We checked 7 multidisciplinary journals on Friday, April 04, 2025 using the Crossref API. For the period March 28 to April 03, we retrieved 15 new paper(s) in 6 journal(s).

Nature

GPT-4o mini: Non-social science research article
Author Correction: Controlled patterning of crystalline domains by frontal polymerization
Justine E. Paul, Yuan Gao, Yoo Kyung Go, Luis E. Rodriguez Koett, Anisha Sharma, Manxin Chen, Jacob J. Lessard, Tolga Topkaya, Cecilia Leal, Jeffrey S. Moore, Philippe H. Geubelle, Nancy R. Sottos
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GPT-4o mini: Non-social science research article
Author Correction: Isoprene nitrates drive new particle formation in Amazon’s upper troposphere
Joachim Curtius, Martin Heinritzi, Lisa J. Beck, Mira L. Pöhlker, Nidhi Tripathi, Bianca E. Krumm, Philip Holzbeck, Clara M. Nussbaumer, Lianet HernĂĄndez Pardo, Thomas Klimach, Konstantinos Barmpounis, Simone T. Andersen, Roman Bardakov, Birger Bohn, Micael A. Cecchini, Jean-Pierre Chaboureau, Thibaut Dauhut, Dirk Dienhart, Raphael Dörich, Achim Edtbauer, Andreas Giez, Antonia Hartmann, Bruna A. Holanda, Philipp Joppe, Katharina Kaiser, Timo Keber, Hannah Klebach, Ovid O. KrĂŒger, Andreas KĂŒrten, Christian Mallaun, Daniel Marno, Monica Martinez, Carolina Monteiro, Carolina Nelson, Linda Ort, Subha S. Raj, Sarah Richter, Akima Ringsdorf, Fabio Rocha, Mario Simon, Sreedev Sreekumar, Anywhere Tsokankunku, Gabriela R. Unfer, Isabella D. Valenti, Nijing Wang, Andreas Zahn, Marcel Zauner-Wieczorek, Rachel I. Albrecht, Meinrat O. Andreae, Paulo Artaxo, John N. Crowley, Horst Fischer, Hartwig Harder, Dirceu L. Herdies, Luiz A. T. Machado, Christopher Pöhlker, Ulrich Pöschl, Anna Possner, Andrea Pozzer, Johannes Schneider, Jonathan Williams, Jos Lelieveld
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Style over substance? What birds’ mating behaviours reveal about sexual selection
Tim Coulson
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How seahorses and pipefish inspired the design of a boat propeller
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Do smartphones and social media really harm teens’ mental health?
Helen Pearson
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Daily briefing: Women’s work is missing from the scientific literature
Flora Graham
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Incredible close-up of colourful crab spiders — March’s best science images
Emma Stoye
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Trump team guts AIDS-eradication programme and slashes HIV research grants
Humberto Basilio
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From bench to bread: how science can enhance your hobbies
Hannah Docter-Loeb
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‘One of the darkest days’: NIH purges agency leadership amid mass layoffs
Max Kozlov
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Could the shingles vaccine help to prevent dementia?
Anupam B. Jena
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Audio long read: How quickly are you ageing? What molecular ‘clocks’ can tell you about your health
Heidi Ledford, Benjamin Thompson
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Daily briefing: Stunning Antarctic ecosystem revealed by calving iceberg
Flora Graham
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Deep dive: How I use robots to survey coral reefs
Nikki Forrester
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How Europe aims to woo US scientists and protect academic freedom
David Matthews
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Sunflower ‘virgin births’ enable accelerated crop breeding
Marco Todesco, Loren H. Rieseberg
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Unicorn slippers in space
Katie Cervenec
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A toolkit for seeing how the fly brain’s visual system works
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Publishers trial paying peer reviewers — what did they find?
Holly Else
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Showing ‘ability’ in ‘disability’ — how I mastered interviews while using a wheelchair
Emilia Krok
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The global scientific community must keep studying LGBT+ health
ClĂĄudia C. Gonçalves, Lana J.  Williams, Alison R. Yung, Ashleigh Lin
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CERN releases detailed plans for supercollider — but no hints about funding
Davide Castelvecchi
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The best foods for healthy ageing ― and the worst
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Can trauma from violence be genetically inherited? Scientists debate Syria refugee study
Miryam Naddaf
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Revealed: first DNA profiles of ancient people who roamed a lush Sahara
Freda Kreier
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Superpowers want to control critical mineral supplies — local communities need a stronger say
Rabah Arezki
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China has already taken steps to reduce retractions of papers from its hospitals
Gong Jie Zhang, Ya Bin Zhou
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Action needed to mitigate effects of slashing USAID
Zaheer Allam, Ali Cheshmehzangi
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Brain implant translates thoughts to speech in an instant
Miryam Naddaf
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AI masters Minecraft: DeepMind program finds diamonds without being taught
Celeste Biever
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Light wins uphill battle to solve enduring problem in organic synthesis
Wenzheng Fan, Guosheng Liu
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Rare ancient DNA from Sahara opens a window on the region’s verdant past
Mary Prendergast
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What if human blood were toxic to mosquitoes? A drug can make it so
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Intriguing features of the interface between water and oil droplets uncovered
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Daily briefing: What happens when you pay peer reviewers?
Flora Graham
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Deadly Myanmar earthquake was probably a rare rupture, scientists say
Alexandra Witze
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How to get rid of toxic ‘forever chemical’ pollution
XiaoZhi Lim
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The neurons that mediate a psychedelic’s long-term antidepressive effects
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These US labs risk imminent closure after Trump cuts
Heidi Ledford
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Six roadblocks to net zero — and how to get around them
Lucas Joppa, Elizabeth Willmott
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Minerals will shape future geopolitical order
Mariusz Baranowski, Piotr Jabkowski, Daniel M. Kammen
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Daily briefing: Pregnancy’s true toll on the body
Jacob Smith
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Daily briefing: Why RNA hasn’t yet had its ‘AlphaFold’ moment
Flora Graham
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El Niños that linger are becoming less of a rarity
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Are screens harming teens? What scientists can do to find answers
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23andMe plans to sell its huge genetic database: could science benefit?
Celeste Biever
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A brain drain would impoverish the United States and diminish world science
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Nature Human Behaviour

GPT-4o mini: Non-social science research article
The next generation of experimental research with LLMs
Gary Charness, Brian Jabarian, John A. List
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GPT-4o mini: Non-social science research article
A neural geometry approach comprehensively explains apparently conflicting models of visual perceptual learning
Yu-Ang Cheng, Mehdi Sanayei, Xing Chen, Ke Jia, Sheng Li, Fang Fang, Takeo Watanabe, Alexander Thiele, Ru-Yuan Zhang
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Visual perceptual learning (VPL), defined as long-term improvement in a visual task, is considered a crucial tool for elucidating underlying visual and brain plasticity. Previous studies have proposed several neural models of VPL, including changes in neural tuning or in noise correlations. Here, to adjudicate different models, we propose that all neural changes at single units can be conceptualized as geometric transformations of population response manifolds in a high-dimensional neural space. Following this neural geometry approach, we identified neural manifold shrinkage due to reduced trial-by-trial population response variability, rather than tuning or correlation changes, as the primary mechanism of VPL. Furthermore, manifold shrinkage successfully explains VPL effects across artificial neural responses in deep neural networks, multivariate blood-oxygenation-level-dependent signals in humans and multiunit activities in monkeys. These converging results suggest that our neural geometry approach comprehensively explains a wide range of empirical results and reconciles previously conflicting models of VPL.
How growing up without siblings affects the adult brain and behaviour in the CHIMGEN cohort
Jie Tang, Jing Zhang, Wei Li, Meiyun Wang, Jingliang Cheng, Bing Zhang, Wenzhen Zhu, Shijun Qiu, Guangbin Cui, Yongqiang Yu, Weihua Liao, Hui Zhang, Bo Gao, Xiaojun Xu, Yunjun Yang, Tong Han, Zhenwei Yao, Quan Zhang, Wen Qin, Feng Liu, Meng Liang, Sijia Wang, Qiang Xu, Jiayuan Xu, Jilian Fu, Yuan Ji, Nana Liu, Peng Zhang, Dapeng Shi, Caihong Wang, Su Lui, Zhihan Yan, Feng Chen, Wen Shen, Yanwei Miao, Dawei Wang, Junfang Xian, Xiaochu Zhang, Kai Xu, Xi-Nian Zuo, Longjiang Zhang, Zhaoxiang Ye, Zuojun Geng, Jia-Hong Gao, Chunshui Yu, character(0), Quan Zhang, Junping Wang, Xue Zhang, Xinjun Suo, Congcong Yuan, Hui Xue, Tianying Gao, Junpeng Liu, Yanjun Li, Xi Guo, Lixue Xu, Jiajia Zhu, Huaigui Liu, Fangshi Zhao, Jie Sun, Yongjie Xu, Huanhuan Cai, Yaodan Zhang, Yongqin Xiong, Xianting Sun, Nannan Pan, Xue Zhang, Jiayang Yang, Ya Wen, Dan Zhu, Bingjie Wu, Wenshuang Zhu, Qingqing Diao, Yujuan Cao, Bingbing Yang, Lining Guo, Yingying Xie, Jiahui Lin, Zhimin Li, Yan Zhang, Kaizhong Xue, Zirui Wang, Junlin Shen, Xuejun Zhang, Hao Ding, Qian Su, Mulin Jun Li, Shijie Zhang, Lun Ma, Yan Bai, Min Guan, Wei Wei, Peifang Miao, Fuhong Duan, Yafei Guo, Weijian Wang, Long Jiang Zhang, Lijuan Zheng, Lilin, Yunfei Wang, Han Zhang, Xinyuan Zhang, Zhao Qing, Sichu Wu, Junxia Wang, Yi Sun, Yang He, Xi-Nian Zuo, Zhe Zhang, Yin-Shan Wang, Quan Zhou, Tian Tian, Yi Liang, Yujie Liu, Hui Zeng, Jingxian Chen, Haitao Ge, Peng Xu, Cailuan Lu, Chen Wu, Xiaoying Yang, Yuzhao Wang, Yankai Wu, Xuran Feng, Ling Li, Duo Gao, Rujing Zha, Ying Li, Lizhuang Yang, Ying Chen, Ling Zuo, Jianqiao Ge, Guoyuan Yang, Wen Wang, Linfeng Yan, Yang Yang, Jin Zhang, Qian Wang, Xiaoxia Qu, Ying Wang, Fei Yuan, Li Hu, Jizhen Li, Weiwei Wang, Yujing Zhou, Miaomiao Long, Lihua Liu, Xiaohu Li, Xiaoshu Li, Jiance Li, Nengzhi Xia, Weihua Liao, Shuai Yang, Youming Zhang, Jing Zhang, Guangyao Liu, Laiyang Ma, Xiaochun Wang, Ying Lei, Bo Gao, Gang Zhang, Kang Yuan, Jingjing Xu, Xiaojun Guan, Yuankai Lin, Hui Juan Chen, Yuchuan Fu, Yi Lu, Jun Guo, Hao Lu, Yue Wu
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Alcohol use disorder and body mass index show genetic pleiotropy and shared neural associations
Samantha G. Malone, Christal N. Davis, Zachary Piserchia, Michael R. Setzer, Sylvanus Toikumo, Hang Zhou, Emma L. Winterlind, Joel Gelernter, Amy Justice, Lorenzo Leggio, Christopher T. Rentsch, Henry R. Kranzler, Joshua C. Gray
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Women shaping behavioural science
Qing Cai, Mar Hicks, Emilia Huerta-Sanchez, Samara Klar, Misaki N. Natsuaki, Tanja van der Lippe
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Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Correction to Supporting Information for Ikeda et al., Seesaw protein: Design of a protein that adopts interconvertible alternative functional conformations and its dynamics
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GPT-4o mini: Non-social science research article
Therapeutic targeting of the NOTCH1 and neddylation pathways in T cell acute lymphoblastic leukemia
Kalay Bertulfo, Pablo Perez-Duran, Hannah Miller, Cindy Ma, Alberto Ambesi-Impiombato, Jeremy Samon, Adam Mackey, Wen-Hsuan Wendy Lin, Adolfo A. Ferrando, Teresa Palomero
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Gamma Secretase Inhibitors (GSIs) effectively block oncogenic Notch homolog-1 (NOTCH1), a characteristic feature of T cell acute lymphoblastic leukemias (T-ALL). However, their clinical application has been stalled by the induction of severe gastrointestinal toxicity resulting from the inhibition of NOTCH signaling in the gut, which translates into increased goblet cell differentiation. Genome-wide CRISPR loss-of-function screen in the colon cancer cell line LS174T identified the neddylation pathway as a main regulator of goblet cell differentiation upon NOTCH1 inhibition. Consistently, pharmacologic inhibition of the neddylation pathway with the small molecule inhibitor MLN4924, rescued GSI-induced differentiation in LS174T cells. Mechanistically, neddylation inhibition by MLN4924 increases the protein stability of Hairy and enhancer of split-1, a direct NOTCH1 transcriptional target and key regulator of absorptive and secretory cell fate decisions. Combined treatment with GSI and MLN4924 in a murine Notch1 -dependent model of T-ALL led to leukemia regression and improved overall survival in the absence of gut toxicity. Overall, these results support the combined targeting of the NOTCH1 and neddylation pathways for the treatment of NOTCH1-induced T-ALL.
GPT-4o mini: Non-social science research article
Phosphatic stromatoporoid sponges formed reefs ~480 Mya
Juwan Jeon, Mar Simonet Roda, Zhong-Yang Chen, Cui Luo, Stephen Kershaw, Daeyeong Kim, Jun-Ye Ma, Jeong-Hyun Lee, Yuan-Dong Zhang
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Stromatoporoid sponges were important reef-builders during the middle Paleozoic, yet their early history and integration into reef ecosystems remain poorly understood. Here, we report Lophiostroma leizunia Jeon sp. nov., the oldest known stromatoporoid from upper Tremadocian to lower Floian (~480 My-old) strata of South China. L. leizunia formed complex reef structures, playing crucial roles in framework construction and binding other components, including calcimicrobes, lithistid sponges, stalked echinoderms, and Calathium . This discovery pushes back the fossil record of stromatoporoids and the reefs that they formed by approximately 20 My, advancing the onset of the Great Ordovician Biodiversification Event in reef evolution. L. leizunia unusually constructed its skeleton using fluorapatite—a feature previously unknown in sponges. This establishes Porifera as the first metazoan phylum known to have utilized all three principal biominerals: silica, calcium carbonate, and calcium phosphate. The presence of phosphatic skeletons in this early stromatoporoid expands our understanding of biomineralization capabilities in early animals and suggests that the genetic toolkit for diverse biomineralization strategies may have been present in early sponges. The unique combination of the earliest known reef-building stromatoporoids and their phosphatic skeletal composition provides insights into the evolutionary dynamics of biomineralization and the rise of metazoan-dominated reef ecosystems during a critical period of Earth’s history.
GPT-4o mini: Non-social science research article
A conserved ARF–DNA interface underlies auxin-triggered transcriptional response
Juriaan Rienstra, Vanessa Polet Carrillo-Carrasco, Martijn de Roij, Jorge Hernandez-Garcia, Dolf Weijers
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Auxin Response Factor (ARF) plant transcription factors are the key effectors in auxin signaling. Their DNA-Binding Domain (DBD) contains a B3 domain that allows base-specific interactions with Auxin Response Elements (AuxREs) in DNA target sites. Land plants encode three phylogenetically distinct ARF classes: the closely related A- and B-classes have overlapping DNA binding properties, contrasting with the different DNA-binding properties of the divergent C-class ARFs. ARF DNA-binding divergence likely occurred early in the evolution of the gene family, but the molecular determinants underlying it remain unclear. Here, we show that the B3 DNA-binding residues are deeply conserved in ARFs, and variability within these is only present in tracheophytes, correlating with greatly expanded ARF families. Using the liverwort Marchantia polymorpha , we confirm the essential role of conserved DNA-contacting residues for ARF function. We further show that ARF B3–AuxRE interfaces are not mutation-tolerant, suggesting low evolvability that has led to the conservation of the B3–DNA interface between ARF classes. Our data support the almost complete interchangeability between A/B-class ARF B3 by performing interspecies domain swaps in M. polymorpha , even between ARF lineages that diverged over half a billion years ago. Our analysis further suggests that C-class ARF DNA-binding specificity diverged early during ARF evolution in a common streptophyte ancestor, followed by strong selection in A and B-class ARFs as part of a competition-based auxin response system.
GPT-4o mini: Non-social science research article
The cingulate cortex facilitates auditory perception under challenging listening conditions
Kelsey L. Anbuhl, Marielisa Diez Castro, Nikki A. Lee, Vivian S. Lee, Dan H. Sanes
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We often exert greater cognitive resources (i.e., listening effort) to understand speech under challenging acoustic conditions. This mechanism can be overwhelmed in those with hearing loss, resulting in cognitive fatigue in adults and potentially impeding language acquisition in children. However, the neural mechanisms that support listening effort are uncertain. Evidence from human studies suggests that the cingulate cortex is engaged under difficult listening conditions and may exert top–down modulation of the auditory cortex (AC). Here, we asked whether the gerbil cingulate cortex (Cg) sends anatomical projections to the AC that facilitate perceptual performance. To model challenging listening conditions, we used a sound discrimination task in which stimulus parameters were presented in either “Easy” or “Hard” blocks (i.e., long or short stimulus duration, respectively). Gerbils achieved statistically identical psychometric performance in Easy and Hard blocks. Anatomical tracing experiments revealed a strong, descending projection from layer 2/3 of the Cg1 subregion of the cingulate cortex to superficial and deep layers of the primary and dorsal AC. To determine whether Cg improves task performance under challenging conditions, we bilaterally infused muscimol to inactivate Cg1 and found that psychometric thresholds were degraded for only Hard blocks. To test whether the Cg-to-AC projection facilitates task performance, we chemogenetically inactivated these inputs and found that performance was only degraded during Hard blocks. Taken together, the results reveal a descending cortical pathway that facilitates perceptual performance during challenging listening conditions.
GPT-4o mini: Non-social science research article
Reactivation of memory-associated neurons induces downstream suppression of competing neuronal populations
Jacob F. Norman, Bahar Rahsepar, Anna Vena, Martin Thunemann, Anna Devor, Steve Ramirez, John A. White
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Inducing apparent memory recall by tagging and optogenetically reactivating cells in the hippocampus was demonstrated over a decade ago. However, the hippocampal dynamics resulting from this reactivation remain largely unknown. While calcium imaging is commonly used as a measure of neuronal activity, GCaMP, the most common calcium indicator, cannot be used with optogenetic neuronal reactivation because both require blue light excitation. To resolve this overlap, we demonstrate optogenetic reactivation with a red-shifted opsin, ChrimsonR. We then conduct dual-color calcium imaging in CA1 during memory reactivation in DG. In addition to measuring population dynamics in CA1, CA1 cells tagged during the original experience were identified. In the fear-conditioned animals (FC+), nontagged cells in CA1 decreased their firing rate during stimulation, while tagged cells maintained their activity level. In the FC+ animals, as the behavioral effect of stimulation decreased across days, so did the changes in neural activity during stimulation. Our results both demonstrate the technical feasibility of calcium imaging during optogenetic reactivation of memory-associated neurons and advance our understanding of the dynamics underlying this reactivation.
GPT-4o mini: Non-social science research article
DDX54 downregulation enhances anti-PD1 therapy in immune-desert lung tumors with high tumor mutational burden
Jeong-Ryeol Gong, Jungeun Lee, Younghyun Han, Kwang-Hyun Cho
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High tumor mutational burden (TMB-H) is a predictive biomarker for the responsiveness of cancer to immune checkpoint inhibitor (ICI) therapy that indicates whether immune cells can sufficiently recognize cancer cells as nonself. However, about 30% of all cancers from The Cancer Genome Atlas (TCGA) are classified as immune-desert tumors lacking T cell infiltration despite TMB-H. Since the underlying mechanism of these immune-desert tumors has yet to be unraveled, there is a pressing need to transform such immune-desert tumors into immune-inflamed tumors and thereby enhance their responsiveness to anti-PD1 therapy. Here, we present a systems framework for identifying immuno-oncotargets, based on analysis of gene regulatory networks, and validating the effect of these targets in transforming immune-desert into immune-inflamed tumors. In particular, we identify DEAD-box helicases 54 (DDX54) as a master regulator of immune escape in immune-desert lung cancer with TMB-H and show that knockdown of DDX54 can increase immune cell infiltration and lead to improved sensitivity to anti-PD1 therapy.
GPT-4o mini: Non-social science research article
Phosphatidylinositol 4,5-bisphosphate activation mechanism of human KCNQ5
Zhenni Yang, Yueming Zheng, Demin Ma, Long Wang, Jiatong Zhang, Tiefeng Song, Yong Wang, Yan Zhang, Fajun Nan, Nannan Su, Zhaobing Gao, Jiangtao Guo
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The human voltage-gated potassium channels KCNQ2, KCNQ3, and KCNQ5 can form homo- and heterotetrameric channels that are responsible for generating the neuronal M current and maintaining the membrane potential stable. Activation of KCNQ channels requires both the depolarization of membrane potential and phosphatidylinositol 4,5-bisphosphate (PIP 2 ). Here, we report cryoelectron microscopy structures of the human KCNQ5–calmodulin (CaM) complex in the apo, PIP 2 -bound, and both PIP 2 - and the activator HN37-bound states in either a closed or an open conformation. In the closed conformation, a PIP 2 molecule binds in the middle of the groove between two adjacent voltage-sensing domains (VSDs), whereas in the open conformation, one additional PIP 2 binds to the interface of VSD and the pore domain, accompanying structural rearrangement of the cytosolic domain of KCNQ and CaM. The structures, along with electrophysiology analyses, reveal the two different binding modes of PIP 2 and elucidate the PIP 2 activation mechanism of KCNQ5.
