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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。
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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}
引用次数: 0
Seasonal stability of the rumen microbiome contributes to the adaptation patterns to extreme environmental conditions in grazing yak and cattle. 瘤胃微生物群的季节稳定性有助于放牧牦牛和牛对极端环境条件的适应模式。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-23 DOI: 10.1186/s12915-024-02035-4
Wei Guo, Mi Zhou, Fuyong Li, André Luis Alves Neves, Tao Ma, Sisi Bi, Weiwei Wang, Ruijun Long, Le Luo Guan

Background: The rumen microbiome plays an essential role in maintaining ruminants' growth and performance even under extreme environmental conditions, however, which factors influence rumen microbiome stability when ruminants are reared in such habitats throughout the year is unclear. Hence, the rumen microbiome of yak (less domesticated) and cattle (domesticated) reared on the Qinghai-Tibetan Plateau through the year were assessed to evaluate temporal changes in their composition, function, and stability.

Results: Rumen fermentation characteristics and pH significantly shifted across seasons in both cattle and yak, but the patterns differed between the two ruminant species. Ruminal enzyme activity varied with season, and production of xylanase and cellulase was greater in yak compared to cattle in both fall and winter. The rumen bacterial community varied with season in both yak and cattle, with higher alpha diversity and similarity (beta diversity) in yak than cattle. The diversity indices of eukaryotic community did not change with season in both ruminant species, but higher similarity was observed in yak. In addition, the similarity of rumen microbiome functional community was higher in yak than cattle across seasons. Moreover, yak rumen microbiome encoded more genes (GH2 and GH3) related to cellulose and hemicellulose degradation compared to cattle, and a new enzyme family (GH160) gene involved in oligosaccharides was uniquely detected in yak rumen. The season affected microbiome attenuation and buffering values (stability), with higher buffering value in yak rumen microbiome than cattle. Positive correlations between antimicrobial resistance gene (dfrF) and CAZyme family (GH113) and microbiome stability were identified in yak, but such relationship was negatively correlated in cattle.

Conclusions: The findings of the potential of cellulose degradation, the relationship between rumen microbial stability and the abundance of functional genes varied differently across seasons and between yak and cattle provide insight into the mechanisms that may underpin their divergent adaptation patterns to the harsh climate of the Qinghai-Tibetan Plateau. These results lay a solid foundation for developing strategies to maintain and improve rumen microbiome stability and dig out the potential candidates for manufacturing lignocellulolytic enzymes in the yak rumen to enhance ruminants' performance under extreme environmental conditions.

背景:即使在极端的环境条件下,瘤胃微生物组在维持反刍动物的生长和性能方面也起着至关重要的作用,然而,当反刍动物全年饲养在这样的生境中时,哪些因素会影响瘤胃微生物组的稳定性尚不清楚。因此,我们对在青藏高原全年饲养的牦牛(驯化程度较低)和牛(驯化)的瘤胃微生物组进行了评估,以评价其组成、功能和稳定性的时间变化:结果:牛和牦牛的瘤胃发酵特性和pH值在不同季节有显著变化,但两种反刍动物的变化模式不同。瘤胃酶的活性随季节而变化,秋季和冬季牦牛的木聚糖酶和纤维素酶的产量均高于牛。牦牛和牛的瘤胃细菌群落随季节而变化,牦牛的α多样性和相似性(β多样性)高于牛。两种反刍动物真核生物群落的多样性指数均未随季节变化,但牦牛的相似性更高。此外,不同季节牦牛瘤胃微生物群功能群落的相似性也高于牛。此外,与牛相比,牦牛瘤胃微生物组编码了更多与纤维素和半纤维素降解相关的基因(GH2 和 GH3),并且在牦牛瘤胃中独特地检测到了一个参与低聚糖的新酶家族(GH160)基因。季节影响微生物群的衰减和缓冲值(稳定性),牦牛瘤胃微生物群的缓冲值高于牛。牦牛的抗菌药耐药性基因(dfrF)和CAZyme家族(GH113)与微生物组稳定性呈正相关,而牛则呈负相关:纤维素降解的潜力、瘤胃微生物稳定性之间的关系以及功能基因的丰度在不同季节以及牦牛和牛之间存在差异,这些研究结果有助于深入了解牦牛和牛对青藏高原恶劣气候的不同适应模式的机制。这些结果为制定维持和改善瘤胃微生物组稳定性的策略奠定了坚实的基础,并挖掘出在牦牛瘤胃中制造木质纤维素分解酶的潜在候选者,以提高反刍动物在极端环境条件下的表现。
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引用次数: 0
Independent, but still observant-dog breeds selected for functional independence learn better from a conspecific demonstrator than cooperative breeds in a detour task. 在迂回任务中,独立但仍善于观察的犬种比合作犬种能更好地从同种示范者身上学习。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-23 DOI: 10.1186/s12915-024-02046-1
Csenge Anna Lugosi, Kata Mária Udvarhelyi-Tóth, Petra Dobos, Péter Pongrácz

