PNAS nexus最新文献

{"title":"Proinsulin C-peptide is a major source of HLA-DQ8 restricted hybrid insulin peptides recognized by human islet-infiltrating CD4⁺ T cells.","authors":"Pushpak Bhattacharjee, Miha Pakusch, Matthew Lacorcia, Eleonora Tresoldi, Alan F Rubin, Abby Foster, Laura King, Chris Y Chiu, Thomas W H Kay, John A Karas, Fergus J Cameron, Stuart I Mannering","doi":"10.1093/pnasnexus/pgae491","DOIUrl":"10.1093/pnasnexus/pgae491","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is an autoimmune disease that develops when T cells destroy the insulin-producing beta cells that reside in the pancreatic islets. Immune cells, including T cells, infiltrate the islets and gradually destroy the beta cells. Human islet-infiltrating CD4⁺ T cells recognize peptide epitopes derived from proinsulin, particularly C-peptide. Hybrid insulin peptides (HIPs) are neoepitopes formed by the fusion of two peptides derived from beta cell granule proteins and are known to be the targets of pathogenic CD4⁺ T cells in the non-obese diabetic (NOD) mouse and human islet-infiltrating CD4⁺ T cells. Proinsulin is widely recognized as a central antigen in T1D, but its role in forming HIPs is unclear. We developed a method to functionally screen TCRs derived from human islet-infiltrating CD4⁺ T cells and applied this to the identification of new proinsulin-derived HIPs. We generated a library of 4,488 candidate HIPs formed by fusion of proinsulin fragments and predicted to bind to HLA-DQ8. This library was screened against 109 islet-infiltrating CD4⁺ T cell receptors (TCRs) isolated from four organ donors who had T1D. We identified 13 unique HIPs recognized by nine different TCRs from two organ donors. HIP-specific T cell avatars responded specifically to a peptide extract from human islets. These new HIPs predominantly stimulated CD4⁺ T cell proliferation in peripheral blood mononuclear cells from individuals with T1D in contrast to HLA-matched controls. This is the first unbiased functional, islet-infiltrating T cell based, screen to identify proinsulin-derived HIPs. It has revealed many new HIPs and a central role of proinsulin C-peptide in their formation.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"3 11","pages":"pgae491"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649931","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":"Learning from and about scientists: Consensus messaging shapes perceptions of climate change and climate scientists.","authors":"Reed Orchinik, Rachit Dubey, Samuel J Gershman, Derek M Powell, Rahul Bhui","doi":"10.1093/pnasnexus/pgae485","DOIUrl":"10.1093/pnasnexus/pgae485","url":null,"abstract":"<p><p>Despite overwhelming scientific consensus on the existence of human-caused climate change, public opinion among Americans remains split. Directly informing people of scientific consensus is among the most prominent strategies for climate communication, yet the reasons for its effectiveness and its limitations are not fully understood. Here, we propose that consensus messaging provides information not only about the existence of climate change but also traits of climate scientists themselves. In a large ( <math><mi>n</mi> <mo>=</mo> <mn>2</mn> <mo>,</mo> <mn>545</mn></math> ) nationally representative survey experiment, we examine how consensus information affects belief in human-caused climate change by shaping perceptions of climate scientist credibility. In the control group ( <math><mi>n</mi> <mo>=</mo> <mn>847</mn></math> ), we first show that people learn both from and about climate scientists when presented with consensus and that perceived scientist credibility (especially skill) mediates up to about 40% of the total effect of consensus information on climate belief. We demonstrate that perceptions of climate scientists are malleable with two novel interventions that increase belief in climate change above and beyond consensus information.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"3 11","pages":"pgae485"},"PeriodicalIF":2.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633409","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":"Public transport across models and scales: A case study of the Munich network.","authors":"Jan Mölter, Joanna Ji, Benedikt Lienkamp, Qin Zhang, Ana T Moreno, Maximilian Schiffer, Rolf Moeckel, Christian Kuehn","doi":"10.1093/pnasnexus/pgae489","DOIUrl":"10.1093/pnasnexus/pgae489","url":null,"abstract":"<p><p>The use of public transport systems is a striking example of complex human behavior. Modeling, planning, and managing public transport is a major future challenge considering the drastically accelerated population growth in many urban areas. The desire to design sustainable cities that can cope with a dynamically increasing demand requires models for transport networks since we are not able to perform real-life experiments before constructing additional infrastructure. Yet, there is a fundamental challenge in the modeling process: we have to understand which basic principles apply to the design of transit networks. In this work, we are going to compare three scientific methods to understand human behavior in public transport modeling: agent-based models, centralized optimization-based models, and minimal physics-based models. As a case study, we focus on the transport network in Munich, Germany. We show that there are certain universal macroscopic emergent features of public transport that arise regardless of the model chosen. In particular, we can obtain with minimal basic assumptions a common and robust distribution for the individual passenger in-vehicle time as well as for several other distributions. Yet, there are other more microscopic features that differ between the individual and centralized organization and/or that cannot be reproduced by a minimal nonlocal random-walk type model. Finally, we cross-validate our results with observed public transport data. In summary, our results provide a key understanding of the basic assumptions that have to underlie transport modeling for human behavior in future sustainable cities.