Yizhong Zhang, Arshia Naaz, Trishia Yi Ning Cheng, Jovian Jing Lin, Mingtong Gao, Rajkumar Dorajoo, Mohammad Alfatah
{"title":"Systematic transcriptomics analysis of calorie restriction and rapamycin unveils their synergistic interaction in prolonging cellular lifespan.","authors":"Yizhong Zhang, Arshia Naaz, Trishia Yi Ning Cheng, Jovian Jing Lin, Mingtong Gao, Rajkumar Dorajoo, Mohammad Alfatah","doi":"10.1038/s42003-025-08178-6","DOIUrl":"https://doi.org/10.1038/s42003-025-08178-6","url":null,"abstract":"<p><p>Aging is a multifaceted biological process marked by the decline in both mitotic and postmitotic cellular function, often central to the development of age-related diseases. In the pursuit of slowing or even reversing the aging process, a prominent strategy of significant interest is calorie restriction (CR), also known as dietary restriction, and the potential influence of a drug called rapamycin (RM). Both CR and RM have demonstrated the capacity to extend healthspan and lifespan across a diverse array of species, including yeast, worms, flies, and mice. Nevertheless, their individual and combined effects on mitotic and postmitotic cells, as well as their comparative analysis, remain areas that demand a thorough investigation. In this study, we employ RNA-sequencing methodologies to comprehensively analyze the impact of CR, RM, and their combination (CR + RM) on gene expression in yeast cells. Our analysis uncovers distinctive, overlapping, and even contrasting patterns of gene regulation, illuminating the unique and shared effects of CR and RM. Furthermore, the transcriptional synergistic interaction of CR + RM is validated in extending the lifespan of both yeast and human cells.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"753"},"PeriodicalIF":5.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076551","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}
Victoria M Bedell, Priya Dubey, Han B Lee, Dondra S Bailey, Jennifer L Anderson, Allison Jamieson-Lucy, Rui Xiao, Elvin V Leonard, Marni J Falk, Michael A Pack, Mary Mullins, Steven A Farber, Roderic G Eckenhoff, Stephen C Ekker
{"title":"Zebrafishology, study design guidelines for rigorous and reproducible data using zebrafish.","authors":"Victoria M Bedell, Priya Dubey, Han B Lee, Dondra S Bailey, Jennifer L Anderson, Allison Jamieson-Lucy, Rui Xiao, Elvin V Leonard, Marni J Falk, Michael A Pack, Mary Mullins, Steven A Farber, Roderic G Eckenhoff, Stephen C Ekker","doi":"10.1038/s42003-025-07496-z","DOIUrl":"10.1038/s42003-025-07496-z","url":null,"abstract":"<p><p>The zebrafish (Danio rerio) is one of the most widely used research model organisms funded by the United States' National Institutes of Health, second only to the mouse. Here, we discuss the advantages and unique qualities of this model organism. Additionally, we discuss key aspects of experimental design and statistical approaches that apply to studies using the zebrafish model organism. Finally, we list critical details that should be considered in the design of zebrafish experiments to enhance rigor and data reproducibility. These guidelines are designed to aid new researchers, journal editors, and manuscript reviewers in supporting the publication of the highest-quality zebrafish research.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"739"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981923","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}
Pedro De-la-Torre, Claudia Martínez-García, Paul Gratias, Matthew Mun, Paula Santana, Nurunisa Akyuz, Wendy González, Artur A Indzhykulian, David Ramírez
{"title":"Identification of druggable binding sites and small molecules as modulators of TMC1.","authors":"Pedro De-la-Torre, Claudia Martínez-García, Paul Gratias, Matthew Mun, Paula Santana, Nurunisa Akyuz, Wendy González, Artur A Indzhykulian, David Ramírez","doi":"10.1038/s42003-025-07943-x","DOIUrl":"10.1038/s42003-025-07943-x","url":null,"abstract":"<p><p>Our ability to hear and maintain balance relies on the proper functioning of inner ear sensory hair cells, which translate mechanical stimuli into electrical signals via mechano-electrical transducer (MET) channels, composed of TMC1/2 proteins. However, the therapeutic use of ototoxic drugs, such as aminoglycosides and cisplatin, which can enter hair cells through MET channels, often leads to profound auditory and vestibular dysfunction. To