PNAS nexus最新文献

{"title":"Mechanistic and structural insights into the itaconate-producing <i>trans</i>-aconitate decarboxylase Tad1.","authors":"Liujuan Zheng, Wei Li, Marvin Christ, Nicole Paczia, Wolfgang Buckel, Christopher-Nils Mais, Michael Bölker, Johannes Freitag, Gert Bange","doi":"10.1093/pnasnexus/pgaf059","DOIUrl":"10.1093/pnasnexus/pgaf059","url":null,"abstract":"<p><p>Itaconic acid belongs to the high-value precursors for the production of biomass-based industrial compounds. It originates from the tricarboxylic acid cycle, and depending on the organism, it is produced by different biosynthetic routes. The basidiomycete fungus <i>Ustilago maydis</i> synthesizes itaconic acid via isomerization of <i>cis</i>-aconitic acid to <i>trans</i>-aconitic acid, and subsequent decarboxylation catalyzed by the <i>trans</i>-aconitate decarboxylase Tad1, which belongs to the aspartase/fumarase superfamily. Since no other decarboxylase has been identified within this protein superfamily, Tad1 constitutes a novel type of decarboxylase. Here, we present high-resolution crystal structures of Tad1, which, together with mutational analysis and nuclear magnetic resonance spectroscopy measurements, provide insight into the molecular mechanism of Tad1-dependent decarboxylation. Specifically, our study shows that decarboxylation is favored in acidic conditions, requires protonation as well as migration of a double bond, and coincides with structural rearrangements in the catalytic center. In summary, our study elucidates the molecular mechanism underlying a novel type of enzymatic decarboxylation and provides a starting point for protein engineering aimed at optimizing the efficient production of itaconic acid.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 3","pages":"pgaf059"},"PeriodicalIF":2.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569216","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":"Engagement, user satisfaction, and the amplification of divisive content on social media.","authors":"Smitha Milli, Micah Carroll, Yike Wang, Sashrika Pandey, Sebastian Zhao, Anca D Dragan","doi":"10.1093/pnasnexus/pgaf062","DOIUrl":"10.1093/pnasnexus/pgaf062","url":null,"abstract":"<p><p>Social media ranking algorithms typically optimize for users' revealed preferences, i.e. user engagement such as clicks, shares, and likes. Many have hypothesized that by focusing on users' revealed preferences, these algorithms may exacerbate human behavioral biases. In a preregistered algorithmic audit, we found that, relative to a reverse-chronological baseline, Twitter's engagement-based ranking algorithm amplifies emotionally charged, out-group hostile content that users say makes them feel worse about their political out-group. Furthermore, we find that users do <i>not</i> prefer the political tweets selected by the algorithm, suggesting that the engagement-based algorithm underperforms in satisfying users' stated preferences. Finally, we explore the implications of an alternative approach that ranks content based on users' stated preferences and find a reduction in angry, partisan, and out-group hostile content, but also a potential reinforcement of proattitudinal content. Overall, our findings suggest that greater integration of stated preferences into social media ranking algorithms could promote better online discourse, though potential trade-offs also warrant further investigation.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 3","pages":"pgaf062"},"PeriodicalIF":2.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607197","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":"One-shot intervention reduces online engagement with distorted content.","authors":"Eeshan Hasan, Gunnar Epping, Lorenzo Lorenzo-Luaces, Johan Bollen, Jennifer Sue Trueblood","doi":"10.1093/pnasnexus/pgaf068","DOIUrl":"10.1093/pnasnexus/pgaf068","url":null,"abstract":"<p><p>Depression is one of the leading causes of disability worldwide. Individuals with depression often experience unrealistic and overly negative thoughts, i.e. cognitive distortions, that cause maladaptive behaviors and feelings. Now that a majority of the US population uses social media platforms, concerns have been raised that they may serve as a vector for the spread of distorted ideas and thinking amid a global mental health epidemic. Here, we study how individuals ( <math><mi>n</mi> <mo>=</mo> <mn>838</mn></math> ) interact with distorted content on social media platforms using a simulated environment similar to Twitter (now X). We find that individuals with higher depression symptoms tend to prefer distorted content more than those with fewer symptoms. However, a simple one-shot intervention can teach individuals to recognize and drastically reduce interactions with distorted content across the entire depression scale. This suggests that distorted thinking on social media may disproportionally affect individuals with depression, but simple awareness training can mitigate this effect. Our findings have important implicasstions for understanding the role of social media in propagating distorted thinking and potential paths to reduce the societal cost of mental health disorders.