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Iterative crRNA design and a PAM-free strategy enabled an ultra-specific RPA-CRISPR/Cas12a detection platform. 迭代 crRNA 设计和无 PAM 策略实现了超特异性 RPA-CRISPR/Cas12a 检测平台。
IF 5.2 1区 生物学
Communications Biology Pub Date : 2024-11-07 DOI: 10.1038/s42003-024-07173-7
Xujian Mao, Jian Xu, Jingyi Jiang, Qiong Li, Ping Yao, Jinyi Jiang, Li Gong, Yin Dong, Bowen Tu, Rong Wang, Hongbing Tang, Fang Yao, Fengming Wang
{"title":"Iterative crRNA design and a PAM-free strategy enabled an ultra-specific RPA-CRISPR/Cas12a detection platform.","authors":"Xujian Mao, Jian Xu, Jingyi Jiang, Qiong Li, Ping Yao, Jinyi Jiang, Li Gong, Yin Dong, Bowen Tu, Rong Wang, Hongbing Tang, Fang Yao, Fengming Wang","doi":"10.1038/s42003-024-07173-7","DOIUrl":"10.1038/s42003-024-07173-7","url":null,"abstract":"<p><p>CRISPR/Cas12a is a highly promising detection tool. However, detecting single nucleotide variations (SNVs) remains challenging. Here, we elucidate Cas12a specificity through crRNA engineering and profiling of single- and double-base mismatch tolerance across three targets. Our findings indicate that Cas12a specificity depends on the number, type, location, and distance of mismatches within the R-loop. We also find that introducing a wobble base pair at position 14 of the R-loop does not affect the free energy change when the spacer length is truncated to 17 bp. Therefore, we develop a new universal specificity enhancement strategy via iterative crRNA design, involving truncated spacers and a wobble base pair at position 14 of the R-loop, which tremendously increases specificity without sacrificing sensitivity. Additionally, we construct a PAM-free one-pot detection platform for SARS-CoV-2 variants, which effectively distinguishes SNV targets across various GC contents. In summary, our work reveals new insights into the specificity mechanism of Cas12a and demonstrates significant potential for in vitro diagnostics.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590129","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 family of menaquinone-targeting cyclic lipodepsipeptides for multidrug-resistant Gram-positive pathogens. 发现一系列针对耐多药革兰氏阳性病原体的甲萘醌靶向环脂二胜肽。
IF 5.2 1区 生物学
Communications Biology Pub Date : 2024-11-07 DOI: 10.1038/s42003-024-07159-5
Runze Sun, Di Zhao, Xuchang Yu, Fei Zhang, Ruixiang You, Xiaoxia Luo, Lei Li
{"title":"Discovery of a family of menaquinone-targeting cyclic lipodepsipeptides for multidrug-resistant Gram-positive pathogens.","authors":"Runze Sun, Di Zhao, Xuchang Yu, Fei Zhang, Ruixiang You, Xiaoxia Luo, Lei Li","doi":"10.1038/s42003-024-07159-5","DOIUrl":"10.1038/s42003-024-07159-5","url":null,"abstract":"<p><p>Menaquinone (MK) in bacterial membrane is an attractive target for the development of novel therapeutic agents. Mining the untapped chemical diversity encoded by Gram-negative bacteria presents an opportunity to identify additional MK-binding antibiotics (MBAs). By MK-binding motif searching of bioinformatically predicted linear non-ribosomal peptides from 14,298 sequenced genomes of 45 underexplored Gram-negative bacterial genera, here we identify a novel MBA structural family, including silvmeb and pseudomeb, using structure prediction-guided chemical synthesis. Both MBAs show rapid bacteriolysis by MK-dependent membrane depolarization to achieve their potent activities against a panel of Gram-positive pathogens. Furthermore, both MBAs are proven to be effective against methicillin-resistant Staphylococcus aureus in a murine peritonitis-sepsis model. Our findings suggest that MBAs are a kind of structurally diverse and still underexplored antibacterial lipodepsipeptide class. The interrogation of underexplored bacterial taxa using synthetic bioinformatic natural product methods is an appealing strategy for discovering novel biomedically relevant agents to confront the crisis of antimicrobial resistance.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590204","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
Underlying drivers of coral reef vulnerability to bleaching in the Mesoamerican Reef. 中美洲珊瑚礁易受白化影响的根本原因。
IF 5.2 1区 生物学
Communications Biology Pub Date : 2024-11-06 DOI: 10.1038/s42003-024-07128-y