GPT-4o mini: Non-social science research article
Optogenetic stimulation of the dorsal striatum bidirectionally controls seizures
Safwan K. Hyder, Willian Lazarini-Lopes, Jonathan Toib, Gabrielle Williams, Alexander Sukharev, Patrick A. Forcelli
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Despite a century of development of antiseizure medications, up to a third of people with epilepsy do not achieve seizure freedom with drug therapy. Deep brain stimulation is of growing use, but just as with pharmacotherapy, is not universally effective. Identifying new targets for deep brain stimulation—and in particular sites that are effective against a range of seizure types—may close this gap. Engagement of the basal ganglia experimental seizures was first observed almost 75 y ago. However, the role of the basal ganglia’s input nucleus, the striatum, in seizure control is relatively understudied. To address this gap, we used an optogenetic approach to activate and inactivate neurons in the dorsal striatum of rats submitted to the gamma-butyrolactone (GBL) model of absence epilepsy, amygdala kindling model of temporal lobe epilepsy, and pilocarpine-induced Status Epilepticus (SE). Open-loop (continuous light delivery) optogenetic activation of dorsal striatal neurons robustly suppressed seizures in all models. By contrast, open-loop optogenetic silencing increased absence seizure expression and facilitated SE onset but had no effect on kindled seizures. In the GBL model, we also tested the effects of closed-loop modulation (light delivery in response to seizure detection). Closed-loop activation reduced duration of spike-wave discharges (SWDs), while closed-loop inhibition increased SWD duration. These results demonstrated previously unrecognized antiabsence effects associated with striatal neuromodulation. These findings demonstrate a robust, bidirectional role of the dorsal striatum in the control of multiple seizure types, suggesting that the striatum is a site that can exert broad-spectrum control of seizures.
GPT-4o mini: Non-social science research article
Bilateral astrocyte reaction to unilateral insult in the optic projection to the brain
Joseph M. Holden, David J. Calkins
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GPT-4o mini: Non-social science research article
Cryo-EM structure of cyanopodophage A4 reveals a pentameric pre-ejectosome in the double-stabilized capsid
Pu Hou, Rui-Qian Zhou, Yong-Liang Jiang, Rong-Cheng Yu, Kang Du, Nanqin Gan, Fei Ke, Qi-Ya Zhang, Qiong Li, Cong-Zhao Zhou
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Upon infection, the podophages usually eject a couple of proteins from the capsid to form a transmembrane ejectosome on the host cell membrane that facilitates the ejection of viral genome. However, it remains unclear how these proteins of pre-ejectosome are finely assembled at the center of highly packaged genome. Here, we report the intact structure of Anabaena cyanopodophage A4, which consists of a capsid stabilized by two types of cement proteins and a short tail attached with six tail fibers. Notably, we find a pentameric pre-ejectosome at the core of capsid, which is composed of four ejection proteins wrapped into a coaxial cylinder of triple layers. Moreover, a segment of genomic DNA runs along the positively charged circular cleft formed by two ejection proteins. Based on the mortise-and-tenon architecture of pre-ejectosome in combination with previous studies, we propose a putative DNA packaging process and ejection mechanism for podophages. These findings largely enrich our knowledge on the assembly mechanism of podophages, which might facilitate the application of A4 as a chassis cyanophage in synthetic biology.
GPT-4o mini: Non-social science research article
In This Issue
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GPT-4o mini: Non-social science research article
LMX1B missense-perturbation of regulatory element footprints disrupts serotonergic forebrain axon arborization
Brent Eastman, Nobuko Tabuchi, Xinrui L. Zhang, William C. Spencer, Evan S. Deneris
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Pathogenic coding mutations are prevalent in human neuronal transcription factors (TFs) but how they disrupt development is poorly understood. Lmx1b is a master transcriptional regulator of postmitotic Pet1 neurons that give rise to mature serotonin (5-HT) neurons; over two hundred pathogenic heterozygous mutations have been discovered in human LMX1B, yet their impact on brain development has not been investigated. Here, we developed mouse models with different LMX1B DNA-binding missense mutations. Missense heterozygosity broadly altered Pet1 neuron transcriptomes, but expression changes converged on axon and synapse genes. Missense heterozygosity effected highly specific deficits in the postnatal maturation of forebrain serotonin axon arbors, primarily in the hippocampus and motor cortex, which was associated with spatial memory defects. Digital genomic footprinting (DGF) revealed that missense heterozygosity caused complete loss of Lmx1b motif protection and chromatin accessibility at sites enriched for a distal active enhancer/active promoter histone signature and homeodomain binding motifs; at other bound Lmx1b motifs, varying levels of losses, gains, or no change in motif binding and accessibility were found. The spectrum of footprint changes was strongly associated with synapse and axon genes. Further, Lmx1b missense heterozygosity caused wide disruption of Lmx1b-dependent GRNs comprising diverse TFs expressed in Pet1 neurons. These findings reveal an unanticipated continuum of Lmx1b missense-forced perturbations on Pet1 neuron regulatory element TF binding and accessibility. Our work illustrates DGF’s utility for gaining unique insight into how expressed TF missense mutations interfere with developing neuronal GRNs.
GPT-4o mini: Non-social science research article
Following phospholipid transfer through the OmpF 3 –MlaA–MlaC lipid shuttle with native mass spectrometry
Carla Kirschbaum, Jack L. Bennett, Qiaoyu Tian, Navoneel Sen, Iain P. S. Smith, Di Wu, Justin L. P. Benesch, Syma Khalid, Georgia Isom, Carol V. Robinson
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The maintenance of lipid asymmetry (Mla) system in gram-negative bacteria transfers phospholipids between the outer and inner membrane to maintain the outer membrane asymmetry. Misplaced phospholipids are extracted from the outer leaflet of the outer membrane by MlaA, transferred to the periplasmic lipid transporter MlaC, and shuttled to the inner membrane. We set out to investigate the lipid transfer between MlaA and MlaC using native mass spectrometry, with the aim of determining the lipid preferences of MlaC and whether MlaA preselected lipids for MlaC. First, we characterized the lipids that copurified with overexpressed MlaC, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE), and following delipidation noted a headgroup-independent enrichment of cyclopropane lipids. Under native expression conditions, we found that PG is three-fold enriched on MlaC compared to its abundance in the membrane. Next, we isolated and characterized OmpF 3 –MlaA complexes and demonstrated their ability to enhance loading of delipidated MlaC with bacterial and nonbacterial phospholipids. We then captured the intact ternary lipid shuttle (OmpF 3 –MlaA–MlaC) and demonstrated that PG dissociates this transient complex, releasing lipid-bound MlaC. Together our results point to a high population of endogenous PG on periplasmic MlaC, which likely arises from disassembly of the lipid shuttle to maintain lipid asymmetry for cell viability.
GPT-4o mini: Non-social science research article
Lenacapavir disrupts HIV-1 core integrity while stabilizing the capsid lattice
Chenglei Li, Ryan C. Burdick, Rokeya Siddiqui, Sanath Kumar Janaka, Ru-ching Hsia, Wei-Shau Hu, Vinay K. Pathak
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Lenacapavir (GS-6207; LEN) is a potent HIV-1 capsid inhibitor approved for treating multidrug-resistant infection. LEN binds to a hydrophobic pocket between neighboring capsid (CA) proteins in hexamers and stabilizes the capsid lattice, but its effect on HIV-1 capsids is not fully understood. Here, we labeled HIV-1 capsids with green fluorescent protein fused to CA (GFP-CA) or a fluid-phase GFP content marker (cmGFP) to assess LEN’s impact on HIV-1 capsids. HIV-1 cores labeled with GFP-CA, but not cmGFP, could be immunostained with an anti-GFP antibody and were less sensitive to the capsid-binding host restriction factor MX2, demonstrating that GFP-CA is incorporated into the capsid lattice and is a marker for capsid lattice stability, whereas cmGFP is an indicator of core integrity. LEN treatment of isolated HIV-1 cores resulted in a dose-dependent loss of cmGFP signal while preserving the GFP-CA signal, indicating that LEN disrupts core integrity but stabilizes the capsid lattice. In contrast, capsid inhibitor PF-3450074 (PF74) induced loss of core integrity and the capsid lattice. Electron microscopy of LEN- or PF74-treated viral cores revealed frequent breakage at the narrow end of the capsid and other morphological changes. Our results suggest that LEN treatment does not prevent nuclear envelope docking but inhibits nuclear import of cores with or without loss of core integrity. In contrast, PF74 treatment blocks nuclear import by inhibiting the nuclear envelope docking of viral cores, highlighting their different mechanisms of nuclear import inhibition.
GPT-4o mini: Non-social science research article
Correction for Benn et al., Phase separation in the outer membrane of Escherichia coli
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GPT-4o mini: Non-social science research article
Correction for Zhu et al., Asymmetric arginine dimethylation of cytosolic RNA and DNA sensors by PRMT3 attenuates antiviral innate immunity
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GPT-4o mini: Non-social science research article
Correction for Singh et al., Structural and functional dynamics of human cone cGMP-phosphodiesterase important for photopic vision
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GPT-4o mini: Non-social science research article
QnAs with Inara S. Tareque, Jorge Guzman, and Dan J. Wang
Matthew Hardcastle
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GPT-4o mini: Non-social science research article
Anatomy of a range contraction: Flow–phenology mismatches threaten salmonid fishes near their trailing edge
Stephanie M. Carlson, Kasey C. Pregler, Mariska Obedzinski, Sean P. Gallagher, Suzanne J. Rhoades, Cleo Woelfle-Hazard, Nathan Queener, Sally E. Thompson, Mary E. Power
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Climate change is redistributing life on Earth, with profound impacts for ecosystems and human well-being. While repeat surveys separated by multidecadal intervals can determine whether observed shifts are in the expected direction (e.g., poleward or upslope due to climate change), they do not reveal their mechanisms or time scales: whether they were gradual responses to environmental trends or punctuated responses to disturbance events. Here, we document population reductions and temporary range contractions at multiple sites resulting from drought for three Pacific salmonids at their ranges’ trailing edge. During California’s 2012 to 2016 historic multiyear drought, the 2013 to 2014 winter stood apart because rainfall was both reduced and delayed. Extremely low river flows during the breeding season (“flow–phenology mismatch”) reduced or precluded access to breeding habitat. While Chinook ( Oncorhynchus tshawytscha) experienced a down-river range shift, entire cohorts failed in individual tributaries (steelhead trout, O. mykiss ) and in entire watersheds (coho salmon, O. kisutch) . Salmonids returned to impacted sites in subsequent years, rescued by reserves in the ocean, life history diversity, and, in one case, a conservation broodstock program. Large population losses can, however, leave trailing-edge populations vulnerable to extinction due to demographic stochasticity, making permanent range contraction more likely. When only a few large storms occur during high flow season, the timing of particular storms plays an outsized role in determining which migratory fish species are able to access their riverine breeding grounds and persist.
GPT-4o mini: Non-social science research article
Onboard recordings reveal how bats maneuver under severe acoustic interference
Aya Goldshtein, Omer Mazar, Lee Harten, Eran Amichai, Reut Assa, Anat Levi, Yotam Orchan, Sivan Toledo, Ran Nathan, Yossi Yovel
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Echolocating bats rely on active acoustic sensing to perceive their environment. When multiple bats fly together, echolocating simultaneously, the calls emitted by nearby conspecifics could interfere with and mask the echoes necessary for orientation. Nowhere is this impairment of sensing more dramatic than when thousands of bats emerge from a cave at the same time. Here, we tracked the movement of tens of greater mouse-tailed bats flying within a group of thousands. By mounting miniature microphones onboard some of the bats, we monitored the acoustic scene from the point of view of an individual bat within the echolocating collective. We found that bats experienced a very high level of conspecific acoustic masking when emerging from their cave, which dropped within seconds as the bats spread out in space. A comprehensive sensorimotor model, based on the unique data that we collected, revealed how bats content with this severe echo masking almost without collisions. Our results demonstrate that even under severe masking, bats are hardly impaired sensorially, and we suggest how they are able to maneuver smoothly and avoid collisions, even at high densities, without applying a jamming avoidance response.
GPT-4o mini: Non-social science research article
Childhood muscle growth: Reference curves for lower leg muscle volumes and their clinical application in cerebral palsy
Bart Bolsterlee, Brian V. Y. Chow, Jonathan Yu, Suzanne Davies, Catherine Morgan, Caroline D. Rae, David I. Warton, Iona Novak, Ann Lancaster, Gordana C. Popovic, Rodrigo R. N. Rizzo, Claudia Y. Rizzo, Iain K. Ball, Robert D. Herbert
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Skeletal muscles grow substantially during childhood. However, quantitative information about the size of typically developing children’s muscles is sparse. Here, the objective was to construct muscle-specific reference curves for lower leg muscle volumes in children aged 5 to 15 y. Volumes of 10 lower leg muscles were measured from magnetic resonance images of 208 typically developing children and 78 ambulant children with cerebral palsy. Deep learning was used to automatically segment the images. Reference curves for typical childhood muscle volumes were constructed with quantile regression. The median total leg muscle volume of a 15-y-old child is nearly five times that of a 5-y-old child. Between the ages of 5 and 15, boys typically have larger muscles than girls, both in absolute terms (medians are greater by 5 to 20%) and per unit of body weight (1 to 13%). Muscle volumes vary widely between children of a particular age: the range of volumes for the central 80% of the distribution (i.e., between the 10th and 90th centiles) is more than 40% of the median volume. Reference curves for individual muscle volumes have a similar shape to reference curves for total lower leg muscle volume. Confidence bands about the centile curves were wide, especially at the youngest and oldest ages. Nonetheless, the reference curves can be used with confidence to identify small-for-age muscles (centile < 10). We show that 56% of children with cerebral palsy in our cohort had total lower leg muscle volumes that were small-for-age and that 80% had at least one lower leg muscle that was small-for-age.
GPT-4o mini: Non-social science research article
Microparticle impact–induced bond strength in metals peaks with velocity
Qi Tang, Yuji Ichikawa, Mostafa Hassani
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Supersonic impact of metallic microparticles onto metallic substrates generates extreme interfacial deformation and high contact pressures, enabling solid-state metallic bonding. Although higher impact velocities are generally believed to improve bond quality and mechanical properties in materials formed by supersonic impact deposition, here we report a peak in bond strength for single microparticle impact bonding, followed by a decline at higher impact velocities. Our in situ micromechanical measurements of interfacial strength for Al microparticles bonded to Al substrates reveal a three-fold increase from the critical bonding velocity (800 m/s) to a peak strength around 1,060 m/s. Interestingly, further increase in impact velocity results in a rapid decline in local interfacial strength. The decline continues up to the highest velocity studied, 1,337 m/s, which is well below the threshold required to induce melting or erosion. We show that a mechanistic transition from material strengthening to intensified elastic recovery is responsible for the peak strength in impact-induced bonding, with evidence linking the intensified elastic recovery to adiabatic softening at high impact velocities. Beyond 1,000 m/s for Al, interfacial damage induced by the intensified elastic recovery offsets the strength gain from higher impact velocities, resulting in a net decline in interfacial strength. This mechanistic understanding shall offer insights into the optimal design of processes that rely on impact bonding.
GPT-4o mini: Non-social science research article
A mechanically resilient soft hydrogel improves drug delivery for treating post-traumatic osteoarthritis in physically active joints
Nitin Joshi, Jing Yan, Mickael Dang, Kai Slaughter, Yufeng Wang, Dana Wu, Trevor Ung, Nutan Bhingaradiya, Virja Pandya, Mu Xian Chen, Shahdeep Kaur, Sachin Bhagchandani, Haya A. Alfassam, John Joseph, Jingjing Gao, Mahima Dewani, Rachel Wai Chun Chu, Ryan Chak Sang Yip, Eli Weldon, Purna Shah, Nishkal Dhiraj Pisal, Chetan Shukla, Nicholas E. Sherman, James N. Luo, Thomas Conway, James P. Eickhoff, Luis Botelho, Ali H. Alhasan, Jeffrey M. Karp, Joerg Ermann
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Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in the early stages of post-traumatic osteoarthritis (PTOA), when symptoms are minimal, and patients remain physically active. To ensure effective therapy, DMOAD delivery systems therefore must withstand repeated mechanical loading without altering the kinetics of drug release. While soft materials are typically preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt controlled drug release. In this study, we present a mechanically resilient soft hydrogel that rapidly self-heals under conditions simulating human running while maintaining sustained release of the cathepsin-K inhibitor L-006235, used as a proof-of-concept DMOAD. This hydrogel demonstrated superior performance compared to a previously reported hydrogel designed for intra-articular drug delivery, which, in our study, neither recovered its structure nor maintained drug release under mechanical loading. When injected into mouse knee joints, the hydrogel provided consistent release kinetics of the encapsulated drug in both treadmill-running and nonrunning mice. In a mouse model of severe PTOA exacerbated by treadmill-running, the L-006235 hydrogel significantly reduced cartilage degeneration, whereas the free drug did not. Overall, our data underscore the hydrogel’s potential for treating PTOA in physically active patients.
GPT-4o mini: Non-social science research article
Design of a halogen bond catalyzed DNA endonuclease
Margaret G. Walker, Cesar Gustavo Mendez, Alexander N. Ho, Ryan S. Czarny, Anthony K. Rappé, Pui Shing Ho
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In this study, we expand the repertoire of biological catalysts by showing that a halogen bond (X-bond) can functionally replace the magnesium (Mg 2+ ) cofactor in mouse endonuclease G ( m EndoG). We mutated the metal coordinating glutamate E136 in m EndoG to a meta- halotyrosine ( m X Y, X = chlorine or iodine) to form a m X Y- m EndoG construct that is both acid and base catalyzed. Under basic conditions, the enzyme is inactivated by the metal chelator ethylene diamine tetraacetic acid (EDTA), indicating that the halogen substituent facilitates deprotonation of the tyrosyl hydroxyl group, allowing recruitment of Mg 2+ to restore the metal-dependent catalytic center. At low pHs, we observe that the m X Y- m EndoG is resistant to EDTA inactivation and that the iodinated constructed is significantly more active than the chlorinated analogue. These results implicate a hydrogen bond (H-bond) enhanced X-bond as the catalyst in the m X Y- m EndoG, with asparagine N103 serving as the H-bond donor that communicates the protonation state of histidine H104 to the halogen. This model is supported by mutation studies and electrostatic potential (ESP) calculations on models for the protonated and unprotonated m X Y···N103···H104 system compared to the Mg 2+ coordination complex of the wild type. Thus, we have designed and engineered an enzyme that utilizes an unnatural catalyst in its active site—a catalytic X-bonding enzyme, or cX- Zyme—by controverting what constitutes a metal catalyst in biochemistry.
GPT-4o mini: Non-social science research article
Prolonged signaling of backbone-modified glucagon‐like peptide‐ 1 analogues with diverse receptor trafficking
Brian P. Cary, Marlies V. Hager, Zamara Mariam, Rylie K. Morris, Matthew J. Belousoff, Giuseppe Deganutti, Patrick M. Sexton, Denise Wootten, Samuel H. Gellman
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Signal duration and subcellular location are emerging as important facets of G protein–coupled receptor (GPCR) function. The glucagon-like peptide-1 receptor (GLP-1R), a clinically relevant class B1 GPCR, stimulates production of the second messenger cyclic adenosine monophosphate (cAMP) upon activation by the native hormone, GLP-1. cAMP production continues after the hormone–receptor complex has been internalized via endocytosis. Here, we report GLP-1 analogues that induce prolonged signaling relative to GLP-1. A single ÎČ-amino acid substitution at position 18, with the residue derived from ( S , S )- trans -2-aminocyclopentanecarboxylic acid (ACPC), enhances signaling duration with retention of receptor endocytosis. Pairing ACPC at position 18 with a second substitution, α-aminoisobutyric acid (Aib) at position 16, abrogates endocytosis, but prolonged signaling is maintained. Prolonged signaling is sensitive to the structure of the ÎČ residue at position 18. Cryoelectron microscopy structures of two GLP-1 analogues bound to the GLP-1R:Gs complex suggest substantial alterations to bound peptide structure and dynamics compared to the GLP-1:GLP-1R:Gs complex. These structural findings strengthen an emerging view that agonist dynamics in the receptor-bound state influence signaling profiles. Our results advance understanding of the structural underpinnings of receptor activation and introduce tools for exploring the impact of spatiotemporal signaling profiles following GLP-1R activation.