Background: While complex dog-human coexistence has been deeply investigated, there is a relative scarcity of similar knowledge regarding dog-dog interactions. Social learning, a fundamental synchronizing mechanism between dogs and humans, was recently found to be influenced by the functional breed selection of dogs: with the cooperative breeds being more effective learners from a human demonstrator than the independent working breeds were. Here, we investigated whether these differences would also be present when dogs had to learn from another dog and how to effectively perform a detour around a transparent V-shaped obstacle. We tested dogs from 28 independent and 19 cooperative breeds in three consecutive trials. In the control groups, all dogs had to detour on their own the obstacle. In the dog demonstration groups, in trial 1, the subjects had to detour on their own, but before the next two trials, a trained dog showed them the solution.

Results: We found that the performance of the two breed groups was the same in the without demonstration groups. However, after observing the dog demonstrator, the independent dogs learned the task more successfully than the cooperative breeds did. In the case of the independent working breeds, detour latencies significantly dropped along the consecutive trials, and these dogs also showed higher rate of successful detours after observing the demonstrator dog's action than in the control group.

Conclusions: This is the first study where the consequences of functional breed selection were confirmed in a scenario that involved conspecific social learning in dogs. The results fit well to the ecologically valid framework of the evolutionary past of dog breed formation, in which cooperative breeds were selected for their interactivity with humans, whereas independent breeds often had to work together with their conspecifics.

背景:虽然对复杂的狗与人的共存问题进行了深入研究,但关于狗与狗之间互动的类似知识却相对匮乏。社会学习是狗与人类之间的一种基本同步机制,最近发现它受到狗的功能性品种选择的影响:与独立工作的品种相比,合作性品种更能有效地向人类示范者学习。在此,我们研究了当狗需要向另一只狗学习如何有效地绕过透明的 V 形障碍物时,这些差异是否也会出现。我们对来自 28 个独立犬种和 19 个合作犬种的犬进行了连续三次试验。在对照组中,所有狗都必须自己绕过障碍物。在狗示范组中,在第 1 次试验中,受试者必须自行绕行,但在接下来的两次试验之前,一只训练有素的狗会向他们展示解决方案:我们发现,在无示范组中,两个犬种组的表现相同。然而,在观察了狗示范员之后,独立犬比合作犬更成功地学会了任务。在独立工作犬种的情况下,迂回潜伏期在连续试验中明显下降,这些犬在观察示范犬的动作后,迂回成功率也高于对照组:这是首次在狗的同种社会学习情景中证实功能性品种选择后果的研究。研究结果非常符合狗种形成进化史的生态学框架,在这个框架中,合作型狗种因其与人类的互动性而被选育出来,而独立型狗种则经常需要与同类一起工作。
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引用次数: 0
SETDB1 targeting SESN2 regulates mitochondrial damage and oxidative stress in renal ischemia-reperfusion injury. SETDB1靶向SESN2调节肾缺血再灌注损伤中的线粒体损伤和氧化应激。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-23 DOI: 10.1186/s12915-024-02048-z
Kang Xia, Yumin Hui, Long Zhang, Qiangmin Qiu, Jiacheng Zhong, Hui Chen, Xiuheng Liu, Lei Wang, Zhiyuan Chen

Background: The role of histone methyltransferase SETDB1 in renal ischemia-reperfusion (I/R) injury has not been explored yet. This study aims to investigate the potential mechanism of SETDB1 in regulating renal I/R injury and its impact on mitochondrial damage and oxidative stress.