Aarón Israel Muñiz-Castillo, Andrea Rivera-Sosa, Melanie McField, Iliana Chollett, C Mark Eakin, Susana Enríquez, Ana Giró, Ian Drysdale, Marisol Rueda, Mélina Soto, Nicole Craig, Jesús Ernesto Arias-González
{"title":"Underlying drivers of coral reef vulnerability to bleaching in the Mesoamerican Reef.","authors":"Aarón Israel Muñiz-Castillo, Andrea Rivera-Sosa, Melanie McField, Iliana Chollett, C Mark Eakin, Susana Enríquez, Ana Giró, Ian Drysdale, Marisol Rueda, Mélina Soto, Nicole Craig, Jesús Ernesto Arias-González","doi":"10.1038/s42003-024-07128-y","DOIUrl":"10.1038/s42003-024-07128-y","url":null,"abstract":"<p><p>Coral bleaching, a consequence of stressed symbiotic relationships between corals and algae, has escalated due to intensified heat stress events driven by climate change. Despite global efforts, current early warning systems lack local precision. Our study, spanning 2015-2017 in the Mesoamerican Reef, revealed prevalent intermediate bleaching, peaking in 2017. By scrutinizing 23 stress exposure and sensitivity metrics, we accurately predicted 75% of bleaching severity variation. Notably, distinct thermal patterns-particularly the climatological seasonal warming rate and various heat stress metrics-emerged as better predictors compared to conventional indices (such as Degree Heating Weeks). Surprisingly, deeper reefs with diverse coral communities showed heightened vulnerability. This study presents a framework for coral reef bleaching vulnerability assessment, leveraging accessible data (including historical and real-time sea surface temperature, habitat variables, and species composition). Its operational potential lies in seamless integration with existing monitoring systems, offering crucial insights for conservation and management.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590247","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
Infrared laser-induced gene expression in single cells characterized by quantitative imaging in Physcomitrium patens. 通过定量成像鉴定红外激光诱导的斑鸠单细胞基因表达。
IF 5.2 1区 生物学
Communications Biology Pub Date : 2024-11-06 DOI: 10.1038/s42003-024-07141-1
Takumi Tomoi, Yuka Yoshida, Suguru Ohe, Yukiko Kabeya, Mitsuyasu Hasebe, Tomohiro Morohoshi, Takashi Murata, Joe Sakamoto, Yosuke Tamada, Yasuhiro Kamei
{"title":"Infrared laser-induced gene expression in single cells characterized by quantitative imaging in Physcomitrium patens.","authors":"Takumi Tomoi, Yuka Yoshida, Suguru Ohe, Yukiko Kabeya, Mitsuyasu Hasebe, Tomohiro Morohoshi, Takashi Murata, Joe Sakamoto, Yosuke Tamada, Yasuhiro Kamei","doi":"10.1038/s42003-024-07141-1","DOIUrl":"10.1038/s42003-024-07141-1","url":null,"abstract":"<p><p>A spatiotemporal understanding of gene function requires the precise control of gene expression in each cell. Here, we use an infrared laser-evoked gene operator (IR-LEGO) system to induce gene expression at the single-cell level in the moss Physcomitrium patens by heating a living cell with an IR laser and thereby activating the heat shock response. We identify the laser irradiation conditions that provide higher inducibility with lower invasiveness by changing the laser power and irradiation duration. Furthermore, we quantitatively characterize the induction profile of the heat shock response using a heat-induced fluorescence reporter system after the IR laser irradiation of single cells under different conditions. Our data indicate that IR laser irradiation with long duration leads to higher inducibility according to increase in the laser power but not vice versa, and that the higher laser power even without conferring apparent damage to the cells decelerates and/or delayed gene induction. We define the temporal shift in expression as a function of onset and duration according to laser power and irradiation duration. This study contributes to the versatile application of IR-LEGO in plants and improves our understanding of heat shock-induced gene expression.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590224","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
Termites and subsocial roaches inherited many bacterial-borne carbohydrate-active enzymes (CAZymes) from their common ancestor. 白蚁和亚社会蟑螂从它们的共同祖先那里继承了许多细菌携带的碳水化合物活性酶(CAZymes)。
IF 5.2 1区 生物学
Communications Biology Pub Date : 2024-11-06 DOI: 10.1038/s42003-024-07146-w