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"3 11","pages":"pgae489"},"PeriodicalIF":2.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649932","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":"Neuromorphic neuromodulation: Towards the next generation of closed-loop neurostimulation.","authors":"Luis Fernando Herbozo Contreras, Nhan Duy Truong, Jason K Eshraghian, Zhangyu Xu, Zhaojing Huang, Thomas Vincenzo Bersani-Veroni, Isabelle Aguilar, Wing Hang Leung, Armin Nikpour, Omid Kavehei","doi":"10.1093/pnasnexus/pgae488","DOIUrl":"10.1093/pnasnexus/pgae488","url":null,"abstract":"<p><p>Neuromodulation techniques have emerged as promising approaches for treating a wide range of neurological disorders, precisely delivering electrical stimulation to modulate abnormal neuronal activity. While leveraging the unique capabilities of AI holds immense potential for responsive neurostimulation, it appears as an extremely challenging proposition where real-time (low-latency) processing, low-power consumption, and heat constraints are limiting factors. The use of sophisticated AI-driven models for personalized neurostimulation depends on the back-telemetry of data to external systems (e.g. cloud-based medical mesosystems and ecosystems). While this can be a solution, integrating continuous learning within implantable neuromodulation devices for several applications, such as seizure prediction in epilepsy, is an open question. We believe neuromorphic architectures hold an outstanding potential to open new avenues for sophisticated on-chip analysis of neural signals and AI-driven personalized treatments. With more than three orders of magnitude reduction in the total data required for data processing and feature extraction, the high power- and memory-efficiency of neuromorphic computing to hardware-firmware co-design can be considered as <i>the</i> solution-in-the-making to resource-constraint implantable neuromodulation systems. This perspective introduces the concept of <i>Neuromorphic Neuromodulation</i>, a new breed of closed-loop responsive feedback system. It highlights its potential to revolutionize implantable brain-machine microsystems for patient-specific treatment.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"3 11","pages":"pgae488"},"PeriodicalIF":2.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649930","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 structure of a Tau fragment bound to tubulin prompts new hypotheses on Tau mechanism and oligomerization.","authors":"Liza Ammar Khodja, Valérie Campanacci, Guy Lippens, Benoît Gigant","doi":"10.1093/pnasnexus/pgae487","DOIUrl":"10.1093/pnasnexus/pgae487","url":null,"abstract":"<p><p>Tau is a protein involved in the regulation of axonal microtubules in neurons. In pathological conditions, it forms filamentous aggregates which are molecular markers of neurodegenerative diseases known as tauopathies. Structures of Tau in fibrils or bound to the microtubule have been reported. We present here a structure of a Tau construct comprising the PHF6 motif, an oligopeptide involved in Tau aggregation, as a complex with tubulin. This Tau fragment binds as a dimer to a new site which, when transposed to the microtubule, would correspond to a pore between protofilaments. These results raise new hypotheses on Tau-induced microtubule assembly and stabilization and on Tau oligomerization.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"3 11","pages":"pgae487"},"PeriodicalIF":2.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636220","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":"Correction to: Redefining the scientific method: as the use of sophisticated scientific methods that extend our mind.","authors":"","doi":"10.1093/pnasnexus/pgae406","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae406","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/pnasnexus/pgae112.].</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"3 10","pages":"pgae406"},"PeriodicalIF":2.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549423","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":"Unraveling the impact of operational parameters and environmental conditions on the quality of viable bacterial aerosols.","authors":"Mathura Thirugnanasampanthar, Lei Tian, Rod G Rhem, Danielle D Libera, Mellissa Gomez, Kyle Jackson, Alison E Fox-Robichaud, Myrna B Dolovich, Zeinab Hosseinidoust","doi":"10.1093/pnasnexus/pgae473","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae473","url":null,"abstract":"<p><p>Viable pathogen-laden droplets of consistent quality are essential for reliably assessing the protection offered by facemasks against airborne infections. We identified a significant gap in guidance within standardized tests for evaluating the filtration efficiencies of facemask materials using viable bacteria-laden aerosol droplets. An aerosol platform, built according to the American Society for Testing and Materials standard F2101-19, was used to validate and standardize facemask filtration test procedures. We utilized this platform to investigate the impact of varying five operating parameters, namely suspension media composition, relative humidity, pathogen concentration, and atomizer airflow and feed flow rates, on the aerosol quality of viable bacteria-laden aerosols. We achieved consistent generation of 1,700 to 3,000 viable bacteria-laden droplets sized between 2.7 and 3.3 µm under the following optimized test conditions: 1.5% w/v peptone water concentration, ≥80% relative humidity at 24 ± 2 °C, 1 × 10⁵ CFU/mL bacterial concentration, 1.5 L/min atomizer airflow rate, and 170 μL/min feed flow rate. We also explored the consequence of deviating from these optimized test parameters on viable bacteria-laden aerosol quality. These results highlight the importance of controlling these parameters when studying airborne transmission and control.