PLoS Biology最新文献

{"title":"Sensory stimuli dominate over rhythmic electrical stimulation in modulating behavior.","authors":"Yuranny Cabral-Calderin, Molly J Henry","doi":"10.1371/journal.pbio.3003180","DOIUrl":"10.1371/journal.pbio.3003180","url":null,"abstract":"<p><p>Neural tracking (entrainment) of auditory rhythms enhances perception. We previously demonstrated that transcranial alternating current stimulation (tACS) can enhance or suppress entrainment to rhythmic auditory stimuli, depending on the timing between the electrical and auditory signals, although tACS effects are primarily modulatory. This study further investigated entrainment to tACS and auditory rhythms when the electrical and auditory signals were presented together (Experiment 1, N = 34) or independently (Experiment 2, N = 24; Experiment 3, N = 12). We hypothesized that tACS effects would be more pronounced when the auditory rhythm was made less perceptually salient to reduce the competition with the electrical rhythm. Participants detected silent gaps in modulated or unmodulated noise stimuli. In Experiment 1, auditory stimuli predominated in entraining behavior. While behavioral entrainment to sound rhythms was affected by the modulation depth of the auditory stimulus, entrainment to tACS was not. In Experiment 2, with no rhythmic information from the sound, 17 of 24 participants showed significant behavioral entrainment to tACS, although the most effective tACS frequency varied across participants. An oscillator model with a free parameter for the individual resonance frequency produced profiles similar to those we observed behaviorally. In Experiment 3, both neural and behavioral entrainment to rhythmic sounds were affected by the auditory stimulus frequency, but again the most effective entraining frequency varied across participants. Our findings suggest that tACS effects depend on the individual's preferred frequency when there is no competition with sensory stimuli, emphasizing the importance of targeting individual frequencies in tACS experiments. When both sensory and electrical stimuli are rhythmic and compete, sensory stimuli prevail, indicating the superiority of sensory stimulation in modulating behavior.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003180"},"PeriodicalIF":9.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235622","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":"Methylation of RBM39 by PRMT6 enhances resistance to Indisulam in non-small cell lung cancer by promoting alternative splicing of proto-oncogenes.","authors":"Tongjia Zhang, Shujie Wang, Yue Zhou, Zitao Jiao, Kejia Lu, Xinyi Liu, Hui Li, Wei Jiang, Xiaowei Zhang","doi":"10.1371/journal.pbio.3002846","DOIUrl":"10.1371/journal.pbio.3002846","url":null,"abstract":"<p><p>Indisulam, a sulfonamide-based compound, is employed as a second-line therapy for NSCLC due to its anti-tumor activity. However, its clinical efficacy is hindered by acquired resistance, the molecular basis of which remains poorly understood. Here, we demonstrate that hypermethylation of RNA-binding protein 39 (RBM39), a specific target of Indisulam, is closely associated with Indisulam resistance. PRMT6 methylates RBM39 at R92. This methylation inhibits Indisulam-induced ubiquitination and proteasomal degradation of RBM39, increases RBM39 protein levels, promotes alternative splicing and expression of proto-oncogenes, and ultimately leads to malignant proliferation and metastasis of NSCLC cells and tumor growth in xenograft mouse models. Inhibiting PRMT6 with MS023 or mutating the RBM39 methylation site enhances Indisulam sensitivity in NSCLC and significantly improves its anti-tumor efficacy. Our findings identify methylated RBM39 as a key biomarker of Indisulam resistance and suggest a potential therapeutic strategy for NSCLC.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3002846"},"PeriodicalIF":9.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227349","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":"Isoflurane activates the type 1 ryanodine receptor to induce anesthesia in mice.","authors":"Hiroyuki J Kanaya, Ken Kuwajima, Yuko Ito, Yuta Shinohara, Yohei Okubo, Shinnosuke Shiono, Fumiya Tatsuki, Rei-Ichiro Ohno, Hideki Ukai, Maki Ukai-Tadenuma, Kenta Sumiyama, Hiroshi Fujishima, Rikuhiro G Yamada, Daisuke Tone, Hiroshi Kiyonari, Masaki Kikuchi, Takashi Umehara, Takashi Murayama, Kazunori Kanemaru, Masamitsu Iino, Koji L Ode, Takatsugu Hirokawa, Hiroki R Ueda","doi":"10.1371/journal.pbio.3003172","DOIUrl":"10.1371/journal.pbio.3003172","url":null,"abstract":"<p><p>Inhaled anesthetics were first introduced into clinical use in the 1840s. Molecular and transgenic animal studies indicate that inhaled anesthetics act through several ion channels, including γ-aminobutyric acid type A receptors (GABAARs) and two-pore domain K+ (K2P) channels, but other targets may mediate anesthetic effects. Mutations in the type 1 ryanodine receptor (RyR1), which is a calcium release channel on the endoplasmic reticulum membrane, are relevant to malignant hyperthermia, a condition that can be induced by inhaled anesthetics. However, it was previously uncertain whether inhaled anesthetics directly interact with RyR1. In our study, we demonstrated that isoflurane and other inhaled anesthetics activate wild-type RyR1. By employing systematic mutagenesis, we discovered that altering just one amino acid residue negates the response to isoflurane, thus helping us to pinpoint the potential binding site. Knock-in mice engineered to express a mutant form of RyR1 that is insensitive to isoflurane exhibited resistance to the loss of righting reflex (LORR) when exposed to isoflurane anesthesia. This observation suggests a connection between RyR1 activation and the anesthetic effects in vivo. Moreover, it was shown that RyR1 is involved in the neuronal response to isoflurane. Additionally, administering new RyR1 agonists, which share the same binding site as isoflurane, resulted in a sedation-like state in mice. We propose that isoflurane directly activates RyR1, and this activation is pertinent to its anesthetic/sedative effects.