IF 6.4 1区生物学

eLife Pub Date : 2025-01-17 DOI: 10.7554/eLife.102440

Svanhild Nornes, Susann Bruche, Niharika Adak, Ian R McCracken, Sarah De Val

{"title":"Evaluating the transcriptional regulators of arterial gene expression via a catalogue of characterized arterial enhancers.","authors":"Svanhild Nornes, Susann Bruche, Niharika Adak, Ian R McCracken, Sarah De Val","doi":"10.7554/eLife.102440","DOIUrl":"https://doi.org/10.7554/eLife.102440","url":null,"abstract":"The establishment and growth of the arterial endothelium requires the coordinated expression of numerous genes. However, regulation of this process is not yet fully understood. Here, we combined in silico analysis with transgenic mice and zebrafish models to characterize arterial-specific enhancers associated with eight key arterial identity genes (Acvrl1/Alk1, Cxcr4, Cxcl12, Efnb2, Gja4/Cx37, Gja5/Cx40, Nrp1 and Unc5b). Next, to elucidate the regulatory pathways upstream of arterial gene transcription, we investigated the transcription factors binding each arterial enhancer compared to a similar assessment of non-arterial endothelial enhancers. These results found that binding of SOXF and ETS factors was a common occurrence at both arterial and pan-endothelial enhancers, suggesting neither are sufficient to direct arterial specificity. Conversely, FOX motifs independent of ETS motifs were over-represented at arterial enhancers. Further, MEF2 and RBPJ binding was enriched but not ubiquitous at arterial enhancers, potentially linked to specific patterns of behaviour within the arterial endothelium. Lastly, there was no shared or arterial-specific signature for WNT-associated TCF/LEF, TGFβ/BMP-associated SMAD1/5 and SMAD2/3, shear stress-associated KLF4 or venous-enriched NR2F2. This cohort of well characterized and in vivo-verified enhancers can now provide a platform for future studies into the interaction of different transcriptional and signalling pathways with arterial gene expression.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Early and delayed STAT1-dependent responses drive local trained immunity of macrophages in the spleen. 早期和延迟的stat1依赖性反应驱动脾脏巨噬细胞的局部训练免疫。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-16 DOI: 10.7554/eLife.100922

Aryeh Solomon, Noa Bossel Ben-Moshe, Dotan Hoffman, Sébastien Trzebanski, Dror Yehezkel, Leia Vainman, Mihai G Netea, Roi Avraham

{"title":"Early and delayed STAT1-dependent responses drive local trained immunity of macrophages in the spleen.","authors":"Aryeh Solomon, Noa Bossel Ben-Moshe, Dotan Hoffman, Sébastien Trzebanski, Dror Yehezkel, Leia Vainman, Mihai G Netea, Roi Avraham","doi":"10.7554/eLife.100922","DOIUrl":"https://doi.org/10.7554/eLife.100922","url":null,"abstract":"Trained immunity (TI) is the process wherein innate immune cells gain functional memory upon exposure to specific ligands or pathogens, leading to augmented inflammatory responses and pathogen clearance upon secondary exposure. While the differentiation of hematopoietic stem cells (HSCs) and reprogramming of bone marrow (BM) progenitors are well-established mechanisms underpinning durable TI protection, remodeling of the cellular architecture within the tissue during TI remains underexplored. Here, we study the effects of peritoneal Bacillus Calmette-Guérin (BCG) administration to find TI-mediated protection in the spleen against a subsequent heterologous infection by the Gram-negative pathogen Salmonella Typhimurium (S.Tm). Utilizing single cell RNA-sequencing and flow cytometry, we discerned STAT1-regulated genes in TI-associated resident and recruited splenic myeloid populations. The temporal dynamics of TI were further elucidated, revealing both early and delayed myeloid subsets with time-dependent, cell-type-specific STAT1 signatures. Using lineage tracing, we find that tissue-resident red pulp macrophages (RPM), initially depleted by BCG exposure, are restored from both tissue-trained, self-renewing macrophages and from bone marrow-derived progenitors, fostering long lasting local defense. Early inhibition of STAT1 activation, using specific JAK-STAT inhibitors, reduces both RPM loss and recruitment of trained monocytes. Our study suggests a temporal window soon after BCG vaccination, in which STAT1-dependent activation of long-lived resident cells in the tissue mediates localized protection.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002305","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

Exploration of the metabolomic mechanisms of postmenopausal hypertension induced by low estrogen state. 低雌激素诱发绝经后高血压的代谢组学机制探讨。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-16 DOI: 10.7554/eLife.101701

