Steven Miletić, Niek Stevenson, Pierre-Louis Bazin, Anneke Alkemade, Scott J. S. Isherwood, Anne C. Trutti, Desmond H. Y. Tse, Asta K. Håberg, Birte U. Forstmann
{"title":"Joint models reveal human subcortical underpinnings of choice and learning behavior","authors":"Steven Miletić, Niek Stevenson, Pierre-Louis Bazin, Anneke Alkemade, Scott J. S. Isherwood, Anne C. Trutti, Desmond H. Y. Tse, Asta K. Håberg, Birte U. Forstmann","doi":"10.1073/pnas.2502269122","DOIUrl":"https://doi.org/10.1073/pnas.2502269122","url":null,"abstract":"Decision making and learning processes together enable adaptive strategic behavior. Animal studies demonstrated the importance of subcortical regions in these cognitive processes, but the human subcortical contributions remain poorly characterized. Here, we study choice and learning processes in the human subcortex, using a tailored ultra-high field 7T functional MRI protocol combined with joint models. Joint models provide unbiased estimates of brain–behavior relations by simultaneously including behavioral and neural data at the participant and group level. Results demonstrate relations between subcortical regions and the adjustment of decision urgency. Value-related blood-oxygenation level dependent (BOLD) differences were found with opposite BOLD polarity in different parts of the striatum. Multiple subcortical regions showed BOLD signatures of reward prediction error processing, but contrary to expectations, these did not include the dopaminergic midbrain. Combined, this study characterizes the human subcortical contributions to choice and learning, and demonstrates the feasibility and value of joint modeling in facilitating our understanding of brain–behavior relationships.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"20 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002986","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}
Rui Yang, Qiaoling Si, Qiang Sheng, Mingyang Yang, Mu Du, Hu Zhang, Xiao-Lei Shi, Guihua Tang, Zhi-Gang Chen
{"title":"Atomic armor for thermal stability in nanoporous structures","authors":"Rui Yang, Qiaoling Si, Qiang Sheng, Mingyang Yang, Mu Du, Hu Zhang, Xiao-Lei Shi, Guihua Tang, Zhi-Gang Chen","doi":"10.1073/pnas.2510746122","DOIUrl":"https://doi.org/10.1073/pnas.2510746122","url":null,"abstract":"Nanoporous structures play a critical role in a wide range of applications, including catalysis, thermoelectrics, energy storage, gas adsorption, and thermal insulation. However, their thermal instability remains a persistent challenge. Inspired by the extraordinary resilience of tardigrades, an “atomic armor” strategy is introduced to enhance the stability of nanoporous structures. Applied to mesoporous silica at parts-per-million levels, the atomic armor provides thermal resistance exceeding that of existing stabilization techniques. Thermal treatment at 1,000 °C for 168 h results in a fivefold increase in specific surface area, 66% lower thermal conductivity, and a sixfold increase in pore volume compared to untreated samples. Surface viscosity is linked to sintering resistance, and glass transition temperature and fragility are introduced as design parameters. Machine-learned interatomic potentials and metabasin escape algorithm-assisted molecular dynamics simulations are employed to reveal that materials traditionally classified as nonglass formers can exhibit glass transition temperatures and display intrinsic fragility. Alumina is identified as having a record-high glass transition temperature. By modulating the surface viscosity of nanoparticles, this approach stabilizes nanoporous structures effectively. The proposed method offers a simple and universal posttreatment process for improving the thermal stability of nanoporous structures.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"33 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002987","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}
Justin Faber, Alexandros C. Alampounti, Marcos Georgiades, Joerg T. Albert, Dolores Bozovic