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 3","pages":"pgaf068"},"PeriodicalIF":2.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659966","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":"Social coordination perpetuates stereotypic expectations and behaviors across generations in deep multiagent reinforcement learning.","authors":"Rebekah A Gelpí, Yikai Tang, Ethan C Jackson, William A Cunningham","doi":"10.1093/pnasnexus/pgaf076","DOIUrl":"10.1093/pnasnexus/pgaf076","url":null,"abstract":"<p><p>Despite often being perceived as morally objectionable, stereotypes are a common feature of social groups, a phenomenon that has often been attributed to biased motivations or limits on the ability to process information. We argue that one reason for this continued prevalence is that preexisting expectations about how others will behave, in the context of social coordination, can change the behaviors of one's social partners, creating the very stereotype one expected to see, even in the absence of other potential sources of stereotyping. We use a computational model of dynamic social coordination to illustrate how this \"feedback loop\" can emerge, engendering and entrenching role-consistent stereotypic behavior and then show that human behavior on the task generates a comparable feedback loop. Notably, people's choices on the task are not related to social dominance or system justification, suggesting biased motivations are not necessary to maintain these stereotypes.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 3","pages":"pgaf076"},"PeriodicalIF":2.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617942","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":"Merging public elementary schools to reduce racial/ethnic segregation.","authors":"Madison Landry, Nabeel Gillani","doi":"10.1093/pnasnexus/pgaf050","DOIUrl":"10.1093/pnasnexus/pgaf050","url":null,"abstract":"<p><p>Diverse schools can help address implicit biases and increase empathy, mutual respect, and reflective thought by fostering connections between students from different racial/ethnic, socioeconomic, and other backgrounds. Unfortunately, demographic segregation remains rampant in US public schools, despite over 70 years since the passing of federal legislation formally outlawing segregation by race. However, changing how students are assigned to schools can help foster more integrated learning environments. In this article, we explore \"school mergers\" as one such under-explored, yet promising, student assignment policy change. School mergers involve merging the school attendance boundaries, or catchment areas, of schools and subsequently changing the grades each school offers. We develop an algorithm to simulate elementary school mergers across 200 large school districts serving 4.5 million elementary school students and find that pairing or tripling schools in this way could reduce racial/ethnic segregation by a median relative 20%-and as much as nearly 60% in some districts-while increasing driving times to schools by an average of a few minutes each way. Districts with many interfaces between racially/ethnically disparate neighborhoods tend to be prime candidates for mergers. We also compare the expected results of school mergers to other typical integration policies, like redistricting, and find that different policies may be more or less suitable in different places. Finally, we make our results available through a public dashboard for policymakers and community members to explore further (https://mergers.schooldiversity.org). Together, our study offers new findings and tools to support integration policy-making across US public school districts.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 3","pages":"pgaf050"},"PeriodicalIF":2.