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"3 11","pages":"pgae473"},"PeriodicalIF":2.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633418","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":"Internet-based surveillance to track trends in seasonal allergies across the United States.","authors":"Elias Stallard-Olivera, Noah Fierer","doi":"10.1093/pnasnexus/pgae430","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae430","url":null,"abstract":"<p><p>Over a quarter of adults in the United States suffer from seasonal allergies, yet the broader spatiotemporal patterns in seasonal allergy trends remain poorly resolved. This knowledge gap persists due to difficulties in quantifying allergies as symptoms are seldom severe enough to warrant hospital visits. We show that we can use machine learning to extract relevant data from Twitter posts and Google searches to examine population-level trends in seasonal allergies at high spatial and temporal resolution, validating the approach against hospital record data obtained from selected counties in California, United States. After showing that internet-derived data can be used as a proxy for aeroallergen exposures, we demonstrate the utility of our approach by mapping seasonal allergy-related online activity across the 144 most populous US counties at daily time steps over an 8-year period, highlighting the spatial and temporal dynamics in allergy trends across the continental United States.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"3 10","pages":"pgae430"},"PeriodicalIF":2.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549425","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":"Routes of importation and spatial dynamics of SARS-CoV-2 variants during localized interventions in Chile.","authors":"Bernardo Gutierrez, Joseph L-H Tsui, Giulia Pullano, Mattia Mazzoli, Karthik Gangavarapu, Rhys P D Inward, Sumali Bajaj, Rosario Evans Pena, Simon Busch-Moreno, Marc A Suchard, Oliver G Pybus, Alejandra Dunner, Rodrigo Puentes, Salvador Ayala, Jorge Fernandez, Rafael Araos, Leo Ferres, Vittoria Colizza, Moritz U G Kraemer","doi":"10.1093/pnasnexus/pgae483","DOIUrl":"10.1093/pnasnexus/pgae483","url":null,"abstract":"<p><p>Human mobility is strongly associated with the spread of SARS-CoV-2 via air travel on an international scale and with population mixing and the number of people moving between locations on a local scale. However, these conclusions are drawn mostly from observations in the context of the global north where international and domestic connectivity is heavily influenced by the air travel network; scenarios where land-based mobility can also dominate viral spread remain understudied. Furthermore, research on the effects of nonpharmaceutical interventions (NPIs) has mostly focused on national- or regional-scale implementations, leaving gaps in our understanding of the potential benefits of implementing NPIs at higher granularity. Here, we use Chile as a model to explore the role of human mobility on disease spread within the global south; the country implemented a systematic genomic surveillance program and NPIs at a very high spatial granularity. We combine viral genomic data, anonymized human mobility data from mobile phones and official records of international travelers entering the country to characterize the routes of importation of different variants, the relative contributions of airport and land border importations, and the real-time impact of the country's mobility network on the diffusion of SARS-CoV-2. The introduction of variants which are dominant in neighboring countries (and not detected through airport genomic surveillance) is predicted by land border crossings and not by air travelers, and the strength of connectivity between <i>comunas</i> (Chile's lowest administrative divisions) predicts the time of arrival of imported lineages to new locations. A higher stringency of local NPIs was also associated with fewer domestic viral importations. Our analysis sheds light on the drivers of emerging respiratory infectious disease spread outside of air travel and on the consequences of disrupting regular movement patterns at lower spatial scales.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"3 11","pages":"pgae483"},"PeriodicalIF":2.2,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11547135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633402","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":"Our times of hyphenated disciplines (and with an insight on sustainability).","authors":"Yannis C Yortsos","doi":"10.1093/pnasnexus/pgae448","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae448","url":null,"abstract":"","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"3 10","pages":"pgae448"},"PeriodicalIF":2.2,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11518853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549428","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}