Pub Date : 2024-10-29DOI: 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.
{"title":"Bridging chemical structure and conceptual knowledge enables accurate prediction of compound-protein interaction.","authors":"Wen Tao, Xuan Lin, Yuansheng Liu, Li Zeng, Tengfei Ma, Ning Cheng, Jing Jiang, Xiangxiang Zeng, Sisi Yuan","doi":"10.1186/s12915-024-02049-y","DOIUrl":"10.1186/s12915-024-02049-y","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Overall, our work provides a general approach for directly injecting conceptual knowledge to enhance the performance of CPI prediction.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"248"},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521059","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}
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.
{"title":"Hoxa5 alleviates adipose tissue metabolic distortions in high-fat diet mice associated with a reduction in MERC.","authors":"Qi Chen, Zeyu Ren, Liping Dang, Zunhai Liu, Simeng Wang, Xinhao Chen, Guiping Qiu, Chao Sun","doi":"10.1186/s12915-024-02047-0","DOIUrl":"10.1186/s12915-024-02047-0","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"247"},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521061","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}
Pub Date : 2024-10-23DOI: 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.
{"title":"Thymosin β4 promotes zebrafish Mauthner axon regeneration by facilitating actin polymerization through binding to G-actin.","authors":"Zheng Song, Along Han, Bing Hu","doi":"10.1186/s12915-024-02045-2","DOIUrl":"10.1186/s12915-024-02045-2","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"244"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495505","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}
Pub Date : 2024-10-23DOI: 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.
{"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}
Pub Date : 2024-10-23DOI: 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.
{"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}
Pub Date : 2024-10-23DOI: 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.
{"title":"Seasonal stability of the rumen microbiome contributes to the adaptation patterns to extreme environmental conditions in grazing yak and cattle.","authors":"Wei Guo, Mi Zhou, Fuyong Li, André Luis Alves Neves, Tao Ma, Sisi Bi, Weiwei Wang, Ruijun Long, Le Luo Guan","doi":"10.1186/s12915-024-02035-4","DOIUrl":"10.1186/s12915-024-02035-4","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"240"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495493","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}
Pub Date : 2024-10-23DOI: 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。
{"title":"Independent, but still observant-dog breeds selected for functional independence learn better from a conspecific demonstrator than cooperative breeds in a detour task.","authors":"Csenge Anna Lugosi, Kata Mária Udvarhelyi-Tóth, Petra Dobos, Péter Pongrácz","doi":"10.1186/s12915-024-02046-1","DOIUrl":"10.1186/s12915-024-02046-1","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"245"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495490","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}
Pub Date : 2024-10-23DOI: 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.
{"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}
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.
{"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}
Pub Date : 2024-10-21DOI: 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.
{"title":"Molecular mechanisms underlying the neural correlates of working memory.","authors":"Xiaotao Xu, Han Zhao, Yu Song, Huanhuan Cai, Wenming Zhao, Jin Tang, Jiajia Zhu, Yongqiang Yu","doi":"10.1186/s12915-024-02039-0","DOIUrl":"10.1186/s12915-024-02039-0","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>These findings may help to shed light on the molecular mechanisms underlying the neural correlates of WM.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"238"},"PeriodicalIF":4.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458570","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}