{"title":"Symmetric cancer spheroid-fibroblast organization revealed in 3D by high-throughput microscopy.","authors":"Noam Zoref, Maytal Avrashami, Nadav Opatovski, Paul Keselman, Yosi Shamay, Yoav Shechtman","doi":"10.1038/s42003-026-10592-3","DOIUrl":"10.1038/s42003-026-10592-3","url":null,"abstract":"<p><p>High-throughput microscopy enables large-scale analysis of cancer spheroid interactions. Integrating this technique with point-spread function (PSF) engineering, a customized modification of the optical system, provides 3D imaging capabilities that enable volumetric analysis of the samples from a minimal number of images, thereby reducing phototoxicity and improving temporal resolution. However, existing methods for extracting volumetric information using PSF engineering have been demonstrated primarily on point sources or rely on supervised training data, limiting their general applicability to complex biological samples. Here, we reveal a unique symmetric spheroid-fibroblast interaction pattern using high-throughput imaging. We further characterize these interactions using a PSF-engineered high-throughput microscope, introducing unsupervised methods for 3D localization from single or dual image acquisitions. Our analysis uncovers surprising spatial cellular trajectories of fibroblasts as they approach and interact with spheroids. It further identifies a characteristic 3D distance between adjacent fibroblast clusters and enables live detection of drug-induced perturbations to these interaction patterns.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599744","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":"Energy paradox in REM sleep: balancing supply and consumption in brain metabolism.","authors":"Yusuke Takahashi, Yoko Ikoma, Ko Matsui","doi":"10.1038/s42003-026-10646-6","DOIUrl":"10.1038/s42003-026-10646-6","url":null,"abstract":"<p><p>The brain's capacity for information processing depends on precisely regulated energy dynamics. Yet how metabolic supply adapts to shifting computational demands across brain states remains unclear. Using wide-field fluorescence imaging through the intact skull of live mice, we simultaneously monitored brain blood volume (BBV), astrocytic pyruvate, and neuronal ATP levels during natural sleep. We found that large-scale metabolic dynamics are coupled to neuronal activity but reorganize in a state-dependent manner. During non-rapid eye movement (NREM) sleep, theta-band electrocorticogram (ECoG) activity predicted subsequent blood volume changes, accompanied by rapid anterior-to-posterior vascular waves. In contrast, REM sleep was marked by a pronounced increase in BBV, originating in the posterior cortex and slowly propagating across the brain. This was accompanied by elevated astrocytic pyruvate; paradoxically, however, neuronal ATP levels declined sharply. These findings reveal a dynamic interplay among neurons, astrocytes, and the vasculature, suggesting that distinct energy-allocation strategies underlie the brain's computational flexibility.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599732","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}
Alex Jinich-Diamant, Sierra Simpson, Juan P Zuniga-Hertz, Ramamurthy Chitteti, Jan M Schilling, Jacqueline A Bonds, Laura Case, Andrei V Chernov, Joe Dispenza, Jacqueline Maree, Natalia Esther Amkie Stahl, Michael Licamele, Narin Fazlalipour, Swetha Devulapalli, Leonardo Christov-Moore, Nicco Reggente, Michelle A Poirier, Tobias Moeller-Bertram, Hemal H Patel
{"title":"Author Correction: Neural and molecular changes during a mind-body reconceptualization, meditation, and open label placebo healing retreat: an observational study.","authors":"Alex Jinich-Diamant, Sierra Simpson, Juan P Zuniga-Hertz, Ramamurthy Chitteti, Jan M Schilling, Jacqueline A Bonds, Laura Case, Andrei V Chernov, Joe Dispenza, Jacqueline Maree, Natalia Esther Amkie Stahl, Michael Licamele, Narin Fazlalipour, Swetha Devulapalli, Leonardo Christov-Moore, Nicco Reggente, Michelle A Poirier, Tobias Moeller-Bertram, Hemal H Patel","doi":"10.1038/s42003-026-10719-6","DOIUrl":"10.1038/s42003-026-10719-6","url":null,"abstract":"","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590652","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}
Ryota Tsuruga, Yu Tajika, Masabumi Minami, Iku Tsutsui-Kimura
