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Proceedings of the National Academy of Sciences
Journal Prestige (SJR): 6.092
Citation Impact (citeScore): 9
Number of Followers: 991  
  Full-text available via subscription Subscription journal
ISSN (Print) 0027-8424 - ISSN (Online) 1091-6490
Published by PNAS Homepage  [1 journal]
  • Accurate timetrees require accurate calibrations [Biological Sciences]
    • Authors: S. Blair Hedges; Qiqing Tao, Mark Walker, Sudhir Kumar
      Abstract: Morris et al. (1) estimate divergence times for land plants (embryophytes), concluding that they originated in the early Phanerozoic (515 to 473 Ma; midpoint, 494 Ma). In contrast, other molecular clock studies have placed that event 40% earlier, in the Precambrian (707 to 670 Ma) (2–4). Knowing the correct time...
      Keywords: Letters
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1812558115
      Issue No: Vol. 115, No. 41 (2018)
  • Reply to Hedges et al.: Accurate timetrees do indeed require accurate
           calibrations [Biological Sciences]
    • Authors: Jennifer L. Morris; Mark N. Puttick, James W. Clark, Dianne Edwards, Paul Kenrick, Silvia Pressel, Charles H. Wellman, Ziheng Yang, Harald Schneider, Philip C. J. Donoghue
      Abstract: We (1) attempted to establish an evolutionary timescale for land plant evolution utilizing available genome-scale data and a new set of calibrations constraining the age of clades based on critical analysis of paleontologic, phylogenetic (2), and geologic evidence. We explored many factors, such as the inclusion or exclusion of a...
      Keywords: Letters
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1812816115
      Issue No: Vol. 115, No. 41 (2018)
  • Phevamine A, a small molecule that suppresses plant immune responses
    • Authors: Erinn M. O’Neill; Tatiana S. Mucyn, Jon B. Patteson, Omri M. Finkel, Eui–Hwan Chung, Joshua A. Baccile, Elisabetta Massolo, Frank C. Schroeder, Jeffery L. Dangl, Bo Li
      Abstract: Bacterial plant pathogens cause significant crop damage worldwide. They invade plant cells by producing a variety of virulence factors, including small-molecule toxins and phytohormone mimics. Virulence of the model pathogen Pseudomonas syringae pv. tomato DC3000 (Pto) is regulated in part by the sigma factor HrpL. Our study of the HrpL...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1803779115
      Issue No: Vol. 115, No. 41 (2018)
  • Energy-dependent quenching adjusts the excitation diffusion length to
           regulate photosynthetic light harvesting [Chemistry]
    • Authors: Doran I. G. Bennett; Graham R. Fleming, Kapil Amarnath
      Abstract: An important determinant of crop yields is the regulation of photosystem II (PSII) light harvesting by energy-dependent quenching (qE). However, the molecular details of excitation quenching have not been quantitatively connected to the fraction of excitations converted to chemical energy by PSII reaction centers (PSII yield), which determines flux to...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1806597115
      Issue No: Vol. 115, No. 41 (2018)
  • Use of scenario ensembles for deriving seismic risk [Earth, Atmospheric,
           and Planetary Sciences]
    • Authors: Tom R. Robinson; Nicholas J. Rosser, Alexander L. Densmore, Katie J. Oven, Surya N. Shrestha, Ramesh Guragain
      Abstract: High death tolls from recent earthquakes show that seismic risk remains high globally. While there has been much focus on seismic hazard, large uncertainties associated with exposure and vulnerability have led to more limited analyses of the potential impacts of future earthquakes. We argue that as both exposure and vulnerability...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1807433115
      Issue No: Vol. 115, No. 41 (2018)
  • Conductively coupled flexible silicon electronic systems for chronic
           neural electrophysiology [Engineering]
    • Authors: Jinghua Li; Enming Song, Chia-Han Chiang, Ki Jun Yu, Jahyun Koo, Haina Du, Yishan Zhong, Mackenna Hill, Charles Wang, Jize Zhang, Yisong Chen, Limei Tian, Yiding Zhong, Guanhua Fang, Jonathan Viventi, John A. Rogers
      Abstract: Materials and structures that enable long-term, intimate coupling of flexible electronic devices to biological systems are critically important to the development of advanced biomedical implants for biological research and for clinical medicine. By comparison with simple interfaces based on arrays of passive electrodes, the active electronics in such systems provide...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1813187115
      Issue No: Vol. 115, No. 41 (2018)
  • ZFAND5/ZNF216 is an activator of the 26S proteasome that stimulates
           overall protein degradation [Biochemistry]
    • Authors: Donghoon Lee; Shinichi Takayama, Alfred L. Goldberg
      Abstract: ZFAND5/ZNF216, a member of the zinc finger AN1-type domain family, is abundant in heart and brain, but is induced in skeletal muscle during atrophy (although not in proteotoxic stress). Because mice lacking ZFAND5 exhibit decreased atrophy, a role in stimulating protein breakdown seemed likely. Addition of recombinant ZFAND5 to purified...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809934115
      Issue No: Vol. 115, No. 41 (2018)
  • ATP hydrolysis-coupled peptide translocation mechanism of Mycobacterium
           tuberculosis ClpB [Biochemistry]