Yao Li, Hui Xin, Zhexun Lian, Wei Zhang

{"title":"Exploration of the metabolomic mechanisms of postmenopausal hypertension induced by low estrogen state.","authors":"Yao Li, Hui Xin, Zhexun Lian, Wei Zhang","doi":"10.7554/eLife.101701","DOIUrl":"https://doi.org/10.7554/eLife.101701","url":null,"abstract":"Estrogen significantly impacts women's health, and postmenopausal hypertension is a common issue characterized by blood pressure fluctuations. Current control strategies for this condition are limited in efficacy, necessitating further research into the underlying mechanisms. Although metabolomics has been applied to study various diseases, its use in understanding postmenopausal hypertension is scarce. Therefore, an ovariectomized rat model was used to simulate postmenopausal conditions. Estrogen levels, blood pressure, and aortic tissue metabolomics were analyzed. Animal models were divided into Sham, OVX, and OVX +E groups. Serum estrogen levels, blood pressure measurements, and aortic tissue metabolomics analyses were performed using radioimmunoassay, UHPLC-Q-TOF, and bioinformatics techniques. Based on the above research content, we successfully established a correlation between low estrogen levels and postmenopausal hypertension in rats. Notable differences in blood pressure parameters and aortic tissue metabolites were observed across the experimental groups. Specifically, metabolites that were differentially expressed, particularly L-alpha-aminobutyric acid (L-AABA), showed potential as a biomarker for postmenopausal hypertension, potentially exerting a protective function through macrophage activation and vascular remodeling. Enrichment analysis revealed alterations in sugar metabolism pathways, such as the Warburg effect and glycolysis, indicating their involvement in postmenopausal hypertension. Overall, this current research provides insights into the metabolic changes associated with postmenopausal hypertension, highlighting the role of L-AABA and sugar metabolism reprogramming in aortic tissue. The findings suggest a potential link between low estrogen levels, macrophage function, and vascular remodeling in the pathogenesis of postmenopausal hypertension. Further investigations are needed to validate these findings and explore their clinical implications for postmenopausal women.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002316","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

Target-agnostic identification of human antibodies to Plasmodium falciparum sexual forms reveals cross-stage recognition of glutamate-rich repeats. 人类恶性疟原虫性形式抗体的目标不可知性鉴定揭示了谷氨酸丰富重复序列的跨阶段识别。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-16 DOI: 10.7554/eLife.97865

Axelle Amen, Randy Yoo, Amanda Fabra-García, Judith Bolscher, William J R Stone, Isabelle Bally, Sebastián Dergan-Dylon, Iga Kucharska, Roos M de Jong, Marloes de Bruijni, Teun Bousema, C Richter King, Randall S MacGill, Robert W Sauerwein, Jean-Philippe Julien, Pascal Poignard, Matthijs M Jore

{"title":"Target-agnostic identification of human antibodies to Plasmodium falciparum sexual forms reveals cross-stage recognition of glutamate-rich repeats.","authors":"Axelle Amen, Randy Yoo, Amanda Fabra-García, Judith Bolscher, William J R Stone, Isabelle Bally, Sebastián Dergan-Dylon, Iga Kucharska, Roos M de Jong, Marloes de Bruijni, Teun Bousema, C Richter King, Randall S MacGill, Robert W Sauerwein, Jean-Philippe Julien, Pascal Poignard, Matthijs M Jore","doi":"10.7554/eLife.97865","DOIUrl":"https://doi.org/10.7554/eLife.97865","url":null,"abstract":"Circulating sexual stages of Plasmodium falciparum (Pf) can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population. It is well established that antibodies can efficiently block parasite transmission. In search for naturally acquired antibodies targets on sexual stages, we established an efficient method for target-agnostic single B cell activation followed by high-throughput selection of human monoclonal antibodies (mAbs) reactive to sexual stages of Pf in the form of gametes and gametocyte extracts. We isolated mAbs reactive against a range of Pf proteins including well-established targets Pfs48/45 and Pfs230. One mAb, B1E11K, was cross-reactive to various proteins containing glutamate-rich repetitive elements expressed at different stages of the parasite life cycle. A crystal structure of two B1E11K Fab domains in complex with its main antigen, RESA, expressed on asexual blood stages, showed binding of B1E11K to a repeating epitope motif in a head-to-head conformation engaging in affinity-matured homotypic interactions. Thus, this mode of recognition of Pf proteins, previously described only for Pf circumsporozoite protein (PfCSP), extends to other repeats expressed across various stages. The findings augment our understanding of immune-pathogen interactions to repeating elements of the Plasmodium parasite proteome and underscore the potential of the novel mAb identification method used to provide new insights into the natural humoral immune response against Pf.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002331","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

Crispant analysis in zebrafish as a tool for rapid functional screening of disease-causing genes for bone fragility. 斑马鱼脆化分析作为骨脆性致病基因快速功能筛选的工具。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-16 DOI: 10.7554/eLife.100060