GPT-4o mini: Non-social science research article
Lung B cells in ectopic germinal centers undergo affinity maturation
Stephane M. Guillaume, William S. Foster, Isabel San MartĂ­n Molina, Emily M. Watson, Silvia Innocentin, Grant M. Kennedy, Alice E. Denton, Michelle A. Linterman
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The lungs are constantly exposed to the external environment and a myriad of antigenic challenges within the air. Chronic exposure to allergens and other airborne antigens can result in the formation of lymphocyte aggregates in the lung, which can harbor ectopic germinal centers (GCs). After allergen exposure, GCs that form in the lung are much smaller and less densely packed with B cells than lymph node GCs. Despite this, ectopic lung GCs support somatic hypermutation and affinity-based maturation as in lymph node GCs, and export memory B cells (MBCs) directly into the lung tissue. This demonstrates that the lung can locally diversify B cell responses and supports the generation of tissue MBC populations in situ.
GPT-4o mini: Non-social science research article
Quirks of track preservation and formation are more likely than pre-avian flight and ultrafast dinosaurs
Peter L. Falkingham, Jens N. Lallensack
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GPT-4o mini: Non-social science research article
Allosterically switchable network orients ÎČ -flap in Clostridioides difficile toxins
Lauren M. Finn, Rebecca Cummer, Bastien Castagner, Bettina G. Keller
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Allosteric proteins exhibit a functional response upon ligand binding far from the active site. Clostridioides difficile toxins use allosteric binding by the endogenous cofactor myo -inositol hexakisphosphate to orchestrate self-cleavage from within the target cell. This binding event induces a conformational shift, primarily effecting a lever-like ÎČ -flap region, with two known orientations. We uncovered a mechanism for this allosteric transition using extensive atomistic molecular dynamics simulations and computational and experimental mutagenesis. The mechanism relies on a switchable interaction network. The most prominent interaction pair is K600-E743, with K600 interactions explaining ∌70% of the allosteric effect. Rather than gradually morphing between two end states, the interaction network adopts two mutually exclusive configurations in the active and inactive state. Similar switchable networks may explain allostery more broadly. This mechanism in particular could aid in drug development targeting the C. difficile toxins autoproteolysis.
GPT-4o mini: Non-social science research article
Structural switching dynamically controls the doubly pseudoknotted Rous sarcoma virus–programmed ribosomal frameshifting element
Christopher P. Jones, Adrian R. FerrĂ©-D’AmarĂ©
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A hallmark of retrovirus replication is the translation of two different polyproteins from one RNA through programmed –1 frameshifting. This is a mechanism in which the actively translating ribosome is induced to slip in the 5â€Č direction at a defined codon and then continues translating in the new reading frame. Programmed frameshifting controls the stoichiometry of viral proteins and is therefore under stringent evolutionary selection. Forty years ago, the first frameshifting stimulatory element was discovered in the Rous sarcoma virus. The ~120 nt RNA segment was predicted to contain a pseudoknot, but its 3D structure has remained elusive. Now, we have determined cryoEM and X-ray crystallographic structures of this classic retroviral element, finding that it adopts a butterfly-like double-pseudoknot fold. One “wing” contains a dynamic pyrimidine-rich helix, observed crystallographically in two conformations and in a third conformation via cryoEM. The other wing encompasses the predicted pseudoknot, which interacts with a second unexpected pseudoknot through a toggle residue, A2546. This key purine switches conformations between structural states and tunes the stability of interacting residues in the two wings. We find that its mutation can modulate frameshifting by as much as 50-fold, likely by altering the relative abundance of different structural states in the conformational ensemble of the RNA. Taken together, our structure–function analyses reveal how a dynamic double pseudoknot junction stimulates frameshifting by taking advantage of conformational heterogeneity, supporting a multistate model in which high Shannon entropy enhances frameshifting efficiency.
GPT-4o mini: Non-social science research article
Intravital imaging of translocated bacteria via fluorogenic labeling of gut microbiota in situ
Xinqi Fan, Yingjun Zhou, Wenjuan Bai, Xue Li, Liyuan Lin, Huibin Lin, Ming Yang, Xiaofei Yu, Jing Wang, Liang Lin, Wei Wang
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The translocation of bacteria from intestinal tracts into blood vessels and distal organs plays pivotal roles in the pathogenesis of numerous severe diseases. Intravital monitoring of bacterial translocation, however, is not yet feasible, which greatly hinders us from comprehending this spatially and temporally dynamic process. Here we report an in vivo fluorogenic labeling method, which enables in situ imaging of mouse gut microbiota and real-time tracking of the translocated bacteria. By mimicking the peptidoglycan stem peptide in bacteria, a tetrapeptide probe composed of alternating D- and L-amino acids and separately equipped with a fluorophore and a quencher on the N- and C-terminal amino acid, is designed. Because of its resistance to host proteases, it can be directly used in gavage and achieves fluorogenic labeling of the microbiota in the gut via the functioning of the L,D-transpeptidases of the labeled bacteria. Using intravital two-photon microscopy, we then successfully visualize the translocation of gut bacteria into the bloodstream and liver in obesity mouse models. This technique can help further exploration into the spatiotemporal activities of gut microbiota in vivo, and be valuable in investigating the less understood pathogenicity of bacterial translocation in many severe diseases.
GPT-4o mini: Non-social science research article
Correction for Kumar et al., Cluster dynamical mean-field study of intra-unit-cell charge nematicity in hole-doped cuprates
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GPT-4o mini: Non-social science research article
Correction for Pitzen et al., Comparative transcriptomics reveals a mixed basal, club, and hillock epithelial cell identity in castration-resistant prostate cancer
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GPT-4o mini: Non-social science research article
Dopaminergic neurons in the paraventricular hypothalamus extend the food consumption phase
Winda Ariyani, Chiharu Yoshikawa, Haruka Tsuneoka, Izuki Amano, Itaru Imayoshi, Hiroshi Ichinose, Chiho Sumi-Ichinose, Noriyuki Koibuchi, Tadahiro Kitamura, Daisuke Kohno
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Feeding behavior is controlled by various neural networks in the brain that are involved in different feeding phases: Food procurement, consumption, and termination. However, the specific neural circuits controlling the food consumption phase remain poorly understood. Here, we investigated the roles of dopaminergic neurons in the paraventricular nucleus of the hypothalamus (PVH) in the feeding behavior in mice. Our results indicated that the PVH dopaminergic neurons were critical for extending the food consumption phase and involved in the development of obesity through epigenetic mechanisms. These neurons synchronized with proopiomelanocortin neurons during consumption, were stimulated by proopiomelanocortin activation, and projected to the lateral habenula (LHb), where dopamine receptor D2 was involved in the increase in food consumption. In addition, upregulated tyrosine hydroxylase (TH) expression in PVH was associated with obesity and indispensable for obesity induction in mice lacking Dnmt3a . Taken together, our results highlight the roles of PVH dopaminergic neurons in promoting food consumption and obesity induction.
GPT-4o mini: Non-social science research article
Nuclear Galectin-1 promotes KRAS -dependent activation of pancreatic cancer stellate cells
Judith Vinaixa, Neus Martínez-Bosch, Joan Gibert, Noemí Manero-Rupérez, Patricia Santofimia-Castaño, Federico G. Baudou, Renzo E. Vera, David R. Pease, Mar Iglesias, Sandhya Sen, Xiyin Wang, Luciana L. Almada, David L. Marks, Mireia Moreno, Juan L. Iovanna, Gabriel A. Rabinovich, Martin E. Fernandez-Zapico, Pilar Navarro
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, primarily due to its complex tumor microenvironment (TME), which drives both disease progression and therapy resistance. Understanding the molecular mechanisms governing TME dynamics is essential for developing new treatment strategies for this devastating disease. In this study, we uncover an oncogenic role for Galectin-1 (Gal1), a glycan-binding protein abundantly expressed by activated pancreatic stellate cells (PSCs), a key component of the PDAC TME that orchestrates tumor progression. Our findings reveal that Gal1 expression is elevated in the nucleus of human PSCs in both tissue samples and cultured cell lines. Using chromatin immunoprecipitation followed by sequencing analysis (ChIP-seq), we identify Gal1 occupancy at the promoters of several cancer-associated genes, including KRAS , a pivotal oncogene involved in PDAC pathogenesis. We demonstrate that Gal1 binds to the KRAS promoter, sustaining KRAS expression in PSCs, which, in turn, maintains PSC activation and promotes the secretion of protumorigenic cytokines. Mechanistically, Gal1 is required to preserve histone H3 lysine 4 monomethylation levels and to recruit the histone methyltransferase MLL1 to target promoters. Collectively, our findings define a nuclear function of Gal1 in modulating the transcriptional landscape of cancer-associated genes in PSCs within the PDAC TME, mediated through an epigenetic mechanism. These insights enhance our understanding of PDAC pathology and open potential avenues for therapeutic interventions targeting intracellular Gal1.
GPT-4o mini: Non-social science research article
The TRPV3 channel is a mediator of zinc influx and homeostasis in murine oocytes
Emily M. Lopes, Hiroki Akizawa, Oguz C. Koc, Edgar Soto-Moreno, Neha Gupta, Goli Ardestani, Ahmed Z. Balboula, Ingrid Carvacho, Rafael A. Fissore
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Zinc (Zn 2+ ) homeostasis is essential for gametogenesis and reproduction, and its deficiency causes infertility. Oocytes contain higher Zn 2+ levels than somatic cells, and Zn 2+ concentrations in oocytes are far higher than those of other transition metals and increase even more during maturation in preparation for fertilization. Remarkably, it is unknown what transporter(s) or channel(s) mediate Zn 2+ influx in oocytes and whether they are expressed uniformly throughout folliculogenesis. Here, we showed that the functional expression of a member of the t ransient r eceptor p otential family, vanilloid 3, TRPV3, closely follows the dynamics of intracellular Zn 2+ during oocyte maturation, raising the prospect that these events may be functionally linked. Using microfluorometry, we monitored in oocytes of Trpv3 null females the expected rise in Zn 2+ concentrations during maturation. Surprisingly, Zn 2+ levels did not climb, and the overall FluoZin3 signal in Trpv3 null eggs was lower than in control eggs. Electrophysiological recordings showed a large TRPV3 current induced by the agonist 2-APB in WT eggs supplemented with extracellular Zn 2+ that was absent in Trpv3 null eggs; TRPV3 showed a clear preference for Zn 2+ over Ca 2+ . Trpv3 null eggs displayed features associated with Zn 2+ deficient conditions, such as lower IP 3 R1 function, abnormal cortical granule distribution, and disturbed cytoskeletal organization with distinct actin nucleation disorders. Notably, Trpv3 null eggs demonstrated undisturbed Zn 2+ sparks. Our results suggest that TRPV3 is a pivotal member of the Zn 2+ toolkit, mediating Zn 2+ intake during maturation. They also indicate that distinct transporters or channels mediate Zn 2+ influx throughout folliculogenesis.
GPT-4o mini: Non-social science research article
Signaling networks in cancer stromal senescent cells establish malignant microenvironment
Yue Zhang, Teh-Wei Wang, Maho Tamatani, Xinyi Zeng, Lindo Nakamura, Satotaka Omori, Kiyoshi Yamaguchi, Seira Hatakeyama, Eigo Shimizu, Satoshi Yamazaki, Yoichi Furukawa, Seiya Imoto, Yoshikazu Johmura, Makoto Nakanishi
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The tumor microenvironment (TME) encompasses various cell types, blood and lymphatic vessels, and noncellular constituents like extracellular matrix (ECM) and cytokines. These intricate interactions between cellular and noncellular components contribute to the development of a malignant TME, such as immunosuppressive, desmoplastic, angiogenic conditions, and the formation of a niche for cancer stem cells, but there is limited understanding of the specific subtypes of stromal cells involved in this process. Here, we utilized p16-Cre ERT2 -tdTomato mouse models to investigate the signaling networks established by senescent cancer stromal cells, contributing to the development of a malignant TME. In pancreatic ductal adenocarcinoma (PDAC) allograft models, these senescent cells were found to promote cancer fibrosis, enhance angiogenesis, and suppress cancer immune surveillance. Notably, the selective elimination of senescent cancer stromal cells improves the malignant TME, subsequently reducing tumor progression in PDAC. This highlights the antitumor efficacy of senolytic treatment alone and its synergistic effect when combined with conventional chemotherapy. Taken together, our findings suggest that the signaling crosstalk among senescent cancer stromal cells plays a key role in the progression of PDAC and may be a promising therapeutic target.
GPT-4o mini: Non-social science research article
Painting rich six-dimensional pictures using polarized fluorescence microscopy
Matthew D. Lew
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GPT-4o mini: Non-social science research article
Peto’s paradox revisited (revisited, revisited, revisited, and revisited yet again)
Vincent J. Lynch
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GPT-4o mini: Non-social science research article
Enamel–dentine junction morphology reveals population replacement and mobility in the late prehistoric Middle Nile Valley
Nicolas Martin, Adrien Thibeault, Lenka VaradzinovĂĄ, Donatella Usai, Stanley H. Ambrose, Daniel Antoine, Petra Brukner HavelkovĂĄ, Matthieu Honegger, Joel D. Irish, Friederike Jesse, Laura MarĂ©chal, Marta OsypiƄska, Piotr OsypiƄski, FrĂ©dĂ©ric Santos, Nicolas Vanderesse, Ladislav Varadzin, Rebecca J. Whiting, ClĂ©ment Zanolli, Petr VelemĂ­nskĂœ, Isabelle Crevecoeur
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Transitions from foraging to food-production represent a worldwide turning point in recent human history. In the Middle Nile Valley this cultural shift occurred between the sixth and beginning of the fifth millennium BCE. Significant craniodental morphological differences remain inadequately tested by biometric analyses of ancestry and may reflect population origins or diet change between the last hunter-fisher-gatherers (Mesolithic) and first food-producers (Neolithic). Moreover, with no ancient DNA data for this region and very few morphological studies including large samples of Mesolithic individuals, the late prehistoric population history of the Nile Valley remains unclear. Here, we present enamel–dentine junction (EDJ) morphological analyses (based on X-ray microtomography) and biological affinities for 88 individuals spanning 14,000 y from Sudan and southern Egypt. Significant EDJ morphological differences between the last foragers and first food-producers suggest major biological discontinuity at the Neolithic transition. Nevertheless, the persistence of the earlier forager population in the Sudanese Eastern Sahara indicates settlement and population replacement mainly along the Nile. We also present biological evidence of interaction and mobility between these contemporaneous populations during the middle Holocene in the region. It supports the phylogenetic value of EDJ morphology for investigating population affinities at a microevolutionary scale. These results yield insights into the deep population history of the Nile Valley. They provide firm evidence for population replacement and migration toward the region at the onset of the Neolithic transition, attesting that these key changes were not solely triggered by cultural diffusion and diet change.
GPT-4o mini: Non-social science research article
Validating new limits for human thermoregulation
Robert D. Meade, Fergus K. O’Connor, Brodie J. Richards, Emily J. Tetzlaff, Katie E. Wagar, Roberto C. Harris-Mostert, Theodore Egube, James J. McCormick, Glen P. Kenny
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Recent projections suggest that large geographical areas will soon experience heat and humidity exceeding limits for human thermoregulation. The survivability limits modeled in that research were based on laboratory studies suggesting that humans cannot effectively thermoregulate in wet bulb temperatures (T wb ) above 26 to 31 °C, values considerably lower than the widely publicized theoretical threshold of 35 °C. The newly proposed empirical limits were derived from the T wb corresponding to the core temperature inflection point in participants exposed to stepped increases in air temperature or relative humidity in a climate-controlled chamber. Despite the increasing use of these thermal-step protocols, their validity has not been established. We used a humidity-step protocol to estimate the T wb threshold for core temperature inflection in 12 volunteers. To determine whether this threshold truly demarcates the T wb above which thermoregulation is impossible, each participant was subsequently exposed to T wb above (~33.7 °C, T above ) and below (~30.9 °C, T below ) their respective inflection point (~32.3 °C, T wb ) for up to 9 h (in random order). Core temperature rose continuously in T above . It was projected that core temperatures associated with heat stroke (40.2 °C) would occur within 10 h. While T below was also uncompensable, the core temperature rate of rise was considerably lower than in T above such that it would take >24 h to reach 40.2 °C. Our study supports thermal-step protocols as an effective technique for evaluating survivability limits for heat exposure and provides a direct assessment of the limits of human thermoregulation.
GPT-4o mini: Non-social science research article
Mechanistic insights into dengue virus inhibition by a clinical trial compound NITD-688
Yan Wang, Long Sun, Luciana Fernandes, Yu-Hsiu Wang, Jing Zou, Samuel J. Franklin, Yanping Hu, Lee K. Palmer, Jason Yeung, Daniela Barriga, William K. Russell, Stephanie A. Moquin, Pei-Yong Shi, Colin Skepper, Xuping Xie
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Dengue, caused by the dengue virus (DENV), presents a significant public health challenge with limited effective treatments. NITD-688 is a potent panserotype DENV inhibitor currently in Phase II clinical trials. However, its mechanism of action is not fully understood. Here, we present the molecular details of how NITD-688 inhibits DENV. NITD-688 binds directly to the nonstructural protein 4B (NS4B) with nanomolar affinities across all four DENV serotypes and specifically disrupts the interaction between NS4B and nonstructural protein 3 (NS3) without significantly changing the interactions between NS4B and other viral or host proteins. NS4B mutations that confer resistance to NITD-688 reduce both NITD-688 binding to NS4B and disruption of the NS4B/NS3 interaction. Specifically, NITD-688 blocks the interaction of NS3 with a cytosolic loop within NS4B. This inhibits the formation of new NS4B/NS3 complexes and disrupts preexisting complexes in vitro and DENV-infected cells, ultimately inhibiting viral replication. Consistent with this mechanism, NITD-688 retains greater potency in cellular assays with delayed treatment compared to JNJ-1802, another NS4B inhibitor that has been studied in Phase II clinical trials. Together, these findings provide critical insights into the mechanism of action of NITD-688, facilitating the development of novel flavivirus NS4B inhibitors and informing future clinical interventions against DENV.
GPT-4o mini: Non-social science research article
Correction for Jenewein et al., Concomitant formation of protocells and prebiotic compounds under a plausible early Earth atmosphere
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GPT-4o mini: Non-social science research article
Correction to Supporting Information for Chakraborty et al., Cryo-ET suggests tubulin chaperones form a subset of microtubule lumenal particles with a role in maintaining neuronal microtubules
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GPT-4o mini: Non-social science research article
PHLPP2 is a pseudophosphatase that lost activity in the metazoan ancestor
Tarik Husremović, Vanessa Meier, Lucas PiĂ«ch, Katharina M. Siess, Sumire Antonioli, Irina Grishkovskaya, Nikoleta Kircheva, Silvia E. Angelova, Karoline Wenzl, Andreas BrandstĂ€tter, Jiri Veis, Fran Miočić-StoĆĄić, Dorothea Anrather, Markus Hartl, Linda Truebestein, Luis M. Cerron-Alvan, Martin Leeb, Bojan Ćœagrović, Stephan Hann, Christoph Bock, Egon Ogris, Todor Dudev, Nicholas A. T. Irwin, David Haselbach, Thomas A. Leonard
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The phosphoinositide 3-kinase (PI3K) pathway is a major regulator of cell and organismal growth. Consequently, hyperactivation of PI3K and its downstream effector kinase, Akt, is observed in many human cancers. Pleckstrin homology domain leucine-rich repeat-containing protein phosphatases (PHLPP), two paralogous members of the metal-dependent protein phosphatase family, have been reported as negative regulators of Akt signaling and, therefore, tumor suppressors. However, the stoichiometry and identity of the bound metal ion(s), mechanism of action, and enzymatic specificity of these proteins are not known. Seeking to fill these gaps in our understanding of PHLPP biology, we unexpectedly found that PHLPP2 has no catalytic activity in vitro. Instead, we found that PHLPP2 is a pseudophosphatase with a single zinc ion bound in its catalytic center. Furthermore, we found that cancer genomics data do not support the proposed role of PHLPP1 or PHLPP2 as tumor suppressors. Phylogenetic analyses revealed an ancestral phosphatase that arose more than 1,000 Mya, but that lost activity at the base of the metazoan lineage. Surface conservation indicates that while PHLPP2 has lost catalytic activity, it may have retained substrate binding. Finally, using phylogenomics, we identify coevolving genes consistent with a scaffolding role for PHLPP2 on membranes. In summary, our results provide a molecular explanation for the inconclusive results that have hampered research on PHLPP and argue for a focus on the noncatalytic roles of PHLPP1 and PHLPP2.
GPT-4o mini: Non-social science research article
Reconfigurable homochiral colloidal clusters assembled under orthogonally applied electric and magnetic fields
Xingrui Zhu, Yuanxing Zhang, Benjamin L. Hanson, David T. Wu, Ning Wu
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Chiral structures assembled from colloids are of great interest for applications in metamaterials and micromachines. However, similar to their molecular counterparts, these assemblies often result in racemic mixtures. Achieving homochirality by breaking the symmetry remains a significant challenge. Here, we report an approach to obtain single-handed clusters from colloidal dimers using orthogonal electric and magnetic fields. Applying an alternating-current electric field perpendicular to the substrate generates a mixture of chiral clusters with both handedness. However, symmetry is broken by superimposing a planar rotating magnetic field, favoring one chirality over the other. The cluster’s chirality can be precisely controlled in situ by adjusting the magnetic field’s direction and strength, as well as the electric field frequency. Remarkably, this method also induces uniform chirality in initially achiral clusters when exposed solely to the electric field. Both experimental and numerical analyses reveal that the stability of specific handedness depends on the competition between forces and torques generated by the magnetic field, electric field, and electrohydrodynamic flow. Furthermore, we propose a strategy for producing colloidal clusters with uniform sizes and single-handedness through dynamic tuning of the electric and magnetic fields. This work not only demonstrates the potential of integrating external fields but also provides a viable way to create reconfigurable chiral colloidal structures.
