Proceedings of the National Academy of Sciences of the United States of America最新文献

{"title":"Relaxation to universal non-Maxwellian equilibria in a collisionless plasma","authors":"Robert J. Ewart, Michael L. Nastac, Pablo J. Bilbao, Thales Silva, Luís O. Silva, Alexander A. Schekochihin","doi":"10.1073/pnas.2417813122","DOIUrl":"https://doi.org/10.1073/pnas.2417813122","url":null,"abstract":"Generic equilibria are derived for turbulent relaxing plasmas via an entropy-maximization procedure that accounts for the short-time conservation of certain collisionless invariants. The conservation of these collisionless invariants endows the system with a partial “memory” of its prior conditions but is imperfect on long time scales due to the development of a turbulent cascade to small scales, which breaks the precise conservation of phase volume, making this memory imprecise. The equilibria are still determined by the short-time collisionless invariants, but the invariants themselves are driven to a universal form by the nature of the turbulence. This is numerically confirmed for the case of beam instabilities in one-dimensional electrostatic plasmas, where sufficiently strong turbulence appears to cause the distribution function of particle energies to develop a universal power-law tail, with exponent −2.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"35 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863071","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}

{"title":"A unified framework for hydromechanical signaling can explain transmission of local and long-distance signals in plants","authors":"Vesna Bacheva, Fulton E. Rockwell, Jean-Baptiste Salmon, Jesse D. Woodson, Margaret H. Frank, Abraham D. Stroock","doi":"10.1073/pnas.2422692122","DOIUrl":"https://doi.org/10.1073/pnas.2422692122","url":null,"abstract":"Local wounding in plants triggers signals that travel locally within the wounded leaf or systemically through the vasculature to distant leaves. Our understanding of the mechanisms of initiation and propagation of this ubiquitous class of signals remains incomplete. Here, we develop a unifying framework based on poroelastic dynamics to study two coupled biophysical processes—propagation of pressure changes and transmission of chemical elicitors via mass flows driven by these pressure changes—as potential mechanisms for the initiation and propagation of wound-induced signals. We show that rapid pressure changes in the xylem can transmit mechanical information across the plant, while their coupling with neighboring nonvascular tissue drives swelling and mass flow that can transport chemical elicitors to distant leaves. We confront predictions from our model with measurements of signaling dynamics in several species to show that i) the poroelastic model can capture the observed dynamics of purely mechanical changes (swelling of distant leaves) induced by wounding; ii) advection and diffusion of hypothetical elicitors with mass flows induced by poroelastic relaxations can explain distant cellular responses observed with gene-encoded reporters of cytosolic calcium concentration and electrical signals; and iii) poroelastic diffusion of pressure changes around local wounds in nonvascular tissue matches the observed cytosolic calcium signals and represents an alternative hypothesis relative to molecular diffusion of chemical elicitors. This framework provides a valuable foundation for assessing mechanisms of signal transmission and for designing future experiments to elucidate factors involved in signal initiation, propagation, and target elicitation.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"40 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863057","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}

{"title":"Proteostasis landscapes of cystic fibrosis variants reveal drug response vulnerability","authors":"Eli Fritz McDonald, Minsoo Kim, John A. Olson, Jens Meiler, Lars Plate","doi":"10.1073/pnas.2418407122","DOIUrl":"https://doi.org/10.1073/pnas.2418407122","url":null,"abstract":"Cystic fibrosis (CF) is a lethal genetic disorder caused by variants in CF transmembrane conductance regulator (CFTR). Many variants are treatable with correctors, which enhance the folding and trafficking of CFTR. However, approximately 3% of persons with CF harbor poorly responsive variants. Here, we used affinity purification mass spectrometry proteomics to profile the protein homeostasis (proteostasis) changes of CFTR variants during correction to assess modulated interactions with protein folding and maturation pathways. Responsive variant interactions converged on similar proteostasis pathways during correction. In contrast, poorly responsive variants subtly diverged, revealing a partial restoration of protein quality control surveillance and partial correction. Computational structural modeling showed that corrector VX-445 failed to confer enough NBD1 stability to poor responders. NBD1 secondary stabilizing mutations rescued poorly responsive variants, revealing structural vulnerabilities in NBD1 required for treating poor responders. Our study provides a framework for discerning the underlying protein quality control and structural defects of CFTR variants not reached with existing drugs to expand therapeutics to all susceptible CFTR variants.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"48 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863074","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}