{"title":"Dopamine dynamics as a regulatory mechanism for shifting between defensive and reward-seeking behaviors.","authors":"Ryota Tsuruga, Yu Tajika, Masabumi Minami, Iku Tsutsui-Kimura","doi":"10.1038/s42003-026-10485-5","DOIUrl":"10.1038/s42003-026-10485-5","url":null,"abstract":"<p><p>Understanding how the brain evaluates aversion and appetition to guide behavior is an important question. Here, we investigated the role of dopamine signaling in the tail of the striatum (TS) in regulating competing valence-based behaviors and learning. TS dopamine dynamics were monitored as mice performed a classical conditioning task in which an odor cue predicted either an aversive air puff or a water reward. Initially, mice exhibited anticipatory blinking, which diminished over time, while anticipatory licking emerged later, coinciding with adaptation to the air puff. Dopamine responses in the TS to the air puff and its associated odor were initially elevated but declined with repeated exposure. Ablation of TS dopamine inhibited avoidance learning and accelerated appetitive learning. Optogenetic disruption of dopaminergic decline suppressed adaptation and hindered appetitive learning. These findings demonstrate that TS dopamine dynamics are essential for avoidance and adaptation to aversive stimuli, which indirectly modulates appetitive learning, underscoring a regulatory mechanism for shifting between defensive and reward-seeking behaviors.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583565","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}
Shi Chen, Saiyu Li, Hejiang Guo, Shuaining Gao, Yue Gao, Lehan Ding, Bin Zhao, Kun Zhong, Hua Guan, Rui-Yun Peng, Ping-Kun Zhou
{"title":"Crotonylation of ACAT1 K181 contributes to radioresistance by impacting lactate metabolism.","authors":"Shi Chen, Saiyu Li, Hejiang Guo, Shuaining Gao, Yue Gao, Lehan Ding, Bin Zhao, Kun Zhong, Hua Guan, Rui-Yun Peng, Ping-Kun Zhou","doi":"10.1038/s42003-026-10701-2","DOIUrl":"10.1038/s42003-026-10701-2","url":null,"abstract":"<p><p>Ionizing radiation (IR)-induced alterations in glucose metabolism are closely associated with radioresistance, yet the underlying mechanisms remain incompletely understood. Here, we identify a post-translational modification axis in which IR induces general control non-repressible protein 5 (GCN5/KAT2A)-mediated crotonylation of acetyl-CoA acetyltransferase 1 (ACAT1) at lysine 181 (K181), thereby enhancing ACAT1 activity and promoting increased acetylation of pyruvate dehydrogenase E1 subunit alpha (PDHA1) along with its phosphorylation at S293.These changes led to inhibition of PDHA1, impaired pyruvate metabolism, and increased lactate accumulation. Functional studies demonstrated that ACAT1 K181R (a decrotonylation-mimicking mutant) increased radiosensitivity and significantly attenuated IR-induced lactate production. Collectively, these findings reveal an unrecognized mechanism by which radiotherapy reprograms cellular metabolism through the GCN5-ACAT1-PDHA1 axis, linking ACAT1 crotonylation to altered pyruvate metabolism, enhanced lactate production, and subsequent radioresistance. These findings suggest that targeting ACAT1 K181 crotonylation represents a potential therapeutic strategy to improve tumor radiosensitivity.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720280","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":"A telomere-to-telomere genome reveals arachidonic acid as a key regulator of hepatic lipid metabolism during hibernation.","authors":"Linjuan Wang, Pengyu Chen, Qingjing Gao, Yating Men, Quanzheng Yun, Qikun Zhang, Xin Xing, Yue Zhou, Chuhan Wang, Qiang Weng, Yingying Han, Yuning Liu, Haolin Zhang, Zhengrong Yuan","doi":"10.1038/s42003-026-10625-x","DOIUrl":"https://doi.org/10.1038/s42003-026-10625-x","url":null,"abstract":"<p><p>Elucidating the molecular mechanisms governing mammalian hibernation is crucial for understanding energy homeostasis and physiological adaptation to extreme environments. In this study, we present the first high-quality telomere-to-telomere (T2T) reference genome (2.69 Gb) of the Daurian ground squirrel (Spermophilus dauricus), a typical hibernating mammal. The assembled genome comprises 19 chromosomes, nine of which are completely gapless chromosomes, and exhibits a scaffold N50 of 160 Mb. Comparative genomic analysis with 17 hibernating and non-hibernating mammals revealed lineage-specific expansions, the arachidonic acid metabolic pathway