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

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• Developing a predictive science of the biosphere requires the integration of scientific cultures AI翻译
  作者：Enquist, Brian J.; Kempes, Christopher P.; West, Geoffrey B.
  作者单位：University of Arizona; The Santa Fe Institute
  摘要：Increasing the speed of scientific progress is urgently needed to address the many challenges associated with the biosphere in the Anthropocene. Consequently, the critical question becomes: How can science most rapidly progress to address large, complex global problems? We suggest that the lag in the development of a more predictive science of the biosphere is not only because the biosphere is so much more complex, or because we do not have enough data, or are not doing enough experiments, but...
• Exacerbated atherosclerosis in progeria is prevented by progerin elimination in vascular smooth muscle cells but not endothelial cells AI翻译
  作者：Benedicto, Ignacio; Carmona, Rosa M.; Barettino, Ana; Espinos-Estevez, Carla; Gonzalo, Pilar; Nevado, Rosa M.; de la Fuente-Perez, Miguel; Andres-Manzano, Maria J.; Gonzalez-Gomez, Cristina; Rolas, Loic; Dorado, Beatriz; Nourshargh, Sussan; Hamczyk, Magda R.; Andres, Vicente
  作者单位：Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Investigaciones Biologicas (CIB); Centro Nacional de Investigaciones Cardiovasculares (CNIC); CIBER - Centro de Investigacion Biomedica en Red; CIBERCV; University of London; Queen Mary University London; University of Oviedo; Instituto Universitario de Oncologia de Asturias
  摘要：Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by the expression of progerin, a mutant protein that accelerates aging and precipitates death. Given that atherosclerosis complications are the main cause of death in progeria, here, we investigated whether progerin - induced atherosclerosis is prevented in HGPSrev - Cdh5 - CreERT2 and HGPSrev - SM22 alpha- Cre mice with progerin suppression in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), respectively. HG...
• Microglia- derived extracellular vesicles trigger age- related neurodegeneration upon DNA damage AI翻译
  作者：Arvanitaki, Ermioni S.; Goulielmaki, Evi; Gkirtzimanaki, Katerina; Niotis, George; Tsakani, Edisona; Nenedaki, Electra; Rouska, Iliana; Kefalogianni, Mary; Xydias, Dionysios; Kalafatakis, Ilias; Psilodimitrakopoulos, Sotiris; Karagogeos, Domna; Schumacher, Bjoern; Stratakis, Emmanuel; Garinis, George A.
  作者单位：University of Crete; Foundation for Research & Technology - Hellas (FORTH); University of Crete; Foundation for Research & Technology - Hellas (FORTH); University of Crete; University of Crete; University of Cologne; University of Cologne
  摘要：DNA damage and neurodegenerative disorders are intimately linked but the underlying mechanism remains elusive. Here, we show that persistent DNA lesions in tissue- resident macrophages carrying an XPF-ERCC1 DNA repair defect trigger neuroinflammation and neuronal cell death in mice. We find that microglia accumulate dsDNAs and chromatin fragments in the cytosol, which are sensed thereby stimulating a viral - like immune response in Er1Cx/- and naturally aged murine brain. Cytosolic DNAs are pa...
• c- di- AMP determines the hierarchical organization of bacterial RCK proteins AI翻译
  作者：Rocha, Rita; Jorge, Joao M. P.; Teixeira-Duarte, Celso M.; Figueiredo-Costa, Ines R.; Cereija, Tatiana B.; Ferreira-Teixeira, Paula F.; Herzberg, Christina; Stuelke, Joerg; Morais-Cabral, Joao H.
  作者单位：Universidade do Porto; i3S - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto; Universidade do Porto; University of Gottingen
  摘要：In bacteria, intracellular K + is involved in the regulation of membrane potential, cytosolic pH, and cell turgor as well as in spore germination, environmental adaptation, cell - to - cell communication in biofilms, antibiotic sensitivity, and infectivity. The second messenger cyclic - di - AMP (c - di - AMP) has a central role in modulating the intracellular K + concentration in many bacterial species, controlling transcription and function of K + channels and transporters. However, our unde...