{"title":"Disrupted sensorimotor predictions in high autistic characteristics","authors":"Antonella Pomè, Eckart Zimmermann","doi":"10.1073/pnas.2501624122","DOIUrl":"https://doi.org/10.1073/pnas.2501624122","url":null,"abstract":"Humans maintain a stable view of the world by omitting self-generated motion during rapid eye movements, or saccades. An efferent copy of the saccade motor command informs visual processing about the self-produced motion. However, efference copy information has been demonstrated to be disrupted in individuals with high autistic traits. Here, we investigated saccadic omission in participants with high vs. low autistic traits. Participants made saccades to peripheral targets and reported the location of drifting gratings that became visible during saccade execution. Sensitivity to motion was also assessed in a fixation condition, where retinal velocities matched those experienced during saccades. Our findings reveal that individuals with heightened autistic traits exhibit significantly reduced sensitivity to motion during saccades compared to those with low autistic traits, while no Autistic Quotient-dependent differences were observed in the fixation condition. These results suggest that impairments in sensorimotor processing affect the ability of individuals with high autistic traits to predict how their own movements affect the sensory input. The lack of sensorimotor integration might explain the sensory overload that autistics frequently experience.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"204 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857391","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}

{"title":"Four-million-year Marinoan snowball shows multiple routes to deglaciation","authors":"Adrian R. Tasistro-Hart, Francis A. Macdonald, James L. Crowley, Mark D. Schmitz","doi":"10.1073/pnas.2418281122","DOIUrl":"https://doi.org/10.1073/pnas.2418281122","url":null,"abstract":"Twice during the Neoproterozoic Era, Earth experienced runaway ice-albedo catastrophes that resulted in multimillion year, low-latitude glaciations: the Sturtian and Marinoan snowball Earths. In the snowball climate state, CO <jats:sub>2</jats:sub> consumption through silicate weathering collapses, and atmospheric CO <jats:sub>2</jats:sub> accumulates via volcanic outgassing until a sufficiently strong greenhouse causes deglaciation. The duration and extent of ice cover are critical for planetary habitability, both on exoplanets and on Earth where animals emerged between the two glaciations. Radioisotopic ages have defined the duration of the Sturtian glaciation to 56 Myr, but the duration of the Marinoan glaciation (4 to 15 Myr) currently has 11 Myr of uncertainty. Here, we show that the Marinoan glaciation in Namibia lasted ca. 4 Myr with less than 10 m of vertical ice grounding line motion through glacial advance-retreat cycles. The stability of a low-latitude ice grounding line is consistent with the strong hysteresis of a hard snowball state. The disparity in durations demonstrates different routes to deglaciation, through slower CO <jats:sub>2</jats:sub> accumulation for the longer Sturtian and radiative perturbation for the Marinoan. The short duration of the Marinoan glaciation may have been essential for the survival and evolution of animals and illustrates an additional path toward habitability on exoplanets.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"11 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857572","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}

