期的更频繁。然而,我们的研究结果拒绝了mtSSB缺失与mt基因组片段化之间的因果关系,因为mtSSB存在于11种寄生虱和一种具有mt基因组片段化的书虱中。结论:mtSSB基因缺失与mt基因组片段化相关,但不是mt基因组片段化的原因。相反,具有多个小尺寸小染色体的碎片化mt基因组可能会使mtSSB基因和mtSSB蛋白变得不那么重要或不必要,从而导致它们最终在具有碎片化mt基因组的物种中丢失。
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引用次数: 0
MCLRP: enhanced prediction of anticancer drug response through low-rank matrix completion and transcriptomic profiling. MCLRP:通过低秩矩阵完成和转录组分析增强抗癌药物反应预测。
IF 4.5 1区 生物学 Q1 BIOLOGY Pub Date : 2025-12-03 DOI: 10.1186/s12915-025-02457-8
Kun Wang, Binhan Li, Miao Xu, Dailin Ding, Qihui Zheng, Geng Tian, Xueying Zeng, Jialiang Yang

Background: Accurate prediction of anticancer drug responses remains a significant challenge due to the intricate interplay between genomic features and pharmacological mechanisms. We present Matrix Completion with Low-rank Regularization and Principal Component Analysis (MCLRP), a multimodal framework that synergistically integrates low-rank matrix completion with transcriptomic principal component analysis through dual-stream feature interaction. This innovative architecture not only leverages the similarities among drugs and mutation patterns in cell lines via matrix completion but also preserves gene-level interpretability of response patterns by incorporating gene expression data into the model.

Results: Benchmarked against seven computational paradigms (including matrix completion, ridge regression, SRMF, and their hybrid variants) across the Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) repositories, MCLRP demonstrated superior predictive performance for 75% of drug responses, alongside enhanced biological plausibility. Notably, the model identified imatinib as a potential therapeutic alternative for M14 melanoma cell lines through cross-drug response extrapolation, suggesting innovative strategies for overcoming doxorubicin resistance. Interestingly, our mutation-response mapping revealed that BRAF-mutated lineages exhibited a 4.7-fold increase in sensitivity (p < 1e-5) to AZ628 compared to wild-type lineages, with synergistic amplification (8.1-fold, p < 1e-7) observed in BRAF/PIK3CA co-mutants.

Conclusions: These findings establish MCLRP as a dual-purpose predictive-analytical tool that not only enhances drug response forecasting but also uncovers mutation-specific pharmacological vulnerabilities through systems-level pattern recognition.

背景:由于基因组特征和药理学机制之间错综复杂的相互作用,准确预测抗癌药物反应仍然是一个重大挑战。我们提出了具有低秩正则化和主成分分析(MCLRP)的矩阵补全,这是一个多模态框架,通过双流特征相互作用协同集成了低秩矩阵补全和转录组主成分分析。这种创新的结构不仅通过基质补全利用了细胞系中药物和突变模式之间的相似性,而且通过将基因表达数据纳入模型,保留了反应模式的基因水平可解释性。结果:针对癌症药物敏感性基因组学(GDSC)和癌症细胞系百科全书(CCLE)知识库中的七种计算范式(包括矩阵补全、脊回归、SRMF及其杂交变体)进行基准测试,MCLRP对75%的药物反应表现出优越的预测性能,同时增强了生物学合理性。值得注意的是,该模型通过跨药物反应外推法确定伊马替尼是M14黑色素瘤细胞系的潜在治疗选择,提出了克服阿霉素耐药的创新策略。有趣的是,我们的突变-反应图谱显示,braf突变谱系的敏感性增加了4.7倍(p)。结论:这些发现确立了MCLRP作为一种双重用途的预测分析工具,不仅可以增强药物反应预测,还可以通过系统级模式识别揭示突变特异性药理学漏洞。
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引用次数: 0
Streptococcus suis avian expansion suggests shared antibiotic use drives host jumps. 猪链球菌在禽类的扩张表明,共同使用抗生素会导致宿主跳跃。
IF 4.5 1区 生物学 Q1 BIOLOGY Pub Date : 2025-12-02 DOI: 10.1186/s12915-025-02477-4
Muriel Dresen, Gemma G R Murray, Peter Valentin-Weigand, Marcus Fulde, Lucy A Weinert

Background: The interconnectedness of human, animal, and environmental health drives emerging threats, such as antimicrobial-resistant pathogens. The widespread use of the same antimicrobials in both human and livestock may play a role in interspecies bacterial transmission by disrupting natural microbial communities and creating an environment favouring resistant bacteria. Pigs and poultry receive high levels of antimicrobials and are reservoirs of multidrug-resistant bacteria, including Streptococcus suis, a zoonotic pig pathogen. S. suis detection in non-porcine hosts, particularly poultry, raises a critical question: is this due to transient spillover or does it represent sustained host jumps and adaptation?