    • Authors: Hongjun Yu; Tania J. Lupoli, Amanda Kovach, Xing Meng, Gongpu Zhao, Carl F. Nathan, Huilin Li
      Abstract: The protein disaggregase ClpB hexamer is conserved across evolution and has two AAA+-type nucleotide-binding domains, NBD1 and NBD2, in each protomer. In M. tuberculosis (Mtb), ClpB facilitates asymmetric distribution of protein aggregates during cell division to help the pathogen survive and persist within the host, but a mechanistic understanding has...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1810648115
      Issue No: Vol. 115, No. 41 (2018)
  • Role for ERK1/2-dependent activation of FCHSD2 in cancer cell-selective
           regulation of clathrin-mediated endocytosis [Cell Biology]
    • Authors: Guan-Yu Xiao; Aparna Mohanakrishnan, Sandra L. Schmid
      Abstract: Clathrin-mediated endocytosis (CME) regulates the uptake of cell-surface receptors as well as their downstream signaling activities. We recently reported that signaling can reciprocally regulate CME in cancer cells and that this crosstalk can contribute to cancer progression. To further explore the nature and extent of the crosstalk between signaling and...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1810209115
      Issue No: Vol. 115, No. 41 (2018)
  • ER{beta}-mediated induction of cystatins results in suppression of
           TGF{beta} signaling and inhibition of triple-negative breast cancer
           metastasis [Cell Biology]
    • Authors: Jordan M. Reese; Elizabeth S. Bruinsma, Adam W. Nelson, Igor Chernukhin, Jason S. Carroll, Ying Li, Malayannan Subramaniam, Vera J. Suman, Vivian Negron, David G. Monroe, James N. Ingle, Matthew P. Goetz, John R. Hawse
      Abstract: Triple-negative breast cancer (TNBC) accounts for a disproportionately high number of deaths due to a lack of targeted therapies and an increased likelihood of distant recurrence. Estrogen receptor beta (ERβ), a well-characterized tumor suppressor, is expressed in 30% of TNBCs, and its expression is associated with improved patient outcomes. We...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1807751115
      Issue No: Vol. 115, No. 41 (2018)
  • Mechanism of drug extrusion by brain endothelial cells via lysosomal drug
           trapping and disposal by neutrophils [Cell Biology]
    • Authors: Andreas Noack; Birthe Gericke, Maren von Kockritz–Blickwede, Arne Menze, Sandra Noack, Ingo Gerhauser, Felix Osten, Hassan Y. Naim, Wolfgang Loscher
      Abstract: The blood–brain barrier protects the brain against a variety of potentially toxic compounds. Barrier function results from tight junctions between brain capillary endothelial cells and high expression of active efflux transporters, including P-glycoprotein (Pgp), at the apical membrane of these cells. In addition to actively transporting drugs out of the...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1719642115
      Issue No: Vol. 115, No. 41 (2018)
  • BRCA1-IRIS promotes human tumor progression through PTEN blockade and
           HIF-1{alpha} activation [Cell Biology]
    • Authors: Andrew G. Li, Elizabeth C. Murphy, Aedin C. Culhane, Emily Powell, Hua Wang, Roderick T. Bronson, Thanh Von, Anita Giobbie-Hurder, Rebecca S. Gelman, Kimberly J. Briggs, Helen Piwnica-Worms, Jean J. Zhao, Andrew L. Kung, William G. Kaelin Jr; David M. Livingston
      Abstract: BRCA1 is an established breast and ovarian tumor suppressor gene that encodes multiple protein products whose individual contributions to human cancer suppression are poorly understood. BRCA1-IRIS (also known as “IRIS”), an alternatively spliced BRCA1 product and a chromatin-bound replication and transcription regulator, is overexpressed in various primary human cancers, including...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1807112115
      Issue No: Vol. 115, No. 41 (2018)
  • Versatility of multivalent orientation, inverted meiosis, and rescued
           fitness in holocentric chromosomal hybrids [Evolution]
    • Authors: Vladimir A. Lukhtanov; Vlad Dincă, Magne Friberg, Jindra Šichova, Martin Olofsson, Roger Vila, František Marec, Christer Wiklund
      Abstract: Chromosomal rearrangements (e.g., fusions/fissions) have the potential to drive speciation. However, their accumulation in a population is generally viewed as unlikely, because chromosomal heterozygosity should lead to meiotic problems and aneuploid gametes. Canonical meiosis involves segregation of homologous chromosomes in meiosis I and sister chromatid segregation during meiosis II. In...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1802610115
      Issue No: Vol. 115, No. 41 (2018)
  • Mutations of mitochondrial DNA are not major contributors to aging of
           fruit flies [Genetics]
    • Authors: Timo E. S. Kauppila; Ana Bratic, Martin Borch Jensen, Francesca Baggio, Linda Partridge, Heinrich Jasper, Sebastian Gronke, Nils–Goran Larsson
      Abstract: Mammals develop age-associated clonal expansion of somatic mtDNA mutations resulting in severe respiratory chain deficiency in a subset of cells in a variety of tissues. Both mathematical modeling based on descriptive data from humans and experimental data from mtDNA mutator mice suggest that the somatic mutations are formed early in...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1721683115
      Issue No: Vol. 115, No. 41 (2018)
  • Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell
           differentiation and {beta}1-integrin function [Immunology and