{"title":"Abiotic origin of the citric acid cycle intermediates","authors":"Mason McAnally, Jana Bocková, Andrew M. Turner, Nana Hara, Daria Mikhnova, Cornelia Meinert, Ralf I. Kaiser","doi":"10.1073/pnas.2501839122","DOIUrl":"https://doi.org/10.1073/pnas.2501839122","url":null,"abstract":"The molecular framework for protometabolism—chemical reactions in a prebiotic environment preceding modern metabolism—has remained unknown in evolutionary biology. Mono-, di-, and tricarboxylic acids that comprise contemporary metabolism, such as the Krebs cycle, are of particular prebiotic relevance and are theorized to predate life on Earth. Researchers have struggled to unravel the molecular origins of respiration, with theories pointing toward abiotic origins later co-opted by the earliest living organisms; however, the molecular network of these molecules has remained elusive. Recent detections of carboxylic acids linked to the Krebs cycle on the Ryugu asteroid and Murchison meteorite rekindled interest in their extraterrestrial origins. Replicating conditions analogous to the environment of dense molecular clouds in laboratory simulation experiments, our work provides compelling evidence on the abiotic synthesis of the complete suite of biorelevant molecules central to the Krebs cycle. The opportunity for these biomolecules forming in deep space could provide molecular origins of protometabolism on early Earth and also provide the molecular feedstock to worlds beyond our own.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"30 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857574","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}

{"title":"MOB1 deletion in murine mature adipocytes ameliorates obesity and diabetes","authors":"Miki Nishio, Keiko Yamaguchi, Junji Otani, Katsuya Yuguchi, Daisuke Kohno, Tsutomu Sasaki, Tadahiro Kitamura, Masakazu Shinohara, Tomoyoshi Soga, Koichi Kawamura, Atsuo T. Sasaki, Masashi Oshima, Hiroki Hikasa, Minna Woo, Takehiko Sasaki, Hiroshi Nishina, Kazuwa Nakao, Tomohiko Maehama, Akira Suzuki","doi":"10.1073/pnas.2424741122","DOIUrl":"https://doi.org/10.1073/pnas.2424741122","url":null,"abstract":"There is currently a global epidemic of obesity and obesity-related diseases such as type 2 diabetes due to decreased physical activity, excessive food intake, and/or genetic predisposition. The Hippo-YAP1 pathway has attracted attention as a potential therapeutic target because YAP1/TAZ activation in murine immature adipocytes in vitro suppresses their differentiation by inhibiting PPARγ activity. However, the role of YAP1 activation in mature adipocytes in vivo remains unclear. MOB1, whose expression is increased in obesity, is the hub of the Hippo core molecule complex and negatively regulates YAP1/TAZ activation. Therefore, we generated aMob1DKO mutant mice, which feature deficiency of <jats:italic>Mob1a/b</jats:italic> specifically in mature adipocytes. Compared to controls, aMob1DKO mice subjected to a high-fat diet showed beneficial changes consistent with resistance to diet-induced obesity. The mutants exhibited increases in basal lipolysis, “beiging,” and energy expenditure, as well as suppression of ROS production and inflammation in white adipose tissue. Insulin sensitivity and glucose tolerance were improved, and ectopic fat accumulation was reduced. Most of these changes were dependent on the YAP1 activation observed in mature white adipose tissue of aMob1DKO mice. FGF21, which improves lipid metabolism, was upregulated directly via YAP1 activation, and many of the phenotypes seen in aMob1DKO mice were also dependent on FGF21. Thus, the aMob1DKO mouse is an interesting model for the study of the metabolic effects of diet-induced obesity and protection against diabetes. Our work suggests that a YAP1-FGF21 axis exists in adipocytes that may be a potential therapeutic target for obesity.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"108 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857387","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}

{"title":"An algorithmic constraint at the transition to complex life.","authors":"Evandro Ferrada","doi":"10.1073/pnas.2505484122","DOIUrl":"https://doi.org/10.1073/pnas.2505484122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"33 1","pages":"e2505484122"},"PeriodicalIF":11.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862012","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}