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003172"},"PeriodicalIF":9.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217359","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":"An auditory cortical-striatal circuit supports sound-triggered timing to predict future events.","authors":"Harini Suri, Karla Salgado-Puga, Yixuan Wang, Nayomie Allen, Kaitlynn Lane, Kyra Granroth, Alberto Olivei, Nathanial Nass, Gideon Rothschild","doi":"10.1371/journal.pbio.3003209","DOIUrl":"10.1371/journal.pbio.3003209","url":null,"abstract":"<p><p>A crucial aspect of auditory perception is the ability to use sound cues to predict future events and to time actions accordingly. For example, the sound of an approaching vehicle signals when it is safe to cross the street; distinct smartphone notification sounds reflect a call that needs to be answered within a few seconds, or a text that can be read later. Other animals similarly use sounds to plan, time and execute behaviors such as hunting, evading predation and tending to offspring. However, the neural mechanisms that underlie sound-guided prediction of upcoming salient event timing are not well understood. To address this gap, we employed an appetitive sound-triggered reward time prediction behavior in head-fixed mice. We find that mice trained on this task reliably estimate the time from a sound cue to upcoming reward on the scale of a few seconds, as demonstrated by learning-dependent well-timed increases in predictive licking for reward. Moreover, mice showed a dramatic impairment in their ability to use sound to predict delayed reward when the auditory cortex was inactivated, demonstrating its causal involvement. To identify the neurophysiological signatures of auditory cortical reward-timing prediction, we recorded local field potentials during learning and performance of this behavior and found that the magnitude of auditory cortical responses to the sound prospectively encoded the duration of the anticipated sound-reward time interval. Next, we explored how and where these sound-triggered time interval prediction signals propagate from the auditory cortex to time and initiate consequent action. We targeted the monosynaptic projections from the auditory cortex to the posterior striatum and found that chemogenetic inactivation of these projections impaired animals' ability to predict sound-triggered delayed reward. Simultaneous neural recordings in the auditory cortex and posterior striatum during task performance revealed coordination of neural activity across these regions during the sound cue predicting the time interval to reward. Collectively, our findings identify an auditory cortical-striatal circuit supporting sound-triggered timing-prediction behaviors.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003209"},"PeriodicalIF":9.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210020","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":"Identification of a large anion channel required for digestive vacuole acidification and amino acid export in Plasmodium falciparum.","authors":"Gagandeep S Saggu, Jinfeng Shao, Mansoor A Siddiqui, Maria Traver, Tatiane Macedo-Silva, Joseph Brzostowski, Sanjay A Desai","doi":"10.1371/journal.pbio.3003202","DOIUrl":"10.1371/journal.pbio.3003202","url":null,"abstract":"<p><p>Malaria parasites survive in human erythrocytes by importing and digesting hemoglobin within a specialized organelle, the digestive vacuole (DV). Although chloroquine and other antimalarials act within the DV, the routes used by drugs, ions, and amino acids to cross the DV membrane remain poorly understood. Here, we used single DV patch-clamp to identify a novel large conductance anion channel as the primary conductive pathway on this organelle in Plasmodium falciparum, the most virulent human pathogen. This Big Vacuolar Anion Channel (BVAC) is primarily open at the DV resting membrane potential and undergoes complex voltage-dependent gating. Ion substitution experiments implicate promiscuous anion flux with Cl- being the primary charged substrate under physiological conditions. Conductance and gating are unaffected by antimalarials targeting essential DV activities and are conserved on parasites with divergent drug susceptibility profiles, implicating an unexploited antimalarial target. A conditional knockdown strategy excluded links to PfCRT and PfMDR1, two drug-resistance transporters with poorly defined transport activities. We propose that BVAC functions to maintain electroneutrality during H+ uptake, allowing DV acidification and efficient hemoglobin digestion. The channel also facilitates amino acid salvage, providing essential building blocks for parasite growth. Direct transport measurements at the DV membrane provide foundational insights into vacuolar physiology, should help clarify antimalarial action and drug resistance, and will guide therapy development against the parasite's metabolic powerhouse.