Sophie Debaenst, Tamara Jarayseh, Hanna De Saffel, Jan Willem Bek, Matthieu Boone, Ivan Josipovic, Pierre Kibleur, Ronald Y Kwon, Paul J Coucke, Andy Willaert

{"title":"Crispant analysis in zebrafish as a tool for rapid functional screening of disease-causing genes for bone fragility.","authors":"Sophie Debaenst, Tamara Jarayseh, Hanna De Saffel, Jan Willem Bek, Matthieu Boone, Ivan Josipovic, Pierre Kibleur, Ronald Y Kwon, Paul J Coucke, Andy Willaert","doi":"10.7554/eLife.100060","DOIUrl":"https://doi.org/10.7554/eLife.100060","url":null,"abstract":"Heritable fragile bone disorders (FBDs), ranging from multifactorial to rare monogenic conditions, are characterized by an elevated fracture risk. Validating causative genes and understanding their mechanisms remain challenging. We assessed a semi-high throughput zebrafish screening platform for rapid in vivo functional testing of candidate FBD genes. Six genes linked to severe recessive osteogenesis imperfecta (OI) and four associated with bone mineral density (BMD) from genome-wide association studies were analyzed. Using CRISPR/Cas9-based crispant screening in F0 mosaic founder zebrafish, Next-generation sequencing confirmed high indel efficiency (mean 88%), mimicking stable knock-out models. Skeletal phenotyping at 7, 14, and 90 days post-fertilization (dpf) using microscopy, Alizarin Red S staining, and microCT was performed. Larval crispants showed variable osteoblast and mineralization phenotypes, while adult crispants displayed consistent skeletal defects, including malformed neural and haemal arches, vertebral fractures and fusions, and altered bone volume and density. In addition, aldh7a1 and mbtps2 crispants experienced increased mortality due to severe skeletal deformities. RT-qPCR revealed differential expression of osteogenic markers bglap and col1a1a, highlighting their biomarker potential. Our results establish zebrafish crispant screening as a robust tool for FBD gene validation, combining skeletal and molecular analyses across developmental stages to uncover novel insights into gene functions in bone biology.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002301","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

Outer hair cells stir cochlear fluids. 外毛细胞搅动耳蜗液。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-16 DOI: 10.7554/eLife.101943

Choongheon Lee, Mohammad Shokrian, Kenneth S Henry, Laurel H Carney, J Christopher Holt, Jong-Hoon Nam

{"title":"Outer hair cells stir cochlear fluids.","authors":"Choongheon Lee, Mohammad Shokrian, Kenneth S Henry, Laurel H Carney, J Christopher Holt, Jong-Hoon Nam","doi":"10.7554/eLife.101943","DOIUrl":"https://doi.org/10.7554/eLife.101943","url":null,"abstract":"We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering the neurotoxin, kainic acid, to the intact round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery. When outer-hair-cell motility was suppressed by salicylate, the facilitation effect was compromised. A low-frequency tone was more effective than broadband noise, especially for drug delivery to apical locations. Computational model simulations provided the physical basis for our observation, which incorporated solute diffusion, fluid advection, fluid-structure interaction, and outer-hair-cell motility. Active outer hair cells deformed the organ of Corti like a peristaltic tube to generate apically streaming flows along the tunnel of Corti and basally streaming flows along the scala tympani. Our measurements and simulations coherently suggest that active outer hair cells in the tail region of cochlear traveling waves drive cochlear fluid circulation.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002320","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

Discovery of a heparan sulfate binding domain in monkeypox virus H3 as an anti-poxviral drug target combining AI and MD simulations. 结合AI和MD模拟发现猴痘病毒H3硫酸肝素结合域作为抗痘病毒药物靶点。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-16 DOI: 10.7554/eLife.100545

Bin Zheng, Meimei Duan, Yifen Huang, Shangchen Wang, Jun Qiu, Zhuojian Lu, Lichao Liu, Guojin Tang, Lin Cheng, Peng Zheng

{"title":"Discovery of a heparan sulfate binding domain in monkeypox virus H3 as an anti-poxviral drug target combining AI and MD simulations.","authors":"Bin Zheng, Meimei Duan, Yifen Huang, Shangchen Wang, Jun Qiu, Zhuojian Lu, Lichao Liu, Guojin Tang, Lin Cheng, Peng Zheng","doi":"10.7554/eLife.100545","DOIUrl":"https://doi.org/10.7554/eLife.100545","url":null,"abstract":"Viral adhesion to host cells is a critical step in infection for many viruses, including monkeypox virus (MPXV). In MPXV, the H3 protein mediates viral adhesion through its interaction with heparan sulfate (HS), yet the structural details of this interaction have remained elusive. Using AI-based structural prediction tools and molecular dynamics (MD) simulations, we identified a novel, positively charged α-helical domain in H3 that is essential for HS binding. This conserved domain, found across orthopoxviruses, was experimentally validated and shown to be critical for viral adhesion, making it an ideal target for antiviral drug development. Targeting this domain, we designed a protein inhibitor, which disrupted the H3-HS interaction, inhibited viral infection in vitro and viral replication in vivo, offering a promising antiviral candidate. Our findings reveal a novel therapeutic target of MPXV, demonstrating the potential of combination of AI-driven methods and MD simulations to accelerate antiviral drug discovery.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002303","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