{"title":"A mosquito-inspired theoretical framework for acoustic signal detection","authors":"Justin Faber, Alexandros C. Alampounti, Marcos Georgiades, Joerg T. Albert, Dolores Bozovic","doi":"10.1073/pnas.2500938122","DOIUrl":"https://doi.org/10.1073/pnas.2500938122","url":null,"abstract":"Distortion products are tones produced through nonlinear effects of a system simultaneously detecting two or more frequencies. These combination tones are ubiquitous to vertebrate auditory systems and are generally regarded as byproducts of nonlinear signal amplification. It has previously been shown that several species of infectious-disease-carrying mosquitoes utilize these distortion products for detecting and locating potential mates. Furthermore, the mechanical tuning curve of the male mosquito flagellum was shown not to be aligned with that of its sensory neural elements. Using a generic theoretical model for acoustic sensing, we evaluate the signal-detection advantages and disadvantages that are implied by these two schemes: distortion product detection and cascading a signal through multiple layers of oscillator elements of different characteristic frequency. Last, we show that the combination of these two schemes yields a signal detector with enhanced frequency selectivity and speed of response, thus enabling the detection of transient, narrowband flight tones.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"14 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002985","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}
Jamie McLauchlan, Jim S. Walker, Vatsal Sanjay, Maziyar Jalaal, Jonathan P. Reid, Adam M. Squires, Anton Souslov
{"title":"Bouncing microdroplets on hydrophobic surfaces","authors":"Jamie McLauchlan, Jim S. Walker, Vatsal Sanjay, Maziyar Jalaal, Jonathan P. Reid, Adam M. Squires, Anton Souslov","doi":"10.1073/pnas.2507309122","DOIUrl":"https://doi.org/10.1073/pnas.2507309122","url":null,"abstract":"Intuitively, slow droplets stick to a surface and faster droplets splash or bounce. However, recent work suggests that on nonwetting surfaces, whether microdroplets stick or bounce depends only on their size and fluid properties, but not on the incoming velocity. Here, we show using theory and experiments that even poorly wetting surfaces have a velocity-dependent criterion for bouncing of aqueous droplets, which is as high as 6 m/s for diameters of 30 to 50 <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mi mathvariant=\"normal\">μ</mml:mi> </mml:math> </jats:inline-formula> m on hydrophobic surfaces such as Teflon. We quantify this criterion by analyzing the interplay of dissipation, surface adhesion, and incoming kinetic energy, and describe a wealth of associated phenomena, including air bubbles and satellite droplets. Our results on inertial microdroplets elucidate fundamental processes crucial to aerosol science and technology.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"49 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995863","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":"Collective behavior of “flexicles”","authors":"Philipp W. A. Schönhöfer, Sharon C. Glotzer","doi":"10.1073/pnas.2426850122","DOIUrl":"https://doi.org/10.1073/pnas.2426850122","url":null,"abstract":"In recent years the functionality of synthetic active microparticles has edged even closer to that of their biological counterparts. However, we still lack the understanding needed to recreate at the microscale key features of autonomous behavior exhibited by microorganisms or swarms of macroscopic robots. In this study, we propose a model for a three-dimensional deformable cellular composite particle consisting of self-propelled rod-shaped colloids confined within a flexible vesicle—representing a superstructure we call a “flexicle” that couples particle deformation to the internal dynamics of the internal active components. Using molecular dynamics simulations, we investigate the collective behavior of dense systems composed of many flexicles. We show that individual flexicles exhibit shape changes upon collisions with other flexicles that lead to rearrangements of the internal active rods, which slows flexicle motion. This shape deformability gives rise to a diverse set of motility-induced phase separation phenomena and the spontaneous flow of flexicles reminiscent of the migration of cells in dense tissues. Our findings establish a foundation for designing responsive, cell-like active particles and developing strategies for controlling swarm migration and other autonomous swarm behaviors at cellular and colloidal scales.