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003202"},"PeriodicalIF":9.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188355","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":"DnaJ mediates phage sensing by the bacterial NLR-related protein bNACHT25.","authors":"Amy N Conte, Madison E Ruchel, Samantha M Ridgeway, Emily M Kibby, Toni A Nagy, Aaron T Whiteley","doi":"10.1371/journal.pbio.3003203","DOIUrl":"10.1371/journal.pbio.3003203","url":null,"abstract":"<p><p>Bacteria encode a wide range of antiphage systems and a subset of these proteins are homologous to components of the human innate immune system. Mammalian nucleotide-binding and leucine-rich repeat containing proteins (NLRs) and bacterial NLR-related proteins use a central NACHT domain to link detection of infection with initiation of an antimicrobial response. Bacterial NACHT proteins provide defense against both DNA and RNA phages. Here we investigate the mechanism of phage detection by the bacterial NLR-related protein bNACHT25 in E. coli. bNACHT25 was specifically activated by Emesvirus ssRNA phages and analysis of MS2 phage escaper mutants that evaded detection revealed a critical role for Coat Protein (CP). A genetic assay showed CP was sufficient to activate bNACHT25 but the two proteins did not directly interact. Instead, we found bNACHT25 requires the host chaperone DnaJ to detect CP and protect against phage. Our data support a model in which bNACHT25 detects a wide range of phages using an indirect mechanism that may involve guarding a host cell process rather than binding a specific phage-derived molecule.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003203"},"PeriodicalIF":9.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188354","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":"Disruption of HaVipR1 confers Vip3Aa resistance in the moth crop pest Helicoverpa armigera.","authors":"Andreas Bachler, Amanda Padovan, Craig J Anderson, Yiyun Wei, Yidong Wu, Stephen Pearce, Sharon Downes, Bill James, Ashley E Tessnow, Gregory A Sword, Michelle Williams, Wee Tek Tay, Karl H J Gordon, Tom K Walsh","doi":"10.1371/journal.pbio.3003165","DOIUrl":"10.1371/journal.pbio.3003165","url":null,"abstract":"<p><p>The global reliance on Bacillus thuringiensis (Bt) proteins for controlling lepidopteran pests in cotton, corn, and soybean crops underscores the critical need to understand resistance mechanisms. Vip3Aa, one of the most widely deployed and currently effective Bt proteins in genetically modified crops, plays a pivotal role in pest management. This study investigates the molecular basis of Vip3Aa resistance in Australian Helicoverpa armigera through genetic crosses, and integrated genomic and transcriptomic analyses. We identified a previously uncharacterized gene, LOC110373801 (designated HaVipR1), as potentially important in Vip3Aa resistance in two field-derived resistant lines. Functional validation using CRISPR/Cas9 knockout in susceptible lines confirmed the gene's role in conferring high-level resistance to Vip3Aa. Despite extensive laboratory selection of Vip3Aa-resistant colonies in Lepidoptera, the biochemical mechanisms underlying resistance have remained elusive. Our research identifies HaVipR1 as a potential contributor to resistance, adding to our understanding of how insects may develop resistance to this important Bt protein. The identification of HaVipR1 contributes to our understanding of potential resistance mechanisms and may inform future resistance management strategies. Future work should explore the biochemical pathways influenced by HaVipR1 and assess its interactions with other resistance mechanisms. The approach utilized here underscores the value of field-derived resistant lines for understanding resistance in agricultural pests and highlights the need for targeted approaches to manage resistance sustainably.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003165"},"PeriodicalIF":9.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182241","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":"The m5C reader Ybx1 regulates embryonic cortical neurogenesis by promoting progenitor cell cycle progression.","authors":"Jian Zhang, Pengfei Che, Zhuoxuan Yang, Pingrui Zhang, Yuxuan Shui, Xibin Lu, Jiuzhou Xu, Yuanchu She, Yanbo Zhang, Jun Yu, Sheng-Jian Ji","doi":"10.1371/journal.pbio.3003175","DOIUrl":"10.1371/journal.pbio.3003175","url":null,"abstract":"<p><p>The reversible epitranscriptomic mark, 5-methylcytosine (m5C) modification, is implicated in numerous cellular processes, but its role in neural development remains largely unexplored. In this study, we discovered high expression of the m5C reader Ybx1 in the developing mouse cortex. To elucidate its role in cortical development, Ybx1 was ablated in embryonic cortical neural stem cells (NSCs). Interestingly, conditional knockout (cKO) of Ybx1 led to perinatal mortality in mice, along with abnormal cortical development. Cortical progenitor cells lacking Ybx1 exhibited impaired proliferation and differentiation. Multi-omics analysis identified the target mRNAs of Ybx1, which encode the key cell cycle regulatory proteins converging on cyclin D2 (Ccnd2). Ybx1 was found to regulate the stability of its target transcripts. Both knockdown and overexpression of Ybx1 targets via in utero electroporation confirmed that they mediated Ybx1 regulation of proliferation and differentiation of neural precursor cells. Further analysis showed that the G1 to S phase transition in cortical progenitor cells is delayed in the Ybx1 cKO. This study highlights the crucial function of the m5C reader protein Ybx1 in promoting cell cycle progression of the embryonic cortical progenitors, essential for proper cortical development.