Encoding of cerebellar dentate neuron activity during visual attention in rhesus macaques. 猕猴视觉注意过程中小脑齿状神经元活动的编码。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-16 DOI: 10.7554/eLife.99696

Nico A Flierman, Sue Ann Koay, Willem S van Hoogstraten, Tom J H Ruigrok, Pieter Roelfsema, Aleksandra Badura, Chris I De Zeeuw

{"title":"Encoding of cerebellar dentate neuron activity during visual attention in rhesus macaques.","authors":"Nico A Flierman, Sue Ann Koay, Willem S van Hoogstraten, Tom J H Ruigrok, Pieter Roelfsema, Aleksandra Badura, Chris I De Zeeuw","doi":"10.7554/eLife.99696","DOIUrl":"https://doi.org/10.7554/eLife.99696","url":null,"abstract":"The role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction indicated by a peripheral visual stimulus while maintaining fixation at the center, and report the direction of the cue by performing a saccadic eye movement into the same direction following a delay. We found that single-unit DN neurons modulated spiking activity over the entire time course of the task, and that their activity often bridged temporally separated intra-trial events, yet in a heterogeneous manner. To better understand the heterogeneous relationship between task structure, behavioral performance, and neural dynamics, we constructed a behavioral, an encoding, and a decoding model. Both NHPs showed different behavioral strategies, which influenced the performance. Activity of the DN neurons reflected the unique strategies, with the direction of the visual stimulus frequently being encoded long before an upcoming saccade. Moreover, the latency of the ramping activity of DN neurons following presentation of the visual stimulus was shorter in the better performing NHP. Labeling with the retrograde tracer Cholera Toxin B in the recording location in the DN indicated that these neurons predominantly receive inputs from Purkinje cells in the D1 and D2 zones of the lateral cerebellum as well as neurons of the principal olive and medial pons, all regions known to connect with neurons in the prefrontal cortex contributing to planning of saccades. Together, our results highlight that DN neurons can dynamically modulate their activity during a visual attention task, comprising not only sensorimotor but also cognitive attentional components.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002310","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

Serum metabolome indicators of early childhood development in the Brazilian National Survey on Child Nutrition (ENANI-2019). 巴西国家儿童营养调查（ENANI-2019）中儿童早期发育的血清代谢组指标。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-15 DOI: 10.7554/eLife.97982

Marina Padilha, Victor Nahuel Keller, Paula Normando, Raquel M Schincaglia, Nathalia C Freitas-Costa, Samary S R Freire, Felipe M Delpino, Inês R R de Castro, Elisa M A Lacerda, Dayana R Farias, Zachary Kroezen, Meera Shanmuganathan, Philip Britz-Mckibbin, Gilberto Kac

{"title":"Serum metabolome indicators of early childhood development in the Brazilian National Survey on Child Nutrition (ENANI-2019).","authors":"Marina Padilha, Victor Nahuel Keller, Paula Normando, Raquel M Schincaglia, Nathalia C Freitas-Costa, Samary S R Freire, Felipe M Delpino, Inês R R de Castro, Elisa M A Lacerda, Dayana R Farias, Zachary Kroezen, Meera Shanmuganathan, Philip Britz-Mckibbin, Gilberto Kac","doi":"10.7554/eLife.97982","DOIUrl":"https://doi.org/10.7554/eLife.97982","url":null,"abstract":"Background: The role of circulating metabolites on child development is understudied. We investigated associations between children's serum metabolome and early childhood development (ECD).Methods: Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children's milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥ 1. The interaction between significant metabolites and the child's age was tested.Results: Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child's nutritional status, diet quality, and infant age. Cresol sulfate (β = -0.07; adjusted-p < 0.001), hippuric acid (β = -0.06; adjusted-p < 0.001), phenylacetylglutamine (β = -0.06; adjusted-p < 0.001), and trimethylamine-N-oxide (β = -0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged -1 SD: β = -0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (-1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03).Conclusion: Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.Funding: Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Functional and structural segregation of overlapping helices in HIV-1. 更正：HIV-1中重叠螺旋的功能和结构分离。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-15 DOI: 10.7554/eLife.105985

Maliheh Safari, Bhargavi Jayaraman, Henni Zommer, Shumin Yang, Cynthia Smith, Jason D Fernandes, Alan D Frankel

引用次数: 0

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