Tereza Beránková, Jigyasa Arora, Johanna Romero Arias, Aleš Buček, Gaku Tokuda, Jan Šobotník, Simon Hellemans, Thomas Bourguignon
{"title":"Termites and subsocial roaches inherited many bacterial-borne carbohydrate-active enzymes (CAZymes) from their common ancestor.","authors":"Tereza Beránková, Jigyasa Arora, Johanna Romero Arias, Aleš Buček, Gaku Tokuda, Jan Šobotník, Simon Hellemans, Thomas Bourguignon","doi":"10.1038/s42003-024-07146-w","DOIUrl":"10.1038/s42003-024-07146-w","url":null,"abstract":"<p><p>Termites digest wood using Carbohydrate-Active Enzymes (CAZymes) produced by gut bacteria with whom they have cospeciated at geological timescales. Whether CAZymes were encoded in the genomes of their ancestor's gut bacteria and transmitted to modern termites or acquired more recently from bacteria not associated with termites is unclear. We used gut metagenomes from 195 termites and one Cryptocercus, the sister group of termites, to investigate the evolution of termite gut bacterial CAZymes. We found 420 termite-specific clusters in 81 bacterial CAZyme gene trees, including 404 clusters showing strong cophylogenetic patterns with termites. Of the 420 clusters, 131 included at least one bacterial CAZyme sequence associated with Cryptocercus or Mastotermes, the sister group of all other termites. Our results suggest many bacterial CAZymes have been encoded in the genomes of termite gut bacteria since termite origin, indicating termites rely upon many bacterial CAZymes endemic to their guts to digest wood.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590244","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
KLF13 promotes SLE pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes. KLF13 通过改变关键促炎细胞因子基因的染色质可及性来促进系统性红斑狼疮的发病。
IF 5.2 1区 生物学
Communications Biology Pub Date : 2024-11-06 DOI: 10.1038/s42003-024-07099-0
Andrew Wang, Anna-Marie Fairhurst, Kui Liu, Benjamin Wakeland, Spencer Barnes, Venkat S Malladi, Kasthuribai Viswanathan, Carlos Arana, Igor Dozmorov, Amrita Singhar, Yong Du, Marjaan Imam, Angela Moses, Christian Chen, Ashwini Sunkavalli, Jose Casco, Dinesh Rakheja, Quan-Zhen Li, Chandra Mohan, Carol Clayberger, Edward K Wakeland, Shaheen Khan
{"title":"KLF13 promotes SLE pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes.","authors":"Andrew Wang, Anna-Marie Fairhurst, Kui Liu, Benjamin Wakeland, Spencer Barnes, Venkat S Malladi, Kasthuribai Viswanathan, Carlos Arana, Igor Dozmorov, Amrita Singhar, Yong Du, Marjaan Imam, Angela Moses, Christian Chen, Ashwini Sunkavalli, Jose Casco, Dinesh Rakheja, Quan-Zhen Li, Chandra Mohan, Carol Clayberger, Edward K Wakeland, Shaheen Khan","doi":"10.1038/s42003-024-07099-0","DOIUrl":"10.1038/s42003-024-07099-0","url":null,"abstract":"<p><p>Although significant progress has been achieved in elucidating the genetic architecture of systemic lupus erythematosus (SLE), identifying genes underlying the pathogenesis has been challenging. The NZM2410-derived lupus susceptibility Sle3 locus is associated with T cell hyperactivity and activated myeloid cells. However, candidate genes associated with these phenotypes have not been identified. Here, we narrow the Sle3 locus to a smaller genomic segment (Sle3k) and show that mice carrying Sle3k and Sle1 loci developed lupus nephritis. We identify Klf13 as the primary candidate gene that is associated with genome-wide transcription changes resulting in higher levels of proinflammatory cytokines, enhanced T cell activation, and hyperresponsiveness of myeloid cells. Correspondingly, Klf13 <sup>-/-</sup> mice display repression of genes involved in mediating immune activation, including key proinflammatory cytokines/chemokines in T cells and dysregulation in cytokine signaling pathways in myeloid cells in response to toll receptor ligands. Klf13 upregulation is associated with increased production of RANTES, a key chemokine in lupus nephritis, in activated T cells and the kidneys of lupus-prone mice. In sum, our findings reveal Klf13 as a key gene in the Sle3 interval in mediating lupus pathogenesis that may have implications in the rational design of new therapies for SLE.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590130","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
Deep functional measurements of Fragile X syndrome human neurons reveal multiparametric electrophysiological disease phenotype. 对脆性 X 综合征人类神经元的深度功能测量揭示了多参数电生理疾病表型。
