PNAS nexus最新文献

{"title":"Enzymes helping enzymes: Oxaloacetate decarboxylase increases malate dehydrogenase's turnover number.","authors":"Gadiel Saper, Henry Hess","doi":"10.1093/pnasnexus/pgaf134","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf134","url":null,"abstract":"<p><p>The catalytic performance of enzymes is largely perceived to be a property of the enzyme itself, altered by environmental conditions, such as temperature and pH. However, the maximal catalytic rates of enzymes differ up to 100-fold between in vivo and in vitro measurements, suggesting that a complex chemical system has additional effects on catalytic performance. In this work, we show that the initial rate of an enzyme can increase 3-fold due to the presence of a second enzyme, which uses the product of the first enzyme as its substrate. This enhancement may originate in an allosteric effect or result from binding competition for the product molecule by the second enzyme.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf134"},"PeriodicalIF":2.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-sustained rhythmic behavior of <i>Synechocystis</i> sp. PCC 6803 under continuous light conditions in the absence of light-dark entrainment.","authors":"Lutz Claus Berwanger, Nikolaus Thumm, Florian Pascal Stirba, Rahil Gholamipoorfard, Alice Pawlowski, Petra Kolkhof, Jeannine Volke, Markus Kollmann, Anika Wiegard, Ilka Maria Axmann","doi":"10.1093/pnasnexus/pgaf120","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf120","url":null,"abstract":"<p><p>Circadian clocks regulate biological activities, providing organisms with a fitness advantage under diurnal conditions by enabling anticipation and adaptation to recurring external changes. Three proteins, KaiA, KaiB, and KaiC, constitute the circadian clock in the cyanobacterial model <i>Synechococcus elongatus</i> PCC 7942. Several techniques established to measure circadian output in <i>Synechococcus</i> yielded comparably weak signals in <i>Synechocystis</i> sp. PCC 6803, a strain important for biotechnological applications. We applied an approach that does not require genetic modifications to monitor the circadian rhythms in <i>Synechococcus</i> and <i>Synechocystis</i>. We placed batch cultures in shake flasks on a sensor detecting backscattered light via noninvasive online measurements. Backscattering oscillated with a period of ∼24 h around the average growth. Wavelet and Fourier transformations are applied to determine the period's significance and length. In <i>Synechocystis</i>, oscillations fulfilled the circadian criteria of temperature compensation and entrainment by external stimuli. Remarkably, dilution alone synchronized oscillations. Western blotting revealed that the backscatter was ∼6.5 h phase-delayed in comparison to KaiC3 phosphorylation.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf120"},"PeriodicalIF":2.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metacognitive sensitivity: The key to calibrating trust and optimal decision making with AI.","authors":"Doyeon Lee, Joseph Pruitt, Tianyu Zhou, Jing Du, Brian Odegaard","doi":"10.1093/pnasnexus/pgaf133","DOIUrl":"10.1093/pnasnexus/pgaf133","url":null,"abstract":"<p><p>Knowing when to trust and incorporate the advice from artificially intelligent (AI) systems is of increasing importance in the modern world. Research indicates that when AI provides high confidence ratings, human users often correspondingly increase their trust in such judgments, but these increases in trust can occur even when AI fails to provide accurate information on a given task. In this piece, we argue that measures of metacognitive sensitivity provided by AI systems will likely play a critical role in (1) helping individuals to calibrate their level of trust in these systems and (2) optimally incorporating advice from AI into human-AI hybrid decision making. We draw upon a seminal finding in the perceptual decision-making literature that demonstrates the importance of metacognitive ratings for optimal joint decisions and outline a framework to test how different types of information provided by AI systems can guide decision making.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf133"},"PeriodicalIF":2.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Air pollutions affect restaurant and foodservice industry in China.","authors":"Xu Tian, Shi Min, Jiexi Shen, Qianqian Hong, Derek Headey, Fangxiao Zhao, Xiaobing Wang","doi":"10.1093/pnasnexus/pgaf124","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf124","url":null,"abstract":"<p><p>This study examines the impact of air pollution on food away from home (FAFH) consumption in 52 cities across 20 provinces of China, focusing on expenditures for online food delivery (online FAFH) and dine-in restaurants (offline FAFH). Using unique daily aggregated city-level consumption data linked with hourly air quality data, we employ both semiparametric and parametric models to uncover a positive relationship between PM2.5 levels and online FAFH, contrasted by a significantly negative relationship with offline FAFH. Our analysis reveals that shifts in consumer demand for food services on polluted days, coupled with changes in urban mobility patterns, contribute to these outcomes. We also detect temporal variations based on meal type, enhancing our understanding of how air pollution influences food consumption behavior. The findings indicate that increased PM2.5 levels lead to a net loss in restaurant revenue, a reduction in greenhouse gas emissions, and an increase in plastic waste. These findings contribute to a deeper understanding of the multifaceted impacts of air pollution on FAFH and corresponding economy and environmental implications.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf124"},"PeriodicalIF":2.