date, our understanding of how small-molecule modulators interact with TMCs remains limited, hampering the discovery of novel drugs. Here, we propose a structure-based drug screening approach, integrating 3D-pharmacophore modeling, molecular dynamics simulations of the TMC1 + CIB2 + TMIE complex, and experimental validation. Our pipeline successfully identified three potential drug-binding sites within the TMC1 pore, phospholipids, and key amino acids involved in the binding of several compounds, as well as FDA-approved drugs that reduced dye uptake in cultured cochlear explants. Our pipeline offers a broad application for discovering modulators for mechanosensitive ion channels.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"742"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969817","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}
Shengke Wang, Yan Zhou, Yuezhuo Wang, Keshu Tang, Danqi Wang, Jiawen Hong, Pengcheng Wang, Sheng Ye, Jie Yan, Shengkai Li, Zhemin Zhou, Jimei Du
{"title":"Genetic landscape and evolution of Acinetobacter pittii, an underestimated emerging nosocomial pathogen.","authors":"Shengke Wang, Yan Zhou, Yuezhuo Wang, Keshu Tang, Danqi Wang, Jiawen Hong, Pengcheng Wang, Sheng Ye, Jie Yan, Shengkai Li, Zhemin Zhou, Jimei Du","doi":"10.1038/s42003-025-08156-y","DOIUrl":"10.1038/s42003-025-08156-y","url":null,"abstract":"<p><p>As a member of Acinetobacter calcoaceticus-baumannii complex, Acinetobacter pittii has been an emerging concern in nosocomial infection due to its increasing prevalence and multidrug resistance (MDR). However, its population structure remains broadly unknown, hampering efficient tracing of its transmission and evolution. In this study, we developed a distributed core genome multilocus sequence typing (dcgMLST) for A. pittii based on 750 genomes and employed it to map the genetic landscape and evolution of A. pittii. The results demonstrated that two hierarchical clustering (HC) levels effectively correspond to genetic diversity from species (HC1100) to natural populations (HC450), as well as that a predominant lineage, HC1100_4, accounts for 33.9% of A. pittii strains. Subsequent analysis revealed that specific gene gain and loss events within HC1100_4 are linked to adaptations to environmental stress. Moreover, we identified a cluster of multidrug-resistant plasmids PT_712 responsible for the dissemination of bla<sub>NDM-1</sub> genes within the genus of Acinetobacter. This study provides a framework for characterizing genetic diversity, evolutionary dynamics, molecular population distribution, and tracing of A. pittii, which has the potential to improve infection control strategies and public health policy.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"738"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962656","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}
{"title":"Inspiring scientific wonder, curiosity and critical thinking in young minds: an interview with Audrey Dussutour.","authors":"","doi":"10.1038/s42003-025-08166-w","DOIUrl":"10.1038/s42003-025-08166-w","url":null,"abstract":"","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"748"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979013","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}
J K Bruce, L Y Li, Y Tang, E G Forster, N J Winsor, P Y Bi, C Krustev, S Keely, J E Lee, J R Rohde, H Y Gaisano, D J Philpott, S E Girardin
{"title":"Gasdermin-D pores induce an inactivating caspase-4 cleavage that limits IL-18 production in the intestinal epithelium.","authors":"J K Bruce, L Y Li, Y Tang, E G Forster, N J Winsor, P Y Bi, C Krustev, S Keely, J E Lee, J R Rohde, H Y Gaisano, D J Philpott, S E Girardin","doi":"10.1038/s42003-025-08183-9","DOIUrl":"10.1038/s42003-025-08183-9","url":null,"abstract":"<p><p>Intestinal epithelial-derived IL-18 is critical for homeostatic intestinal barrier function and is secreted through Gasdermin D (GSDMD) pores. Inflammasome activation is a prerequisite for both IL-18 maturation and GSDMD pore formation. However, GSDMD pores also cause pyroptotic cell death, which could be detrimental to the intestinal epithelial barrier. How epithelial cells balance the need to secrete IL-18 and to maintain barrier integrity remains poorly understood. In human intestinal epithelial cell lines and in primary human epithelial intestinal organoids, but not in immune cells, GSDMD plasma