Pub Date : 2026-02-20DOI: 10.1038/s41467-025-67901-3
Wei Yu Tang, Ning Dai, Tianshuo Zhou, David H. Mathews, Liang Huang
{"title":"SamplingDesign: RNA design via continuous optimization with coupled variables and Monte-Carlo sampling","authors":"Wei Yu Tang, Ning Dai, Tianshuo Zhou, David H. Mathews, Liang Huang","doi":"10.1038/s41467-025-67901-3","DOIUrl":"https://doi.org/10.1038/s41467-025-67901-3","url":null,"abstract":"","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"7 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20DOI: 10.1038/s41467-026-69485-y
Meredith Townsend, Pablo Moreno-Yaeger, Andrew Harp, Christian Huber, Brad S. Singer
{"title":"Stress pinch points from glacial loading modulate magma ascent and storage in continental arcs","authors":"Meredith Townsend, Pablo Moreno-Yaeger, Andrew Harp, Christian Huber, Brad S. Singer","doi":"10.1038/s41467-026-69485-y","DOIUrl":"https://doi.org/10.1038/s41467-026-69485-y","url":null,"abstract":"","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"43 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20DOI: 10.1038/s41467-026-69625-4
Anna M Hancock, Arabella S Dill-Macky, Jenna A Moore, Catherine Day, Mohamed S Donia, Sujit S Datta
Antibiotic resistance is a growing global health threat. Although antibiotic activity is well studied in homogeneous liquid cultures, many infections are caused by spatially structured multicellular populations where consumption of scarce nutrients establishes strong spatial variations in their abundance. These nutrient variations have long been hypothesized to help bacterial populations tolerate antibiotics, since liquid culture studies link antibiotic tolerance to metabolic activity, and thus, local nutrient availability. Here, we test this hypothesis by visualizing cell death in structured Escherichia coli populations exposed to select nutrients and antibiotics. We find that nutrient availability acts as a bottleneck to antibiotic killing, causing death to propagate through the population as a traveling front. By integrating our measurements with biophysical theory and simulations, we establish quantitative principles that explain how collective nutrient consumption can limit the progression of this "death front," protecting a population from a nominally deadly antibiotic dose. While increasing nutrient supply can overcome this bottleneck, in some cases, excess nutrient unexpectedly promotes the regrowth of resistant cells. Altogether, this work provides a key step toward predicting and controlling antibiotic treatment of spatially structured bacterial populations, yielding biophysical insights into collective behavior and guiding strategies for effective antibiotic stewardship.
{"title":"A nutrient bottleneck controls antibiotic efficacy in structured bacterial populations.","authors":"Anna M Hancock, Arabella S Dill-Macky, Jenna A Moore, Catherine Day, Mohamed S Donia, Sujit S Datta","doi":"10.1038/s41467-026-69625-4","DOIUrl":"https://doi.org/10.1038/s41467-026-69625-4","url":null,"abstract":"<p><p>Antibiotic resistance is a growing global health threat. Although antibiotic activity is well studied in homogeneous liquid cultures, many infections are caused by spatially structured multicellular populations where consumption of scarce nutrients establishes strong spatial variations in their abundance. These nutrient variations have long been hypothesized to help bacterial populations tolerate antibiotics, since liquid culture studies link antibiotic tolerance to metabolic activity, and thus, local nutrient availability. Here, we test this hypothesis by visualizing cell death in structured Escherichia coli populations exposed to select nutrients and antibiotics. We find that nutrient availability acts as a bottleneck to antibiotic killing, causing death to propagate through the population as a traveling front. By integrating our measurements with biophysical theory and simulations, we establish quantitative principles that explain how collective nutrient consumption can limit the progression of this \"death front,\" protecting a population from a nominally deadly antibiotic dose. While increasing nutrient supply can overcome this bottleneck, in some cases, excess nutrient unexpectedly promotes the regrowth of resistant cells. Altogether, this work provides a key step toward predicting and controlling antibiotic treatment of spatially structured bacterial populations, yielding biophysical insights into collective behavior and guiding strategies for effective antibiotic stewardship.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20DOI: 10.1038/s41467-026-69413-0
Rachel Scheck, Mark Melzer, Gregory Gladkov, Louise Leyre, Adam R. Ward, Daniel B. Reeves, Naomi Perkins, T. Thinh Huynh, Deborah K. McMahon, Ronald J. Bosch, Bernard J. Macatangay, Joshua C. Cyktor, Joseph J. Eron, John W. Mellors, Rajesh T. Gandhi, Lisa Buchauer, R. Brad Jones, Christian Gaebler
