Proceedings of the National Academy of Sciences of the United States of America

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• Direct binding to sterols accelerates endoplasmic reticulum- associated degradation of HMG CoA reductase AI翻译
  作者：Faulkner, Rebecca A.; Yang, Yangyan; Tsien, Jet; Qin, Tian; DeBose-Boyd, Russell A.
  作者单位：University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
  摘要：The maintenance of cholesterol homeostasis is crucial for normal function at both the cellular and organismallevels. Two integral membrane proteins, 3- hydroxy-3- methylglutaryl coenzyme A reductase (HMGCR) and Scap, are key targets of a complex feedback regulatory system that operates to ensure cholesterol homeostasis. HMGCR catalyzes the rate- limiting step in the transformation of the 2- carbon precursor acetate to 27- carbon cholesterol. Scap mediates proteolytic activation of sterol regul...
• Homophily, selection, and choice in segregation models AI翻译
  作者：Xu, Bing; Clark, William A. V.; Pak, Maxwell
  作者单位：Southwestern University of Finance & Economics - China; University of California System; University of California Los Angeles
  摘要：Schelling's 1971 work on the dynamics of segregation showed that even a small degree of homophily, the desire to live among like neighbors, can lead to a starkly segregated population. One of the driving factors for this result is that the notion of homophily used is based on group identities that are exogenous and immutable. In contrast, we consider a homophily that arises from the desire to be with neighbors who are behaviorally similar, not necessarily those who have the same group identity...
• Collective chemomechanical oscillations in active hydrogels AI翻译
  作者：Blanc, Baptiste; Agyapong, Johnson N.; Hunter, Ian; Galas, Jean-Christophe; Fernandez-Nieves, Alberto; Fraden, Seth
  作者单位：Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); University of Barcelona; Brandeis University; Syracuse University; University of Barcelona; ICREA
  摘要：We report on the collective response of an assembly of chemomechanical BelousovZhabotinsky (BZ) hydrogel beads. We first demonstrate that a single isolated spherical BZ hydrogel bead with a radius below a critical value does not oscillate, whereas an assembly of the same BZ hydrogel beads presents chemical oscillation. A BZ chemical model with an additional flux of chemicals out of the BZ hydrogel captures the experimentally observed transition from oxidized nonoscillating to oscillating BZ hy...
• Pharmacological modulation of RB1 activity mitigates resistance to neoadjuvant chemotherapy in locally advanced rectal cancer AI翻译
  作者：Yu, Zhaoliang; Deng, Peng; Chen, Yufeng; Lin, Dezheng; Liu, Shini; Hong, Jinghan; Guan, Peiyong; Chen, Jianfeng; Zhong, Min-er; Chen, Jinghong; Chen, Xiaochuan; Sun, Yichen; Wang, Yali; Wang, Peili; Cai, Zerong; Chan, Jason Yongsheng; Huang, Yulin; Xiao, Rong; Guo, Yaoyu; Zeng, Xian; Wang, Wenyu; Zou, Yifeng; Yu, Qiang; Lan, Ping; Teh, Bin Tean; Wu, Xiaojian; Tan, Jing
  作者单位：Sun Yat Sen University; Sun Yat Sen University; State Key Lab Oncology South China; Sun Yat Sen University; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); Sun Yat Sen University; National Cancer Centre Singapore (NCCS); Sun Yat Sen University; Sun Yat Sen University
  摘要：Resistance to neoadjuvant chemotherapy leads to poor prognosis of locally advanced rectal cancer (LARC), representing an unmet clinical need that demands further exploration of therapeutic strategies to improve clinical outcomes. Here, we identified a noncanonical role of RB1 for modulating chromatin activity that contributes to oxaliplatin resistance in colorectal cancer (CRC). We demonstrate that oxaliplatin induces RB1 phosphorylation, which is associated with the resistance to neoadjuvant ...