was one of the pathways enriched in 222 expanded gene families. To explore the temporal regulation of metabolic pathways during hibernation, we performed multi-omics analysis using liver tissue samples collected at four distinct periods: pre-hibernation (PH), hibernation (H), emergence from hibernation (EH), and summer active (SA). Transcriptomic and metabolomic analysis identified a cluster of lipid metabolism-related genes dynamically regulated during hibernation, highlighting the arachidonic acid (20:4 n-6) as a key regulatory molecule for lipid energy remodeling. Molecular docking and in vitro assays using primary hepatocytes from the Daurian ground squirrel demonstrated that arachidonic acid interacts with PPARα (Peroxisome proliferator-activated receptor alpha) and TRPV channel (Transient receptor potential vanilloid subfamily member), triggering intracellular Ca<sup>2+</sup> signaling and increasing the expression of lipid metabolic enzymes, thereby modulating hepatic lipid metabolism during hibernation. Collectively, our study not only provides the first T2T genome of a hibernating mammal but also uncovers an arachidonic acid-mediated lipid metabolic regulatory mechanism, offering evolutionary and biomedical insights into metabolic plasticity during hibernation.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548164","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}
Kiarash Behrouzfar, Win Min Han, Rashindrie Perera, Jason Li, Katherine E Scull, Kerryn Howlett, Mark Bloch, David A Baker, Beng Eu, Ellen Bowden-Reid, Don E Smith, Jennifer F Hoy, Ian Woolley, Robert Finlayson, David J Templeton, Gail V Matthews, Jane Costello, Mark A Dawson, Sarah-Jane Dawson, Mark N Polizzotto, Kathy Petoumenos, Nila J Dharan, Paul Yeh
{"title":"Mosaic chromosomal alterations are suppressed in older adults with HIV.","authors":"Kiarash Behrouzfar, Win Min Han, Rashindrie Perera, Jason Li, Katherine E Scull, Kerryn Howlett, Mark Bloch, David A Baker, Beng Eu, Ellen Bowden-Reid, Don E Smith, Jennifer F Hoy, Ian Woolley, Robert Finlayson, David J Templeton, Gail V Matthews, Jane Costello, Mark A Dawson, Sarah-Jane Dawson, Mark N Polizzotto, Kathy Petoumenos, Nila J Dharan, Paul Yeh","doi":"10.1038/s42003-026-10532-1","DOIUrl":"10.1038/s42003-026-10532-1","url":null,"abstract":"<p><p>Somatic gene mutations (SGMs) that drive clonal haematopoiesis (CH) have been shown to be more prevalent in people with HIV (PWH), potentially contributing to the higher risk of comorbidities in PWH compared to those without HIV. It is unknown whether mosaic chromosomal alterations (mCA), another form of CH, are associated with HIV. We demonstrate, for the first time, a markedly lower prevalence of mosaic chromosomal alterations (mCA), particularly loss of chromosome Y, in PWH compared to participants without HIV - an opposing pattern to SGMs. Our findings that mCA development may be suppressed in HIV infection suggest that the selective pressures driving mCA-related CH differ fundamentally from those driving SGM-related CH.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548033","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}
Adrian W Gilmore, Leonardo Claudino, Cassandra M Levesque, Anna M Agron, Peter J Molfese, Vinai Roopchansingh, Michael D Rugg, Stephen J Gotts, Alex Martin
{"title":"Repetition-related reductions in neural activity support improved behavior through increases in oscillatory power.","authors":"Adrian W Gilmore, Leonardo Claudino, Cassandra M Levesque, Anna M Agron, Peter J Molfese, Vinai Roopchansingh, Michael D Rugg, Stephen J Gotts, Alex Martin","doi":"10.1038/s42003-026-10668-0","DOIUrl":"10.1038/s42003-026-10668-0","url":null,"abstract":"<p><p>Repeatedly processing an object leads to subsequent behavioral improvements in its identification and reductions in associated neural activity, a form of neural processing efficiency that multiple theoretical models have attempted to explain. Using simultaneous EEG/fMRI in humans during object naming, we find that stimulus-driven oscillatory power from high (gamma) to low frequencies (theta) increases and resolves earlier with repetition in task-engaged frontal and occipitotemporal brain regions identified as showing repetition suppression in fMRI. Repetition-related increases and decreases in gamma oscillatory power in these regions were correlated with behavioral priming across subjects (|rs| ≥ 0.39) and additionally with fMRI repetition suppression in left frontal cortex (r = -0.37). Similar correlations were observed between behavioral priming and oscillatory power changes when effects were examined within subjects (|rs| ≥ 0.34). Collectively, these data provide multimodal support for a novel mixture of the previously proposed Synchrony and Facilitation models.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548170","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}