GPT-4o mini: Non-social science research article
Phenotypic changes of auditory nerve fibers after excitotoxicity
Artem Diuba, Paul Gratias, Penelope W. C. Jeffers, RĂ©gis Nouvian, Jean-Luc Puel, Sharon G. Kujawa, JĂ©rĂŽme Bourien
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There is a substantial body of evidence elucidating the pathophysiological aspects of excitotoxicity in the mammalian cochlea. However, the question of whether the resultant damage is reversible remains unresolved. To replicate an excitotoxic event, we investigated the long-term effects of kainate application in gerbil cochleae. Surprisingly, despite persistent synapse loss, the compound action potential of the auditory nerve fully recovered. This functional retrieval was associated with a phenotypic change in auditory nerve fibers. Thresholds were improved along the tonotopic axis. High-spontaneous rate (SR) fibers largely populated the apical region, while low-SR fibers from the basal region exhibited sound-driven activity indistinguishable from control high-SR fibers. This functional phenotype change may support the full recovery of neural response thresholds and amplitudes after excitotoxicity. Furthermore, hyperresponsiveness of the auditory nerve fibers could be a crucial factor in the development of hyperactivity in the central auditory pathways, a common occurrence following acoustic overstimulation.
GPT-4o mini: Non-social science research article
Structural basis for neutralizing antibody binding to pertussis toxin
Jory A. Goldsmith, Annalee W. Nguyen, Rebecca E. Wilen, Wassana Wijagkanalan, Jason S. McLellan, Jennifer A. Maynard
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Pertussis toxin (PT) is a key protective antigen in vaccine- and natural immunity-mediated protection from Bordetella pertussis infection. Despite its importance, no PT-neutralizing epitopes have been characterized structurally. To define neutralizing epitopes and identify key structural elements to preserve during PT antigen design, we determined a 3.6 Å cryoelectron microscopy structure of genetically detoxified PT (PTg) bound to hu11E6 and hu1B7, two potently neutralizing anti-PT antibodies with complementary mechanisms: disruption of toxin adhesion to cells and intracellular activities, respectively. Hu11E6 binds the paralogous S2 and S3 subunits of PTg via a conserved epitope but surprisingly did not span the previously identified sialic acid–binding site implicated in toxin adhesion. Hu11E6 specifically prevented PTg binding to sialylated N-glycans and a sialylated model receptor, as demonstrated by high-throughput glycan array analysis and ELISA, while a T cell activation assay showed that it blocks PTg mitogenic activities to define its neutralizing mechanism. Hu1B7 bound a quaternary epitope spanning the S1 and S5 subunits, although functional studies of hu1B7 variants suggested that S5 binding is not involved in its PT neutralization mechanism. These results structurally define neutralizing epitopes on PT, improving our molecular understanding of immune protection from B. pertussis and providing key information for the future development of PT immunogens.
GPT-4o mini: Non-social science research article
Discovery and functional characterization of a bombesin-type neuropeptide signaling system in an invertebrate
Weiling Huang, Xingxing Zhong, Cleidiane G. Zampronio, Andrew R. Bottrill, Kite G. E. Jones, Ana B. Tinoco, Lijin Guo, Michaela EgertovĂĄ, Olivier Mirabeau, Maurice R. Elphick
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Neuropeptide signaling systems are key regulators of physiological and behavioral processes in animals. However, the evolutionary history of some neuropeptides originally discovered in vertebrates is unknown. The peptide bombesin (BN) was first isolated from the skin of the toad Bombina bombina and subsequently BN-related neuropeptides have been identified in other chordates, including gastrin-releasing peptide (GRP) and neuromedin B (NMB) in mammals, and a GRP-like peptide in the cephalochordate Branchiostoma japonicum . However, BN-type neuropeptides have hitherto not been identified in any nonchordate animals. Here, we report the discovery and functional characterization of a BN-type neuropeptide signaling system in an echinoderm—the starfish Asterias rubens . BN-type precursor proteins were identified in several echinoderm species based on their amino acid sequences and gene structures, and the mature structure of the A. rubens BN-type neuropeptide ArBN was determined using mass spectrometry. A protein related to vertebrate GRP/NMB-type G protein–coupled receptors was identified experimentally as the receptor for ArBN in A. rubens . Analysis of the distribution of the ArBN precursor in A. rubens using mRNA in situ hybridization and immunohistochemistry revealed a widespread pattern of expression in the central nervous system, digestive system, and locomotory organs. Moreover, effects of ArBN in A. rubens included contraction and retraction of the evertible stomach and inhibition of feeding behavior. Our findings show that the evolutionary history of BN-type neuropeptide signaling can be traced back to the deuterostome common ancestor of echinoderms and chordates. Furthermore, an ancient role of BN-type neuropeptides as regulators of feeding behavior has been revealed.
GPT-4o mini: Non-social science research article
Linear Recursive Feature Machines provably recover low-rank matrices
Adityanarayanan Radhakrishnan, Mikhail Belkin, Dmitriy Drusvyatskiy
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A fundamental problem in machine learning is to understand how neural networks make accurate predictions, while seemingly bypassing the curse of dimensionality. A possible explanation is that common training algorithms for neural networks implicitly perform dimensionality reduction—a process called feature learning. Recent work [A. Radhakrishnan, D. Beaglehole, P. Pandit, M. Belkin, Science 383 , 1461–1467 (2024).] posited that the effects of feature learning can be elicited from a classical statistical estimator called the average gradient outer product (AGOP). The authors proposed Recursive Feature Machines (RFMs) as an algorithm that explicitly performs feature learning by alternating between 1) reweighting the feature vectors by the AGOP and 2) learning the prediction function in the transformed space. In this work, we develop theoretical guarantees for how RFM performs dimensionality reduction by focusing on the class of overparameterized problems arising in sparse linear regression and low-rank matrix recovery. Specifically, we show that RFM restricted to linear models (lin-RFM) reduces to a variant of the well-studied Iteratively Reweighted Least Squares (IRLS) algorithm. Furthermore, our results connect feature learning in neural networks and classical sparse recovery algorithms and shed light on how neural networks recover low rank structure from data. In addition, we provide an implementation of lin-RFM that scales to matrices with millions of missing entries. Our implementation is faster than the standard IRLS algorithms since it avoids forming singular value decompositions. It also outperforms deep linear networks for sparse linear regression and low-rank matrix completion.
GPT-4o mini: Non-social science research article
Correction for Wijnakker et al., Integrin-activating Yersinia protein Invasin sustains long-term expansion of primary epithelial cells as 2D organoid sheets
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GPT-4o mini: Non-social science research article
Unveiling Cas8 dynamics and regulation within a transposon-encoded Cascade–TniQ complex
Amun C. Patel, Souvik Sinha, Pablo R. Arantes, Giulia Palermo
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The Vibrio cholerae Cascade–TniQ complex unveiled a new paradigm in biology, demonstrating that CRISPR-associated proteins can direct DNA transposition. Despite the tremendous potential of “knocking-in” genes at desired sites, the mechanisms underlying DNA binding and transposition remain elusive. In this system, a conformational change of the Cas8 protein is essential for DNA binding, yet how it occurs is unclear. Here, structural modeling and free energy simulations reconstruct the Cas8 helical bundle and reveal an open–closed conformational change that is key for the complex’s function. We show that when Cascade–TniQ binds RNA, the Cas8 bundle changes conformation mediated by the interaction with the Cas7.1 protein. This interaction promotes the bundle’s transition toward the open state, priming the complex for DNA binding. As the target DNA binds the guide RNA, the opening of the Cas8 bundle becomes more favorable, exposing positively charged residues and facilitating their interaction with DNA, which ultimately leads the DNA-binding process to completion. These outcomes provide a dynamic representation of a critical conformational change in one of the largest CRISPR systems and illustrate its role at critical steps of the Cascade–TniQ biophysical function, advancing our understanding of nucleic acid binding and transposition mechanisms.
GPT-4o mini: Non-social science research article
microRNA-218-5p coordinates scaling of excitatory and inhibitory synapses during homeostatic synaptic plasticity
David Colameo, Sara M. Maley, Jochen Winterer, Waleed ElGrawani, Carlotta Gilardi, Simon Galkin, Roberto Fiore, Steven A. Brown, Gerhard Schratt
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Homeostatic synaptic plasticity (HSP) is a neuronal mechanism that allows networks to compensate for prolonged changes in activity by adjusting synaptic strength. This process is crucial for maintaining stable brain function and has been implicated in memory consolidation during sleep. While scaling of both excitatory and inhibitory synapses plays an important role during homeostatic synaptic plasticity, molecules coordinating these processes are unknown. In this study, we investigate the role of miR-218-5p as a regulator of inhibitory and excitatory synapses in the context of picrotoxin (PTX)-induced homeostatic synaptic downscaling (HSD) in rat hippocampal neurons. Using enrichment analysis of microRNA-binding sites in genes changing upon PTX-induced HSD, we bioinformatically predict and experimentally validate increased miR-218-5p activity upon PTX treatment. By electrophysiological recordings and confocal microscopy, we demonstrate that inhibiting miR-218-5p activity exerts a dual effect during HSD: It occludes the downscaling of excitatory synapses and dendritic spines, while at the same time attenuating inhibitory synapse upscaling. Furthermore, we identify the Neuroligin2 interacting molecule Mdga1 as a direct miR-218-5p target which potentially mediates the effect of miR-218-5p on homeostatic upscaling of inhibitory synapses. By performing long-term electroencephalographic recordings, we further reveal that local inhibition of miR-218-5p in the somatosensory cortex reduces local slow-wave activity during non-rapid-eye-movement sleep. In summary, this study uncovers miR-218-5p as a key player in coordinating inhibitory and excitatory synapses during homeostatic plasticity and sleep. Our findings contribute to a deeper understanding of how neural circuits maintain stability in the face of activity-induced perturbations, with implications for pathophysiology.
GPT-4o mini: Non-social science research article
Biphasic mechanochemistry of single-chain polymerization
Udit Kumar Chakraborty, Muwen Yang, Susil Baral, Chunming Liu, AnQi Chen, Peng Chen
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Mechanical forces can induce chemical reactions, produce chemical signals, and alter reaction kinetics. Here, using magnetic tweezers–based single-molecule force spectroscopy, we study the force effects on the ring-opening metathesis polymerization (ROMP) of single-polymer chains, during which nonequilibrium conformational entanglements can form and unravel stochastically. We find a surprising, biphasic force dependence of polymerization kinetics: The single-chain polymerization rate initially slows down with increasing stretching forces, reaching a minimum, and then accelerates at higher forces. Analysis of real-time single-chain growth trajectories allows for dissecting the polymerization process into two distinct regimes, one with and the other without entanglement formation, unveiling the biphasic force dependence in both regimes. Two different mechanisms likely operate for the biphasic dependence: a force-induced entanglement tightening and then splitting and a force-induced catalyst structural distortion that switches the reaction pathway between reactant states of different stability and reactivity. These findings and insights point to opportunities of using force to manipulate polymerization reactions and tune the physiochemical properties of synthetic polymers.
GPT-4o mini: Non-social science research article
Quina lithic technology indicates diverse Late Pleistocene human dynamics in East Asia
Qi-Jun Ruan, Hao Li, Pei-Yuan Xiao, Bo Li, HĂ©lĂšne Monod, Alexandra Sumner, Ke-Liang Zhao, Jian-Hui Liu, Zhen-Xiu Jia, Chun-Xin Wang, An-Chuan Fan, Marie-HĂ©lĂšne Moncel, Ben Marwick, Marco Peresani, You-Ping Wang, Fa-Hu Chen, Davide Delpiano
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The Late Pleistocene of Eurasia is key for understanding interactions between early modern humans and different types of archaic human groups. During this period, lithic technology shows more diversity and complexity, likely indicating flexible adaptative strategies. However, cultural variability as expressed by technological types remains vague in large parts of eastern Eurasia, like in China. Here, we report a complete Quina technological system identified from the study of the Longtan site in Southwest China. The site has been securely dated to ca. 60 to 50 thousand years ago (ka), with compelling evidence of core exploitation, production of large and thick flakes, shaping and maintenance of scrapers exhibiting the whole Quina concept, typical of contemporary European Middle Paleolithic technologies developed by Neanderthal groups adapted to climatic oscillations during Marine Isotope Stage (MIS) 4 and early MIS 3. The finding of a Quina lithic assemblage in China not only demonstrates the existence of a Middle Paleolithic technology in the region but also shows large-scale analogies with Neanderthal behaviors in western Europe. Longtan substantially extends the geographic distribution of this technical behavior in East Asia. Although its origin remains unclear, implications for Pleistocene hominin dispersal and adaptation to diverse ecological settings are considered. The Longtan lithic evidence also provides perspectives for understanding the cultural evolutionary situation before the large-scale arrivals of early modern humans in East Asia predating ~45 ka.
GPT-4o mini: Non-social science research article
Cotranslational membrane insertion of the voltage-sensitive K + channel KvAP
Justin M. Westerfield, Petra KozojedovĂĄ, Cara Juli, Ane Metola, Gunnar von Heijne
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Voltage-sensor domains (VSDs), found in many voltage-sensitive ion channels and enzymes, are composed of four transmembrane helices (TMHs), including the atypical, highly positively charged S4 helix. VSDs are cotranslationally inserted into the membrane, raising the question of how the highly charged S4 helix is integrated into the lipid bilayer as it exits the ribosome. Here, we have used force profile analysis (FPA) to follow the cotranslational insertion of the six-TMH KvAP voltage-sensitive ion channel into the Escherichia coli inner membrane. We find that the insertion process proceeds through three semi-independent steps: i) insertion of the S1-S2 helix hairpin, ii) insertion of the S3-S5 helices, and iii) insertion of the Pore and S6 helices. Our analysis highlights the importance of the concerted insertion of helical hairpins, the dramatic influence of the positively charged residues in S4, and the unexpectedly strong forces and effects on downstream TMHs elicited by amphipathic and re-entrant helices.
GPT-4o mini: Non-social science research article
Reconciling ecology and evolutionary game theory or “When not to think cooperation”
Corina E. Tarnita, Arne Traulsen
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Evolutionary game theory (EGT)—overwhelmingly employed today for the study of cooperation in various systems, from microbes to cancer and from insect to human societies—started with the seminal 1973 paper by Maynard Smith and Price showing that limited animal conflict can be selected at the individual level. Owing to the explanatory potential of this paper and enabled by the powerful machinery of the soon-to-be-developed replicator dynamics, EGT took off at an accelerated pace and began to shape expectations across systems and scales. But, even as EGT has expanded its reach, and even as its mathematical foundations expanded with the development of adaptive dynamics and inclusion of stochastic processes, the replicator equation remains, half a century later, its most widely used equation. Owing to its early development and its staying power, the replicator dynamics has helped set both the baseline expectations and the terminology of the field. However, much like the original 1973 paper, replicator dynamics rests on the assumption that individual differences in reproduction are determined only by the payoff from the game (i.e., in isolation, all individuals, regardless of their strategy, have identical intrinsic growth rates). Here, we argue that this assumption limits the scope of replicator dynamics to such an extent as to warrant not just a more deliberative application process, but also a reconsideration of the broad predictions and terminology that it has generated. Simultaneously, we reestablish a dialog with ecology that can be mutually fruitful, e.g., by providing an explanation for how diverse ecological communities can assemble evolutionarily.
GPT-4o mini: Non-social science research article
Single cell–resolved cellular, transcriptional, and epigenetic changes in mouse T cell populations linked to age-associated immune decline
Jing He, Elena Burova, Chandrika Taduriyasas, Min Ni, Christina Adler, Yi Wei, Nicole Negron, Kun Xiong, Yu Bai, Tea Shavlakadze, Ella Ioffe, John C. Lin, Adolfo Ferrando, David J. Glass
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Splenic T cells are pivotal to the immune system, yet their function deteriorates with age. To elucidate the specific aspects of T cell biology affected by aging, we conducted a comprehensive multi–time point single-cell RNA sequencing study, complemented by single-cell Assay for Transposase Accessible Chromatin (ATAC) sequencing and single-cell T cell repertoire (TCR) sequencing on splenic T cells from mice across 10 different age groups. This map of age-related changes in the distribution of T cell lineages and functional states reveals broad changes in T cell function and composition, including a prominent enrichment of Gzmk+ T cells in aged mice, encompassing both CD4+ and CD8+ T cell subsets. Notably, there is a marked decrease in TCR diversity across specific T cell populations in aged mice. We identified key pathways that may underlie the perturbation of T cell functions with aging, supporting cytotoxic T cell clonal expansion with age. This study provides insights into the aging process of splenic T cells and also highlights potential targets for therapeutic intervention to enhance immune function in the elderly. The dataset should serve as a resource for further research into age-related immune dysfunction and for identifying potential therapeutic strategies.
GPT-4o mini: Non-social science research article
Reply to Falkingham et al.: Trackway shows flap-running in feathered dinosaurs
T. Alexander Dececchi, Kyung Soo Kim, Martin G. Lockley, Hans C. E. Larsson, Thomas H. Holtz, James O. Farlow, Michael Pittman
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Meltdown of trust in weakly governed economies
Stephen Polasky, Marten Scheffer, John M. Anderies
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A well-functioning society requires well-functioning institutions that ensure prosperity, fair distribution of wealth, social participation, security, and informative media. Such institutions are built on a foundation of trust. However, while trust is essential for economic success and good governance, interconnected mechanisms inherent in weakly governed market economies tend to undermine the very trust on which such success depends. These mechanisms include the intrinsic tendency for inequality to grow, media to boost perceived unfairness, and self-interest to gain rewards at the expense of others. These mechanisms, if left unchecked, allow wealth concentration to result in state capture where institutions facilitate further wealth concentration instead of the promoting the common good. As a result, people may become alienated and untrusting of fellow citizens and of institutions. Several democracies now experience such dynamics, the United States being a prime example. We discuss ways in which well-functioning democracies can design institutions to help avoid this social trap, and the much harder challenge of escaping the trap once in it. Successful cases such as the ability of Scandinavian democracies to maintain high-trust, and the US progressive era in the early 20th century provide instructive examples.
Removing masculine defaults in the hiring process
Sapna Cheryan, Gregg A. Muragishi
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No compelling evidence of sex differences in brain maturation during COVID-19 lockdowns when the sexes are compared statistically
Andrew W. Brown, Simon Chung, Timothy Koscik, Colby J. Vorland, Donna L. Maney
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Reply to Brown et al.: Significant sex differences in accelerated cortical thinning associated with the COVID-19 lockdowns
Neva M. Corrigan, Ariel Rokem, Patricia K. Kuhl
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Demographic interactions between the last hunter-gatherers and the first farmers
Alfredo Cortell-Nicolau, Javier Rivas, Enrico R. Crema, Stephen Shennan, Oreto García-Puchol, Jan Koláƙ, Robert Staniuk, Adrian Timpson
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Demographic interaction processes play a pivotal role during episodes of cultural diffusion between different populations, particularly when these episodes can lead to competition for the same resources and geographic space. The diffusion of farming is one prototypical case within this broader scenario, where groups of incumbent hunter-gatherers occupied a space which would later be claimed by expanding farmers. In this work, we tackle such processes through a two-population mathematical model, where farmers and foragers compete and interact in the same geographic space. We present this work as a conceptual approach where, first, we assess the implications of our theoretical model and its general applicability and, second, we empirically test it on three case studies: Denmark, Eastern Iberia, and the island of Kyushu (Japan). While these regional case studies do not encompass the full range of processes observed in the interaction between migrant farmers and incumbent hunter-gatherers they provide reasonable variation to illustrate how our model can be fitted to a diverse range of empirical data and provide insights into these demographic processes. In particular, our theoretical model and case studies illustrate how endogenous interaction processes alone can explain the demographic fluctuations observed in the archaeological record during this transition, highlighting how these should be accounted for before invoking external forces as primary drivers.
Correction for Kuan et al., Behavioral nudges prevent loan delinquencies at scale: A 13-million-person field experiment
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Digital phenotyping using smartphones could help steer mental health treatment
David Adam
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Quirks of cognition explain why we dramatically overestimate the size of minority groups
Brian Guay, Tyler Marghetis, Cara Wong, David Landy
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Americans dramatically overestimate the size of African American, Latino, Muslim, Asian, Jewish, immigrant, and LGBTQ populations, leading to concerns about downstream racial attitudes and policy preferences. Such errors are common whenever the public is asked to estimate proportions relevant to political issues, from refugee crises and polarization to climate change and COVID-19. Researchers across the social sciences interpret these errors as evidence of widespread misinformation that is topic-specific and potentially harmful. Here, we show that researchers and journalists have misinterpreted the origins and meaning of these misestimates by overlooking systematic distortions introduced by the domain-general psychological processes involved in estimating proportions under uncertainty. In general, people systematically rescale estimates of proportions toward more central prior expectations, resulting in the consistent overestimation of smaller groups and underestimation of larger groups. We formalize this process and show that it explains much of the systematic error in estimates of demographic groups ( N = 100 , 170 estimates from 22 countries). This domain-general account far outperforms longstanding group-specific explanations (e.g., biases toward specific groups). We find, moreover, that people make the same errors when estimating the size of racial, nonracial, and entirely nonpolitical groups, such as the proportion of Americans who have a valid passport or own a washing machine. Our results call for researchers, journalists, and pundits alike to reconsider how to interpret misperceptions about the demographic structure of society.