Results: Analysing over 3000 S. suis genomes from a diverse range of hosts-including pigs, wild boar, humans, cats, dogs, cattle, fish, otter, and birds-we identify a multidrug-resistant lineage, distinct from the lineage responsible for most zoonoses, that has undergone multiple host jump events into birds. Unlike transmission to humans, which is exclusively derived through contacts with pigs, we find evidence of S. suis adaptation to birds. This includes phylogenetic persistence, independent acquisition of bird-specific mobile genomic islands, enhanced survival in chicken versus pig blood, and subsequent transmission from poultry to wild birds.

Conclusions: While chickens may not be a source of zoonotic S. suis infections, shared antibiotic usage in pigs and poultry may have promoted host jumps of multidrug-resistant S. suis, leading to onward transmission to wild bird populations. Our results suggest that antibiotic use in livestock production may promote transmission of antimicrobial-resistant bacteria to other hosts, thereby expanding the ecological range of bacterial pathogens.

背景:人类、动物和环境健康的相互联系推动了新出现的威胁,如耐药病原体。在人类和牲畜中广泛使用相同的抗菌剂可能通过破坏天然微生物群落和创造有利于耐药细菌的环境,在种间细菌传播中发挥作用。猪和家禽接受高水平的抗菌素,是多重耐药细菌的宿主,包括猪链球菌,一种人畜共患的猪病原体。猪链球菌在非猪宿主,特别是家禽中的检测,提出了一个关键问题:这是由于短暂的溢出,还是代表了持续的宿主跳跃和适应?结果:分析了来自不同宿主(包括猪、野猪、人类、猫、狗、牛、鱼、水獭和鸟类)的3000多个猪链球菌基因组,我们确定了一个多重耐药谱系,不同于大多数人畜共患病的谱系,它经历了多次宿主跳到鸟类的事件。与人类的传播完全是通过与猪的接触而获得的不同,我们发现了猪链球菌对鸟类适应的证据。这包括系统发育持久性、鸟类特异性移动基因组岛的独立获得、鸡血与猪血中存活率的提高,以及随后从家禽向野生鸟类的传播。结论:虽然鸡可能不是人畜共患猪链球菌感染的来源,但猪和家禽共同使用抗生素可能促进了多重耐药猪链球菌的宿主跳跃,从而导致野生鸟类种群的进一步传播。我们的研究结果表明,在畜牧生产中使用抗生素可能会促进耐药细菌向其他宿主的传播,从而扩大细菌病原体的生态范围。
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引用次数: 0
Kelch-type F-box protein TaFBK34 improves wheat seedling tolerance to heat stress. kelch型F-box蛋白TaFBK34提高小麦幼苗耐热性。
IF 4.5 1区 生物学 Q1 BIOLOGY Pub Date : 2025-12-02 DOI: 10.1186/s12915-025-02475-6
Jinbing Yang, Chunru Wei, Yiming Yang, Xinyan Wei, Yifan Huang, Zhiruo Han, Nora A Foroud, Xiaodong Wang, Weiquan Zhao, Shijuan Dou, Xiumei Yu

Background: Based on the climate change and more extreme temperature events in the past 30 years, heat stress (HS) has become one of the most detrimental abiotic stresses that affect crop growth and development, limit their geographical distribution, and reduce yield. As a typical chimonophilous crop, wheat is very sensitive to high temperature. Deciphering the molecular mechanism of the wheat response to high temperature will help in the development of cultivars that perform better under HS.

Results: In this study, we identified a wheat Kelch-type F-box gene, TaFBK34. Overexpression of TaFBK34 wheat plants (TaFBK34-OE) showed stronger heat tolerance compared to the wild type, while plants with attenuated TaFBK34 (TaFBK34-RNAi) exhibited the phenotype of heat sensitivity. Increased expression of antioxidant-related genes and a heat-shock protein gene was observed in TaFBK34-OE plants compared with the wild type, coinciding with higher activities of the antioxidant enzymes, accumulation of proline and soluble sugar, reduced malondialdehyde and reactive oxygen species content. The opposite trends were observed in TaFBK34-RNAi lines. TaFBK34 interacts with the ADP-ribosylation factor, TaARL2. Compared to the wild type, more TaARL2 protein accumulated in TaFBK34-RNAi lines after HS treatment; moreover, TaARL2 continued to increase after MG132 (a proteasome inhibitor) injection for 12 h + 37 °C for 12 h, indicating that TaARL2 is involved in the response to HS and is degraded by the 26S proteasome.