Methods: The in vivo model of renal I/R in mice and the in vitro model of hypoxia/reoxygenation (H/R) in human renal tubular epithelial cells (HK-2) were constructed to detect the expression of SETDB1. Next, the specific inhibitor (R,R)-59 and knockdown viruses were used to inhibit SETDB1 and verify its effects on mitochondrial damage and oxidative stress. Chromatin immunoprecipitation (ChIP) and coimmunoprecipitation (CoIP) were implemented to explore the in-depth mechanism of SETDB1 regulating renal I/R injury.

Results: The study found that SETDB1 had a regulatory role in mitochondrial damage and oxidative stress during renal I/R injury. Notably, SESN2 was identified as a target of SETDB1, and its expression was under the influence of SETDB1. Besides, SESN2 mediated the regulation of SETDB1 on renal I/R injury. Through deeper mechanistic studies, we uncovered that SETDB1 collaborates with heterochromatin HP1β, facilitating the labeling of H3K9me3 on the SESN2 promoter and impeding SESN2 expression.

Conclusions: The SETDB1/HP1β-SESN2 axis emerges as a potential therapeutic strategy for mitigating renal I/R injury.

背景:组蛋白甲基转移酶SETDB1在肾缺血再灌注(I/R)损伤中的作用尚未探明。本研究旨在探讨 SETDB1 调节肾脏 I/R 损伤的潜在机制及其对线粒体损伤和氧化应激的影响:方法:构建小鼠肾脏 I/R 体内模型和人肾小管上皮细胞(HK-2)缺氧/再缺氧(H/R)体外模型,检测 SETDB1 的表达。接着,使用特异性抑制剂(R,R)-59 和基因敲除病毒抑制 SETDB1,并验证其对线粒体损伤和氧化应激的影响。通过染色质免疫沉淀(ChIP)和共免疫沉淀(CoIP),深入探讨了SETDB1调控肾脏I/R损伤的机制:结果:研究发现,SETDB1在肾脏I/R损伤过程中对线粒体损伤和氧化应激具有调控作用。值得注意的是,SESN2 被确定为 SETDB1 的靶标,且其表达受 SETDB1 的影响。此外,SESN2还介导了SETDB1对肾脏I/R损伤的调控。通过更深入的机理研究,我们发现SETDB1与异染色质HP1β合作,促进了SESN2启动子上H3K9me3的标记,阻碍了SESN2的表达:SETDB1/HP1β-SESN2轴是减轻肾脏I/R损伤的潜在治疗策略。
{"title":"SETDB1 targeting SESN2 regulates mitochondrial damage and oxidative stress in renal ischemia-reperfusion injury.","authors":"Kang Xia, Yumin Hui, Long Zhang, Qiangmin Qiu, Jiacheng Zhong, Hui Chen, Xiuheng Liu, Lei Wang, Zhiyuan Chen","doi":"10.1186/s12915-024-02048-z","DOIUrl":"10.1186/s12915-024-02048-z","url":null,"abstract":"<p><strong>Background: </strong>The role of histone methyltransferase SETDB1 in renal ischemia-reperfusion (I/R) injury has not been explored yet. This study aims to investigate the potential mechanism of SETDB1 in regulating renal I/R injury and its impact on mitochondrial damage and oxidative stress.</p><p><strong>Methods: </strong>The in vivo model of renal I/R in mice and the in vitro model of hypoxia/reoxygenation (H/R) in human renal tubular epithelial cells (HK-2) were constructed to detect the expression of SETDB1. Next, the specific inhibitor (R,R)-59 and knockdown viruses were used to inhibit SETDB1 and verify its effects on mitochondrial damage and oxidative stress. Chromatin immunoprecipitation (ChIP) and coimmunoprecipitation (CoIP) were implemented to explore the in-depth mechanism of SETDB1 regulating renal I/R injury.</p><p><strong>Results: </strong>The study found that SETDB1 had a regulatory role in mitochondrial damage and oxidative stress during renal I/R injury. Notably, SESN2 was identified as a target of SETDB1, and its expression was under the influence of SETDB1. Besides, SESN2 mediated the regulation of SETDB1 on renal I/R injury. Through deeper mechanistic studies, we uncovered that SETDB1 collaborates with heterochromatin HP1β, facilitating the labeling of H3K9me3 on the SESN2 promoter and impeding SESN2 expression.</p><p><strong>Conclusions: </strong>The SETDB1/HP1β-SESN2 axis emerges as a potential therapeutic strategy for mitigating renal I/R injury.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"246"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495494","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
MdSVWC1, a new pattern recognition receptor triggers multiple defense mechanisms against invading bacteria in Musca domestica. MdSVWC1是一种新的模式识别受体,它能触发多种防御机制,抵御家蝇细菌的入侵。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-23 DOI: 10.1186/s12915-024-02042-5
Ting Tang, Siyu Sun, Ruirui Wang, Mengnan Li, Yongpeng Wang, Feifei Li, Yun Wang, Fengsong Liu