The rising income gradient in life expectancy in Sweden over six decades
Johannes Hagen, Lisa Laun, Charlotte Lucke, MĂ„rten Palme
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This study examines the long-term association between income and life expectancy in Sweden between 1960 and 2021. The study is based on register data that include all Swedish permanent residents aged 40 y and older. The results show that the gap in life expectancy between the top and bottom income percentiles widened substantially: For men, it increased from 3.5 y in the 1960s to 10.9 y by the 2010s, and for women, from 3.8 y in the 1970s to 8.6 y by the 2010s. Despite a reduction in income inequality and an expansion of social spending from the 1960s to the 1990s, health inequality continuously increased over the period under study. The changes of the relation between real income and life expectancy, the so-called Preston curve, reveal a much faster improvement in life expectancy in the upper half of the income distribution than suggested by the cross-sectional relation between income and life expectancy. Analysis of causes of death identified circulatory diseases as the main contributor to improved longevity, while cancer contributed more to the increased gap in life expectancy for women and equally for men. Finally, analysis of the change in the income gradient in avoidable causes of death showed the strongest contribution of preventable causes, both for men and women.

Science

GPT-4o mini: Non-social science research article
Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans
Natalie J. Wallis, Alyce McClellan, Alexander Mörseburg, Katherine A. Kentistou, Aqfan Jamaluddin, Georgina K. C. Dowsett, Ellen Schofield, Anna Morros-Nuevo, Sadia Saeed, Brian Y. H. Lam, Natasha T. Sumanasekera, Justine Chan, Sambhavi S. Kumar, Rey M. Zhang, Jodie F. Wainwright, Marie Dittmann, Gabriella Lakatos, Kara Rainbow, David Withers, Rebecca Bounds, Marcella Ma, Alexander J. German, Jane Ladlow, David Sargan, Philippe Froguel, I. Sadaf Farooqi, Ken K. Ong, Giles S. H. Yeo, John A. Tadross, John R. B. Perry, Caroline M. Gorvin, Eleanor Raffan
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Obesity is a heritable disease, but its genetic basis is incompletely understood. Canine population history facilitates trait mapping. We performed a canine genome-wide association study for body condition score—a measure of obesity—in 241 Labrador retrievers. Using a cross-species approach, we showed that canine obesity genes are also associated with rare and common forms of obesity in humans. The lead canine association was within the gene DENN domain containing 1B ( DENND1B ). Each copy of the alternate allele was associated with ~7% greater body fat. We demonstrate a role for this gene in regulating signaling and trafficking of melanocortin 4 receptor, a critical controller of energy homeostasis. Thus, canine genetics identified obesity genes and mechanisms relevant to both dogs and humans.
GPT-4o mini: Non-social science research article
Sulfonyl hydrazides as a general redox-neutral platform for radical cross-coupling
Jiawei Sun, Áron Péter, Jiayan He, Jet Tsien, Haoxiang Zhang, David A. Cagan, Benjamin P. Vokits, David S. Peters, Martins S. Oderinde, Michael D. Mandler, Paul Richardson, Doris Chen, Maximilian D. Palkowitz, Nicholas Raheja, Yu Kawamata, Phil S. Baran
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Sulfonyl hydrazides are stable and usually crystalline substances that can be accessed in a variety of ways, including transiently from hydrazones, to achieve a net reductive arylation of carbonyl compounds. We show their utility as versatile radical precursors, as exemplified with seven C–C bond–forming, redox-neutral cross-couplings with activated olefins, alkyl halides, redox-active esters, aryl halides, alkenyl halides, alkynyl halides, and a trifluoromethylating reagent, to forge C(sp 3 )-C(sp 3 ), C(sp 3 )-C(sp 2 ), and C(sp 3 )-C(sp) bonds. Exogenous redox (chemical, photo/electrochemical) additives are not necessary because these functional groups serve the dual role of radical precursor and electron donor. The homogeneous, water-compatible reaction conditions are operationally simple and contribute to streamlining synthesis and mild late-stage functionalization.
GPT-4o mini: Non-social science research article
Telomeric transposons are pervasive in linear bacterial genomes
Shan-Chi Hsieh, MĂĄtĂ© FĂŒlöp, Richard Schargel, Michael T. Petassi, Orsolya Barabas, Joseph E. Peters
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Eukaryotes have linear DNA, and their telomeres are hotspots for transposons, which in some cases took over telomere maintenance. We identified several families of independently evolved telomeric transposons in linear chromosomes and plasmids of cyanobacteria and Streptomyces . Although these elements have one specific transposon end sequence, with the second boundary being the telomere, we can show that they move using two transposon ends, likely when transiently bridged by the telomere maintenance systems. Mobilization of the element and the associated telomere allows replacement of native telomeres, making the host cell dependent on the new transposon telomere system for genome maintenance. This work indicates how telomeric transposons can promote gene transfer both between and within genomes, substantially influencing the evolutionary dynamics of linear genomes.

Science Advances

GPT-4o mini: Non-social science research article
Circadian clock is critical for fungal pathogenesis by regulating zinc starvation response and secondary metabolism
Qiaojia Lu, Muqun Yu, Xianyun Sun, Xin Zhou, Rui Zhang, Yahao Zhang, Xiao-Lan Liu, Zhanbiao Li, Lei Cai, Hongwei Liu, Shaojie Li, Yunkun Dang, Xiaodong Xu, Qun He, Yi Liu, Xiao Liu
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Circadian clocks are known to modulate host immune responses to pathogen infections, yet their role in influencing pathogen pathogenesis remains unclear. Here, we investigated the role of circadian clocks in regulating the pathogenesis of the fungal pathogen Fusarium oxysporum , which has multiple genes homologous to the Neurospora crassa frq due to gene duplication events, with Fofrq1 being the primary circadian clock gene. The pathogenesis of F. oxysporum in plants is controlled by its circadian clock, with infections causing severe disease symptoms at dawn. Notably, disruption of clock genes dramatically reduces fungal pathogenicity. Circadian clocks regulate the rhythmic expression of several transcription factors, including FoZafA, which enables the pathogen to adapt to zinc starvation within the plant, and FoCzf1, which governs the production of the toxin fusaric acid. Together, our findings highlight the critical roles of circadian clocks in F. oxysporum pathogenicity by regulating zinc starvation response and secondary metabolite production.
GPT-4o mini: Non-social science research article
ÎŒSonic-hand: Biomedical micromanipulation driven by acoustic gas-liquid-solid interactions
Xiaoming Liu, Yuyang Li, Fengyu Liu, Qing Shi, Lixin Dong, Qiang Huang, Tatsuo Arai, Toshio Fukuda
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Micromanipulation is crucial for operating and analyzing microobjects in advanced biomedical applications. However, safe, low-cost, multifunctional micromanipulation for operating bio-objects across scales and modalities remains inaccessible. Here, we propose a versatile micromanipulation method driven by acoustic gas-liquid-solid interactions, named ÎŒSonic-hand. The bubble contained at the end of a micropipette and the surrounding liquid form a gas-liquid multiphase system susceptible to acoustic waves. Driven by a piezoelectric transducer, the oscillating gas-liquid interface induces acoustic microstreaming, markedly increasing the mass transfer efficiency. It enables multiple liquid micromanipulations, including mixing, dispersion, enhancing cell membrane permeability, and harvesting selected cells. Furthermore, a controllable three-dimensional axisymmetric vortex in an open environment overcomes the constraints of microfluidic chip, enabling stable trapping, rapid transportation, and multidirectional rotation of HeLa cells, embryos, and other bio-objects ranging from micrometers to millimeters. A variety of applications demonstrate that the ÎŒSonic-hand, with its wide-range capabilities, inherent biocompatibility, and extremely low cost could remarkably advance biomedical science.
GPT-4o mini: Non-social science research article
Liquid palladium for high-turnover carbon-carbon bond formation
Md. Hasan Al Banna, Nieves Flores, Ziqi Zhou, Nastaran Meftahi, Salvy P. Russo, Pramod Koshy, Francois-Marie Allioux, Mohammad B. Ghasemian, Junma Tang, Sarina Sarina, Jianbo Tang, Andrew J. Christofferson, Kourosh Kalantar-Zadeh, Md. Arifur Rahim
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Carbon-carbon (C─C) bond formation is a key step in diverse chemical processes and requires high-performance catalysts to enable energy-efficient technologies. Here, we present liquid Pd catalysts, formed by dissolving Pd in liquid Ga, for high-turnover C─C coupling reactions. The liquid Pd catalyst achieved a turnover frequency of 2.5 Ă— 10 8 hour −1 for a model coupling reaction at 70°C, surpassing all reported Pd catalysts by 1000-fold. Our results show that Pd atoms in the Ga matrix are liquid-like, exhibiting unique electronic and interfacial properties that substantially lower the energy barrier and enhance reaction kinetics. The system retained full activity over five cycles and showed no Pd leaching, highlighting the transformative potential of liquid-phase metals to advance high-throughput and sustainable C─C bond-forming strategies.
GPT-4o mini: Non-social science research article
Autocatalytic assembly of a chimeric aminoacyl-RNA synthetase ribozyme
Aleksandar Radakovic, Marco Todisco, Anmol Mishra, Jack W. Szostak
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Autocatalytic reactions driving the self-assembly of biological polymers are important for the origin of life, yet few experimental examples of such reactions exist. Here we report an autocatalytic assembly pathway that generates a chimeric, amino acid–bridged aminoacyl-RNA synthetase ribozyme. The noncovalent complex of ribozyme fragments initiates low-level aminoacylation of one of the fragments, which, after loop-closing ligation, generates a highly active covalently linked chimeric ribozyme. The generation of this ribozyme is increasingly efficient over time due to the autocatalytic assembly cycle that sustains the ribozyme over indefinite cycles of serial dilution. Because of its trans activity, this ribozyme also assembles ribozymes distinct from itself, such as the hammerhead, suggesting that RNA aminoacylation, coupled with nonenzymatic ligation, could have facilitated the emergence and propagation of ribozymes.
GPT-4o mini: Non-social science research article
Real-time antiproton annihilation vertexing with submicrometer resolution
Michael Berghold, Davide Orsucci, Francesco Guatieri, Sara Alfaro, Marcis Auzins, Benedikt Bergmann, Petr Burian, Roberto Sennen Brusa, Antoine Camper, Ruggero Caravita, Fabrizio Castelli, Giovanni Cerchiari, Roman Jerzy CiuryƂo, Ahmad Chehaimi, Giovanni Consolati, Michael Doser, Kamil Eliaszuk, Riley Craig Ferguson, Matthias Germann, Anna Giszczak, Lisa Glöggler, Ɓukasz Graczykowski, Malgorzata Grosbart, Natali Gusakova, Fredrik Gustafsson, Stefan Haider, Saiva Huck, Christoph Hugenschmidt, Malgorzata Anna Janik, Tymoteusz Henryk Januszek, Grzegorz Kasprowicz, Kamila Kempny, Ghanshyambhai Khatri, Ɓukasz KƂosowski, Georgy Kornakov, Valts Krumins, Lidia Lappo, Adam Linek, Sebastiano Mariazzi, Pawel Moskal, Dorota Nowicka, Piyush Pandey, Daniel PĘcak, Luca Penasa, Vojtech Petracek, Mariusz PiwiƄski, Stanislav Pospisil, Luca Povolo, Francesco Prelz, Sadiqali Rangwala, Tassilo Rauschendorfer, Bharat Rawat, Benjamin RienĂ€cker, Volodymyr Rodin, Ole RĂžhne, Heidi Sandaker, Sushil Sharma, Petr Smolyanskiy, Tomasz SowiƄski, Dariusz Tefelski, Theodoros Vafeiadis, Marco Volponi, Carsten Peter Welsch, Michal Zawada, Jakub Zielinski, Nicola Zurlo, character(0)
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Primary goal of the AEឥIS experiment is to precisely measure the free fall of antihydrogen within Earth’s gravitational field. To this end, cold (≈50 K) antihydrogen will traverse a two-grid moirĂ© deflectometer before annihilating onto a position-sensitive detector, which shall determine the vertical position of the annihilation vertex relative to the grids with micrometric accuracy. Here, we introduce a vertexing detector based on a modified mobile camera sensor and experimentally demonstrate that it can measure the position of antiproton annihilations within 0.62 − 0.22 + 0.40 ÎŒm, a 35-fold improvement over the previous state of the art for real-time antiproton vertexing. These methods are directly applicable to antihydrogen. Moreover, the sensitivity to light of the sensor enables in situ calibration of the moirĂ© deflectometer, substantially reducing systematic errors. This sensor emerges as a breakthrough technology toward the AEឥIS scientific goals and will constitute the basis for the development of a large-area detector for conducting antihydrogen gravity measurements.
GPT-4o mini: Non-social science research article
Mechanism of high-temperature superconductivity in compressed H 2 -molecular–type hydride
Pengye Liu, Quan Zhuang, Qiang Xu, Tian Cui, Zhao Liu
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The discovery of compressed atomic-type hydrides offers a promising avenue toward achieving room-temperature superconductivity, but it necessitates extremely high pressures to completely dissociate hydrogen molecules to release free electrons. Here, we report a remarkable finding of compressed H 2 -molecular–type hydride CaH 14 exhibiting an unusual transition temperature ( T c ) of 204.0 kelvin. The peculiarity of its electronic structure lies in the pronounced emergence of near-free electrons, which manifest metallic bonding, but molecular hydrogen fragments persist. This finding indicates that the necessary condition for superconducting transition is forming the Fermi sea with Cooper pairs rather than the monatomic hydrogen. Notably, the formation mechanism of free electrons can be effectively explained by the finite-depth potential wells model. Intriguingly, this H 2 -molecular–type hydride can downgrade the required pressure to 80 gigapascal while maintaining a high T c of 84 kelvin, well above the liquid-nitrogen temperature. Our study has established a high-temperature superconducting paradigm and opened the prospect for achieving high- T c superconductors in H 2 -molecular–type hydrides at low pressure.
GPT-4o mini: Non-social science research article
Preemptive optimization of a clinical antibody for broad neutralization of SARS-CoV-2 variants and robustness against viral escape
Fangqiang Zhu, Saravanan Rajan, Conor F. Hayes, Ka Yin Kwong, Andre R. Goncalves, Adam T. Zemla, Edmond Y. Lau, Yi Zhang, Yingyun Cai, John W. Goforth, Mikel Landajuela, Pavlo Gilchuk, Michael Kierny, Andrew Dippel, Bismark Amofah, Gilad Kaplan, Vanessa Cadevilla Peano, Christopher Morehouse, Ben Sparklin, Vancheswaran Gopalakrishnan, Kevin M. Tuffy, Amy Nguyen, Jagadish Beloor, Gustavo Kijak, Chang Liu, Aiste Dijokaite-Guraliuc, Juthathip Mongkolsapaya, Gavin R. Screaton, Brenden K. Petersen, Thomas A. Desautels, Drew Bennett, Simone Conti, Brent W. Segelke, Kathryn T. Arrildt, Samantha Kaul, Emilia A. Grzesiak, Felipe Leno da Silva, Thomas W. Bates, Christopher G. Earnhart, Svetlana Hopkins, Shivshankar Sundaram, Mark T. Esser, Joseph R. Francica, Daniel M. Faissol, character(0)
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Most previously authorized clinical antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have lost neutralizing activity to recent variants due to rapid viral evolution. To mitigate such escape, we preemptively enhance AZD3152, an antibody authorized for prophylaxis in immunocompromised individuals. Using deep mutational scanning (DMS) on the SARS-CoV-2 antigen, we identify AZD3152 vulnerabilities at antigen positions F456 and D420. Through two iterations of computational antibody design that integrates structure-based modeling, machine-learning, and experimental validation, we co-optimize AZD3152 against 24 contemporary and previous SARS-CoV-2 variants, as well as 20 potential future escape variants. Our top candidate, 3152-1142, restores full potency (100-fold improvement) against the more recently emerged XBB.1.5+F456L variant that escaped AZD3152, maintains potency against previous variants of concern, and shows no additional vulnerability as assessed by DMS. This preemptive mitigation demonstrates a generalizable approach for optimizing existing antibodies against potential future viral escape.
GPT-4o mini: Non-social science research article
Excess surface area of the nuclear lamina enables unhindered cell migration through constrictions
Brendan McKee, Samere Abolghasemzade, Ting-Ching Wang, Kajol Harsh, Simran Kaur, Ryan Blanchard, Krishna Belraj Menon, Mohammad Mohajeri, Richard B. Dickinson, Tanmay P. Lele
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Cell migration through narrow spaces is essential in wound healing and metastatic spread of cancer. Cells must deform the large nucleus to fit through constricting channels. To understand the role of the nuclear lamina in limiting cell migration through constrictions, we imaged it in cells migrating through periodic constricting channels in a microdevice. The lamina underwent cycles of wrinkling and smoothing as the nucleus changed from an irregular, rounded shape in the wide channel regions between constrictions to a smooth, hourglass shape as the nucleus passed through the center of a constriction. The laminar surface area of nuclei within constrictions was measured to be at or above the computationally predicted threshold area for the nuclear volume. The channels excluded control nuclei that had insufficient excess surface area, but not nuclei lacking lamin A/C. Thus, the excess surface area of the nuclear lamina enables cell migration through constricting channels.
GPT-4o mini: Non-social science research article
Nanoscale engineering and dynamic stabilization of mesoscopic spin textures
Kieren Harkins, Christoph Fleckenstein, Noella D’Souza, Paul M. Schindler, David Marchiori, Claudia Artiaco, Quentin Reynard-Feytis, Ushoshi Basumallick, William Beatrez, Arjun Pillai, Matthias Hagn, Aniruddha Nayak, Samantha Breuer, Xudong Lv, Maxwell McAllister, Paul Reshetikhin, Emanuel Druga, Marin Bukov, Ashok Ajoy
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Thermalization, while ubiquitous in physics, has traditionally been viewed as an obstacle to be mitigated. In contrast, we demonstrate here the use of thermalization in the generation, control, and readout of “shell-like” spin textures with interacting 13 C nuclear spins in diamond, wherein spins are polarized oppositely on either side of a critical radius. The textures span several nanometers and encompass many hundred spins; they are created and interrogated without manipulating the nuclear spins individually. Long-time stabilization is achieved via prethermalization to a Floquet-engineered Hamiltonian under the electronic gradient field: The texture is therefore metastable and robust against spin diffusion. This enables the state to endure over multiple minutes before it decays. Our work on spin-state engineering paves the way for applications in quantum simulation and nanoscale imaging.
GPT-4o mini: Non-social science research article
A dual chemodrug-loaded hyaluronan nanogel for differentiation induction therapy of refractory AML via disrupting lysosomal homeostasis
Shilin Xu, Tao Wang, Xuechun Hu, Hong Deng, Yiyi Zhang, Lei Xu, Yang Zeng, Jia Yu, Weiqi Zhang, Lin Wang, Haiyan Xu
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Relapsed/refractory acute myeloid leukemia (rrAML) is a malignant blood cancer with an extremely poor prognosis, largely ascribed to the drug-resistant leukemia stem cells (LSCs). Most patients suffer from a risk of difficult-to-cure as well as severe systemic toxicity when receiving standard chemotherapies. As hyaluronic acid (HA) is a specific ligand of CD44 highly expressed by LSCs, we had HA self-assembled with cisplatin and daunorubicin to form a dual chemodrug nanogel (HA/Cis/Dau) to afford the targeted therapeutic interventions of rrAML. HA/Cis/Dau displayed an extra therapeutic function of inducing the granulocyte-monocyte differentiation in CD44 + rrAML cells, an rrAML mouse model, and primary blasts isolated from patients with AML. Unlike free drugs directly diffusing and killing rrAML cells, HA/Cis/Dau transported the drugs into lysosomes, causing lysosomal membrane permeabilization, ROS accumulation, and thus a metabolic reprogramming of the rrAML cells. Moreover, HA/Cis/Dau was featured with alleviated side effects, ease of preparation, and cost effectiveness, therefore holding great promises for the targeted treatment of rrAML.
GPT-4o mini: Non-social science research article
Replication-dependent histone labeling dissects the physical properties of euchromatin/heterochromatin in living human cells
Katsuhiko Minami, Kako Nakazato, Satoru Ide, Kazunari Kaizu, Koichi Higashi, Sachiko Tamura, Atsushi Toyoda, Koichi Takahashi, Ken Kurokawa, Kazuhiro Maeshima
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A string of nucleosomes, where genomic DNA is wrapped around histones, is organized in the cell as chromatin, ranging from euchromatin to heterochromatin, with distinct genome functions. Understanding physical differences between euchromatin and heterochromatin is crucial, yet specific labeling methods in living cells remain limited. Here, we have developed replication-dependent histone (Repli-Histo) labeling to mark nucleosomes in euchromatin and heterochromatin based on DNA replication timing. Using this approach, we investigated local nucleosome motion in the four known chromatin classes, from euchromatin to heterochromatin, of living human and mouse cells. The more euchromatic (earlier-replicated) and more heterochromatic (later-replicated) regions exhibit greater and lesser nucleosome motions, respectively. Notably, the motion profile in each chromatin class persists throughout interphase. Genome chromatin is essentially replicated from regions with greater nucleosome motions, although the replication timing is perturbed. Our findings, combined with computational modeling, suggest that earlier-replicated regions have more accessibility, and local chromatin motion can be a major determinant of genome-wide replication timing.