IF 5.2 1区 生物学
Communications Biology Pub Date : 2024-11-06 DOI: 10.1038/s42003-024-07120-6
James J Fink, Nathaniel Delaney-Busch, Ryan Dawes, Evanthia Nanou, Christopher Folts, Karthiayani Harikrishnan, Chris Hempel, Hansini Upadhyay, Trinh Nguyen, Himali Shroff, David Stoppel, Steven J Ryan, Jane Jacques, Jennifer Grooms, Elizabeth Berry-Kravis, Mark F Bear, Luis A Williams, David Gerber, Mark Bunnage, Brinley Furey, Graham T Dempsey
{"title":"Deep functional measurements of Fragile X syndrome human neurons reveal multiparametric electrophysiological disease phenotype.","authors":"James J Fink, Nathaniel Delaney-Busch, Ryan Dawes, Evanthia Nanou, Christopher Folts, Karthiayani Harikrishnan, Chris Hempel, Hansini Upadhyay, Trinh Nguyen, Himali Shroff, David Stoppel, Steven J Ryan, Jane Jacques, Jennifer Grooms, Elizabeth Berry-Kravis, Mark F Bear, Luis A Williams, David Gerber, Mark Bunnage, Brinley Furey, Graham T Dempsey","doi":"10.1038/s42003-024-07120-6","DOIUrl":"10.1038/s42003-024-07120-6","url":null,"abstract":"<p><p>Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by hypermethylation of expanded CGG repeats (>200) in the FMR1 gene leading to gene silencing and loss of Fragile X Messenger Ribonucleoprotein (FMRP) expression. FMRP plays important roles in neuronal function, and loss of FMRP in mouse and human FXS cell models leads to aberrant synaptic signaling and hyperexcitability. Multiple drug candidates have advanced into clinical trials for FXS, but no efficacious treatment has been identified to date, possibly as a consequence of poor translation from pre-clinical animal models to human. Here, we use a high resolution all-optical electrophysiology platform applied to multiple FXS patient-derived and CRISPR/Cas9-generated isogenic neuronal cell lines to develop a multi-parametric FXS disease phenotype. This neurophysiological phenotype was optimized and validated into a high throughput assay based on the amount of FMRP re-expression and the number of healthy neurons in a mosaic network necessary for functional rescue. The resulting highly sensitive and multiparameter functional assay can now be applied as a discovery platform to explore new therapeutic approaches for the treatment of FXS.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590203","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
Structural mechanisms of potent lysophosphatidic acid receptor 1 activation by nonlipid basic agonists. 非脂质碱性激动剂强效激活溶血磷脂酸受体 1 的结构机制。
IF 5.2 1区 生物学
Communications Biology Pub Date : 2024-11-06 DOI: 10.1038/s42003-024-07152-y
Hiroaki Akasaka, Fumiya K Sano, Wataru Shihoya, Osamu Nureki
{"title":"Structural mechanisms of potent lysophosphatidic acid receptor 1 activation by nonlipid basic agonists.","authors":"Hiroaki Akasaka, Fumiya K Sano, Wataru Shihoya, Osamu Nureki","doi":"10.1038/s42003-024-07152-y","DOIUrl":"10.1038/s42003-024-07152-y","url":null,"abstract":"<p><p>Lysophosphatidic acid receptor 1 (LPA<sub>1</sub>) is one of the G protein-coupled receptors activated by the lipid mediator, lysophosphatidic acid (LPA). LPA<sub>1</sub> is associated with a variety of diseases, and LPA<sub>1</sub> agonists have potential therapeutic value for treating obesity and depression. Although potent nonlipid LPA<sub>1</sub> agonists have recently been identified, the mechanisms of nonlipid molecule-mediated LPA<sub>1</sub> activation remain unclear. Here, we report a cryo-electron microscopy structure of the human LPA<sub>1</sub>-G<sub>i</sub> complex bound to a nonlipid basic agonist, CpY, which has 30-fold higher agonistic activity as compared with LPA. Structural comparisons of LPA<sub>1</sub> with other lipid GPCRs revealed that the negative charge in the characteristic binding pocket of LPA<sub>1</sub> allows the selective recognition of CpY, which lacks a polar head. In addition, our structure show that the ethyl group of CpY directly pushes W271<sup>6.48</sup> to fix the active conformation. Endogenous LPA lacks these chemical features, which thus represent the crucial elements of nonlipid agonists that potently activate LPA<sub>1</sub>. This study provides detailed mechanistic insights into the ligand recognition and activation of LPA<sub>1</sub> by nonlipid agonists, expanding the scope for drug development targeting the LPA receptors.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590240","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