{"title":"Multiple sclerosis and gut microbiota: Lachnospiraceae from the ileum of MS twins trigger MS-like disease in germfree transgenic mice—An unbiased functional study","authors":"Hongsup Yoon, Lisa Ann Gerdes, Florian Beigel, Yihui Sun, Janine Kövilein, Jiancheng Wang, Tanja Kuhlmann, Andrea Flierl-Hecht, Dirk Haller, Reinhard Hohlfeld, Sergio E. Baranzini, Hartmut Wekerle, Anneli Peters","doi":"10.1073/pnas.2419689122","DOIUrl":"https://doi.org/10.1073/pnas.2419689122","url":null,"abstract":"We developed a two-tiered strategy aiming to identify gut bacteria functionally linked to the development of multiple sclerosis (MS). First, we compared gut microbial profiles in a cohort of 81 monozygotic twins discordant for MS. This approach allowed to minimize confounding effects by genetic and early environmental factors and identified over 50 differently abundant taxa with the majority of increased taxa within the <jats:italic>Firmicutes</jats:italic> . These included taxa previously described to be associated with MS ( <jats:italic>Anaerotruncus colihominis</jats:italic> and <jats:italic>Eisenbergiella tayi</jats:italic> ), along with newly identified taxa, such as <jats:italic>Copromonas</jats:italic> and <jats:italic>Acutalibacter</jats:italic> . Second, we interrogated the intestinal habitat and functional impact of individual taxa on the development of MS-like disease. In an exploratory approach, we enteroscopically sampled microbiota from different gut segments of selected twin pairs and compared their compositional profiles. To assess their functional potential, samples were orally transferred into germfree transgenic mice prone to develop spontaneous MS-like experimental autoimmune encephalomyelitis (EAE) upon bacterial colonization. We found that MS-derived ileal microbiota induced EAE at substantially higher rates than analogous material from healthy twin donors. Furthermore, female mice were more susceptible to disease development than males. The likely active organisms were identified as <jats:italic>Eisenbergiella tayi</jats:italic> and <jats:italic>Lachnoclostridium,</jats:italic> members of the Lachnospiraceae family. Our results identify potentially disease-facilitating bacteria sampled from the ileum of MS affected twins. The experimental strategy may pave the way to functionally understand the role of gut microbiota in initiation of MS.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"64 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857569","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}

{"title":"Unbalanced social–ecological acceleration led to state formation failure in early medieval Poland","authors":"Adam Izdebski, Sambor Czerwiński, Marek Jankowiak, Marcin Danielewski, Sabina Fiołna, Raphael Gromig, Piotr Guzowski, Negar Haghipour, Irka Hajdas, Piotr Kołaczek, Mariusz Lamentowicz, Katarzyna Marcisz, Jakub Niebieszczański, Paweł Sankiewicz, Bernd Wagner","doi":"10.1073/pnas.2409056122","DOIUrl":"https://doi.org/10.1073/pnas.2409056122","url":null,"abstract":"Rapid social–ecological intensification is a recurrent feature of human history. It occurred in different forms and contexts; its outcomes may have been sustainable or transient. Until recently, such intensifications usually accompanied state formation: Consolidation of political power was often coupled with exponential increase in human exploitation of the environment of a given area. Here, we study one such case, uniquely well-documented through our rich paleoecological, archaeological, numismatic, and literary data. Triggered by the Eurasian slave trade, the first “Polish” polity was founded in Central Europe c. 900 common era. It undertook unprecedented ecological intensification in its core territory, connected with large construction projects, and engaged in rapid territorial expansion. We provide new crucial evidence on this process by publishing here a high-resolution pollen profile from a location close to the polity’s capital and by an application of social network analysis to numismatic data. This state collapsed within a few generations after its foundation. The collapse of the political elites, however, did not produce a complete social and ecological disintegration of the polity’s former core region. We thus show how collapse and continuity can remain closely intertwined. Last but not least, the rich evidence on the mechanism of the collapse reveals that successful maintenance of social–ecological intensification requires reliance on a number of cultural, economic, religious, and social networks underlying the political expansion. The polity’s elite lacked access to or failed to mobilize such networks, which led to its demise.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"219 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857382","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}