    • Authors: Virginia Andreani; Senthilkumar Ramamoorthy, Abhinav Pandey, Ekaterina Lupar, Stephen L. Nutt, Tim Lammermann, Rudolf Grosschedl
      Abstract: Plasma cell differentiation involves coordinated changes in gene expression and functional properties of B cells. Here, we study the role of Mzb1, a Grp94 cochaperone that is expressed in marginal zone (MZ) B cells and during the terminal differentiation of B cells to antibody-secreting cells. By analyzing Mzb1−/−Prdm1+/gfp mice, we...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809739115
      Issue No: Vol. 115, No. 41 (2018)
  • Hypoxia-inducible factor 1-dependent expression of adenosine receptor 2B
           promotes breast cancer stem cell enrichment [Medical Sciences]
    • Authors: Jie Lan; Haiquan Lu, Debangshu Samanta, Shaima Salman, You Lu, Gregg L. Semenza
      Abstract: Breast cancer stem cells (BCSCs), which are characterized by a capacity for unlimited self-renewal and for generation of the bulk cancer cell population, play a critical role in cancer relapse and metastasis. Hypoxia is a common feature of the cancer microenvironment that stimulates the specification and maintenance of BCSCs. In...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809695115
      Issue No: Vol. 115, No. 41 (2018)
  • Commercial AHAS-inhibiting herbicides are promising drug leads for the
           treatment of human fungal pathogenic infections [Microbiology]
    • Authors: Mario D. Garcia; Sheena M. H. Chua, Yu-Shang Low, Yu-Ting Lee, Kylie Agnew-Francis, Jian-Guo Wang, Amanda Nouwens, Thierry Lonhienne, Craig M. Williams, James A. Fraser, Luke W. Guddat
      Abstract: The increased prevalence of drug-resistant human pathogenic fungal diseases poses a major threat to global human health. Thus, new drugs are urgently required to combat these infections. Here, we demonstrate that acetohydroxyacid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthesis pathway, is a promising new target for...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809422115
      Issue No: Vol. 115, No. 41 (2018)
  • IL-15 regulates susceptibility of CD4+ T cells to HIV infection
    • Authors: Lara Manganaro; Patrick Hong, Matthew M. Hernandez, Dionne Argyle, Lubbertus C. F. Mulder, Uma Potla, Felipe Diaz-Griffero, Benhur Lee, Ana Fernandez-Sesma, Viviana Simon
      Abstract: HIV integrates into the host genome to create a persistent viral reservoir. Stimulation of CD4+ memory T lymphocytes with common γc-chain cytokines renders these cells more susceptible to HIV infection, making them a key component of the reservoir itself. IL-15 is up-regulated during primary HIV infection, a time when the...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1806695115
      Issue No: Vol. 115, No. 41 (2018)
  • Let-7i inhibition enhances progesterone-induced functional recovery in a
           mouse model of ischemia [Neuroscience]
    • Authors: Trinh Nguyen; Chang Su, Meharvan Singh
      Abstract: Progesterone (P4) is a potent neuroprotectant and a promising therapeutic for stroke treatment. However, the underlying mechanism(s) remain unclear. Our laboratory recently reported that brain-derived neurotrophic factor (BDNF) is a critical mediator of P4’s protective actions and that P4-induced BDNF release from cortical astrocytes is mediated by a membrane-associated progesterone...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1803384115
      Issue No: Vol. 115, No. 41 (2018)
  • FUS interacts with ATP synthase beta subunit and induces mitochondrial
           unfolded protein response in cellular and animal models [Neuroscience]
    • Authors: Jianwen Deng; Peng Wang, Xiaoping Chen, Haipeng Cheng, Jianghong Liu, Kazuo Fushimi, Li Zhu, Jane Y. Wu
      Abstract: FUS (fused in sarcoma) proteinopathy is a group of neurodegenerative diseases characterized by the formation of inclusion bodies containing the FUS protein, including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Previous studies show that mitochondrial damage is an important aspect of FUS proteinopathy. However, the molecular mechanisms by which FUS...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1806655115
      Issue No: Vol. 115, No. 41 (2018)
  • Blood-derived plasminogen drives brain inflammation and plaque deposition
           in a mouse model of Alzheimer’s disease [Neuroscience]
    • Authors: Sarah K. Baker; Zu-Lin Chen, Erin H. Norris, Alexey S. Revenko, A. Robert MacLeod, Sidney Strickland
      Abstract: Two of the most predominant features of the Alzheimer’s disease (AD) brain are deposition of β-amyloid (Aβ) plaques and inflammation. The mechanism behind these pathologies remains unknown, but there is evidence to suggest that inflammation may predate the deposition of Aβ. Furthermore, immune activation is increasingly being recognized as a...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1811172115
      Issue No: Vol. 115, No. 41 (2018)
  • Single-molecule analysis of endogenous {beta}-actin mRNA trafficking
           reveals a mechanism for compartmentalized mRNA localization in axons
    • Authors: Benita Turner-Bridger; Maximillian Jakobs, Leila Muresan, Hovy Ho-Wai Wong, Kristian Franze, William A. Harris, Christine E. Holt
      Abstract: During embryonic nervous system assembly, mRNA localization is precisely regulated in growing axons, affording subcellular autonomy by allowing controlled protein expression in space and time. Different sets of mRNAs exhibit different localization patterns across the axon. However, little is known about how mRNAs move in axons or how these patterns...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1806189115