Conclusions: These findings show that TaFBK34 improves wheat tolerance to HS, at least in part through an interaction with the TaARL2 protein, and provides potential applications of these genes for the improvement of wheat.

背景:在近30年气候变化和极端温度事件频发的背景下,热胁迫(HS)已成为影响作物生长发育、限制作物地理分布、降低作物产量的最有害的非生物胁迫之一。小麦作为典型的嗜温作物,对高温非常敏感。破解小麦对高温响应的分子机制,将有助于培育高温条件下表现更好的品种。结果:本研究鉴定了一个小麦kelch型F-box基因TaFBK34。过表达TaFBK34的小麦植株(TaFBK34- oe)表现出比野生型更强的耐热性,而TaFBK34- rnai弱表达植株表现出热敏表型。与野生型相比,TaFBK34-OE植株抗氧化相关基因和一个热休克蛋白基因的表达增加,同时抗氧化酶活性提高,脯氨酸和可溶性糖积累增加,丙二醛和活性氧含量降低。在TaFBK34-RNAi系中观察到相反的趋势。TaFBK34与adp核糖化因子TaARL2相互作用。与野生型相比,HS处理后TaFBK34-RNAi细胞系中积累了更多的TaARL2蛋白;此外,在注射蛋白酶体抑制剂MG132 12 h + 37°C 12 h后,TaARL2继续增加,表明TaARL2参与了对HS的应答,并被26S蛋白酶体降解。结论:这些发现表明,TaFBK34至少在一定程度上通过与TaARL2蛋白的相互作用提高了小麦对HS的耐受性,并为这些基因在小麦改良中的潜在应用提供了可能。
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引用次数: 0
Staphylococcus aureus-induced degeneration of nociceptive neurons in Caenorhabditis elegans. 金黄色葡萄球菌诱导的秀丽隐杆线虫痛觉神经元变性。
IF 4.5 1区 生物学 Q1 BIOLOGY Pub Date : 2025-12-02 DOI: 10.1186/s12915-025-02470-x
Elizabeth M DiLoreto, Xavier Gonzalez, Khursheed A Wani, Jiali Shen, Javier E Irazoqui, Jagan Srinivasan

Background: The nervous system senses microbial signals to influence host defense. Pain-sensing nociceptor neurons are key regulators of the host response to infection, but how they perceive infections is not well understood. Using Caenorhabditis elegans as a tractable model host that shares many features with mammalian systems, we investigated the effects of infection on nociceptor function in vivo.

Results: In vivo intracellular Ca2+ imaging of C. elegans nociceptor ASH neurons revealed a drastic reduction in ASH responses to aversive stimuli in Staphylococcus aureus-infected animals compared to noninfected controls. Morphological examination revealed that ASH neurons lost integrity in the sensory processes reaching the mouth. Neighboring neurons did not show this pathogen-induced neurite pathology (PaIN) phenotype. During acute pathogen exposure, ASH neurons experience Ca2⁺ suppression. Genetic analysis indicated that apoptosis, necrosis, ferroptosis, and autophagy are not essential for the PaIN phenotype. Conversely, loss of the evolutionarily conserved stress-response transcription factor HLH-30/TFEB decreased the penetrance of ASH PaIN by approximately 50%. Additionally, infected animals exhibited defective ASH-mediated evasive behaviors, suggesting that the S. aureus-triggered reduction in ASH activation and morphological degeneration is physiologically relevant.

Conclusions: S. aureus damages nociceptor integrity in C. elegans: ASH neurons experience acute Ca2⁺ suppression-most pronounced with stationary-phase cultures-and extended exposure leads to structural damage and decreased avoidance behavior. This connection between pathogen physiology and circuit failure suggests that infection-evoked nociceptor PaIN may contribute to sensory dysfunction, highlighting the need to identify the responsible bacterial factor(s) and their host targets.