membrane pore formation by LPS electroporation and by gram-negative bacterial infection induced a non-conventional p37 caspase-4 fragment that was associated with reduced levels of mature IL-18. By contrast, limiting GSDMD plasma membrane pores pharmacologically and via point-mutagenesis prevented caspase-4 cleavage and increased IL-18 production, suggesting that p37 caspase-4 cleavage may regulate IL-18 maturation in the intestinal epithelium. In support, co-expression of caspase-4 cleavage mutants and IL-18 in HEK293T cells revealed that non-cleavable caspase-4 produced more mature IL-18 than cleaved caspase-4. Overall, these studies suggest that epithelial inflammasomes encode feedback pathways that control the balance between cytokine secretion and cell death. This may be an important mechanism to ensure homeostatic IL-18 production in the intestinal epithelium.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"737"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992512","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}
Xianmei Wang, Kun Guo, Zhili Shan, Zhu Ying, Zifu Zhu, Shiman Yang, Na Yang, Qun Liu, Lifang Wang, Jing Liu
{"title":"Unveiling the impact of cGMP-dependent protein kinase of Neospora caninum on calcium fluxes and egress functions through quantitative phosphoproteome analysis.","authors":"Xianmei Wang, Kun Guo, Zhili Shan, Zhu Ying, Zifu Zhu, Shiman Yang, Na Yang, Qun Liu, Lifang Wang, Jing Liu","doi":"10.1038/s42003-025-08173-x","DOIUrl":"10.1038/s42003-025-08173-x","url":null,"abstract":"<p><p>Neospora caninum, a pathogen associated with abortion in pregnant cattle and motor nerve disorders in dogs, poses a substantial threat. Cyclic GMP-dependent protein kinase (PKG) functions as a central signal transduction hub in apicomplexan parasites. However, PKG has not been characterized in N. caninum, and its targets and pathways controlled by PKG remain unknown. Using a mini auxin-inducible degron system (mAID), we knocked down PKG in N. caninum, demonstrating its indispensable role in tachyzoite invasion and egress from host cells. PKG promotes microneme secretion and enhances tachyzoite gliding motility by elevating intracellular Ca<sup>2+</sup> levels ([Ca<sup>2+</sup>]<sub>i</sub>). Phosphoproteomics identified 1125 proteins as potential downstream targets of PKG, showing significantly reduced phosphorylation after treatment with the PKG inhibitor MBP146-78. These proteins are involved in signal transduction, transcriptional regulation, lipid transport and metabolism, vesicle transport, and ion transport. Additionally, CACNAP, a calcium channel-associated protein that facilitates calcium influx at the plasma membrane, plays a supportive role in the egress process of N. caninum. These findings underscore the importance of PKG and its downstream molecules in regulating egress, offering novel insights into the mechanisms underlying the activation of [Ca<sup>2+</sup>]<sub>i</sub>.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"744"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987316","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}
Tabea Gewalt, Anna M Dmitrieva, Felix Elsner, Xinlei Zhao, Daniel Dimitri Sieber, Ilayda Gülsen Kocak, Qian Yang, Claudia Viktoria Orschel, Naja Maria Eckert, Bianca Goebel, Marieke Nill, Franziska Peter, Arndt Hartmann, Filippo Beleggia, Margarete Odenthal, Hans Christian Reinhardt, Roland Tillmann Ullrich, Frederik Graw, Lydia Meder
{"title":"TAT-CRE inhalation enables tumor induction corresponding to adenoviral Cre-recombinase in a lung cancer mouse model.","authors":"Tabea Gewalt, Anna M Dmitrieva, Felix Elsner, Xinlei Zhao, Daniel Dimitri Sieber, Ilayda Gülsen Kocak, Qian Yang, Claudia Viktoria Orschel, Naja Maria Eckert, Bianca Goebel, Marieke Nill, Franziska Peter, Arndt Hartmann, Filippo Beleggia, Margarete Odenthal, Hans Christian Reinhardt, Roland Tillmann Ullrich, Frederik Graw, Lydia Meder","doi":"10.1038/s42003-025-08146-0","DOIUrl":"10.1038/s42003-025-08146-0","url":null,"abstract":"<p><p>Cre-recombinase inducible model systems are extensively used in cancer research to manipulate gene expression in specific tissues and induce autochthonous tumor growth. These systems often involve the cross-breeding of genetically engineered organisms containing loxP-flanked alleles with those expressing Cre-recombinase. This approach, while effective, has the challenge