GPT-4o mini: Non-social science research article
Ocean alkalinity destruction by anthropogenic seafloor disturbances generates a hidden CO 2 emission
Sebastiaan J. van de Velde, Astrid Hylén, Filip J. R. Meysman
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The seafloor is responsible for 40% of the alkalinity input to the ocean, thus contributing to the ocean’s capacity to sequester atmospheric CO 2 . Anthropogenic seafloor disturbances induced by mobile bottom-contact fishing and dredging influence this natural carbon sink, yet the human impact on the ocean’s alkalinity cycle remains poorly quantified. Model simulations show that the combined impact of mobile bottom-contact fishing (e.g., trawling) and dredging reduces natural alkalinity generation by 60 to 220 gigaequivalent year −1 , which is equivalent to a reduction of the natural marine carbon sink by 2 to 8 teragrams CO 2 year −1 . Alkalinity destruction by anthropogenic seafloor disturbance hence generates a hidden CO 2 emission, of which the impact is comparable to the estimated reduction of organic carbon burial by mobile bottom-contact fishing. Our analysis emphasizes that carbon accounting in marine systems should consider the anthropogenic impact on both the organic and inorganic carbon cycles.
GPT-4o mini: Non-social science research article
Sustainable regeneration of 20 aminoacyl-tRNA synthetases in a reconstituted system toward self-synthesizing artificial systems
Katsumi Hagino, Keiko Masuda, Yoshihiro Shimizu, Norikazu Ichihashi
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In vitro construction of self-reproducible artificial systems is a major challenge in bottom-up synthetic biology. Here, we developed a reconstituted system capable of sustainably regenerating all 20 aminoacyl-transfer RNA synthetases (AARS), which are major components of the translation system. To achieve this, we needed five types of improvements: (i) optimization of AARS sequences for efficient translation, (ii) optimization of the composition of the translation system to enhance translation, (iii) employment of another bacterial AlaRS and SerRS to improve each aminoacylation activity, (iv) diminishing the translational inhibition caused by certain AARS sequences by codon optimization and EF-P addition, and (v) balancing the DNA concentrations of 20 AARS to match each requirement. After these improvements, we succeeded in the sustainable regeneration of all 20 AARS for up to 20 cycles of 2.5-fold serial dilutions. These methodologies and results provide a substantial advancement toward the realization of self-reproducible artificial systems.
GPT-4o mini: Non-social science research article
Genomic insights and the conservation potential of captive breeding: The case of Chinese alligator
Tao Pan, Jiashun Miao, Ke Sun, Haitao Nie, Nicholas M. Luscombe, Wengang Li, Song Zhang, Liuyang Yang, Huan Wang, Yongkang Zhou, Genjun Tu, Yilin Shu, Baowei Zhang, Xiaobing Wu
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Despite 40 years of conservation of the critically endangered Chinese alligator ( Alligator sinensis ), the genomic underpinnings of its status remained uncharted. Genome sequencing data of 244 individuals uncovered relatively low overall genomic diversity/heterozygosity and long runs of homozygosity, with captive populations exhibiting higher heterozygosity and smaller inbreeding coefficients compared to wild individuals. The decreased level of inbreeding in the captive population demonstrates the contribution of the large captive breeding population. The estimated recent effective population size was around a few dozen. To combat challenges of inbreeding depression and reduced adaptability, we used genome-wide SNP-based kinship analysis on captive populations to enable a genome-informed breeding program that minimizes inbreeding. Long-term field monitoring revealed that the Chinese government greatly advanced the conservation of A. sinensis through conservation measures and reintroduction programs. Our research enriches the understanding of the Chinese alligator’s genetic landscape, offering invaluable genomic resources for breeding and conservation strategies.
GPT-4o mini: Non-social science research article
Neural stimulation suppresses mTORC1-mediated protein synthesis in skeletal muscle
Ana G. Dumitras, Giorgia Piccoli, Frederik Tellkamp, Lena Keufgens, Martina Baraldo, Sabrina Zorzato, Laura Cussonneau, Leonardo Nogara, Marcus KrĂŒger, Bert Blaauw
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Skeletal muscle fibers are classified as glycolytic or oxidative, with differing susceptibilities to muscle wasting. However, the intracellular signaling pathways regulating fiber-specific muscle trophism remain unclear because of a lack of experimental models measuring protein synthesis. We developed a mouse model overexpressing a mutated transfer RNA synthetase in muscle fibers, enabling specific protein labeling using an artificial methionine substitute, which can be revealed through click chemistry. This model revealed that denervation increases protein labeling in oxidative muscle fibers through mammalian target of rapamycin complex 1 (mTORC1) activation, while deleting the mTORC1 scaffold protein Raptor reduces labeling in glycolytic fibers. On the other hand, increased muscle activity acutely decreases protein synthesis, accompanied by reduced mTORC1 signaling, glycogen depletion, and adenosine 5â€Č-monophosphate kinase activation. Our findings identify nerve activity as an inhibitory signal for mTORC1-dependent protein synthesis in skeletal muscle, enhancing the understanding of fiber-specific responses to exercise and pathological conditions.
GPT-4o mini: Non-social science research article
Reconstructing historical climate fields with deep learning
Nils Bochow, Anna Poltronieri, Martin Rypdal, Niklas Boers
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Historical records of climate fields are often sparse because of missing measurements, especially before the introduction of large-scale satellite missions. Several statistical and model-based methods have been introduced to fill gaps and reconstruct historical records. Here, we use a recently introduced deep learning approach based on Fourier convolutions, trained on numerical climate model output, to reconstruct historical climate fields. Using this approach, we are able to realistically reconstruct large and irregular areas of missing data and to reproduce known historical events, such as strong El Niño or La Niña events, with very little given information. Our method outperforms the widely used statistical kriging method, as well as other recent machine learning approaches. The model generalizes to higher resolutions than the ones it was trained on and can be used on a variety of climate fields. Moreover, it allows inpainting of masks never seen before during the model training.
GPT-4o mini: Non-social science research article
Direct observation and force modulation of single-bond reactions at the ion/metal interface
Cong Zhao, Kun Li, Jie Hao, Yanlei Wang, Hongyan He, Chuancheng Jia, Xuefeng Guo
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Elucidating the mechanisms of ion-involved interfacial reactions at the single-bond level is important for understanding interface science. Here, the reaction between pyridine ions and protons at the solid-liquid interface is studied in situ using a single-molecule conductance measurement technique. By manipulating the interfacial electrostatic potential, an ion/metal interfacial state relying on electrostatic interactions has been discovered, comprising terminal group-hydrogen-gold in specific. The reversible interfacial protonation reaction mechanism is revealed in situ at the single-bond level based on this interfacial state. Experiment results also indicate that external forces can effectively regulate this ion-involved interfacial reaction. This work provides a single-bond approach for in situ investigations of ion-involved interfacial reactions with an ion/metal interfacial state, thus promoting the development of interface science.
GPT-4o mini: Non-social science research article
Quantification of low-temperature gas emissions reveals CO 2 flux underestimates at SoufriĂšre Hills volcano, Montserrat
Alexander Riddell, Mike Burton, Ben Esse, Brendan McCormick Kilbride, Antonio Chiarugi, Thomas Christopher, Francesco D’Amato, Graham A. Ryan, Adam Stinton, Silvia Viciani
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We performed helicopter-borne optical MultiGAS measurements of volcanic gas emissions from SoufriĂšre Hills Volcano, Montserrat, revealing distinct spikes in SO 2 and HCl concentrations within a larger CO 2 -rich plume. Acid-rich concentration spikes matched the distribution of high-temperature fumaroles, whereas CO 2 is emitted broadly from high- and low-temperature fumaroles. The CO 2 flux was 15 to 41 kilograms per second from hot fumaroles and 61 to 131 kilograms per second for the overall plume. The typical CO 2 flux calculation of multiplying CO 2 /SO 2 ratio with SO 2 flux underestimates total CO 2 flux by at least threefold. We quantified substantial magmatic gas scrubbing by the hydrothermal system, with 56 to 79% of initial HCl and 33 to 68% of initial SO 2 lost. This study highlights the importance of precise acid-gas measurements for detecting heterogeneous degassing and suggests that traditional CO 2 flux measurements may substantially underestimate contributions from cold CO 2 degassing, leading to underestimated global volcanic fluxes.
GPT-4o mini: Non-social science research article
Contorted acene ribbons for stable and ultrasensitive neural probes
Shayan Louie, Qifeng Jiang, Duncan J. Wisniewski, Si Tong Bao, Honghu Zhang, Kaushik Chivukula, Qiyi Fang, Ashutosh Garudapalli, Scott R. Docherty, Fay Ng, Michael Steigerwald, Yu Zhong, Dion Khodagholy, Colin Nuckolls
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Organic materials that conduct both electrons and ions are integral to implantable bioelectronics because of their conformable nature. There is a dearth of these materials that are highly sensitive to cations, which are the majority ions on the surface of neurons. This manuscript offers a solution using an extended ribbon structure that is defect-free, providing high electronic mobility along its fused backbone, while the edge structure of these ribbons promotes high ionic conductivity. We incorporated these mixed ion/electron conductors into neural probes and implanted them in a rodent brain where they offer a suite of useful properties: high cation sensitivity, stability over several weeks after implantation, and biocompatibility. These materials represent an innovative class of implantable biosensors.
GPT-4o mini: Non-social science research article
Autism-like atypical face processing in Shank3 mutant dogs
Siqi Yuan, Chenyu Pang, Liang Wu, Li Yi, Kun Guo, Yong-hui Jiang, Yong Q. Zhang, Shihui Han
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Atypical face processing is a neurocognitive basis of social deficits in autism spectrum disorder (ASD) and a candidate cognitive marker for the disease. Although hundreds of risk genes have been identified in ASD, it remains unclear whether mutations in a specific gene may cause ASD-like atypical face processing. Dogs have acquired exquisite face processing abilities during domestication and may serve as an effective animal model for studying genetic associations of ASD-like atypical face processing. Here, we showed that dogs with Shank3 mutations exhibited behavioral and attentional avoidance of faces, contrasting with wild-type controls. Moreover, neural responses specific to faces (versus objects) recorded from the electrodes over the temporal cortex were significantly decreased and delayed in Shank3 mutants compared to wild-type controls. Cortical responses in the frontal/parietal region underlying categorization of faces by species/breeds were reduced in Shank3 mutants. Our findings of atypical face processing in dogs with Shank3 mutations provide a useful animal model for studying ASD mechanisms and treatments.
GPT-4o mini: Non-social science research article
WWC1 mutation drives dopamine dysregulation and synaptic imbalance in Tourette’s syndrome
Junkai Lv, Shiqi Liang, Pengwei Qin, Xinlu Liu, Xiangyu Ge, Yiqing Guo, Shili Xia, Wei Jing, Youming Lu, Tongmei Zhang, Hao Li
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Tourette’s syndrome (TS) is a major neurodevelopmental disorder characterized by childhood-onset motor and vocal tics. A W88C mutation in WWC1 gene is a notable risk factor for TS, but the underlying molecular mechanisms remain unclear due to the lack of suitable animal models. Here, we generate a mutant mouse line with human W88C mutation (W88C Mut mice), which exhibits behavioral deficits similar to those observed in patients with TS, including repetitive motor behaviors and sensorimotor gating abnormalities. The W88C mutation leads to the degradation of kidney and brain (KIBRA) protein via a proteasomal pathway, evokes dopamine release in the dorsal striatum, and disrupts synaptic function through the dysregulation of Hippo pathway. Neuron-specific overexpression of wild-type WWC1 rescues synaptic and behavioral phenotypes in W88C Mut mice. Together, this study not only provides a valuable mouse model for studying TS but also offers fresh insights into the molecular and synaptic mechanisms underlying neurodevelopmental abnormalities in TS.
GPT-4o mini: Non-social science research article
Neuraminidase-specific antibodies drive differential cross-protection between contemporary FLUBV lineages
Caroline K. Page, Justin D. Shepard, Sean D. Ray, James A. Ferguson, Alesandra J. Rodriguez, Julianna Han, Joel C. Jacob, Dawne K Rowe-Haas, Jasmine Y. Akinpelu, Lilach M. Friedman, Tomer Hertz, Andrew B. Ward, Stephen M. Tompkins
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The two influenza B virus (FLUBV) lineages have continuously diverged from each other since the 1980s, with recent (post-2015) viruses exhibiting accelerated evolutionary rates. Emerging data from human studies and epidemiological models suggest that increased divergence in contemporary viruses may drive differential cross-protection, where infection with Yamagata lineage viruses provides limited immunity against Victoria lineage viruses. Here, we developed animal models to investigate the mechanisms behind asymmetric cross-protection between contemporary FLUBV lineages. Our results show that contemporary Victoria immunity provides robust cross-protection against the Yamagata lineage, whereas Yamagata immunity offers limited protection against the Victoria lineage. This differential cross-protection is driven by Victoria-elicited neuraminidase (NA)–specific antibodies, which show cross-lineage reactivity, unlike those from Yamagata infections. These findings identify a phenomenon in contemporary FLUBV that may help explain the recent disappearance of the Yamagata lineage from circulation, highlighting the crucial role of targeting NA in vaccination strategies to enhance cross-lineage FLUBV protection.
GPT-4o mini: Non-social science research article
Metal-assisted vacuum transfer enabling in situ visualization of charge density waves in monolayer MoS 2
Jichuang Shen, Xiaopeng Xie, Wenhao Li, Chaoyue Deng, Yaqing Ma, Han Chen, Huixia Fu, Fang-Sen Li, Bingkai Yuan, Chen Ji, Ruihua He, Jiaqi Guan, Wei Kong
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Recent advancements in quantum materials research have focused on monolayer transition metal dichalcogenides and their heterostructures, known for complex electronic phenomena. While macroscopic electrical and magnetic measurements provide valuable insights, understanding these electronic states requires direct experimental observations. Yet, the extreme two-dimensionality of these materials demands surface-sensitive measurements with exceptionally clean surfaces. Here, we present the metal-assisted vacuum transfer method combined with in situ measurements in ultrahigh vacuum (UHV), enabling pristine monolayer MoS 2 with ultraclean surfaces unexposed to ambient conditions. Consequently, in situ scanning tunneling microscopy revealed charge density waves (CDWs) in MoS 2 /Cu(111), previously unobserved in monolayer MoS 2 . Additionally, angle-resolved photoelectron spectroscopy identified notable Fermi surface nesting due to substrate interactions, elucidating the mechanisms behind CDW formation. This method is broadly applicable to other monolayer two-dimensional materials, enabling the high-fidelity in situ UHV characterization and advancing the understanding of correlated electronic behaviors in these material systems.
GPT-4o mini: Non-social science research article
Scalable fabrication of Chip-integrated 3D-nanostructured electronic devices via DNA-programmable assembly
Aaron Michelson, Lior Shani, Jason S. Kahn, Daniel C. Redeker, Won-Il Lee, Katerina R. DeOlivares, Kim Kisslinger, Nikhil Tiwale, Hanfei Yan, Ajith Pattammattel, Chang-Yong Nam, Vlad S. Pribiag, Oleg Gang
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DNA-based self-assembly methods have demonstrated powerful and unique capabilities to encode nanomaterial structures through the prescribed placement of inorganic and biological nanocomponents. However, the challenge of selectively growing DNA superlattices on specific locations of surfaces and their integration with conventional nanofabrication has hindered the fabrication of three-dimensional (3D) DNA-assembled functional devices. Here, we present a scalable nanofabrication technique that combines bottom-up and top-down approaches for selective growth of 3D DNA superlattices on gold microarrays. This approach allows for the fabrication of self-assembled 3D-nanostructured electronic devices. DNA strands are bound onto the gold arrays, which anchor DNA origami frames and promote ordered framework growth on the specific areas of the surface, enabling control of the lateral placement and orientation of superlattices. DNA frameworks selectively grown on the pads are subsequently templated to nanoscale silica and tin oxide (SnO x ) that follow the architecture, as confirmed by structural and chemical characterizations. The fabricated SnO x superlattices are integrated into devices that demonstrate photocurrent response.
GPT-4o mini: Non-social science research article
Untethered subcentimeter flying robots
Fanping Sui, Wei Yue, Kamyar Behrouzi, Yuan Gao, Mark Mueller, Liwei Lin
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The miniaturization of insect-scale flying robots with untethered flights is extremely challenging as the tradeoff between mass and power becomes problematic. Here, a subcentimeter rotating-wing robot of 21 mg in weight and 9.4 mm in wingspan driven by a single-axis alternating magnetic field has accomplished navigable flights. This artificial flying robot is the lightest and smallest to realize untethered and controllable aerial travels including hovering, collision recovery, and route adjustments. Experimentally, it has achieved a high aerodynamic efficacy with a measured lift-to-drag ratio of 0.7 and lift–to–flying power ratio of 7.2 Ă— 10 −2 N/W at a Reynolds number of ~2500. The wireless driving mechanism, system operation principle, and flight characteristics can be further optimized for the advancement and miniaturization of subcentimeter scale flying robots.
GPT-4o mini: Non-social science research article
Steroid hormone levels vary with sex, aging, lifestyle, and genetics
LĂ©a G. Deltourbe, Jamie Sugrue, Elizabeth Maloney, Florian Dubois, Anthony Jaquaniello, Jacob Bergstedt, Etienne Patin, Lluis Quintana-Murci, Molly A. Ingersoll, Darragh Duffy, character(0)
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Steroid hormone levels vary greatly among individuals, between sexes, with age, and across health and disease. What drives variance in steroid hormones and how they vary in individuals over time are not well studied. To address these questions, we measured 17 steroid hormones in a sex-balanced cohort of 949 healthy donors aged 20 to 69 years. We investigated associations between steroid levels and biological sex, age, clinical and demographic data, genetics, and plasma proteomics. Steroid hormone levels were strongly affected by sex and age, and a high number of lifestyle habits. Key observations were the broad impact of hormonal birth control in female donors and the relationship with smoking in male donors. In a 10-year follow-up study, we identified significant associations between steroid hormone levels and health status only in male donors. These observations highlight biological and lifestyle parameters affecting steroid hormones, and underlie the importance of considering sex, age, and potentially gendered behaviors in the treatment of hormone-related diseases.
GPT-4o mini: Non-social science research article
Electrophoretic digital colorimetry integrated with electrochemical sweat sensor
Daeun Sung, Seunghun Han, Sumin Kim, Heeseok Kang, Bon Jekal, Giheon Kim, Jaewon Kim, Minki Hong, Gyounghwan Moon, Sungeun Kim, Yerim Lee, Suk-Won Hwang, Hyoyoung Jeong, Yong-Sang Ryu, Sungbong Kim, Jahyun Koo
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Recent advancements in wearable sweat sensors, which use standardized electrochemical and colorimetric mechanisms, offer holistic representation of health status for users. However, the constraints of standardized sweat sensors present ongoing challenges to realization of personalized health management. This study presents an electrocolorimetric (EC) platform that enables the reversible and multiple-time use of colorimetric data visualization using electrophoretic display (EPD). This platform represents the application of low-power EPD in epidermal sweat sensor, evaluated through CIELAB-based methodology which is the first systematic evaluation tool of wearable display performance. Moreover, our platform has been demonstrated in human exercise trials for its ability to detect the lactate threshold (LT). This digital colorimetric system has the potential to play a pivotal role by integrating various health monitoring biomarkers. While providing real-time, continuous, and adjustable range information with high sensitivity, this platform validates its extensive probability as a next-generation wearable epidermal sensor.
GPT-4o mini: Non-social science research article
Curriculum is more influential than haptic feedback when learning object manipulation
Pegah Ojaghi, Romina Mir, Ali Marjaninejad, Andrew Erwin, Michael Wehner, Francisco J. Valero-Cuevas
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Dexterous manipulation remains an aspirational goal for autonomous robotic systems, particularly when learning to lift and rotate objects against gravity with intermittent finger contacts. We use model-free reinforcement learning to compare the effect of curriculum (i.e., combinations of lift and rotation tasks) and haptic information (i.e., no-tactile versus 3D-force) on learning with a simulated three-finger robotic hand. In addition, a novel curriculum-based learning rate scheduler accelerates convergence. We demonstrate that the choice of curriculum biases the progression of learning for dexterous manipulation across objects with different weights, sizes, and shapes—underscoring the robustness of our learning approach. Unexpectedly, learning is achieved even in the absence of haptic information. This challenges conventional thinking about task “complexity” and the necessity of haptic information for dexterous manipulation for this task. This work invites the analogy of curriculum learning as a malleable developmental process from a pluripotent state driven by the nature of the learning experience.