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotics in the global river system arising from human consumption.","authors":"Heloisa Ehalt Macedo, Bernhard Lehner, Jim A Nicell, Usman Khan, Eili Y Klein","doi":"10.1093/pnasnexus/pgaf096","DOIUrl":"10.1093/pnasnexus/pgaf096","url":null,"abstract":"<p><p>The presence of antibiotics in surface waters poses risks to aquatic ecosystems and human health due to their toxicity and influence on antimicrobial resistance. After human consumption and partial metabolism, antibiotic residues are excreted and undergo complex accumulation and decay processes along their pathway from wastewater to natural river systems. Here, we use a global contaminant fate model to estimate that of the annual human consumption of the 40 most used antibiotics (29,200 tonnes), 8,500 tonnes (29%) are released into the river system and 3,300 tonnes (11%) reach the world's oceans or inland sinks. Even when only domestic sources are considered (i.e. not including veterinary or industrial sources), we estimate that 6 million km of rivers worldwide are subject to total antibiotic concentrations in excess of thresholds that are protective of ecosystems and resistance promotion during low streamflow conditions, with the dominant contributors being amoxicillin, ceftriaxone, and cefixime. Therefore, it is of concern that human consumption alone represents a significant risk for rivers across all continents, with the largest extents found in Southeast Asia. Global antibiotic consumption has grown rapidly over the last 15 years and continues to increase, particularly in low- and middle-income countries, requiring new strategies to safeguard water quality and protect human and ecosystem health.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 4","pages":"pgaf096"},"PeriodicalIF":2.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion of senescent cells improves surgery-induced neuroinflammation in aged mice.","authors":"Sajeeshkumar Madhurakkat Perikamana, Hunter Newman, Yuru Vernon Shih, Lavonia Duncan, Hilal Ahmad Rather, Jiaoni Li, Ravikanth Velagapudi, Niccolò Terrando, Shyni Varghese","doi":"10.1093/pnasnexus/pgaf103","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf103","url":null,"abstract":"<p><p>Aging has been identified as a leading risk factor for many diseases, including neurodegenerative disorders. While cellular senescence has been linked to age-related neurodegenerative conditions, its involvement in peripheral stress-associated brain disorders is just beginning to be explored. In this study, we investigated the impact of senescent cells on peripheral stress-induced neuroinflammation using orthopedic surgery as a model. Our results demonstrate an increased accumulation of senescent cells and neuroinflammation in the aged mouse hippocampus following surgery. Intermittent treatment of the mice with the senolytic drugs dasatinib and quercetin (D/Q) showed a significant reduction in surgery-induced senescent cell burden. This reduction in senescent cell accumulation was correlated with reduced surgery-induced neuroinflammation, as evidenced by decreased glial cell activity. Consistent with these observations, we also observed reduced levels of proinflammatory senescence-associated secretory phenotype factors in circulation, following fracture surgery, in mice treated with D/Q. Overall, our findings underscore the pivotal role of cellular senescence in surgery-induced neuroinflammation and highlight the therapeutic potential of eliminating senescent cells as a potential strategy to manage peripheral stress-induced neuroinflammatory conditions.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 4","pages":"pgaf103"},"PeriodicalIF":2.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of hallucinogen persisting perception disorder and thought disturbance symptoms following psychedelic use.","authors":"Katie Zhou, David de Wied, Robin L Carhart-Harris, Hannes Kettner","doi":"10.1093/pnasnexus/pgae560","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae560","url":null,"abstract":"<p><p>Interest in using psychedelic drugs to treat psychiatric disorders is growing rapidly. While modern controlled clinical trials show a favorable safety and efficacy profile, it remains unclear if the risk of side effects would increase with broader use in more heterogeneous populations. To address this, we investigated the frequency and baseline predictors of delusional ideation, magical thinking, and \"hallucinogen persisting perception disorder\" (HPPD)-related symptoms following psychedelic use in a self-selected naturalistic sample. Using a prospective cohort study, symptoms were assessed in ( <math><mi>N</mi> <mo>=</mo> <mn>654</mn></math> ) participants at one week before a planned psychedelic experience, and at two and four weeks afterward. Across the sample, delusional ideation was found to be reduced one month after psychedelic use ( <math><mi>P</mi> <mo><</mo> <mn>0.001</mn></math> ) with no changes detected in magical thinking. These findings were in seeming opposition to positive correlations between lifetime psychedelic use at baseline with magical thinking ( <math><msub><mi>r</mi> <mi>s</mi></msub> <mo>=</mo> <mn>0.12</mn></math> , <math><mi>P</mi> <mo>=</mo> <mn>0.003</mn></math> ) and delusional ideation ( <math><msub><mi>r</mi> <mi>s</mi></msub> <mo>=</mo> <mn>0.11</mn></math> , <math><mi>P</mi> <mo>=</mo> <mn>0.01</mn></math> ), suggesting that schizotypal traits, instead of being caused by, may merely correlate with psychedelic use. Importantly, over 30% of the sample reported HPPD-type effects at the 4-week endpoint, although rarely perceived as distressing (< 1% of the population). Younger age, female gender, history of a psychiatric diagnosis and baseline trait absorption predicted the occurrence of HPPD-like effects. This is in line with prior studies showing a high prevalence of HPPD-like symptoms in psychedelic users, which, however, appear to remain at a subclinical severity in most cases, explaining the comparatively lower prevalence of HPPD diagnoses.