Precise and scalable quantification of the intact HIV reservoir is critical for advancing curative strategies. Current reservoir assays, such as the intact proviral DNA assay (IPDA), are limited by quantification failures or misclassification of defective proviruses due to HIV sequence heterogeneity. Q4ddPCR is a modular, droplet digital PCR simultaneously targeting four conserved regions in the HIV genome to improve specificity, reduce quantification gaps, and provide multi-layered readouts. It comprises two configurations: one fully based on Q4PCR primer/probes and one combining IPDA with gag and pol primer/probes from Q4PCR. We benchmark Q4ddPCR against 3650 near full-length proviral sequences from 13 virally suppressed people with HIV (PWH) generated by Q4PCR. Q4ddPCR closely matches sequence-confirmed reservoir measurements, and multi-probe readouts reveal clonal reservoir dynamics not detectable by IPDA. Q4ddPCR enables intact reservoir quantification in 95% of samples across four independent cohorts and in 16 PWH, strongly correlates with viral outgrowth. In longitudinal samples from 42 participants over the first 4.5 years on antiretroviral therapy (ART), Q4ddPCR reports lower proviral frequencies and a steeper decline in intact proviral DNA compared to IPDA. Collectively, our findings confirm key predictions from mathematical modeling, demonstrating that multi-target assays improve specificity and more accurately capture intact reservoir dynamics.
{"title":"Q4ddPCR: a flexible, 4-target assay for high-resolution HIV reservoir profiling","authors":"Rachel Scheck, Mark Melzer, Gregory Gladkov, Louise Leyre, Adam R. Ward, Daniel B. Reeves, Naomi Perkins, T. Thinh Huynh, Deborah K. McMahon, Ronald J. Bosch, Bernard J. Macatangay, Joshua C. Cyktor, Joseph J. Eron, John W. Mellors, Rajesh T. Gandhi, Lisa Buchauer, R. Brad Jones, Christian Gaebler","doi":"10.1038/s41467-026-69413-0","DOIUrl":"https://doi.org/10.1038/s41467-026-69413-0","url":null,"abstract":"Precise and scalable quantification of the intact HIV reservoir is critical for advancing curative strategies. Current reservoir assays, such as the intact proviral DNA assay (IPDA), are limited by quantification failures or misclassification of defective proviruses due to HIV sequence heterogeneity. Q4ddPCR is a modular, droplet digital PCR simultaneously targeting four conserved regions in the HIV genome to improve specificity, reduce quantification gaps, and provide multi-layered readouts. It comprises two configurations: one fully based on Q4PCR primer/probes and one combining IPDA with <jats:italic>gag</jats:italic> and <jats:italic>pol</jats:italic> primer/probes from Q4PCR. We benchmark Q4ddPCR against 3650 near full-length proviral sequences from 13 virally suppressed people with HIV (PWH) generated by Q4PCR. Q4ddPCR closely matches sequence-confirmed reservoir measurements, and multi-probe readouts reveal clonal reservoir dynamics not detectable by IPDA. Q4ddPCR enables intact reservoir quantification in 95% of samples across four independent cohorts and in 16 PWH, strongly correlates with viral outgrowth. In longitudinal samples from 42 participants over the first 4.5 years on antiretroviral therapy (ART), Q4ddPCR reports lower proviral frequencies and a steeper decline in intact proviral DNA compared to IPDA. Collectively, our findings confirm key predictions from mathematical modeling, demonstrating that multi-target assays improve specificity and more accurately capture intact reservoir dynamics.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"322 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20DOI: 10.1038/s41467-026-69626-3
Finia Uecker, Frederik M Ahrens, Tim Ruder, Thomas Pfannschmidt
Photosynthesis genes in plant chloroplasts are transcribed by the plastid-encoded RNA polymerase called PEP. Consequently, PEP-deficient mutants cannot generate a photosynthetic apparatus and develop non-viable albino seedlings. Inducible complementation of such mutants thus could provide interesting insights in PEP action and chloroplast biogenesis. Here we show the effects of photo-inducible complementation in the albino Arabidopsis mutant pap7-1 using a red/blue optoswitch with monochromatic LEDs. Expression of a blue-light-induced PAP7 construct that is silent under red light reconstitutes PEP at any time point of pap7-1 development resulting in proper chloroplast biogenesis that rescues the non-viable mutant. Induction of chloroplast biogenesis, however, can only occur in very young leaf tissues indicating the existence of a cell-autonomous, biogenic coupling between cell and organelle development. We further uncover that initial PEP formation and function is independent of photosynthesis. The optoswitch termed blue-light valved biogenesis opens experimental avenues to study non-viable plant mutants.