Andrés F Bedoya-López, Sandra Íñiguez-Muñoz, Javier I J Orozco, Miquel Ensenyat-Méndez, Betsy J Valdez, Alexander D Boiko, Mar Morote-Llabrés, Huiwen Bill Xie, Maggie L DiNome, Pere Llinàs-Arias, Diego M Marzese
{"title":"DNA methylation reprogramming of gene regulatory elements is associated with lung metastasis in triple-negative breast cancer.","authors":"Andrés F Bedoya-López, Sandra Íñiguez-Muñoz, Javier I J Orozco, Miquel Ensenyat-Méndez, Betsy J Valdez, Alexander D Boiko, Mar Morote-Llabrés, Huiwen Bill Xie, Maggie L DiNome, Pere Llinàs-Arias, Diego M Marzese","doi":"10.1038/s42003-026-10698-8","DOIUrl":"10.1038/s42003-026-10698-8","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a major cause of cancer mortality, with distant metastases, particularly to the lungs, presenting a significant clinical challenge. While epigenetic mechanisms like DNA methylation (DNAm) are known to influence TNBC progression, their association with lung metastasis remains underexplored. To address this gap, we analyze epigenomic and transcriptomic profiles from TNBC cells, xenograft models, and patient cohorts. DNAm profiling of primary tumors, lymph nodes, and lung metastases in our xenograft model reveals significant genome-wide hypomethylation in lung lesions, consistent with findings on patient samples from the AURORA US cohort. Promoter-methylation changes are enriched in pathways linked to invasion and proliferation, and transcriptomic integration identifies 22 regulated genes, with outcome effects varying according to the histone chromatin context. In vitro demethylation in TNBC cells partially recapitulates the expression changes of several candidate genes. Beyond promoters, enhancer elements are also dysregulated in lung metastases, potentially affecting the expression of their associated genes. Among others, elevated AK1, TPI1, and ENO1 expression correlates with a higher risk of lung dissemination in primary TNBC tumors. These findings highlight DNAm alterations associated with TNBC lung colonization and identify candidate prognostic markers, emphasizing DNAm reprogramming as a feature of breast-to-lung-metastatic progression.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548182","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}
Dani Beck, Chloe Carrick, Eira R Aksnes, Niamh MacSweeney, Lars T Westlye, Delia Fuhrmann, Christian K Tamnes
{"title":"Synchrony between brain age and internalising and externalising symptoms across adolescence.","authors":"Dani Beck, Chloe Carrick, Eira R Aksnes, Niamh MacSweeney, Lars T Westlye, Delia Fuhrmann, Christian K Tamnes","doi":"10.1038/s42003-026-10722-x","DOIUrl":"10.1038/s42003-026-10722-x","url":null,"abstract":"<p><p>Adolescence is a period of rapid neurobiological and behavioural change, yet how brain maturation deviations relate to psychopathology remains unclear. Here, we show, using data from the Adolescent Brain Cognitive Development Study, that deviations in brain age are coupled with internalising and externalising symptom development across adolescence. Combining multimodal brain age prediction across four waves (ages ~8.3-17.5) with bivariate latent growth curve models of ten symptom waves, we found coordinated nonlinear development between brain maturation and symptoms: adolescents whose brains increasingly diverged from age-expected maturation showed increasing symptoms. Effects were most consistent for internalising symptoms in females (r = 0.15-0.23) and broader for externalising symptoms in both sexes (r = 0.15-0.32); intercept-level associations were weaker (r = 0.08-0.09). Sex differences were not robust after correction. Vulnerability to adolescent psychopathology appears more closely linked to changes in brain maturational tempo than to fixed differences in brain age.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548139","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}