Background: Single-domain von Willebrand factor type C (SVWC) constitute a protein family predominantly identified in arthropods, characterized by a SVWC domain and involved in diverse physiological processes such as host defense, stress resistance, and nutrient metabolism. Nevertheless, the physiological mechanisms underlying these functions remain inadequately comprehended.

Results: A massive expansion of the SVWC gene family in Musca domestica (MdSVWC) was discovered, with a count of 35. MdSVWC1 was selected as the representative of the SVWC family for functional analysis, which led to the identification of the immune function of MdSVWC1 as a novel pattern recognition receptor. MdSVWC1 is highly expressed in both the fat body and intestines and displays acute induction upon bacterial infection. Recombinant MdSVWC1 binds to surfaces of both bacteria and yeast through the recognition of multiple pathogen-associated molecular patterns and exhibits Ca2+-dependent agglutination activity. MdSVWC1 mutant flies exhibited elevated mortality and hindered bacterial elimination following bacterial infection as a result of reduced hemocyte phagocytic capability and weakened expression of antimicrobial peptide (AMP) genes. In contrast, administration of recombinant MdSVWC1 provided protection to flies from bacterial challenges by promoting phagocytosis and AMP genes expression, thereby preventing bacterial colonization. MdSPN16, a serine protease inhibitor, was identified as a target protein of MdSVWC1. It was postulated that the interaction of MdSVWC1 with MdSPN16 would result in the activation of an extracellular proteolytic cascade, which would then initiate the Toll signaling pathway and facilitate the expression of AMP genes.

Conclusions: MdSVWC1 displays activity as a soluble pattern recognition receptor that regulates cellular and humoral immunity by recognizing microbial components and facilitating host defense.

背景:单结构域von Willebrand因子C型(SVWC)是主要在节肢动物中发现的一个蛋白家族,以SVWC结构域为特征,参与宿主防御、抗应激和营养代谢等多种生理过程。然而,这些功能背后的生理机制仍未得到充分理解:结果:在家蚕中发现了一个大规模扩展的 SVWC 基因家族(MdSVWC),共有 35 个。结果:研究人员发现了家麝中一个大规模扩展的 SVWC 基因家族(MdSVWC),共有 35 个,并选择 MdSVWC1 作为 SVWC 家族的代表进行功能分析,从而确定了 MdSVWC1 作为新型模式识别受体的免疫功能。MdSVWC1 在脂肪体和肠道中高度表达,并在细菌感染时显示出急性诱导。重组 MdSVWC1 可通过识别多种病原体相关分子模式与细菌和酵母表面结合,并表现出 Ca2+ 依赖性凝集活性。MdSVWC1 突变体苍蝇在细菌感染后死亡率升高,细菌清除受阻,这是由于血细胞吞噬能力降低和抗菌肽(AMP)基因表达减弱所致。与此相反,重组 MdSVWC1 通过促进吞噬作用和 AMP 基因的表达,从而防止细菌定植,保护苍蝇免受细菌挑战。研究发现,丝氨酸蛋白酶抑制剂 MdSPN16 是 MdSVWC1 的靶蛋白。据推测,MdSVWC1 与 MdSPN16 的相互作用将导致细胞外蛋白水解级联的激活,进而启动 Toll 信号通路,促进 AMP 基因的表达:结论:MdSVWC1 具有可溶性模式识别受体的活性,可通过识别微生物成分和促进宿主防御来调节细胞和体液免疫。
{"title":"MdSVWC1, a new pattern recognition receptor triggers multiple defense mechanisms against invading bacteria in Musca domestica.","authors":"Ting Tang, Siyu Sun, Ruirui Wang, Mengnan Li, Yongpeng Wang, Feifei Li, Yun Wang, Fengsong Liu","doi":"10.1186/s12915-024-02042-5","DOIUrl":"10.1186/s12915-024-02042-5","url":null,"abstract":"<p><strong>Background: </strong>Single-domain von Willebrand factor type C (SVWC) constitute a protein family predominantly identified in arthropods, characterized by a SVWC domain and involved in diverse physiological processes such as host defense, stress resistance, and nutrient metabolism. Nevertheless, the physiological mechanisms underlying these functions remain inadequately comprehended.</p><p><strong>Results: </strong>A massive expansion of the SVWC gene family in Musca domestica (MdSVWC) was discovered, with a count of 35. MdSVWC1 was selected as the representative of the SVWC family for functional analysis, which led to the identification of the immune function of MdSVWC1 as a novel pattern recognition receptor. MdSVWC1 is highly expressed in both the fat body and intestines and displays acute induction upon bacterial infection. Recombinant MdSVWC1 binds to surfaces of both bacteria and yeast through the recognition of multiple pathogen-associated molecular patterns and exhibits Ca<sup>2+</sup>-dependent agglutination activity. MdSVWC1 mutant flies exhibited elevated mortality and hindered bacterial elimination following bacterial infection as a result of reduced hemocyte phagocytic capability and weakened expression of antimicrobial peptide (AMP) genes. In contrast, administration of recombinant MdSVWC1 provided protection to flies from bacterial challenges by promoting phagocytosis and AMP genes expression, thereby preventing bacterial colonization. MdSPN16, a serine protease inhibitor, was identified as a target protein of MdSVWC1. It was postulated that the interaction of MdSVWC1 with MdSPN16 would result in the activation of an extracellular proteolytic cascade, which would then initiate the Toll signaling pathway and facilitate the expression of AMP genes.</p><p><strong>Conclusions: </strong>MdSVWC1 displays activity as a soluble pattern recognition receptor that regulates cellular and humoral immunity by recognizing microbial components and facilitating host defense.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"242"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495491","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
Molecular mechanisms underlying the neural correlates of working memory. 工作记忆神经相关性的分子机制。
IF 4.4 1区 生物学 Q1 BIOLOGY Pub Date : 2024-10-21 DOI: 10.1186/s12915-024-02039-0
Xiaotao Xu, Han Zhao, Yu Song, Huanhuan Cai, Wenming Zhao, Jin Tang, Jiajia Zhu, Yongqiang Yu