GPT-4o mini: Non-social science research article
A predatory gene drive for targeted control of self-transmissible plasmids
Ryan Tsoi, Hye-In Son, Grayson S. Hamrick, Katherine Tang, Jonathan H. Bethke, Jia Lu, Rohan Maddamsetti, Lingchong You
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Suppressing plasmid transfer in microbial communities has profound implications due to the role of horizontal gene transfer (HGT) in spreading and maintaining diverse functional traits such as metabolic functions, virulence factors, and antibiotic resistance. However, existing tools for inhibiting HGT are limited in their modes of delivery, efficacy, and scalability. Here, we present a versatile denial-of-spread (DoS) strategy to target and eliminate specific conjugative plasmids. Our strategy exploits retrotransfer, whereby an engineered DoS plasmid is introduced into host cells containing a target plasmid. Acting as a predatory gene drive, DoS propagates itself at the expense of the target plasmid, through competition or active elimination. Once the target plasmid is eradicated, DoS is removed via induced plasmid suicide, resulting in a community containing neither plasmid. The strategy is tunable and scalable for various conjugative plasmids, different mechanisms of plasmid inheritance interruption, and diverse environmental contexts. DoS represents a new tool for precise control of gene persistence in microbial communities.
GPT-4o mini: Non-social science research article
Ultrafast momentum-resolved visualization of the interplay between phonon-mediated scattering and plasmons in graphite
Francesco Barantani, RĂ©mi Claude, Fadil Iyikanat, Ivan Madan, Alexey A. Sapozhnik, Michele Puppin, Bruce Weaver, Thomas LaGrange, F. Javier GarcĂ­a de Abajo, Fabrizio Carbone
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Scattering between charges and collective modes in materials governs phenomena such as electrical resistance, energy dissipation, and phase switching. Studying such scattering requires simultaneous access to ultrafast and momentum-resolved dynamics of single-particle and collective excitations, which remains an experimental challenge. Here, we present time- and momentum-resolved electron energy loss spectroscopy, and we apply it to graphite, demonstrating that large (Δ q ≃1.2 Å −1 ) photoexcited electron-hole pockets induce a renormalization of in-plane and bulk plasmons. This effect is explained by intra- and intervalley scattering processes mediated by E 2g and A â€Č 1 phonon modes, which we directly observe via ultrafast electron diffraction and identify via ab initio calculations. Conversely, smaller electron-hole pockets (Δ q ≃0.7 Å −1 ) result in the renormalization of in-plane plasmons, which can only be partially explained by phonon-mediated scattering and thermal expansion. Our results highlight the importance of combining momentum- and time-resolved information to elucidate electronic scattering processes.
GPT-4o mini: Non-social science research article
Structural dynamics-guided engineering of a riboswitch RNA for evolving c-di-AMP synthases
Dian Chen, Jun Li, You Wu, Liang Hong, Yu Liu
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Cyclic diadenosine monophosphate (C-di-AMP) synthases are key enzymes for synthesizing c-di-AMP, a potent activator of the stimulator of interferon genes (STING) immune pathway. However, characterizing these enzymes has been hampered by the lack of effective sensors. While c-di-AMP riboswitches, as natural aptamers, hold the potential as RNA biosensors, their poorly comprehended structural dynamics and inherent "OFF" genetic output pose substantial challenges. To address these limitations, we synthesized over 10 fluorophore-labeled samples to probe the conformational changes of the riboswitch at the single-molecule level. By integrating these dynamic findings with steady-state fluorescence titration, mutagenesis, in vivo assays, and strand displacement strategy, we transformed the natural aptamer into a c-di-AMP biosensor. This engineered biosensor reversed its genetic output from "OFF" to "ON" upon c-di-AMP binding, exhibiting a 50-fold improvement in the c-di-AMP detection limit. Leveraging this refined biosensor, we developed a robust strategy for high-throughput in vivo evolution of c-di-AMP synthases.
GPT-4o mini: Non-social science research article
Starfish-inspired wearable bioelectronic systems for physiological signal monitoring during motion and real-time heart disease diagnosis
Sicheng Chen, Qunle Ouyang, Xianglin Meng, Yibo Yang, Can Li, Xuanbo Miao, Zehua Chen, Ganggang Zhao, Yaguo Lei, Bernard Ghanem, Sandeep Gautam, Jianlin Cheng, Zheng Yan
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Soft bioelectronics enable noninvasive, continuous monitoring of physiological signals, essential for precision health care. However, capturing biosignals during physical activity, particularly biomechanical signals like cardiac mechanics, remains challenging due to motion-induced interference. Inspired by starfish’s pentaradial symmetry, we introduce a starfish-like wearable bioelectronic system designed for high-fidelity signal monitoring during movement. The device, featuring five flexible, free-standing sensing arms connected to a central electronic hub, substantially reduces mechanical interference and enables high-fidelity acquisition of cardiac electrical (electrocardiogram) and mechanical (seismocardiogram and gyrocardiogram) signals during motion when coupled with signal compensation and machine learning. Using these three cardiac signal types as inputs, machine learning models deployed on smart devices achieve real-time, high-accuracy (more than 91%) diagnoses of heart conditions such as atrial fibrillation, myocardial infarction, and heart failure. These findings open previously undiscovered avenues by leveraging bioinspired device concepts combined with cutting-edge data science to boost bioelectronic performance and diagnostic precision.
GPT-4o mini: Non-social science research article
Structural basis for hygromycin B inhibition of yeast pseudouridine-deficient ribosomes
Yu Zhao, Chong Xu, Xin Chen, Hong Jin, Hong Li
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Eukaryotic ribosomes are enriched with pseudouridine, particularly at the functional centers targeted by antibiotics. Here, we investigated the roles of pseudouridine in aminoglycoside-mediated translation inhibition by comparing the structural and functional properties of the yeast wild-type and the pseudouridine-free ribosomes. We showed that the pseudouridine-free ribosomes have decreased thermostability and high sensitivity to aminoglycosides. When presented with a model internal ribosomal entry site RNA, elongation factor eEF2, GTP (guanosine triphosphate), and sordarin, hygromycin B preferentially binds to the pseudouridine-free ribosomes during initiation by blocking eEF2 binding, stalling ribosomes in a nonrotated conformation. The structures captured hygromycin B bound at the intersubunit bridge B2a enriched with pseudouridine and a deformed codon-anticodon duplex, revealing a functional link between pseudouridine and aminoglycoside inhibition. Our results suggest that pseudouridine enhances both thermostability and conformational fitness of the ribosomes, thereby influencing their susceptibility to aminoglycosides.
GPT-4o mini: Non-social science research article
Alpha-synuclein seed amplification assays: Data sharing, standardization needed for clinical use
Hilal A. Lashuel, D. James Surmeier, Tanya Simuni, Kalpana Merchant, Byron Caughey, Claudio Soto, Mohamed-Bilal Fares, Roland G. Heym, Ronald Melki
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Alpha-synuclein seed amplification assays can improve neurodegenerative disease diagnosis and care, but widespread use depends on a framework that standardizes protocols and encourages data sharing.
GPT-4o mini: Non-social science research article
Fibroblast atlas: Shared and specific cell types across tissues
Kaidong Liu, Yanrui Cui, Huiming Han, Erliang Guo, Xingyang Shi, Kai Xiong, Nan Zhang, Songmei Zhai, Shaocong Sang, Mingyue Liu, Bo Chen, Yunyan Gu
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Understanding the heterogeneity of fibroblasts depends on decoding the complexity of cell subtypes, their origin, distribution, and interactions with other cells. Here, we integrated 249,156 fibroblasts from 73 studies across 10 tissues to present a single-cell atlas of fibroblasts. We provided a high-resolution classification of 18 fibroblast subtypes. In particular, we revealed a previously undescribed cell population, TSPAN8 + chromatin remodeling fibroblasts, characterized by high expression of genes with functions related to histone modification and chromatin remodeling. Moreover, TSPAN8 + chromatin remodeling fibroblasts were detectable in spatial transcriptome data and multiplexed immunofluorescence assays. Compared with other fibroblast subtypes, TSPAN8 + chromatin remodeling fibroblasts exhibited higher scores in cell differentiation and resident fibroblast, mainly interacting with endothelial cells and T cells through ligand VEGFA and receptor F2R , and their presence was associated with poor prognosis. Our analyses comprehensively defined the shared and specific characteristics of fibroblast subtypes across tissues and provided a user-friendly data portal, Fibroblast Atlas.
GPT-4o mini: Non-social science research article
Neuroecology of alcohol risk and reward: Methanol boosts pheromones and courtship success in Drosophila melanogaster
Ian W. Keesey, Georg Doll, Sudeshna Das Chakraborty, Amelie Baschwitz, Marion Lemoine, Martin Kaltenpoth, AleĆĄ SvatoĆĄ, Silke Sachse, Markus Knaden, Bill S. Hansson
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Attraction of Drosophila melanogaster toward by-products of alcoholic fermentation, especially ethanol, has been extensively studied. Previous research has provided several interpretations of this attraction, including potential drug abuse, or a self-medicating coping strategy after mate rejection. We posit that the ecologically adaptive value of alcohol attraction has not been fully explored. Here, we assert a simple yet vital biological rationale for this alcohol preference. Flies display attraction to fruits rich in alcohol, specifically ethanol and methanol, where contact results in a rapid amplification of fatty acid–derived pheromones that enhance courtship success. We also identify olfactory sensory neurons that detect these alcohols, where we reveal roles in both attraction and aversion, and show that valence is balanced around alcohol concentration. Moreover, we demonstrate that methanol can be deadly, and adult flies must therefore accurately weigh the trade-off between benefits and costs for exposure within their naturally fermented and alcohol-rich environments.
GPT-4o mini: Non-social science research article
The inflammatory and genetic mechanisms underlying the cumulative effect of co-occurring pain conditions on depression
Rongtao Jiang, Paul Geha, Matthew Rosenblatt, Yunhe Wang, Zening Fu, Maya Foster, Wei Dai, Vince D. Calhoun, Jing Sui, Marisa N. Spann, Dustin Scheinost
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Chronic pain conditions frequently coexist and share common genetic vulnerabilities. Despite evidence showing associations between pain and depression, the additive effect of co-occurring pain conditions on depression risk and the underlying mechanisms remain unclear. Leveraging data from 431,038 UK Biobank participants with 14-year follow-up, we found a significantly increased risk of depression incidence in individuals reporting pain, irrespective of body site or duration (acute or chronic), compared with pain-free individuals. The depression risk increased with the number of co-occurring pain sites. Mendelian randomization supported potential causal inference. We constructed a composite pain score by combining individual effects of acute or chronic pain conditions across eight body sites in a weighted manner. We found that depression risks increased monotonically in parallel with composite pain scores. Moreover, some inflammatory markers, including C-reactive protein, partially mediated the association between composite pain scores and depression risk. Considering the high prevalence of comorbid depression and pain, pain screening may help identify high-risk individuals for depression.
GPT-4o mini: Non-social science research article
Tuning catalyst-support interactions enable steering of electrochemical CO 2 reduction pathways
Meng Wang, Yuke Li, Jinfeng Jia, Tanmay Ghosh, Ping Luo, Yu-Jhih Shen, Sibo Wang, Jiguang Zhang, Shibo Xi, Ziyu Mi, Mingsheng Zhang, Wan Ru Leow, Bernt Johannessen, Zainul Aabdin, Sung-Fu Hung, Jia Zhang, Yanwei Lum
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Tuning of catalyst-support interactions potentially offers a powerful means to control activity. However, rational design of the catalyst support is challenged by a lack of clear property-activity relationships. Here, we uncover how the electronegativity of a support influences reaction pathways in electrochemical CO 2 reduction. This was achieved by creating a model system consisting of Cu nanoparticles hosted on a series of carbon supports, each with a different heteroatom dopant of varying electronegativity. Notably, we discovered that dopants with high electronegativity reduce the electron density on Cu and induce a selectivity shift toward multicarbon (C 2+ ) products. With this design principle, we built a composite Cu and F-doped carbon catalyst that achieves a C 2+ Faradaic efficiency of 82.5% at 400 mA cm −2 , with stable performance for 44 hours. Using simulated flue gas, the catalyst attains a C 2+ FE of 27.3%, which is a factor of 5.3 times higher than a reference Cu catalyst.
GPT-4o mini: Non-social science research article
Understanding DNA-encoded carbon nanotube sorting and sensing via sub-nm-resolution structural determination
Yinong Li, Yawei Wen, Leticia C. BeltrĂĄn, Li Zhu, Shishan Tian, Jialong Liu, Xuan Zhou, Piaoyi Chen, Edward H. Egelman, Ming Zheng, Zhiwei Lin
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DNA has demonstrated the abilities to differentiate single-wall carbon nanotubes (SWCNTs) with various chiralities and manipulate their analyte sensing properties. However, the fundamental mechanisms underlying these remarkable abilities remain unclear due to the lack of high-resolution determination of DNA structures on SWCNTs. Here, we combine atomic force microscopy and single-particle cryo–electron microscopy to determine DNA structures on five different types of single-chirality SWCNTs, achieving unprecedented subnanometer resolution. This resolution enables the direct observation of left-handed helical DNA structures with pitches ranging from 1.59 to 2.20 nm, depending on the DNA sequence and nanotube chirality. These findings provide structural insights into the mechanisms by which DNA differentiates the chirality of SWCNTs, and governs the sensitivity, dynamic response range, and analyte differentiability of SWCNT sensors. We propose a non–Watson-Crick hydrogen-bonding network model, which not only accounts for the observed ordered DNA structures but also facilitates the design of DNA sequences for targeted SWCNT purification and desired SWCNT sensor performance.
GPT-4o mini: Non-social science research article
Microbial dipeptidyl peptidases of the S9B family as host-microbe isozymes
Mashael R. Aljumaah, Jeffery Roach, Yunan Hu, John Gunstad, M. Andrea Azcarate-Peril
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Human dipeptidyl peptidase 4 (hDPP-4) has been a pharmacological target for metabolic diseases, particularly diabetes, since the early 2000s. As a ubiquitous enzyme found in both prokaryotic and eukaryotic organisms, hDPP-4 plays crucial roles in host homeostasis and disease progression. While many studies have explored hDPP-4’s properties, research on gut microbially derived DPP-4 (mDPP-4) remains limited. This review discusses the significance of mDPP-4 and its health implications, analyzing crystal structures of mDPP-4 in comparison to human counterparts. We examine how hDPP-4 inhibitors could influence gut microbiome composition and mDPP-4 activity. Additionally, this review connects ongoing discussions regarding DPP-4 substrate specificity and potential access routes for mDPP-4, emphasizing the urgent need for further research on mDPP-4’s role in health and improve the precision of DPP-4 inhibitor therapies.
GPT-4o mini: Non-social science research article
Structural basis for the pore-forming activity of a complement-like toxin
Bronte A. Johnstone, Michelle P. Christie, Riya Joseph, Craig J. Morton, Hamish G. Brown, Eric Hanssen, Tristan C. Sanford, Hunter L. Abrahamsen, Rodney K. Tweten, Michael W. Parker
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Pore-forming proteins comprise a highly diverse group of proteins exemplified by the membrane attack complex/perforin (MACPF), cholesterol-dependent cytolysin (CDC), and gasdermin superfamilies, which all form gigantic pores (>150 angstroms). A recently found family of pore-forming toxins, called CDC-like proteins (CDCLs), are wide-spread in gut microbes and are a prevalent means of antibacterial antagonism. However, the structural aspects of how CDCLs assemble a pore remain a mystery. Here, we report the crystal structure of a proteolytically activated CDCL and cryo–electron microscopy structures of a prepore-like intermediate and a transmembrane pore providing detailed snapshots across the entire pore-forming pathway. These studies reveal a sophisticated array of regulatory features to ensure productive pore formation, and, thus, CDCLs straddle the MACPF, CDC, and gasdermin lineages of the giant pore superfamilies.
GPT-4o mini: Non-social science research article
Computational capacity of life in relation to the universe
Philip Kurian
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As physical systems, all life in the universe processes information according to physical laws. Estimates for the computational capacity of living systems generally assume that the fundamental information-processing unit is the Hodgkin-Huxley neuron, thereby excluding aneural organisms. Assuming the laws of quantum mechanics, the relativistic speed limit set by light, a universe at critical mass-energy density, and a recent experimental demonstration of single-photon superradiance in cytoskeletal protein fibers at thermal equilibrium, it is conjectured that the number of elementary logical operations that can have been performed by all eukaryotic life in the history of Earth, which is shown to be approximately equal to the ratio of the age of the universe to the Planck time, is about the square root of the number by the entire observable universe from the beginning. The existence of ultraviolet-excited ∣ W âŒȘ states in these protein fibers, operating within two orders of magnitude of the Margolus-Levitin speed limit, motivates state-of-the-art performance comparisons with contemporary quantum computers.
GPT-4o mini: Non-social science research article
Perturbed cell fate decision by schizophrenia-associated AS3MT d2d3 isoform during corticogenesis
Seunghyun Kim, Youngsik Woo, Dahun Um, Inseop Chun, Su-Jin Noh, Hyeon Ah Ji, Namyoung Jung, Bon Seong Goo, Jin Yeong Yoo, Dong Jin Mun, Tran Diem Nghi, Truong Thi My Nhung, Seung Hyeon Han, Su Been Lee, Wonhyeok Lee, Jonghyeok Yun, Ki Hurn So, Dae-Kyum Kim, Hyunsoo Jang, Yeongjun Suh, Jong-Cheol Rah, Seung Tae Baek, Ki-Jun Yoon, Min-Sung Kim, Tae-Kyung Kim, Sang Ki Park
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The neurodevelopmental theory of schizophrenia emphasizes early brain development in its etiology. Genome-wide association studies have linked schizophrenia to genetic variations of AS3MT (arsenite methyltransferase) gene, particularly the increased expression of AS3MT d2d3 isoform. To investigate the biological basis of this association with schizophrenia pathophysiology, we established a transgenic mouse model (AS3MT d2d3 -Tg) ectopically expressing AS3MT d2d3 at the cortical neural stem cells. AS3MT d2d3 -Tg mice exhibited enlarged ventricles and deficits in sensorimotor gating and sociability. Single-cell and single-nucleus RNA sequencing analyses of AS3MT d2d3 -Tg brains revealed cell fate imbalances and altered excitatory neuron composition. AS3MT d2d3 localized to centrosome, disrupting mitotic spindle orientation and differentiation in developing neocortex and organoids, in part through NPM1 (Nucleophosmin 1). The structural analysis identified that hydrophobic residues exposed in AS3MT d2d3 are critical for its pathogenic function. Therefore, our findings may help to explain the early pathological features of schizophrenia.
GPT-4o mini: Non-social science research article
Synthesis of Ti 4 Au 3 C 3 and its derivative trilayer goldene through chemical exfoliation
Yuchen Shi, Shun Kashiwaya, Jun Lu, Martin Dahlqvist, Davide G. Sangiovanni, Vladyslav Rogoz, Martin Magnuson, Grzegorz Greczynski, Mike Andersson, Johanna Rosen, Lars Hultman
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Achieving large two-dimensional (2D) sheets of any metal is challenging due to their tendency to coalescence or cluster into 3D shapes. Recently, single-atom-thick gold sheets, termed goldene, was reported. Here, we ask if goldene can be extended to include multiple layers. The answer is yes, and trilayer goldene is the magic number, for reasons of electronegativity. Experiments are made to synthesize the atomically laminated phase Ti 4 Au 3 C 3 through substitutional intercalation of Si layers in Ti 4 SiC 3 for Au. Density functional theory calculations suggest that it is energetically favorable to insert three layers of Au into Ti 4 SiC 3 , compared to inserting a monolayer, a bilayer, or more than three layers. Isolated trilayer goldene sheets, ~100 nanometers wide and 6.7 angstroms thick, were obtained by chemically etching the Ti 4 C 3 layers from Ti 4 Au 3 C 3 templates. Furthermore, trilayer goldene is found in both hcp and fcc forms, where the hcp is ~50 milli–electron volts per atom more stable at room temperature from ab initio molecular dynamic simulations.
GPT-4o mini: Non-social science research article
Xenotopic synthetic biology: Prospective tools for delaying aging and age-related diseases
Andrey A. Parkhitko, Valentin Cracan
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Metabolic dysregulation represents one of the major driving forces in aging. Although multiple genetic and pharmacological manipulations are known to extend longevity in model organisms, aging is a complex trait, and targeting one’s own genes may be insufficient to prevent age-dependent deterioration. An alternative strategy could be to use enzymes from other species to reverse age-associated metabolic changes. In this review, we discuss a set of enzymes from lower organisms that have been shown to affect various metabolic parameters linked to age-related processes. These enzymes include modulators of steady-state levels of amino acids (METase, ASNase, and ADI), NADPH/NADP + and/or reduced form of coenzyme Q (CoQH 2 )/CoQ redox potentials (NDI1, AOX, Lb NOX, TPNOX, Ec STH, RquA, LOXCAT, Grubraw, and ScURA), GSH (StGshF), mitochondrial membrane potential (mtON and mito-dR), or reactive oxygen species (DAAO and KillerRed-SOD1). We propose that leveraging non-mammalian enzymes represents an untapped resource that can be used to delay aging and age-related diseases.