Sources of variation in the serum metabolome of female participants of the HUNT2 study. HUNT2 研究女性参与者血清代谢组的变异来源。
IF 5.2 1区 生物学
Communications Biology Pub Date : 2024-11-06 DOI: 10.1038/s42003-024-07137-x
Julia Debik, Katarzyna Mrowiec, Agata Kurczyk, Piotr Widłak, Karol Jelonek, Tone F Bathen, Guro F Giskeødegård
{"title":"Sources of variation in the serum metabolome of female participants of the HUNT2 study.","authors":"Julia Debik, Katarzyna Mrowiec, Agata Kurczyk, Piotr Widłak, Karol Jelonek, Tone F Bathen, Guro F Giskeødegård","doi":"10.1038/s42003-024-07137-x","DOIUrl":"10.1038/s42003-024-07137-x","url":null,"abstract":"<p><p>The aim of this study was to explore the intricate relationship between serum metabolomics and lifestyle factors, shedding light on their impact on health in the context of breast cancer risk. Detailed metabolic profiles of 2283 female participants in the Trøndelag Health Study (HUNT study) were obtained through nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS).We show that lifestyle-related variables can explain up to 30% of the variance in individual metabolites. Age and obesity were the primary factors affecting the serum metabolic profile, both associated with increased levels of triglyceride-rich very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL), amino acids and glycolysis-related metabolites, and decreased levels of high-density lipoproteins (HDL). Moreover, factors like hormonal changes associated with menstruation and contraceptive use or education level influence the metabolite levels.Participants were clustered into three distinct clusters based on lifestyle-related factors, revealing metabolic similarities between obese and older individuals, despite diverse lifestyle factors, suggesting accelerated metabolic aging with obesity. Our results show that metabolic associations to cancer risk may partly be explained by modifiable lifestyle factors.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590148","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
Cross-comparison of gut metagenomic profiling strategies. 肠道元基因组剖析策略的交叉比较。
IF 5.2 1区 生物学
Communications Biology Pub Date : 2024-11-06 DOI: 10.1038/s42003-024-07158-6
Gábor Gulyás, Balázs Kakuk, Ákos Dörmő, Tamás Járay, István Prazsák, Zsolt Csabai, Miksa Máté Henkrich, Zsolt Boldogkői, Dóra Tombácz
{"title":"Cross-comparison of gut metagenomic profiling strategies.","authors":"Gábor Gulyás, Balázs Kakuk, Ákos Dörmő, Tamás Járay, István Prazsák, Zsolt Csabai, Miksa Máté Henkrich, Zsolt Boldogkői, Dóra Tombácz","doi":"10.1038/s42003-024-07158-6","DOIUrl":"10.1038/s42003-024-07158-6","url":null,"abstract":"<p><p>The rapid advancements in sequencing technologies and bioinformatics have enabled metagenomic research of complex microbial systems, but reliable results depend on consistent laboratory and bioinformatics approaches. Current efforts to identify best practices often focus on optimizing specific steps, making it challenging to understand the influence of each stage on microbial population analysis and compare data across studies. This study evaluated DNA extraction, library construction methodologies, sequencing platforms, and computational approaches using a dog stool sample, two synthetic microbial community mixtures, and various sequencing data sources. Our work, the most comprehensive evaluation of metagenomic methods to date. We developed a software tool, termed minitax, which provides consistent results across the range of platforms and methodologies. Our findings showed that the Zymo Research Quick-DNA HMW MagBead Kit, Illumina DNA Prep library preparation method, and the minitax bioinformatics tool were the most effective for high-quality microbial diversity analysis. However, the effectiveness of pipelines or method combinations is sample-specific, making it difficult to identify a universally optimal approach. Therefore, employing multiple approaches is crucial for obtaining reliable outcomes in microbial systems.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590199","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
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