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"18 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995749","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":"Evidence for coopetition at the maternal-fetal interface shaping placental invasion.","authors":"Junaid Afzal,Yasir Suhail,Wenqiang Du,Yamin Liu,Ramalakshmi Ramasamy,Zukai Liu,Ruchi Goyal,Ashkan Novin,Sameera Suhail,Jamie Maziarz,Khadija Wali,Paul Robson,Günter P Wagner, Kshitiz","doi":"10.1073/pnas.2323038122","DOIUrl":"https://doi.org/10.1073/pnas.2323038122","url":null,"abstract":"Coopetition is a term from game theory that describes a mix of cooperative and competitive behavior. The maternal-fetal interface (MFI) among eutherian mammals presents close interaction of two distinct individuals. These interactions have resulted in a remarkable diversity in MFI structure, often interpreted as the outcome of maternal-fetal conflict. Nevertheless, the fetus and the mother share evolutionary interests since 50% of fetal genes are maternal. In hemochorial species, characterized by invasive placentation, endometrial stromal fibroblasts (ESFs) undergo decidualization to regulate embryo implantation. In great apes, hemochorial placentation is driven by highly invasive extravillous trophoblast cells (EVT). Here, using EVTs differentiated from trophoblast stem cells, term placenta, as well as HTR8/SVneo, we demonstrate that EVTs orchestrate a transformation of the maternal stroma, reducing its resistance to invasion acquired during decidualization. Through paracrine signals, in particular IL-11, trophoblasts transform decidual ESFs from a matrix-producing to a matrix-degrading state. Notably, noninvasive cytotrophoblast cells, do not transform decidual ESFs. We further provide evidence that maternal coadaptation is critical to EVT-induced decidual transformation. Decidual ESFs upregulate expression of Suppressor of Cytokine Signaling 3 in response to EVTs, rewiring downstream IL-11 signaling from JAK/STAT to AP-1 specific transcription. We conclude that the evolution of highly invasive placentation is the outcome of both the evolution of invasive EVTs, as well as the evolution of maternal traits, i.e., the switch from JAK/STAT to AP-1 signaling. We interpret this as evidence for co-opetition (cooperation among competitors).","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 1","pages":"e2323038122"},"PeriodicalIF":11.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995841","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":"Correction for Pang et al., Structural elucidation of how ARF small GTPases induce membrane tubulation for vesicle fission.","authors":"","doi":"10.1073/pnas.2522054122","DOIUrl":"https://doi.org/10.1073/pnas.2522054122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"53 1","pages":"e2522054122"},"PeriodicalIF":11.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995933","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}
Raymond Adkins, Joanna Robaszewski, Seungwoo Shin, Fridtjof Brauns, Leroy Jia, Ayantika Khanra, Prerna Sharma, Robert A. Pelcovits, Thomas R. Powers, Zvonimir Dogic
{"title":"Topology and kinetic pathways of colloidosome assembly and disassembly","authors":"Raymond Adkins, Joanna Robaszewski, Seungwoo Shin, Fridtjof Brauns, Leroy Jia, Ayantika Khanra, Prerna Sharma, Robert A. Pelcovits, Thomas R. Powers, Zvonimir Dogic","doi":"10.1073/pnas.2427024122","DOIUrl":"https://doi.org/10.1073/pnas.2427024122","url":null,"abstract":"Closed capsules, such as lipid vesicles, soap bubbles, and emulsion droplets, are ubiquitous throughout biology, engineered matter, and everyday life. Their creation and disintegration are defined by a singularity that separates a topologically distinct extended liquid film from a boundary-free closed shell. Such topology-changing processes are of fundamental interest. They are also essential for intercellular transport, transcellular communication, and drug delivery. However, studies of vesicle formation are challenging because of the rapid dynamics and small length scale involved. We develop fluid colloidosomes, micrometer-sized analogues of lipid vesicles. The mechanics of colloidosomes and lipid vesicles are described by the same theoretical model. We study colloidosomes close to their disk-to-sphere topological transition. Intrinsic colloidal length and time scales slow down the dynamics to reveal colloidosome conformations in real time during their assembly and disassembly. Remarkably, the lowest-energy pathway by which a closed vesicle transforms into a flat disk involves a topologically distinct cylinder-like intermediate. These results reveal aspects of topological changes that are relevant to all liquid capsules. They also provide a robust platform for the encapsulation, transport, and delivery of nanosized cargoes.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"42 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995865","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}
Clarissa C. Pasiliao, Evan C. Thomas, Theodora Yung, Min Zhu, Hirotaka Tao, Yu Sun, Sidhartha Goyal, Sevan Hopyan