Background: Working memory (WM), a core component of executive functions, relies on a dedicated brain system that maintains and stores information in the short term. While extensive neuroimaging research has identified a distributed set of neural substrates relevant to WM, their underlying molecular mechanisms remain enigmatic. This study investigated the neural correlates of WM as well as their underlying molecular mechanisms.

Results: Our voxel-wise analyses of resting-state functional MRI data from 502 healthy young adults showed that better WM performance (higher accuracy and shorter reaction time of the 3-back task) was associated with lower functional connectivity density (FCD) in the left inferior temporal gyrus and higher FCD in the left anterior cingulate cortex. A combination of transcriptome-neuroimaging spatial correlation and the ensemble-based gene category enrichment analysis revealed that the identified neural correlates of WM were associated with expression of diverse gene categories involving important cortical components and their biological processes as well as sodium channels. Cross-region spatial correlation analyses demonstrated significant associations between the neural correlates of WM and a range of neurotransmitters including dopamine, glutamate, serotonin, and acetylcholine.

Conclusions: These findings may help to shed light on the molecular mechanisms underlying the neural correlates of WM.

背景:工作记忆(WM)是执行功能的核心组成部分,它依赖于一个专门的大脑系统来维持和存储短期信息。虽然广泛的神经影像学研究已经发现了一系列与工作记忆相关的分布式神经基底,但其潜在的分子机制仍然是个谜。本研究调查了 WM 的神经相关性及其潜在的分子机制:结果:我们对 502 名健康年轻人的静息态功能磁共振成像数据进行了体素分析,结果表明,更好的 WM 表现(更高的准确率和更短的 3 回任务反应时间)与左侧颞下回较低的功能连接密度(FCD)和左侧扣带回前皮层较高的功能连接密度有关。结合转录组-神经影像空间相关性和基于集合的基因类别富集分析发现,已确定的 WM 神经相关性与涉及重要皮层成分及其生物过程以及钠通道的不同基因类别的表达有关。跨区域空间相关性分析表明,WM 的神经相关因素与一系列神经递质(包括多巴胺、谷氨酸、5-羟色胺和乙酰胆碱)之间存在显著关联:这些发现可能有助于揭示 WM 神经相关性的分子机制。
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引用次数: 0
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