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569218","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":"Multicriteria models provide enhanced insight for siting US offshore wind.","authors":"Rudolph Santarromana, Ahmed Abdulla, M Granger Morgan, Joana Mendonça","doi":"10.1093/pnasnexus/pgaf051","DOIUrl":"10.1093/pnasnexus/pgaf051","url":null,"abstract":"<p><p>Offshore wind can be a key contributor to energy system decarbonization, but its deployment in certain regions has been slow, partly due to opposition from disparate interests. Failure to sufficiently address the concerns of external stakeholders could continue to hamper deployment. Here, we use a multi criteria model to assess all possible sites in a 2 km × 2 km grid of all potential locations in continental US federal waters, contrasting the perspectives of developers and other stakeholders. Our model elucidates how developers and policymakers could better approach future deployment. First, while developers prefer larger plants, we find that these facilities are more fragile-they are sensitive to location, and their impacts are more uncertain than smaller plants. Second, there is 600 GW of capacity where both developer and stakeholder interests align-developing these locations should be prioritized. Third, there are few areas on the US West Coast where developer and stakeholder preferences align, suggesting a need to reduce stakeholder-plant interactions or locate facilities in deeper waters than current technology allows.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 3","pages":"pgaf051"},"PeriodicalIF":2.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569221","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":"Deep oxygen-depleted depressions in a Red Sea coral reef sustain resistant ecosystems.","authors":"Shannon G Klein, Larissa Frühe, Anieka J Parry, Fabio Marchese, Megan K B Nolan, Elisa Laiolo, Kah Kheng Lim, Alexandra Steckbauer, Jessica Breavington, Christopher A Hempel, Kate von Krusenstiern, Froukje M van der Zwan, Eleonora Re, Taiba Alamoudi, Jacqueline V Alva Garcia, Silvia Arossa, Carlos Angulo-Preckler, Mattie Rodrigue, Vincent A Pieribone, Mohammad A Qurban, Francesca Benzoni, Carlos M Duarte","doi":"10.1093/pnasnexus/pgaf049","DOIUrl":"10.1093/pnasnexus/pgaf049","url":null,"abstract":"<p><p>Persistent oxygen-depleted zones in the ocean are known primarily from enclosed basins in temperate regions or the open ocean (including oxygen minimum and limiting zones) (1). However, little is known about the possibility of such zones forming in tropical coastal domains, even though the combination of warmer temperatures and complex geological features in some tropical regions makes their occurrence more likely (1, 2). Here, we report two subsurface oxygen-depleted zones within deep (>490 m) depressions of the Red Sea's Difaht Farasan-a carbonate platform hosting the world's third largest contiguous tropical coral reef system. One zone maintains suboxic oxygen levels (∼11-14 µmol O₂ kg⁻¹), while the other sustains oxygen levels below detection (<2 µmol O₂ kg⁻¹). The suboxic zone shows no fixed nitrogen loss, while the near-anoxic zone hosts anaerobic microbial populations and shows signs of nitrogen loss. We propose that the warm and saline environment of the Red Sea interacts with the semienclosed depressions to restrict vertical mixing, limiting oxygen resupply at depth. However, unlike most other oxygen-depleted zones, our deep-sea vehicle surveys demonstrate that these zones support resistant aerobically respiring taxa, indicating an unusual capacity to reduce aerobic oxygen demands at high temperatures (>21 °C). Targeted exploration of deep tropical coastal environments is crucial for determining whether similar zones exist beyond the Red Sea and understanding their potential responses to climate change.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 3","pages":"pgaf049"},"PeriodicalIF":2.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569166","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":"Terminating pandemics with smartwatches.","authors":"Märt Vesinurm, Martial Ndeffo-Mbah, Dan Yamin, Margaret L Brandeau","doi":"10.1093/pnasnexus/pgaf044","DOIUrl":"10.1093/pnasnexus/pgaf044","url":null,"abstract":"<p><p>Recent studies have demonstrated that wearable devices, such as smartwatches, can accurately detect infections in presymptomatic and asymptomatic individuals. Yet, the extent to which smartwatches can contribute to prevention and control of infectious diseases through a subsequent reduction in social contacts is not fully understood. We developed a multiscale modeling framework that integrates within-host viral dynamics and between-host interactions to estimate the risk of viral disease outbreaks within a given population. We used the model to evaluate the population-level effectiveness of smartwatch detection in reducing the transmission of three COVID-19 variants and seasonal and pandemic influenza. With a 66% reduction in contacts after smartwatch-based disease detection, we estimate that the reproduction number <i>R</i> would drop from 2.55 (interquartile range [IQR]: 2.09-2.97) to 1.37 (IQR: 1.00-1.55) for the ancestral COVID-19 variant; from 1.54 (IQR: 1.41-1.69) to 0.82 (IQR: 0.68-0.85) for the delta variant; from 4.15 (IQR: 3.38-4.91) to 2.20 (IQR: 1.57-2.52) for the omicron variant; from 1.55 (IQR: 1.34-1.74) to 0.81 (IQR: 0.63-0.87) for pandemic influenza; and from 1.28 (IQR: 1.18-1.35) to 0.74 (IQR: 0.64-0.79) for seasonal influenza. With a 75% reduction in contacts, <i>R</i> decreases below 1 for the delta variant and for pandemic and seasonal influenza. Sensitivity analyses across a wide array of parameter values confirm that self-isolation initiated shortly after smartwatch detection could significantly reduce <i>R</i> under diverse epidemiological conditions, different levels of smartwatch detection accuracy, and realistic self-isolation levels. Our study underscores the revolutionary potential of smartwatches to manage seasonal diseases and alter the course of future pandemics.