{"title":"A thermodynamic perspective on mammalian neural crest ingression","authors":"Clarissa C. Pasiliao, Evan C. Thomas, Theodora Yung, Min Zhu, Hirotaka Tao, Yu Sun, Sidhartha Goyal, Sevan Hopyan","doi":"10.1073/pnas.2504185122","DOIUrl":"https://doi.org/10.1073/pnas.2504185122","url":null,"abstract":"The ingression of neural crest cells from an ectodermal to a mesodermal layer is regulated by instructive, directional cues and potentially stochastic, biophysical parameters such as differential cell adhesion and tension heterogeneity. However, a cohesive framework in which to consider how various influences contribute to ingression remains elusive. Here, we observe the cell behaviors of the murine neural crest in three dimensions over time and apply a free energy framework to more wholly understand why cells ingress. Guided by work on granular matter that provides a path by which to define the roles of stochastic mechanisms in nonequilibrium systems, we measured and manipulated biophysical parameters in vivo. The data suggest that an energy barrier to cell ingression is overcome by a combination of relatively favorable cell adhesion energies, high cell shape fluctuations, and entropic cell packing configurations. Under those conditions, cell ingression may proceed spontaneously. Recognized biophysical cues likely tilt these parameters to make the process more robust. The results imply that dissipative mechanisms which transiently disorder tissue may underlie some morphogenetic events. Variations of a thermodynamic framework can potentially be applied to integrate various inputs that drive morphogenesis in different contexts.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"21 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995867","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}
Andres Chang, Adam N. Pelletier, Donald J. McGuire, Maria Tsagiopoulou, Maria Karipidou, Amy Ayers, Alyssa M. K. Leal, Michael C. Churnetski, Colin B. O’Leary, Jeffrey M. Switchenko, Carl Davis, David A. Frank, Jean L. Koff, Jonathon B. Cohen, Rafick P. Sekaly, Kostas Stamatopoulos, Christopher R. Flowers, Rafi Ahmed
{"title":"PD-1 expression identifies proliferating malignant CLL B cells and is a potential biomarker of response to BTK inhibitor therapy","authors":"Andres Chang, Adam N. Pelletier, Donald J. McGuire, Maria Tsagiopoulou, Maria Karipidou, Amy Ayers, Alyssa M. K. Leal, Michael C. Churnetski, Colin B. O’Leary, Jeffrey M. Switchenko, Carl Davis, David A. Frank, Jean L. Koff, Jonathon B. Cohen, Rafick P. Sekaly, Kostas Stamatopoulos, Christopher R. Flowers, Rafi Ahmed","doi":"10.1073/pnas.2426935122","DOIUrl":"https://doi.org/10.1073/pnas.2426935122","url":null,"abstract":"Chronic lymphocytic leukemia (CLL) remains incurable despite treatment advances, and a major challenge is that biomarkers that predict response and resistance to current therapies are lacking. We report that activated and proliferating malignant CLL B cells in circulation express PD-1, a protein normally expressed in T cells. PD-1 expression is absent in circulating B cells from healthy controls and nonmalignant B cells from patients with CLL. Circulating PD-1 <jats:sup>+</jats:sup> CLL cells are found in all treatment naïve patients, regardless of immunoglobulin heavy-chain variable region gene mutation status or cytogenetic abnormalities. PD-1 <jats:sup>+</jats:sup> CLL cells are transcriptionally distinct compared to PD-1 <jats:sup>−</jats:sup> CLL cells and upregulate genes associated with cell activation, proliferation, and B cell receptor (BCR) and toll-like receptor (TLR) signaling. Indeed, ex vivo stimulation of the BCR and TLR9 readily increased PD-1 expression in CLL cells from treatment-naïve patients within 24 h, an effect that was blocked by Bruton’s tyrosine kinase inhibitors (BTKi). More importantly, patients initiating BTKi therapy experienced profound reductions in circulating PD-1 <jats:sup>+</jats:sup> CLL cell numbers within 1 mo, which is in line with reduction in Ki-67 <jats:sup>+</jats:sup> CLL cells. Elevated percentages of circulating PD-1 <jats:sup>+</jats:sup> CLL cells also preceded a clinical diagnosis of disease progression in patients receiving BTKi. Thus, our findings indicate that PD-1 expression is a potential biomarker to identify proliferating CLL cells in vivo and will be useful to predict response and resistance to BTKi. In addition, eliminating PD-1 <jats:sup>+</jats:sup> CLL cells with depleting anti-PD-1 monospecific or bispecific antibodies should be explored as a potential therapeutic strategy.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"24 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995869","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}