      Issue No: Vol. 115, No. 41 (2018)
  • Activation of autophagy rescues synaptic and cognitive deficits in fragile
           X mice [Neuroscience]
    • Authors: Jingqi Yan; Morgan W. Porch, Brenda Court-Vazquez, Michael V. L. Bennett, R. Suzanne Zukin
      Abstract: Fragile X syndrome (FXS) is the most frequent form of heritable intellectual disability and autism. Fragile X (Fmr1-KO) mice exhibit aberrant dendritic spine structure, synaptic plasticity, and cognition. Autophagy is a catabolic process of programmed degradation and recycling of proteins and cellular components via the lysosomal pathway. However, a role...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1808247115
      Issue No: Vol. 115, No. 41 (2018)
  • ASTN2 modulates synaptic strength by trafficking and degradation of
           surface proteins [Neuroscience]
    • Authors: Hourinaz Behesti; Taylor R. Fore, Peter Wu, Zachi Horn, Mary Leppert, Court Hull, Mary E. Hatten
      Abstract: Surface protein dynamics dictate synaptic connectivity and function in neuronal circuits. ASTN2, a gene disrupted by copy number variations (CNVs) in neurodevelopmental disorders, including autism spectrum, was previously shown to regulate the surface expression of ASTN1 in glial-guided neuronal migration. Here, we demonstrate that ASTN2 binds to and regulates the...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809382115
      Issue No: Vol. 115, No. 41 (2018)
  • Genetically defined cellular correlates of the baseline brain MRI signal
    • Authors: Jie Wen; Manu S. Goyal, Serguei V. Astafiev, Marcus E. Raichle, Dmitriy A. Yablonskiy
      Abstract: fMRI revolutionized neuroscience by allowing in vivo real-time detection of human brain activity. While the nature of the fMRI signal is understood as resulting from variations in the MRI signal due to brain-activity-induced changes in the blood oxygenation level (BOLD effect), these variations constitute a very minor part of a...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1808121115
      Issue No: Vol. 115, No. 41 (2018)
  • Cold exposure causes cell death by depolarization-mediated Ca2+ overload
           in a chill-susceptible insect [Physiology]
    • Authors: Jeppe Seamus Bayley; Christian Bak Winther, Mads Kuhlmann Andersen, Camilla Gronkȷar, Ole Bakgaard Nielsen, Thomas Holm Pedersen, Johannes Overgaard
      Abstract: Cold tolerance of insects is arguably among the most important traits defining their geographical distribution. Even so, very little is known regarding the causes of cold injury in this species-rich group. In many insects it has been observed that cold injury coincides with a cellular depolarization caused by hypothermia and...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1813532115
      Issue No: Vol. 115, No. 41 (2018)
  • Nanoscale remodeling of ryanodine receptor cluster size underlies cerebral
           microvascular dysfunction in Duchenne muscular dystrophy [Physiology]
    • Authors: Harry A. T. Pritchard; Paulo W. Pires, Evan Yamasaki, Pratish Thakore, Scott Earley
      Abstract: Duchenne muscular dystrophy (DMD) results from mutations in the gene encoding dystrophin which lead to impaired function of skeletal and cardiac muscle, but little is known about the effects of the disease on vascular smooth muscle cells (SMCs). Here we used the mdx mouse model to study the effects of...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1804593115
      Issue No: Vol. 115, No. 41 (2018)
  • Correction for Mittal et al., Codon usage influences fitness through RNA
           toxicity [Corrections]
    • Abstract: SYSTEMS BIOLOGY Correction for “Codon usage influences fitness through RNA toxicity,” by Pragya Mittal, James Brindle, Julie Stephen, Joshua B. Plotkin, and Grzegorz Kudla, which was first published August 6, 2018; 10.1073/pnas.1810022115 (Proc Natl Acad Sci USA 115:8639–8644). The authors note that the following statement should be added as a...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1815812115
      Issue No: Vol. 115, No. 41 (2018)
  • Correction to Supporting Information for Reid-Bayliss and Loeb, Accurate
           RNA consensus sequencing for high-fidelity detection of transcriptional
           mutagenesis-induced epimutations [SI Correction]
    • Abstract: GENETICS Correction to Supporting Information for “Accurate RNA consensus sequencing for high-fidelity detection of transcriptional mutagenesis-induced epimutations,” by Kate S. Reid-Bayliss and Lawrence A. Loeb, which was first published August 10, 2017; 10.1073/pnas.1709166114 (Proc Natl Acad Sci USA 114:9415–9420). The authors note that, in the Supporting Information, page 1, right...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1815350115
      Issue No: Vol. 115, No. 41 (2018)
  • In This Issue [This Week in PNAS]
    • Pages: 10185 - 10187
      Abstract: Genetic correlates of fox domestication Silver fox. Image courtesy of iStock/ChristiLaLiberte. The genetic changes that underpin animal domestication are difficult to identify. Xu Wang et al. (pp. 10398–10403) attempted to pinpoint genetic variations tied to tameness in a group of silver foxes (Vulpes vulpes) domesticated under controlled conditions for more...