of requiring high numbers of animals due to breeding requirements. Other frequently used tumor induction methods in cancer research involve the direct application of viral Cre-recombinase vectors. This approach presents the challenge of the accessibility of facilities that meet the necessary safety level. In this context, we perform a comprehensive comparison between TAT-CRE (biosafety level S1) and adenoviral Cre-recombinase induced (biosafety level S2) lung adenocarcinomas driven by Kras<sup>G12D</sup> expression and Trp53 depletion. We use in vivo lung tumor monitoring via computed tomography, single-cell RNA sequencing, immunohistochemistry and flow cytometry to elucidate similarities and differences between TAT-CRE and adenoviral Cre-recombinase induced lung adenocarcinomas. TAT-CRE induced lung tumors present differences in micro-vessels and macrophages but with corresponding tumor onset and growth characteristics compared to adenoviral-Cre recombinase induced lung tumors. Taken together, TAT-CRE is a valuable genetic engineering safety level S1 alternative for cancer induction and may be implemented in other cancer models than lung cancer.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"741"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972546","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}
Thomas F Varley, Olaf Sporns, Nathan J Stevenson, Pauliina Yrjölä, Martha G Welch, Michael M Myers, Sampsa Vanhatalo, Anton Tokariev
{"title":"Emergence of a synergistic scaffold in the brains of human infants.","authors":"Thomas F Varley, Olaf Sporns, Nathan J Stevenson, Pauliina Yrjölä, Martha G Welch, Michael M Myers, Sampsa Vanhatalo, Anton Tokariev","doi":"10.1038/s42003-025-08082-z","DOIUrl":"10.1038/s42003-025-08082-z","url":null,"abstract":"<p><p>The human brain is a complex organ comprising billions of interconnected neurons, which enables interaction with both physical and social environments. Neural dynamics of the whole brain go far beyond just the sum of its individual elements; a property known as \"synergy\". Previously it has been shown that synergy is crucial for many complex brain functions and cognition, however, it remains unknown how and when the large number of discrete neurons evolve into the unified system able to support synergistic interactions. Here we analyzed high-density electroencephalography data from the late fetal period to one month after term age. We found that the human brain transitions from a redundancy-dominated to a synergy-dominated system around birth. Frontal regions lead the emergence of a synergistic scaffold comprised of overlapping subsystems, while the integration of sensory areas developed gradually, from occipital to central regions. Strikingly, early developmental trajectories of brain synergy were modulated by environmental enrichment associated with enhanced mother-infant interactions, and the level of synergy near term equivalent age was associated with later neurocognitive development.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"743"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956820","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}
Apostolos Zournas, Matthew R Incha, Tijana Radivojevic, Vincent Blay, Jose Manuel Martí, Zak Costello, Matthias Schmidt, Tan Chung, Mitchell G Thompson, Allison Pearson, Patrick C Kinnunen, Thomas Eng, Christopher E Lawson, Stephen Tan, Tadeusz Ogorzalek, Nurgul Kaplan, Mark Forrer, Tyler Backman, Aindrila Mukhopadhyay, Nathan J Hillson, Jay D Keasling, Hector Garcia Martin
{"title":"Author Correction: Machine learning-led semi-automated medium optimization reveals salt as key for flaviolin production in Pseudomonas putida.","authors":"Apostolos Zournas, Matthew R Incha, Tijana Radivojevic, Vincent Blay, Jose Manuel Martí, Zak Costello, Matthias Schmidt, Tan Chung, Mitchell G Thompson, Allison Pearson, Patrick C Kinnunen, Thomas Eng, Christopher E Lawson, Stephen Tan, Tadeusz Ogorzalek, Nurgul Kaplan, Mark Forrer, Tyler Backman, Aindrila Mukhopadhyay, Nathan J Hillson, Jay D Keasling, Hector Garcia Martin","doi":"10.1038/s42003-025-08141-5","DOIUrl":"10.1038/s42003-025-08141-5","url":null,"abstract":"","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"747"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971962","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}
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