{"title":"A red/blue optoswitch for temporal control of chloroplast transcription and biogenesis in Arabidopsis.","authors":"Finia Uecker, Frederik M Ahrens, Tim Ruder, Thomas Pfannschmidt","doi":"10.1038/s41467-026-69626-3","DOIUrl":"https://doi.org/10.1038/s41467-026-69626-3","url":null,"abstract":"<p><p>Photosynthesis genes in plant chloroplasts are transcribed by the plastid-encoded RNA polymerase called PEP. Consequently, PEP-deficient mutants cannot generate a photosynthetic apparatus and develop non-viable albino seedlings. Inducible complementation of such mutants thus could provide interesting insights in PEP action and chloroplast biogenesis. Here we show the effects of photo-inducible complementation in the albino Arabidopsis mutant pap7-1 using a red/blue optoswitch with monochromatic LEDs. Expression of a blue-light-induced PAP7 construct that is silent under red light reconstitutes PEP at any time point of pap7-1 development resulting in proper chloroplast biogenesis that rescues the non-viable mutant. Induction of chloroplast biogenesis, however, can only occur in very young leaf tissues indicating the existence of a cell-autonomous, biogenic coupling between cell and organelle development. We further uncover that initial PEP formation and function is independent of photosynthesis. The optoswitch termed blue-light valved biogenesis opens experimental avenues to study non-viable plant mutants.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20DOI: 10.1038/s41467-026-69885-0
Channah M Gaasbeek, Eric R A Vos, Annika M van Roon, Dimphey van Meijeren, Gaby Smits, Marjan Kuijer, Marion Koopmans, Hester de Melker, Fiona R M van der Klis, Rob van Binnendijk, Gerco den Hartog
After relative absence of Bordetella pertussis during the COVID-19 pandemic, notifications in the Netherlands were increased from May 2023 till September 2024. We monitored the largest pertussis outbreak in decades and investigated underlying immunological dynamics based on IgG and IgA antibodies against pertussis antigens (Ptx, FHA & Prn). We analyzed serum from 418 participants (2-87 years) at five timepoints (November 2022-October 2024) from a nationwide prospective serosurveillance study (PIENTER-Corona). Weighted incidence over two years was 6.3% (95% CI: 4.4-8.2) in the Dutch population, and 35% (95% CI: 26.2-44.6) in 6-18y-olds. Children aged 6-12 years, who received a booster vaccination at 4 years, showed lowest anti-Ptx IgG concentrations after the period of reduced circulation. Infected individuals had lower pre-infection anti-FHA IgG and IgA concentrations than matched uninfected individuals. Prolonged coughing was reported by 16% of the infected individuals. Our findings highlight the B. pertussis outbreak was preceded by waning immunity, particularly after acellular pertussis booster vaccination. The small proportion of symptomatic infections implies sufficient protection by the vaccine against disease but not transmission.