      Keywords: In This Issue
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/iti4118115
      Issue No: Vol. 115, No. 41 (2018)
  • Inner Workings: The mysterious parentage of the coveted black truffle
    • Authors: Amber Dance
      Pages: 10188 - 10190
      Abstract: In the winter of 2016, ecologist Laure Schneider-Maunoury went truffle hunting in France. But she wasn’t looking to add the fungus to a culinary delicacy. Schneider-Maunoury, a graduate student at the National Museum of Natural History in Paris, was on the hunt for the truffle’s missing father, the form that...
      Keywords: Inner Workings, Front Matter
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1814128115
      Issue No: Vol. 115, No. 41 (2018)
  • Profile of Jonathan D. G. Jones [Profiles]
    • Authors: Jennifer Viegas
      Pages: 10191 - 10194
      Abstract: Plant molecular geneticist Jonathan D. G. Jones has made seminal contributions to understanding mechanisms underlying resistance to plant disease. A group leader at The Sainsbury Laboratory in Norwich, United Kingdom, Jones was among the first to isolate and characterize disease resistance genes. His discovery of receptor-like proteins (RLPs) preceded discovery...
      Keywords: PNAS Profiles
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1815072115
      Issue No: Vol. 115, No. 41 (2018)
  • Ryanodine receptor cluster size sets the tone in cerebral smooth muscle
    • Authors: Christian Soeller
      Pages: 10195 - 10197
      Abstract: Ryanodine receptors (RyRs) are large intracellular Ca2+ channels that provide the molecular basis of the process termed Ca2+-induced Ca2+ release (1). Ca2+ signaling through RyRs has been shown to be critical for skeletal, cardiac, and smooth muscle physiology (2) as well as for neurons (3) and secretory cells like pancreatic...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1814207115
      Issue No: Vol. 115, No. 41 (2018)
  • Direct visualization of ion-channel gating in a native environment
           [Biophysics and Computational Biology]
    • Authors: Yvonne Gicheru; Sudha Chakrapani
      Pages: 10198 - 10200
      Abstract: Pentameric ligand-gated ion channels (pLGICs), also known as Cys-loop receptors, are localized primarily in the postsynaptic membranes, and mediate fast chemical transmission in the central and peripheral nervous systems. Binding of neurotransmitter activates these receptors, causing changes in postsynaptic membrane potential and consequently modulation of neuronal or muscle activity. pLGIC...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1814277115
      Issue No: Vol. 115, No. 41 (2018)
  • Collusion between neutralizing antibodies and other immune factions in the
           destruction of adenoviral vectors [Microbiology]
    • Authors: P. J. Klasse
      Pages: 10201 - 10203
      Abstract: Adenoviral vectors hold great promise for gene therapy, the induction of antitumor immunity, and vaccination against viral infections (1, 2). But sometimes, preexisting antibodies elicited by natural infection with particular types of adenovirus prevent the desired expression of the transgene carried by the vector, such as a replication-defective adenovirus 5....
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1814275115
      Issue No: Vol. 115, No. 41 (2018)
  • Identity and novelty in the avian syrinx [Evolution]
    • Authors: Evan P. Kingsley; Chad M. Eliason, Tobias Riede, Zhiheng Li, Tom W. Hiscock, Michael Farnsworth, Scott L. Thomson, Franz Goller, Clifford J. Tabin, Julia A. Clarke
      Pages: 10209 - 10217
      Abstract: In its most basic conception, a novelty is simply something new. However, when many previously proposed evolutionary novelties have been illuminated by genetic, developmental, and fossil data, they have refined and narrowed our concept of biological “newness.” For example, they show that these novelties can occur at one or multiple...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1804586115
      Issue No: Vol. 115, No. 41 (2018)
  • Distinct modes of derepression of an Arabidopsis immune receptor complex
           by two different bacterial effectors [Plant Biology]
    • Authors: Yan Ma; Hailong Guo, Lanxi Hu, Paula Pons Martinez, Panagiotis N. Moschou, Volkan Cevik, Pingtao Ding, Zane Duxbury, Panagiotis F. Sarris, Jonathan D. G. Jones
      Pages: 10218 - 10227
      Abstract: Plant intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors often function in pairs to detect pathogen effectors and activate defense. The Arabidopsis RRS1-R–RPS4 NLR pair recognizes the bacterial effectors AvrRps4 and PopP2 via an integrated WRKY transcription factor domain in RRS1-R that mimics the effector’s authentic targets. How the complex activates...