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 4","pages":"pgae560"},"PeriodicalIF":2.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The lives of intersex people: Socioeconomic and health disparities in Mexico.","authors":"Ercio Muñoz, Melanie Saavedra, Dario Sansone","doi":"10.1093/pnasnexus/pgaf126","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf126","url":null,"abstract":"<p><p>This paper reports socioeconomic and health outcomes for individuals born with sex variations (i.e. intersex individuals) in Mexico based on large, nationally representative survey data collected between 2021 and 2022 (<i>n</i> = 44,189). The sample includes 608 intersex respondents, corresponding to a weighted estimate of ∼1.6% of individuals aged 15-64 years, i.e. almost 1.3 million intersex people. The main empirical analyses document substantial negative outcomes for intersex individuals. There are significant disparities in mental, physical, and sexual health between intersex respondents and the endosex population, including higher rates of bullying during childhood (26 vs. 15% for endosex male and female individuals), harassment and violence in adulthood (20 vs. 10% for endosex male individuals), and mental health issues (46 vs. 34% for endosex male individuals). Additionally, intersex individuals have lower educational levels and are more likely to experience workplace rejection, exclusion, and discrimination and to face substantial barriers in healthcare environments.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf126"},"PeriodicalIF":2.2,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The future of in silico trials and digital twins in medicine.","authors":"Ehsan Samei","doi":"10.1093/pnasnexus/pgaf123","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf123","url":null,"abstract":"<p><p>In silico trials and digital twins are emerging as transformative medical technologies, as they offer a unique way to design medical innovations, optimize their application, and evaluate their utility. Their use spans from individual care-appropriating the technology for personalized decision, to population care-presenting an alternative to design, supplement, or replace clinical trials. They effectually offer a new way to efficiently qualify, quantify, and personalize healthcare innovations in advance or in conjunction with clinical application. While much progress is underway to advance these technologies across diverse developments, realizing their full potential requires a cohesive goal to unify separate activities towards a common objective. Such a cohesive goal-moonshot-can be defined as forming and fostering a digital twin of every single human person, owned by the individual, progressively updated with new data, and used to deliver optimized care, technology assessment, and real-world evidence. The feasibility of such a vision builds upon a growing body of work in computational modeling, regulatory science, and digital healthcare. Bringing this vision to reality requires ownership and active engagement of all stakeholders to contribute diverse expertise and resources for transforming medicine and medical appropriation towards a more accurate, efficient, and quantitative future.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf123"},"PeriodicalIF":2.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clear as mud redefined: Tunable transparent mineral scaffolds for visualizing microbial processes below ground.","authors":"Laura K Quinn, Kriti Sharma, Katherine T Faber, Victoria J Orphan","doi":"10.1093/pnasnexus/pgaf118","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf118","url":null,"abstract":"<p><p>Microbes inhabiting complex porous microenvironments in sediments and aquifers catalyze reactions that are critical to global biogeochemical cycles and ecosystem health. However, the opacity and complexity of porous sediment and rock matrices have considerably hindered the study of microbial processes occurring within these habitats. Here, we generated microbially compatible, optically transparent mineral scaffolds to visualize and investigate microbial colonization and activities occurring in these environments, in laboratory settings and in situ. Using inexpensive synthetic cryolite mineral, we produced optically transparent scaffolds mimicking the complex 3D structure of sediments and rocks by adapting a suspension-based, freeze-casting technique commonly used in materials science. Fine-tuning of parameters, such as freezing rate and choice of solvent, provided full control of pore size and architecture. The combined effects of scaffold porosity and structure on the movement of microbe-sized particles, tested using velocity tracking of fluorescent beads, showed diverse yet reproducible behaviors. The scaffolds we produced are compatible with epifluorescence microscopy, allowing the fluorescence-based identification of colonizing microbes by DNA-based staining and fluorescence in situ hybridization (FISH) to depths of 100 µm. Additionally, Raman spectroscopy analysis indicates minimal background signal in regions used for measuring deuterium and ¹³C enrichment in microorganisms, highlighting the potential to directly couple D₂O or ¹³C stable isotope probing and Raman-FISH for quantifying microbial activity at the single-cell level. To demonstrate the relevance of cryolite scaffolds for environmental field studies, we visualized their colonization by diverse microorganisms within rhizosphere sediments of a coastal seagrass plant using epifluorescence microscopy. The tool presented here enables highly resolved, spatially explicit, and multimodal investigations into the distribution, activities, and interactions of underground microbes typically obscured within opaque geological materials until now.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 5","pages":"pgaf118"},"PeriodicalIF":2.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}