背景:神经系统感知微生物信号影响宿主防御。痛觉伤害感受器神经元是宿主对感染反应的关键调节器,但它们如何感知感染尚不清楚。我们以秀丽隐杆线虫为模型宿主,研究了感染对体内伤害感受器功能的影响。结果:秀丽隐杆线虫伤害感受器ASH神经元的体内细胞内Ca2+成像显示,与未感染的对照相比,金黄色葡萄球菌感染动物的ASH对厌恶刺激的反应急剧减少。形态学检查显示,在到达口腔的感觉过程中,ASH神经元失去了完整性。邻近的神经元没有表现出这种病原体诱导的神经突病理(PaIN)表型。在急性病原体暴露期间,ASH神经元经历Ca2 +抑制。遗传分析表明,细胞凋亡、坏死、铁下垂和自噬不是PaIN表型所必需的。相反,进化上保守的应激反应转录因子HLH-30/TFEB的缺失使ASH疼痛的外显率降低了约50%。此外,感染动物表现出有缺陷的ASH介导的逃避行为,这表明金黄色葡萄球菌引发的ASH激活减少和形态退化与生理相关。结论:金黄色葡萄球菌损害秀丽隐杆线虫伤害受体的完整性:ASH神经元经历急性Ca2 +抑制——在静止期培养中最为明显——长时间暴露导致结构损伤和回避行为减少。病原体生理学和电路失效之间的这种联系表明,感染诱发的伤害感受器PaIN可能导致感觉功能障碍,强调需要确定负责的细菌因子及其宿主靶点。
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引用次数: 0
Gut dysbiosis leads to cognitive decline through CNTF-mediated activation of microglia in mice. 肠道生态失调通过cntf介导的小胶质细胞激活导致小鼠认知能力下降。
IF 4.5 1区 生物学 Q1 BIOLOGY Pub Date : 2025-12-01 DOI: 10.1186/s12915-025-02454-x
Krishnapriya, Rishikesh, Dayamrita Kollaparampil Kishanchand, Isabell Haack, Shirin Hosseini, Ayswaria Deepti, Tara Sudhadevi, Kristin Michaelsen-Preusse, Unnikrishnan Sivan, Martin Korte, Baby Chakrapani Pulikkaparambil Sasidharan

Background: The gut microbiota is essential for maintaining host homeostasis through its influence on metabolism, immunity, and neural signalling. Disruption of this microbial balance, known as gut dysbiosis, can alter gut-brain communication and has been associated with cognitive decline, with impairments in learning and memory. However, the cellular and molecular factors that lead to cognitive decline are not well understood. In this study we used an antibiotic-induced gut dysbiosis model.

Results: We observed that the animals with antibiotic-induced gut dysbiosis showed deficits in cognition, especially long-term memory consolidation. There was an increase in astrocytes and microglial activation in the CA1 subregion of the hippocampus. The microglia were observed to engage in synaptic pruning at the presynaptic terminals. This aberrant pruning might have disrupted synaptic plasticity and connectivity, contributing to the observed cognitive deficiency. CNTF was also observed to be elevated along with activation of the JAK/STAT3 pathway. CNTF can activate microglia. Our findings revealed that astrocytes, microglia, and CNTF form an inflammatory activation loop within the CA1 region of the hippocampus following antibiotic-induced gut dysbiosis.

Conclusions: In summary, our study demonstrates that antibiotic-induced gut dysbiosis triggers a cascade of neuroinflammatory events in the hippocampus, involving the elevation of CNTF, microglial pruning at presynaptic terminals, and reciprocal activation of glial cells, resulting in cognitive deficits. These findings highlight the critical role of gut-brain communication in maintaining neural homeostasis and identify CNTF as a potential therapeutic target for dysbiosis-associated cognitive disorders.

背景:肠道菌群通过影响代谢、免疫和神经信号传导对维持宿主体内平衡至关重要。这种微生物平衡的破坏被称为肠道生态失调,可以改变肠-脑沟通,并与认知能力下降、学习和记忆障碍有关。然而,导致认知能力下降的细胞和分子因素尚不清楚。在这项研究中,我们使用了抗生素诱导的肠道生态失调模型。结果:我们观察到抗生素引起的肠道失调的动物表现出认知缺陷,特别是长期记忆巩固。海马CA1亚区星形胶质细胞和小胶质细胞活化增加。观察到小胶质细胞参与突触前末端的突触修剪。这种异常的修剪可能破坏了突触的可塑性和连通性,导致了观察到的认知缺陷。CNTF也被观察到随着JAK/STAT3通路的激活而升高。CNTF可以激活小胶质细胞。我们的研究结果显示,星形胶质细胞、小胶质细胞和CNTF在抗生素诱导的肠道生态失调后,在海马的CA1区域形成炎症激活环。结论:总之,我们的研究表明,抗生素诱导的肠道生态失调引发了海马体的一系列神经炎症事件,包括CNTF的升高、突触前末端的小胶质细胞修剪和胶质细胞的相互激活,从而导致认知缺陷。这些发现强调了肠-脑通讯在维持神经稳态中的关键作用,并确定了CNTF作为生态失调相关认知障碍的潜在治疗靶点。
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