      Keywords: Inaugural Articles
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1811858115
      Issue No: Vol. 115, No. 41 (2018)
  • Symmetric coalescence of two hydraulic fractures [Applied Mathematics]
    • Authors: Niall J. O’Keeffe; Zhong Zheng, Herbert E. Huppert, P. F. Linden
      Pages: 10228 - 10232
      Abstract: The formation of a fracture network is a key process for many geophysical and industrial practices from energy resource recovery to induced seismic management. We focus on the initial stage of a fracture network formation using experiments on the symmetric coalescence of two equal coplanar, fluid-driven, penny-shaped fractures in a...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809233115
      Issue No: Vol. 115, No. 41 (2018)
  • Stable Frank-Kasper phases of self-assembled, soft matter spheres [Applied
           Physical Sciences]
    • Authors: Abhiram Reddy; Michael B. Buckley, Akash Arora, Frank S. Bates, Kevin D. Dorfman, Gregory M. Grason
      Pages: 10233 - 10238
      Abstract: Single molecular species can self-assemble into Frank–Kasper (FK) phases, finite approximants of dodecagonal quasicrystals, defying intuitive notions that thermodynamic ground states are maximally symmetric. FK phases are speculated to emerge as the minimal-distortional packings of space-filling spherical domains, but a precise measure of this distortion and how it affects assembly...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809655115
      Issue No: Vol. 115, No. 41 (2018)
  • Crimping-induced structural gradients explain the lasting strength of poly
           l-lactide bioresorbable vascular scaffolds during hydrolysis [Applied
           Physical Sciences]
    • Authors: Karthik Ramachandran; Tiziana Di Luccio, Artemis Ailianou, Mary Beth Kossuth, James P. Oberhauser, Julia A. Kornfield
      Pages: 10239 - 10244
      Abstract: Biodegradable polymers open the way to treatment of heart disease using transient implants (bioresorbable vascular scaffolds, BVSs) that overcome the most serious complication associated with permanent metal stents—late stent thrombosis. Here, we address the long-standing paradox that the clinically approved BVS maintains its radial strength even after 9 mo of...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1807347115
      Issue No: Vol. 115, No. 41 (2018)
  • SAR by kinetics for drug discovery in protein misfolding diseases
           [Biophysics and Computational Biology]
    • Authors: Sean Chia; Johnny Habchi, Thomas C. T. Michaels, Samuel I. A. Cohen, Sara Linse, Christopher M. Dobson, Tuomas P. J. Knowles, Michele Vendruscolo
      Pages: 10245 - 10250
      Abstract: To develop effective therapeutic strategies for protein misfolding diseases, a promising route is to identify compounds that inhibit the formation of protein oligomers. To achieve this goal, we report a structure−activity relationship (SAR) approach based on chemical kinetics to estimate quantitatively how small molecules modify the reactive flux toward oligomers....
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1807884115
      Issue No: Vol. 115, No. 41 (2018)
  • Predicting polymorphism in molecular crystals using orientational entropy
    • Authors: Pablo M. Piaggi; Michele Parrinello
      Pages: 10251 - 10256
      Abstract: We introduce a computational method to discover polymorphs in molecular crystals at finite temperature. The method is based on reproducing the crystallization process starting from the liquid and letting the system discover the relevant polymorphs. This idea, however, conflicts with the fact that crystallization has a timescale much longer than...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1811056115
      Issue No: Vol. 115, No. 41 (2018)
  • Revised M06 density functional for main-group and transition-metal
           chemistry [Chemistry]
    • Authors: Ying Wang; Pragya Verma, Xinsheng Jin, Donald G. Truhlar, Xiao He
      Pages: 10257 - 10262
      Abstract: We present a hybrid metageneralized-gradient-approximation functional, revM06, which is based on adding Hartree–Fock exchange to the revM06-L functional form. Compared with the original M06 suite of density functionals, the resulting revM06 functional has significantly improved across-the-board accuracy for both main-group and transition-metal chemistry. The revM06 functional improves on the M06-2X...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1810421115
      Issue No: Vol. 115, No. 41 (2018)
  • Two-dimensional dry ices with rich polymorphic and polyamorphic phase
           behavior [Chemistry]
    • Authors: Jaeil Bai; Joseph S. Francisco, Xiao Cheng Zeng
      Pages: 10263 - 10268
      Abstract: Both carbon dioxide (CO2) and water (H2O) are triatomic molecules that are ubiquitous in nature, and both are among the five most abundant gases in the Earth’s atmosphere. At low temperature and ambient pressure, both CO2 and H2O form molecular crystals––dry ice I and ice Ih. Because water possesses distinctive...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809198115
      Issue No: Vol. 115, No. 41 (2018)
  • Multiscale wavelet decomposition of time-resolved X-ray diffraction
           signals in cyclohexadiene [Chemistry]
    • Authors: Vladimir Al. Osipov; Markus Kowalewski, Shaul Mukamel
      Pages: 10269 - 10274
      Abstract: We demonstrate how the wavelet transform, which is a powerful tool for compression, filtering, and scaling analysis of signals, may be used to separate large- and short-scale electron density features in X-ray diffraction patterns. Wavelets can isolate the electron density associated with delocalized bonds from the much stronger background of...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1811983115
      Issue No: Vol. 115, No. 41 (2018)
  • Interferometric plasmonic imaging and detection of single exosomes
    • Authors: Yuting Yang; Guangxia Shen, Hui Wang, Hongxia Li, Ting Zhang, Nongjian Tao, Xianting Ding, Hui Yu
      Pages: 10275 - 10280
      Abstract: Exosomes play an important role in numerous cellular processes. Fundamental study and practical use of exosomes are significantly constrained by the lack of analytical tools capable of physical and biochemical characterization. In this paper, we present an optical approach capable of imaging single exosomes in a label-free manner, using interferometric...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1804548115
      Issue No: Vol. 115, No. 41 (2018)
  • Sediment starvation destroys New York City marshes’ resistance to
           sea level rise [Ecology]
    • Authors: Dorothy M. Peteet; Jonathan Nichols, Timothy Kenna, Clara Chang, James Browne, Mohammad Reza, Stephen Kovari, Louisa Liberman, Stephanie Stern-Protz
      Pages: 10281 - 10286