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003175"},"PeriodicalIF":9.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175488","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":"qByte: An open-source isothermal fluorimeter for democratizing analysis of nucleic acids, proteins and cells.","authors":"Francisco J Quero, Guy Aidelberg, Hortense Vielfaure, Yann Huon de Kermadec, Severine Cazaux, Amir Pandi, Ana Pascual-Garrigos, Anibal Arce, Samuel Sakyi, Urs Gaudenz, Fernan Federici, Jennifer C Molloy, Ariel B Lindner","doi":"10.1371/journal.pbio.3003199","DOIUrl":"10.1371/journal.pbio.3003199","url":null,"abstract":"<p><p>Access to affordable and reliable scientific instrumentation remains a significant barrier to the democratization of healthcare and scientific research. In the field of biotechnology, in particular, the complexity, cost, and infrastructure requirements of many instruments continue to limit their accessibility, especially in resource-limited environments. Despite the recent increase in the development of open-source tools, driven by advances in digital fabrication and electronic prototyping, few of these projects have reached large-scale implementation or validation in real-world settings. Here, we present qByte, an open-source, 8-tube isothermal fluorimeter designed to overcome these barriers by offering a cost-effective ($60) yet production-ready solution. qByte leverages standard digital manufacturing and Printed Circuit Board (PCB) assembly techniques and is designed to be portable, making it ideal for both laboratory and field use. The device has been benchmarked against commercial real-time thermocyclers and spectrophotometers, showing comparable results across four key applications: nucleic acid amplification and detection, including the on-site diagnosis of human parasites in Ghana, analysis of protein activity and stability, genetic construct characterization, and bacterial viability tests. Taken together, our results proved qByte as flexible and reliable equipment for a variety of biological tests and applications, while its affordability and open-source design simplify further development and allow adaptation to the needs of future users.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003199"},"PeriodicalIF":9.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175484","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":"Rhythm profiling using COFE reveals multi-omic circadian rhythms in human cancers in vivo.","authors":"Bharath Ananthasubramaniam, Ramji Venkataramanan","doi":"10.1371/journal.pbio.3003196","DOIUrl":"10.1371/journal.pbio.3003196","url":null,"abstract":"<p><p>The study of ubiquitous circadian rhythms in human physiology requires regular measurements across time. Repeated sampling of the different internal tissues that house circadian clocks is both practically and ethically infeasible. Here, we present a novel unsupervised machine learning approach (COFE) that can use single high-throughput omics samples (without time labels) from individuals to reconstruct circadian rhythms across cohorts. COFE can simultaneously assign time labels to samples and identify rhythmic data features used for temporal reconstruction, while also detecting invalid orderings. With COFE, we discovered widespread de novo circadian gene expression rhythms in 11 different human adenocarcinomas using data from The Cancer Genome Atlas (TCGA) database. The arrangement of peak times of core clock gene expression was conserved across cancers and resembled a healthy functional clock except for the mistiming of a few key genes. Moreover, rhythms in the transcriptome were strongly associated with the cancer-relevant proteome. The rhythmic genes and proteins common to all cancers were involved in metabolism and the cell cycle. Although these rhythms were synchronized with the cell cycle in many cancers, they were uncoupled with clocks in healthy matched tissue. The targets of most of FDA-approved and potential anti-cancer drugs were rhythmic in tumor tissue with different amplitudes and peak times. These findings emphasize the utility of considering \"time\" in cancer therapy, and suggest a focus on clocks in healthy tissue rather than free-running clocks in cancer tissue. Our approach thus creates new opportunities to repurpose data without time labels to study circadian rhythms.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003196"},"PeriodicalIF":9.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163025","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}