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 3","pages":"pgaf044"},"PeriodicalIF":2.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569226","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":"Quantitative mapping of key glucose metabolic rates in the human brain using dynamic deuterium magnetic resonance spectroscopic imaging.","authors":"Xin Li, Xiao-Hong Zhu, Yudu Li, Tao Wang, Guangle Zhang, Hannes M Wiesner, Zhi-Pei Liang, Wei Chen","doi":"10.1093/pnasnexus/pgaf072","DOIUrl":"10.1093/pnasnexus/pgaf072","url":null,"abstract":"<p><p>Deuterium (²H) magnetic resonance spectroscopic imaging (DMRSI) is a newly developed technology for assessing glucose metabolism by simultaneously measuring deuterium-labeled glucose and its downstream metabolites (1) and has a potential to provide a powerful neurometabolic imaging tool for quantitative studies of cerebral glucose metabolism involving multiple metabolic pathways in the human brain. In this work, we developed a dynamic DMRSI method that combines advanced radiofrequency coil and postprocessing techniques to substantially improve the imaging signal-to-noise ratio for detecting deuterated metabolites and enable robust dynamic DMRSI of the human brain at 7 T with very high resolution (HR; 0.7 cc nominal voxel and 2.5 min/image) and whole-brain coverage. Utilizing this capability, we were able to map and differentiate metabolite contents and dynamics throughout the human brain following oral administration of deuterated glucose. Furthermore, by introducing a sophisticated kinetic model, we demonstrated that three key cerebral metabolic rates of glucose consumption (CMR_Glc), lactate production (CMR_Lac), and tricarboxylic acid (TCA) cycle (<i>V</i> _TCA), as well as the maximum apparent rate of forward glucose transport (<i>T</i> _max) can be simultaneously imaged in the human brain through a single dynamic DMRSI measurement. The results clearly show that the glucose transport, neurotransmitter turnover, CMR_Glc, and <i>V</i> _TCA are significantly higher in gray matter than in white matter in the human brain; and the mean metabolic rates and their ratios measured in this study are consistent with the values reported in the literature. The HR dynamic DMRSI methodology presented herein is of great significance and value for the quantitative assessment of human brain glucose metabolism, aerobic glycolysis, and metabolic reprogramming under physiopathological conditions.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 3","pages":"pgaf072"},"PeriodicalIF":2.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665641","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":"Analytical methods for cytoplasmic streaming in elongated cells.","authors":"Pyae Hein Htet, Eric Lauga","doi":"10.1093/pnasnexus/pgaf057","DOIUrl":"10.1093/pnasnexus/pgaf057","url":null,"abstract":"<p><p>Cytoplasmic streaming, the coherent flow of cytoplasm, plays a critical role in transport and mixing over large scales in eukaryotic cells. In many large cells, this process is driven by active forces at the cell boundary, such as cortical cytoskeletal contractions in <i>Drosophila</i> and <i>Caenorhabiditis elegans</i> embryos, or intracellular cargo transport in plant cells. These cytoplasmic flows are approximately Newtonian and governed by the Stokes equations. In this article, we use lubrication theory-a powerful technique for simplifying the fluid mechanics equations in elongated geometries-to derive a general solution for boundary-driven cytoplasmic flows. We apply this framework to predict cytoplasmic fluid dynamics and cortical stresses in four systems of biological significance: the <i>Drosophila</i> and <i>C. elegans</i> embryos (including pseudocleavage furrow formation), the pollen tube of seed plants, and plant root hair cells. Our results showcase the elegance and accuracy of asymptotic solutions in capturing the complex flows and stress patterns in diverse biological contexts, reinforcing its utility as a robust tool for cellular biophysics.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 3","pages":"pgaf057"},"PeriodicalIF":2.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659958","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}