      Abstract: New York City (NYC) is representative of many vulnerable coastal urban populations, infrastructures, and economies threatened by global sea level rise. The steady loss of marshes in NYC’s Jamaica Bay is typical of many urban estuaries worldwide. Essential to the restoration and preservation of these key wetlands is an understanding...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1715392115
      Issue No: Vol. 115, No. 41 (2018)
  • Origin and significance of Si and O isotope heterogeneities in
           Phanerozoic, Archean, and Hadean zircon [Earth, Atmospheric, and Planetary
    • Authors: Dustin Trail; Patrick Boehnke, Paul S. Savage, Ming-Chang Liu, Martha L. Miller, Ilya Bindeman
      Pages: 10287 - 10292
      Abstract: Hydrosphere interactions and alteration of the terrestrial crust likely played a critical role in shaping Earth’s surface, and in promoting prebiotic reactions leading to life, before 4.03 Ga (the Hadean Eon). The identity of aqueously altered material strongly depends on lithospheric cycling of abundant and water-soluble elements such as Si...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1808335115
      Issue No: Vol. 115, No. 41 (2018)
  • Earth’s outgoing longwave radiation linear due to H2O greenhouse effect
           [Earth, Atmospheric, and Planetary Sciences]
    • Authors: Daniel D. B. Koll; Timothy W. Cronin
      Pages: 10293 - 10298
      Abstract: Satellite measurements and radiative calculations show that Earth’s outgoing longwave radiation (OLR) is an essentially linear function of surface temperature over a wide range of temperatures (≳60 K). Linearity implies that radiative forcing has the same impact in warmer as in colder climates and is thus of fundamental importance for...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809868115
      Issue No: Vol. 115, No. 41 (2018)
  • Generalized least squares can overcome the critical threshold in
           respondent-driven sampling [Social Sciences]
    • Authors: Sebastien Roch; Karl Rohe
      Pages: 10299 - 10304
      Abstract: To sample marginalized and/or hard-to-reach populations, respondent-driven sampling (RDS) and similar techniques reach their participants via peer referral. Under a Markov model for RDS, previous research has shown that if the typical participant refers too many contacts, then the variance of common estimators does not decay like O(n−1), where n...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1706699115
      Issue No: Vol. 115, No. 41 (2018)
  • Glyphosate perturbs the gut microbiota of honey bees [Applied Biological
    • Authors: Erick V. S. Motta; Kasie Raymann, Nancy A. Moran
      Pages: 10305 - 10310
      Abstract: Glyphosate, the primary herbicide used globally for weed control, targets the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme in the shikimate pathway found in plants and some microorganisms. Thus, glyphosate may affect bacterial symbionts of animals living near agricultural sites, including pollinators such as bees. The honey bee gut microbiota is dominated by...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1803880115
      Issue No: Vol. 115, No. 41 (2018)
  • Parallel reaction pathways and noncovalent intermediates in thymidylate
           synthase revealed by experimental and computational tools [Biophysics and
           Computational Biology]
    • Authors: Svetlana A. Kholodar; Ananda K. Ghosh, Katarzyna Świderek, Vicent Moliner, Amnon Kohen
      Pages: 10311 - 10314
      Abstract: Thymidylate synthase was one of the most studied enzymes due to its critical role in molecular pathogenesis of cancer. Nevertheless, many atomistic details of its chemical mechanism remain unknown or debated, thereby imposing limits on design of novel mechanism-based anticancer therapeutics. Here, we report unprecedented isolation and characterization of a...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1811059115
      Issue No: Vol. 115, No. 41 (2018)
  • Single-stranded telomere-binding protein employs a dual rheostat for
           binding affinity and specificity that drives function [Biochemistry]
    • Authors: Leslie W. Glustrom; Kenneth R. Lyon, Margherita Paschini, Cynthia M. Reyes, Nicholas V. Parsonnet, Tasha B. Toro, Victoria Lundblad, Deborah S. Wuttke
      Pages: 10315 - 10320
      Abstract: ssDNA, which is involved in numerous aspects of chromosome biology, is managed by a suite of proteins with tailored activities. The majority of these proteins bind ssDNA indiscriminately, exhibiting little apparent sequence preference. However, there are several notable exceptions, including the Saccharomyces cerevisiae Cdc13 protein, which is vital for yeast...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1722147115
      Issue No: Vol. 115, No. 41 (2018)
  • On the control of the proton current in the voltage-gated proton channel
           Hv1 [Biophysics and Computational Biology]
    • Authors: Myungjin Lee; Chen Bai, Mikolaj Feliks, Raphael Alhadeff, Arieh Warshel
      Pages: 10321 - 10326
      Abstract: The nature of the action of voltage-activated proton transport proteins is a conundrum of great current interest. Here we approach this issue by exploring the action of Hv1, a voltage-gated proton channel found in different cells in humans and other organisms. Our study focuses on evaluating the free energy of...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809766115
      Issue No: Vol. 115, No. 41 (2018)
  • Exploring the free-energy landscape of GPCR activation [Biophysics and
           Computational Biology]
    • Authors: Raphael Alhadeff; Igor Vorobyov, Han Wool Yoon, Arieh Warshel
      Pages: 10327 - 10332
      Abstract: G-protein–coupled receptors (GPCRs) are a large group of membrane-bound receptor proteins that are involved in a plethora of diverse processes (e.g., vision, hormone response). In mammals, and particularly in humans, GPCRs are involved in many signal transduction pathways and, as such, are heavily studied for their immense pharmaceutical potential. Indeed,...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1810316115
      Issue No: Vol. 115, No. 41 (2018)
  • Structural titration of receptor ion channel GLIC gating by HS-AFM
           [Biophysics and Computational Biology]
    • Authors: Yi Ruan; Kevin Kao, Solene Lefebvre, Arin Marchesi, Pierre–Jean Corringer, Richard K. Hite, Simon Scheuring
      Pages: 10333 - 10338
      Abstract: Gloeobacter violaceus ligand-gated ion channel (GLIC), a proton-gated, cation-selective channel, is a prokaryotic homolog of the pentameric Cys-loop receptor ligand-gated ion channel family. Despite large changes in ion conductance, small conformational changes were detected in X-ray structures of detergent-solubilized GLIC at pH 4 (active/desensitized state) and pH 7 (closed state)....