• Reversal of C9orf72 mutation- induced transcriptional dysregulation and pathology in cultured human neurons by allele- specific excision AI翻译
  作者：Sachdev, Aradhana; Gill, Kamaljot; Sckaff, Maria; Birk, Alisha M.; Arogundade, Olubankole Aladesuyi; Brown, Katherine A.; Chouhan, Runvir S.; Issagholian-Lewin, Patrick Oliver; Patel, Esha; Watry, Hannah L.; Bernardi, Mylinh T.; Keough, Kathleen C.; Tsai, Yu-Chih; Smith, Alec Simon Tulloch; Conklin, Bruce R.; Clelland, Claire Dudley
  作者单位：University of California System; University of California San Francisco; The J David Gladstone Institutes; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; 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：Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus. We generated five different genomic excisions at the C9orf72 locus in a patient - derived induced pluripotent stem cell (iPSC) line and a non - diseased wild - type (WT) line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 frontotemporal dementia/amyotrophic lateral sclerosis in motor neurons differentiated from th...
• Pathogenic gating pore current conducted by autism-related mutations in the NaV1.2 brain sodium channel AI翻译
  作者：Eltokhi, Ahmed; Lundstrom, Brian Nils; Li, Jin; Zweifel, Larry S.; Catterall, William A.; El-Din, Tamer M. Gamal
  作者单位：University of Washington; University of Washington Seattle; Mayo Clinic; University of Washington; University of Washington Seattle; Mercer University
  摘要：Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social and communication deficits and repetitive behaviors. The genetic heterogeneity of ASD presents a challenge to the development of an effective treatment targeting the underlying molecular defects. ASD gating charge mutations in the KCNQ/K(V)7 potassium channel cause gating pore currents (I-gp) and impair action potential (AP) firing of dopaminergic neurons in brain slices. Here, we investigated ASD ...
• The continental divide in range-shifting birds of North America AI翻译
  作者：Lenoir, Jonathan
  作者单位：Centre National de la Recherche Scientifique (CNRS); Universite de Picardie Jules Verne (UPJV)
• The length and spacing of river tributaries AI翻译
  作者：Robinson, Michael J.; Scheingross, Joel S.
  作者单位：Nevada System of Higher Education (NSHE); University of Nevada Reno; Nevada System of Higher Education (NSHE); University of Nevada Reno
  摘要：River networks are composed of a mainstem and tributaries. These tributaries dissect landscapes, regulate water and habitat availability, and transport sediment and nutrients. Despite the importance of tributaries, we currently lack theory and data describing whether and how tributary length and spacing varies within watersheds, thereby limiting our ability to accurately describe river network geometry. We address this knowledge gap by analyzing 4,696 tributaries across six landscapes with var...
• Optimal reaching subject to computational and physical constraints reveals structure of the sensorimotor control system AI翻译
  作者：Greene, Patrick; Bastian, Amy J.; Schieber, Marc H.; Sarma, Sridevi, V
  作者单位：Johns Hopkins University; Kennedy Krieger Institute; Johns Hopkins University; University of Rochester; Johns Hopkins University
  摘要：Optimal feedback control provides an abstract framework describing the architecture of the sensorimotor system without prescribing implementation details such as what coordinate system to use, how feedback is incorporated, or how to accommodate changing task complexity. We investigate how such details are determined by computational and physical constraints by creating a model of the upper limb sensorimotor system in which all connection weights between neurons, feedback, and muscles are unkno...
• Dual topologies of myotomal collagen XV and Tenascin C act in concert to guide and shape developing motor axons AI翻译
  作者：Nemoz-Billet, Laurie; Balland, Martial; Gilquin, Laurent; Gillet, Benjamin; Stevant, Isabelle; Guillon, Emilie; Hughes, Sandrine; Carpentier, Gilles; Vaganay, Elisabeth; Sohm, Frederic; Misiak, Vladimir; Melo, Mary-Julieth Gonzalez-; Koch, Manuel; Ghavi-Helm, Yad; Bretaud, Sandrine; Ruggiero, Florence
  作者单位：Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); INRAE; CHU Lyon; Ecole Normale Superieure de Lyon (ENS de LYON); Universite Claude Bernard Lyon 1; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Universite Paris-Est-Creteil-Val-de-Marne (UPEC); University of Cologne
  摘要：During development, motor axons are guided toward muscle target by various extrinsic cues including extracellular matrix (ECM) proteins whose identities and cellular source remain poorly characterized. Here, using single - cell RNAseq of sorted GFP+ cells from smyhc1:gfp- injected zebrafish embryos, we unravel the slow muscle progenitors (SMP) pseudotemporal trajectory at the single - cell level and show that differentiating SMPs are a major source of ECM proteins. The SMP core- matrisome was ...