{"title":"Antibody waning and Bordetella pertussis resurgence after the COVID-19 pandemic in the Netherlands.","authors":"Channah M Gaasbeek, Eric R A Vos, Annika M van Roon, Dimphey van Meijeren, Gaby Smits, Marjan Kuijer, Marion Koopmans, Hester de Melker, Fiona R M van der Klis, Rob van Binnendijk, Gerco den Hartog","doi":"10.1038/s41467-026-69885-0","DOIUrl":"https://doi.org/10.1038/s41467-026-69885-0","url":null,"abstract":"<p><p>After relative absence of Bordetella pertussis during the COVID-19 pandemic, notifications in the Netherlands were increased from May 2023 till September 2024. We monitored the largest pertussis outbreak in decades and investigated underlying immunological dynamics based on IgG and IgA antibodies against pertussis antigens (Ptx, FHA & Prn). We analyzed serum from 418 participants (2-87 years) at five timepoints (November 2022-October 2024) from a nationwide prospective serosurveillance study (PIENTER-Corona). Weighted incidence over two years was 6.3% (95% CI: 4.4-8.2) in the Dutch population, and 35% (95% CI: 26.2-44.6) in 6-18y-olds. Children aged 6-12 years, who received a booster vaccination at 4 years, showed lowest anti-Ptx IgG concentrations after the period of reduced circulation. Infected individuals had lower pre-infection anti-FHA IgG and IgA concentrations than matched uninfected individuals. Prolonged coughing was reported by 16% of the infected individuals. Our findings highlight the B. pertussis outbreak was preceded by waning immunity, particularly after acellular pertussis booster vaccination. The small proportion of symptomatic infections implies sufficient protection by the vaccine against disease but not transmission.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Exploring dielectrics with high gate capacitance and artificial tailoring of electronic states is highly desirable for the development of 2D electronics. Here, we report the synthesis of a single-crystalline ionic dielectric Sb4O5Cl2 with aligned ionic channels, achieving a dielectric constant of 23.3 (at a thickness of ~ 25 nm) and non-volatile programmable regulation of the ionic migration. The fabricated 2D MoS2 transistors display on/off ratios up to 109, leakage currents down to 10-14 A, and mobility of 33.4 cm2 V-1 s-1. Oriented ionic channels facilitate efficient and controllable migration of Cl- ions, thus realizing a non-structural-damage and reconfigurable transition between a quasi-metallic and semiconducting state in MoS2, with a retention time exceeding 3000 s. During 100 cycles of state transitions, the quasi-metallic state exhibits a conductivity of 10-5 S, which is 103 times that of the semiconducting state. Bio-inspired ionic channel further allows neuromorphic devices to integrate image storage, processing, and recognition capabilities, achieving a recognition accuracy improvement from 80.7% to 90.9% within just 5 training epochs through non-volatile preprocessing lasting over 300 s. Our study highlights the significant potential of this single-crystal ionic dielectric as a promising platform for fundamental research on electronic state modulation and advanced electronics.
{"title":"Oriented ion migration in dielectric Sb<sub>4</sub>O<sub>5</sub>Cl<sub>2</sub> single crystals for multifunctional two-dimensional electronics.","authors":"Zexin Li, Genchang Gou, Xiang Xu, Haoyun Wang, Teng Liu, Hao Luo, Jinsong Wu, Kailang Liu, Liang Gao, Tianyou Zhai, Xing Zhou","doi":"10.1038/s41467-026-69869-0","DOIUrl":"https://doi.org/10.1038/s41467-026-69869-0","url":null,"abstract":"<p><p>Exploring dielectrics with high gate capacitance and artificial tailoring of electronic states is highly desirable for the development of 2D electronics. Here, we report the synthesis of a single-crystalline ionic dielectric Sb<sub>4</sub>O<sub>5</sub>Cl<sub>2</sub> with aligned ionic channels, achieving a dielectric constant of 23.3 (at a thickness of ~ 25 nm) and non-volatile programmable regulation of the ionic migration. The fabricated 2D MoS<sub>2</sub> transistors display on/off ratios up to 10<sup>9</sup><sub>,</sub> leakage currents down to 10<sup>-14</sup> A, and mobility of 33.4 cm<sup>2 </sup>V<sup>-1</sup> s<sup>-1</sup>. Oriented ionic channels facilitate efficient and controllable migration of Cl<sup>-</sup> ions, thus realizing a non-structural-damage and reconfigurable transition between a quasi-metallic and semiconducting state in MoS<sub>2</sub>, with a retention time exceeding 3000 s. During 100 cycles of state transitions, the quasi-metallic state exhibits a conductivity of 10<sup>-5</sup> S, which is 10<sup>3</sup> times that of the semiconducting state. Bio-inspired ionic channel further allows neuromorphic devices to integrate image storage, processing, and recognition capabilities, achieving a recognition accuracy improvement from 80.7% to 90.9% within just 5 training epochs through non-volatile preprocessing lasting over 300 s. Our study highlights the significant potential of this single-crystal ionic dielectric as a promising platform for fundamental research on electronic state modulation and advanced electronics.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":" ","pages":""},"PeriodicalIF":15.7,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}