GPT-4o mini: Non-social science research article
Coassembly of hybrid microscale biomatter for robust, water-processable, and sustainable bioplastics
Yijin Qiu, Dachuan Zhang, Min Long, Zhixuan Zhou, Changdan Gao, Shuai Ma, Jinfa Qin, Kaijuan Chen, Chaoji Chen, Ze Zhao, Hongbing Deng
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Unlike conventional methods that typically involve extracting biopolymers/monomers from biomass using lots of hazardous chemicals and high energy, the direct utilization of biological matter (biomatter) without extraction offers a more sustainable alternative for bioplastic production. However, it often suffers from insufficient mechanical performances or limited processabilities. Herein, we proposed a hybrid microscale biomatter coassembly strategy that leverages the interactions between the inherent microarchitectures of waste cotton fiber and pollen particles. With minimal preprocessing, they form a castable slurry that can spontaneously organize into a dense fiber-laminate bioplastic network, exhibiting high mechanical properties (52.22 megapascals and 2.24 gigapascals) without using toxic organic chemicals or heavy machinery. The resulting bioplastic features controlled hydration-induced microstructural disassembly/reassembly, enabling water-based processability into complex, dynamic architectural systems. In addition, it demonstrates good biodegradability, closed-loop recyclability, and satisfactory environmental benefits, outperforming most common plastics. This study provides an instant nature-derived paradigm for bioplastics’ sustainable production, processing, and recycling, offering a promising solution for facilitating eco-friendly advanced applications.
GPT-4o mini: Non-social science research article
Rapid sorting and auxiliary evaluation of malignant breast tumors by accurate imaging analysis of metastasis-related biomarker
Shan Zuo, Yanhua Li, Yushi Chen, Gangwei Jiang, Zhixuan Zhou, Tian-Bing Ren, Lanlan Chen, Sulai Liu, Shulin Huang, Xiao-Bing Zhang, Lin Yuan
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Accurate differentiation of benign and malignant breast tumors is paramount for establishing schemes of breast cancer treatment and prognosis. Here we report a near-infrared (NIR) fluorescence probe (YF-1) with the overexpressed cathepsin C (CTSC) in metastatic breast tumors as the detecting substrate. This probe allows accurate identification of malignant tumor tissue specimens among tumor tissue specimens with unknown properties in a blind study. Importantly, a series of visible to NIR CTSC-activated fluorescence probes based on the same strategy realize effective identification of malignant tumor tissues, suggesting that CTSC could be the specific identification substrate of malignant breast tumors. Furthermore, a hydrophilic PEG moiety is coupled into YF-1, producing another CTSC-activated NIR probe (YF-2). YF-2 has excellent tumor-targeting capability, enabling the visualization of lung-metastatic breast tumors. The excellent detection accuracy and construction versatility of CTSC probes pave the way for preoperative diagnosis of malignant breast tumors.
GPT-4o mini: Non-social science research article
Chronic ethanol exposure produces sex-dependent impairments in value computations in the striatum
Yifeng Cheng, Robin Magnard, Angela J. Langdon, Daeyeol Lee, Patricia H. Janak
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Value-based decision-making relies on the striatum, where neural plasticity can be altered by chronic ethanol (EtOH) exposure, but the effects of such plasticity on striatal neural dynamics during decision-making remain unclear. This study investigated the long-term impacts of EtOH on reward-driven decision-making and striatal neurocomputations in male and female rats using a dynamic probabilistic reversal learning task. Following a prolonged withdrawal period, EtOH-exposed male rats exhibited deficits in adaptability and exploratory behavior, with aberrant outcome-driven value updating that heightened preference for chosen action. These behavioral changes were linked to altered neural activity in the dorsomedial striatum (DMS), where EtOH increased outcome-related encoding and decreased choice-related encoding. In contrast, female rats showed minimal behavioral changes with distinct EtOH-evoked alterations of neural activity, revealing significant sex differences in the impact of chronic EtOH. Our findings underscore the impact of chronic EtOH exposure on adaptive decision-making, revealing enduring changes in neurocomputational processes in the striatum underlying cognitive deficits that differ by sex.
GPT-4o mini: Non-social science research article
Neural heterogeneity enhances reliable neural information processing: Local sensitivity and globally input-slaved transient dynamics
Shengdun Wu, Haiping Huang, Shengjun Wang, Guozhang Chen, Changsong Zhou, Dongping Yang
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Cortical neuronal activity varies over time and across repeated trials, yet consistently represents stimulus features. The dynamical mechanism underlying this reliable representation and computation remains elusive. This study uncovers a mechanism for reliable neural information processing, leveraging a biologically plausible network model incorporating neural heterogeneity. First, we investigate neuronal timescale diversity, revealing that it disrupts intrinsic coherent spatiotemporal patterns, induces firing rate heterogeneity, enhances local responsive sensitivity, and aligns network activity closely with input. The system exhibits globally input-slaved transient dynamics, essential for reliable neural information processing. Other neural heterogeneities, such as nonuniform input connections, spike threshold heterogeneity, and network in-degree heterogeneity, play similar roles, highlighting the importance of neural heterogeneity in shaping consistent stimulus representation. This mechanism offers a potentially general framework for understanding neural heterogeneity in reliable computation and informs the design of reservoir computing models endowed with liquid wave reservoirs for neuromorphic computing.
GPT-4o mini: Non-social science research article
Ligand spin immobilization in metal-organic frameworks enables high-performance chemispintronic detection of radical gas molecules
Cheng Liu, Xiao-Cheng Zhou, Guoao Li, Jian Su, Lingyu Tang, Qinglong Liu, Xiao Han, Sen Lv, Zhangyan Mu, Yamei Sun, Shuai Yuan, Fei Gao, Jing-Lin Zuo, Shuhua Li, Mengning Ding
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The precise quantification of gaseous radicals in exhaled breath, such as fractional exhaled nitric oxide, serves as an invaluable noninvasive clinical diagnosis particularly in discerning various respiratory disorders. To date, the development of high-performance nitric oxide sensors compatible to modern electronic devices remains fundamentally challenging. We report that metal-organic frameworks (MOFs) with ligand spin immobilization demonstrate superior chemispintronic sensitivity and selectivity toward nitric oxide. Tetrathiafulvalene radical cations (TTF· + ) within the MOF lattice considerably enhance the nitric oxide recognition via spin exchange interactions, leading to a five–order of magnitude reduction in the limit of detection (LOD), as compared to volatile organic compounds (VOCs) via carrier-doping mechanism. Record-low LOD of 0.12 parts per billion was achieved in M-TTF-spin (M = cobalt, zinc, and cadmium) MOFs, which also demonstrates exceptional selectivity over typical nitrogen oxides (NO x ) and VOCs. This work opens up a distinct sensing platform for radical-like analytes through strategic design of spin-immobilized molecular functional motifs toward the spintronic device configurations.
GPT-4o mini: Non-social science research article
Self-supervised machine learning framework for high-throughput electron microscopy
Joodeok Kim, Jinho Rhee, Sungsu Kang, Mingyu Jung, Jihoon Kim, Miji Jeon, Junsun Park, Jimin Ham, Byung Hyo Kim, Won Chul Lee, Soung-Hun Roh, Jungwon Park
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Transmission electron microscopy (TEM) is a crucial analysis method in materials science and structural biology, as it offers a high spatiotemporal resolution for structural characterization and reveals structure-property relationships and structural dynamics at atomic and molecular levels. Despite technical advancements in EM, the nature of the electron beam makes the EM imaging inherently detrimental to materials even in low-dose applications. We introduce SHINE, the Self-supervised High-throughput Image denoising Neural network for Electron microscopy, accelerating minimally invasive low-dose EM of diverse material systems. SHINE uses only a single raw image dataset with intrinsic noise, which makes it suitable for limited-size datasets and eliminates the need for expensive ground-truth training datasets. We quantitatively demonstrate that SHINE overcomes the information limit in the current high-resolution TEM, in situ liquid phase TEM, time-series scanning TEM, and cryo-TEM, facilitating unambiguous high-throughput structure analysis across a broad spectrum of materials.
GPT-4o mini: Non-social science research article
An engineering-reinforced extracellular vesicle–integrated hydrogel with an ROS-responsive release pattern mitigates spinal cord injury
Jian Cao, Xunqi Zhang, Jing Guo, Jiahe Wu, Lingmin Lin, Xurong Lin, Jiafu Mu, Tianchen Huang, Manning Zhu, Lan Ma, Weihang Zhou, Xinchi Jiang, Xuhua Wang, Shiqing Feng, Zhen Gu, Jian-Qing Gao
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The local delivery of mesenchymal stem cell–derived extracellular vesicles (EVs) via hydrogel has emerged as an effective approach for spinal cord injury (SCI) treatment. However, achieving on-demand release of EVs from hydrogel to address dynamically changing pathology remains challenging. Here, we used a series of engineering methods to further enhance EVs’ efficacy and optimize their release pattern from hydrogel. Specifically, the pro-angiogenic, neurotrophic, and anti-inflammatory effects of EVs were reinforced through three-dimensional culture and dexamethasone (Dxm) encapsulation. Then, the prepared Dxm-loaded 3EVs (3EVs-Dxm) were membrane modified with ortho-dihydroxy groups (-2OH) and formed an EV-integrated hydrogel (3EVs-Dxm-Gel) via the cross-link with phenylboronic acid–modified hyaluronic acid and tannic acid. The phenylboronic acid ester in 3EVs-Dxm-Gel enabled effective immobilization and reactive oxygen species–responsive release of EVs. Topical injection of 3EVs-Dxm-Gel in SCI rats notably mitigated injury severity and promoted functional recovery, which may offer opportunities for EV-based therapeutics in central nervous system injury.
GPT-4o mini: Non-social science research article
Viscosity-dependent hydrothermal synthesis of multinary titanate perovskites
Hong-Bo Cui, Guijian Guan, Ming-Yong Han
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An innovative viscosity-dependent hydrothermal strategy is developed for the controlled synthesis of multinary titanate perovskites, specifically Na 0.5 Y 0.39 Yb 0.1 Er 0.01 TiO 3 . By manipulating the viscosity of the reaction solution using various stable additives in both type and quantity, we identify a critical viscosity threshold of ~100 centipoise, which is essential for producing uniform faceted particles. With sodium hydroxide as an additive, a clear morphological evolution occurs as hydroxide concentration increases, shifting from regular cubes to edge-truncated, half-corner-truncated, and fully corner-truncated cube particles. Furthermore, the inclusion of additional sodium chloride and acetate substantially increases the viscosity, facilitating the formation of uniform faceted particles with reduced sizes ranging from ~2.0 micrometers to 200 nanometers. This method is successfully applied to synthesize other uniform perovskites, including Na 0.5 Y 0.395 Yb 0.1 Tm 0.005 TiO 3 , Na 0.5 Y 0.4 Eu 0.1 TiO 3 , Na 0.5 Y 0.39 Yb 0.1 Ho 0.01 TiO 3 , and Na 0.5 Bi 0.5 TiO 3 . Our findings provide valuable insights into viscosity-controlled synthesis for creating multinary perovskites and enhance their potential for designing optical functional materials and advancing various applications in optical temperature sensing, anti-counterfeiting security, and fingerprint recognition.
GPT-4o mini: Non-social science research article
Predicting Atlantic and Benguela Niño events with deep learning
Marie-Lou BachĂšlery, Julien Brajard, Massimiliano Patacchiola, Serena Illig, Noel Keenlyside
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Atlantic and Benguela Niño events substantially affect the tropical Atlantic region, with far-reaching consequences on local marine ecosystems, African climates, and El Niño Southern Oscillation. While accurate forecasts of these events are invaluable, state-of-the-art dynamic forecasting systems have shown limited predictive capabilities. Thus, the extent to which the tropical Atlantic variability is predictable remains an open question. This study explores the potential of deep learning in this context. Using a simple convolutional neural network architecture, we show that Atlantic/Benguela Niños can be predicted up to 3 to 4 months ahead. Our model excels in forecasting peak-season events with remarkable accuracy extending lead time to 5 months. Detailed analysis reveals our model’s ability to exploit known physical precursors, such as long-wave ocean dynamics, for accurate predictions of these events. This study challenges the perception that the tropical Atlantic is unpredictable and highlights deep learning’s potential to advance our understanding and forecasting of critical climate events.
GPT-4o mini: Non-social science research article
Genomic insights into evolution of parthenogenesis and triploidy in the flowerpot snake
Yunyun Lv, Wei Wu, Jin-Long Ren, Matthew K. Fujita, Menghuan Song, Zeng Wang, Ke Jiang, Dechun Jiang, Chaochao Yan, Changjun Peng, Zhongliang Peng, Jia-Tang Li
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The flowerpot snake ( Indotyphlops braminus ) is the only known parthenogenetic and triploid species within Serpentes. However, the genetic basis underlying this phenomenon remains unresolved. We investigated the genomic complexities of this rare all-female triploid reptile. On the basis of the newly assembled genome, we revealed 40 chromosomes grouped into three subgenomes (A, B, and C). Comparative genomic analysis with related diploid species revealed a chromosome fusion event in ancestral genomes. This event shaped the unique genetic landscape of the flowerpot snake. We examined gene expression specificity in ovarian tissues and identified pathways essential for DNA replication and repair. Our findings suggest a potential mechanism of homologous chromosome pairing during meiosis in allopolyploid parthenogenesis. This research provides insights into the evolutionary adaptations and genetic mechanisms underlying parthenogenesis in reptilian species, challenging traditional views on reproductive strategies and genomic evolution in asexual organisms.
GPT-4o mini: Non-social science research article
Tempests in the troposphere: Mapping the impact of giant storms on Jupiter’s deep atmosphere
Chris Moeckel, Huazhi Ge, Imke de Pater
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Storms are emerging as key drivers in shaping hydrogen-dominated atmospheres. Trace gas condensation can suppress convection and disrupt the distribution of energy and material in hydrogen atmospheres. On Jupiter, the presence of water has been invoked to control the occurrence of large-scale storms; however, the impact of storms on the ammonia and temperature distribution is unknown. We use Juno Microwave Radiometer observations of a large-scale storm in 2017 to study the aftermath of such a storm on the atmosphere. Anomalies in the retrieved ammonia abundance and atmospheric temperature show how storms deplete and heat the upper atmosphere while simultaneously depositing material well below the layers they were triggered at. These observations, aided by simulations, show that the water and ammonia cycles are coupled and that their combined effect plays a key role in explaining the depletion of ammonia in the tropospheres of Jupiter and Saturn.
GPT-4o mini: Non-social science research article
Alternatives to photorespiration: A system-level analysis reveals mechanisms of enhanced plant productivity
Edward N. Smith, Marvin van Aalst, Andreas P. M. Weber, Oliver Ebenhöh, Matthias Heinemann
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Photorespiration causes a substantial decrease in crop yield because of mitochondrial decarboxylation. Alternative pathways (APs) have been designed to relocate the decarboxylation step or even fix additional carbon. To improve the success of transferring those engineered APs from model species to crops, we must understand how they will interact with metabolism and how plant physiology affects their performance. Here, we used multiple mathematical modeling techniques to analyze and compare existing AP designs. We show that carbon-fixing APs are the most promising candidates to replace native photorespiration in major crop species. Our results demonstrate the different metabolic routes that APs use to increase yield and which plant physiology can profit the most from them. We anticipate our results to guide the design of new APs and to help improve existing ones.
GPT-4o mini: Non-social science research article
Permafrost thawing under overlaying salt water
Yumin Wang, Jin-Han Xie, Wei Yang, Xiaotian Li, Zulikaer Abulaiti, Shuai Zheng, Jingwei Zhu, Ke Xu
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Thawing of permafrost substantially affects the local environment and global energy balance. When salt water overlays permafrost, Rayleigh-Darcy (R-D) instability emerges because of the density mismatch and regulates melting (thawing) dynamics. Contrary to expectations that a higher Rayleigh number ( R ) would amplify instability, our experiments revealed fingering and stable melting fronts at low and high R , respectively. We attribute the occurrence of the two melting patterns to the interplay between two competing flow structures: local circumfluence modulated by front perturbation and transversal chaotic mixing. We propose theories that rationalize the melting pattern transition and finger-scale evolution. In addition, the classic mass transport theory for R-D convection drastically underestimates the melting rate and misses key variable(s). The presence of fingering patterns and accelerated dynamics may have led to earlier penetration of the permafrost layer than previously anticipated. These findings have implications for understanding similar processes in magma migration, carbon sequestration, and subsurface energy recovery.
GPT-4o mini: Non-social science research article
Drosophila and human Headcase define a new family of ribonucleotide granule proteins required for stress response
Delia Ricolo, Jordi Casanova, Panagiotis Giannios
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Cells have means to adapt to environmental stresses such as temperature fluctuations, toxins, or nutrient availability. Stress responses, being dynamic, extend beyond transcriptional control and encompass post-transcriptional mechanisms allowing for rapid changes in protein synthesis. Previous research has established headcase as a fundamental gene for stress responses and survival of the Drosophila adult progenitor cells (APCs). However, the molecular role of Headcase has remained elusive. Here, we identify Headcase as a component of ribonucleoprotein (RNP) granules. We also show that, Headcase is required for proper RNP granule formation and remodeling upon stress and is crucial for translation control. Likewise, the human Headcase homolog (HECA) is identified as a component of RNP granules and has similar roles in translational regulation and stress protection. Thus, Headcase proteins define a new family contributing to specific roles among the RNP heterogeneous network.
GPT-4o mini: Non-social science research article
Anatomy of a foreseeable disaster: Lessons from the 2023 dam-breaching flood in Derna, Libya
Moshe Armon, Yuval Shmilovitz, Elad Dente
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Was the catastrophic flooding in Derna, Libya—one of the deadliest hydrometeorological disasters on record—an inevitable outcome of rare weather conditions, or did the design of the infrastructure fail to account for probable risks? On 10 to 11 September 2023, Storm Daniel, a Mediterranean tropical-like cyclone, caused heavy rainfall that led to the collapse of two dams and more than 5000 casualties in Derna. Using a combination of atmospheric reanalysis, satellite data, and hydrologic modeling, we overcame key limitations typical of data-scarce, high-variability regions and revealed that despite the catastrophic impact, the return periods of the rainfall and flood were only a few decades. Hydraulic simulations revealed that the dam failures amplified the damage nearly 20-fold compared to a dam-free scenario. With extensive and timely implications, our findings underscore the importance of uncertainty-aware risk assessment and highlight the value of distributed flood prevention and early warning systems in mitigating risks in vulnerable regions.
GPT-4o mini: Non-social science research article
Current crowding–free superconducting nanowire single-photon detectors
Stefan Strohauer, Fabian Wietschorke, Christian Schmid, Stefanie Grotowski, Lucio Zugliani, Björn Jonas, Kai MĂŒller, Jonathan J. Finley
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Detecting single photons is essential for applications such as dark matter detection, quantum science and technology, and biomedical imaging. Superconducting nanowire single-photon detectors (SNSPDs) excel in this task due to their near-unity detection efficiency, subhertz dark count rates, and picosecond timing jitter. However, a local increase of current density (current crowding) in the bends of meander-shaped SNSPDs limits these performance metrics. By locally irradiating the SNSPD’s straight segments with helium ions while leaving the bends unirradiated, we realize current crowding–free SNSPDs with simultaneously enhanced sensitivity: After irradiation with 800 ions nm −2 , locally irradiated SNSPDs showed a relative saturation plateau width of 37%, while fully irradiated SNSPDs reached only 10%. This larger relative plateau width allows operation at lower relative bias currents, thereby reducing the dark count rate while still detecting single photons efficiently. We achieve an internal detection efficiency of 94% with 7 mHz dark count rate near the onset of saturating detection efficiency for a wavelength of 780 nm.

Socio-Economic Review

Review symposium on: Jens Beckert, How we sold our future. The failure to fight climate change (Polity 2025)
Juliet B Schor, Neil Fligstein, Anita Engels, Jens Beckert
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Social debtfare policies and the rise of the creditor-state: The creditization of social policy in Argentina
Tomås Nougués
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This article examines the financialization of social policy in Argentina, focusing on the administration of Mauricio Macri (2015–19). Utilizing a case study methodology, it investigates the emergence of state-provided credit programs designed to meet the welfare needs of low-income households. Through document analysis, in-depth interviews, and non-participant observations, this article offers a comprehensive analysis of this policy shift. The article argues that creditization represents a new trend in the financialization of social policy with profound implications for welfare provision. It introduces the concept of “social debtfare policies,” illustrating how these credit programs have redefined social policy. These policies establish a debt relationship between the state, now acting as a creditor, and welfare recipients, who become debtors to bridge the welfare gap. This growing trend challenges traditional welfare foundations, emphasizing the increasing reliance on credit to fulfill welfare functions and reshaping the dynamics between the state and its citizens.
Rising inequality: is the public response really lacking? A comparative longitudinal analysis of perceived inequality and evaluative attitudes
Timo Wiesner
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Rising income inequality in the past decades has triggered an ongoing discussion about how the public perceives and evaluates this trend. Contrary to predictions derived from political economy models, one of the most common conclusions is that there is a lack of public response to rising income inequality. Using multilevel hybrid models and five waves of ISSP data, this article re-examines the core question whether the conclusion of a lacking popular response to rising inequality is indeed warranted. Results show that rising inequality is associated with increased perceived inequality, and both rising inequality and perceived inequality foster critical evaluations—that is, lead to greater concern for inequality and support for redistribution—challenging the notion of a lacking popular response to contemporary inequality dynamics. Furthermore, the analyses also underscore the importance of decomposing country-level effects by revealing substantial differences between cross-sectional and longitudinal effects, especially regarding attitudinal differences across income groups.