• Gut microbiota: A key susceptibility factor in social anxiety disorder AI翻译
  作者：Heijtz, Rochellys Diaz
  作者单位：Karolinska Institutet
• An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy AI翻译
  作者：Lee, Vivian K.; Lee, Taewoo; Ghosh, Amrit; Saha, Tanmoy; Bais, Manish, V; Bharani, Kala Kumar; Chag, Milan; Parikh, Keyur; Bhatt, Parloop; Namgung, Bumseok; Venkataramanan, Geethapriya; Agrawal, Animesh; Sonaje, Kiran; Mavely, Leo; Sengupta, Shiladitya; Mashelkar, Raghunath Anant; Jang, Hae Lin
  作者单位：Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Boston University; Council of Scientific & Industrial Research (CSIR) - India; CSIR - National Chemical Laboratory (NCL)
  摘要：Hemostatic devices are critical for managing emergent severe bleeding. With the increased use of anticoagulant therapy, there is a need for next- generation hemostats. We rationalized that a hemostat with an architecture designed to increase contact with blood, and engineered from a material that activates a distinct and undrugged coagulation pathway can address the emerging need. Inspired by lung alveolar architecture, here, we describe the engineering of a next- generation single - phase chi...
• Tracking the role of Aire in immune tolerance to the eye with a TCR transgenic mouse model AI翻译
  作者：Yin, Mianmian; Smith, Jennifer A.; Chou, Marissa; Chan, Jackie; Jittayasothorn, Yingyos; Gould, Douglas B.; Caspi, Rachel R.; Anderson, Mark S.; Defranco, Anthony L.
  作者单位：University of California System; University of California San Francisco; University of California System; University of California San Francisco; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI); University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
  摘要：Roughly one - half of mice with partial defects in two immune tolerance pathways (AireGW/+Lyn-/- mice) spontaneously develop severe damage to their retinas due to T cell reactivity to Aire- regulated interphotoreceptor retinoid-binding protein (IRBP). Single - cell T cell receptor (TCR) sequencing of CD4+ T cells specific for a predominate epitope of IRBP showed a remarkable diversity of autoantigen- specific TCRs with greater clonal expansions in mice with disease. TCR transgenic mice made wi...
• Positive associations fuel soil biodiversity and ecological networks worldwide AI翻译
  作者：Liu, Xu; Chu, Haiyan; Godoy, Oscar; Fan, Kunkun; Gao, Gui- Feng; Yang, Teng; Ma, Yuying; Delgado-Baquerizo, Manuel
  作者单位：Chinese Academy of Sciences; Nanjing Institute of Soil Science, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Universidad de Cadiz; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Recursos Naturales y Agrobiologia de Sevilla (IRNAS)
  摘要：Microbial interactions are key to maintaining soil biodiversity. However, whether nega- tive or positive associations govern the soil microbial system at a global scale remains virtually unknown, limiting our understanding of how microbes interact to support soil biodiversity and functions. Here, we explored ecological networks among multitrophic soil organisms involving bacteria, protists, fungi, and invertebrates in a global soil survey across 20 regions of the planet and found that positive...
• Early Oligocene kelp holdfasts and stepwise evolution of the kelp ecosystem in the North Pacific AI翻译
  作者：Kiel, Steffen; Goedert, James L.; Huynh, Tony L.; Krings, Michael; Parkinson, Dula; Romero, Rosemary; Looy, Cindy V.
  作者单位：Swedish Museum of Natural History; University of Washington; University of Washington Seattle; University of California System; University of California San Francisco; University of Munich; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of California System; University of California Berkeley
  摘要：Kelp forests are highly productive and economically important ecosystems worldwide, especially in the North Pacific Ocean. However, current hypotheses for their evolutionary origins are reliant on a scant fossil record. Here, we report fossil hapteral kelp holdfasts from western Washington State, USA, indicating that kelp has existed in the northeastern Pacific Ocean since the earliest Oligocene. This is consistent with the proposed North Pacific origin of kelp associated with global cooling a...
• Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production AI翻译
  作者：Bennett, Neal K.; Lee, Megan; Orr, Adam L.; Nakamura, Ken
  作者单位：University of California System; University of California San Francisco; The J David Gladstone Institutes; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
  摘要：Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are differentially regulated. To address this question, we adapted a CRISPRi- and FACS-based platform to compare the effects of respiratory gene knockdown on ROS to their effects on ATP. Focusing on genes whose knockdown is known to decrease mitoch...