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1805621115
      Issue No: Vol. 115, No. 41 (2018)
  • The interaction of talin with the cell membrane is essential for integrin
           activation and focal adhesion formation [Biophysics and Computational
    • Authors: Krishna Chinthalapudi; Erumbi S. Rangarajan, Tina Izard
      Pages: 10339 - 10344
      Abstract: Multicellular organisms have well-defined, tightly regulated mechanisms for cell adhesion. Heterodimeric αβ integrin receptors play central roles in this function and regulate processes for normal cell functions, including signaling, cell migration, and development, binding to the extracellular matrix, and senescence. They are involved in hemostasis and the immune response, participate...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1806275115
      Issue No: Vol. 115, No. 41 (2018)
  • Structural evidence for the roles of divalent cations in actin
           polymerization and activation of ATP hydrolysis [Biophysics and
           Computational Biology]
    • Authors: Clement P. M. Scipion; Umesh Ghoshdastider, Fernando J. Ferrer, Tsz-Ying Yuen, Jantana Wongsantichon, Robert C. Robinson
      Pages: 10345 - 10350
      Abstract: The structure of the actin filament is known at a resolution that has allowed the architecture of protein components to be unambiguously assigned. However, fully understanding the chemistry of the system requires higher resolution to identify the ions and water molecules involved in polymerization and ATP hydrolysis. Here, we find...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1806394115
      Issue No: Vol. 115, No. 41 (2018)
  • VEGF-B is a potent antioxidant [Cell Biology]
    • Authors: Pachiappan Arjunan; Xianchai Lin, Zhongshu Tang, Yuxiang Du, Anil Kumar, Lixian Liu, Xiangke Yin, Lijuan Huang, Wei Chen, Qishan Chen, Zhimin Ye, Shasha Wang, Haiqing Kuang, Linbin Zhou, Kai Xu, Xue Chen, Haitao Zeng, Weisi Lu, Yihai Cao, Yizhi Liu, Chen Zhao, Xuri Li
      Pages: 10351 - 10356
      Abstract: VEGF-B was discovered a long time ago. However, unlike VEGF-A, whose function has been extensively studied, the function of VEGF-B and the mechanisms involved still remain poorly understood. Notwithstanding, drugs that inhibit VEGF-B and other VEGF family members have been used to treat patients with neovascular diseases. It is therefore...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1801379115
      Issue No: Vol. 115, No. 41 (2018)
  • PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic
           leukemia in mice [Cell Biology]
    • Authors: Laura Jamrog; Guillaume Chemin, Vincent Fregona, Lucie Coster, Marlene Pasquet, Chloe Oudinet, Nelly Rouquie, Nais Prade, Stephanie Lagarde, Charlotte Cresson, Sylvie Hebrard, Ngoc Sa Nguyen Huu, Marina Bousquet, Cathy Quelen, Pierre Brousset, Stephane J. C. Mancini, Eric Delabesse, Ahmed Amine Khamlichi, Bastien Gerby, Cyril Broccardo
      Pages: 10357 - 10362
      Abstract: PAX5 is a well-known haploinsufficient tumor suppressor gene in human B-cell precursor acute lymphoblastic leukemia (B-ALL) and is involved in various chromosomal translocations that fuse a part of PAX5 with other partners. However, the role of PAX5 fusion proteins in B-ALL initiation and transformation is ill-known. We previously reported a...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1721678115
      Issue No: Vol. 115, No. 41 (2018)
  • The Atg2-Atg18 complex tethers pre-autophagosomal membranes to the
           endoplasmic reticulum for autophagosome formation [Cell Biology]
    • Authors: Tetsuya Kotani; Hiromi Kirisako, Michiko Koizumi, Yoshinori Ohsumi, Hitoshi Nakatogawa
      Pages: 10363 - 10368
      Abstract: The biogenesis of double-membrane vesicles called autophagosomes, which sequester and transport intracellular material for degradation in lysosomes or vacuoles, is a central event in autophagy. This process requires a unique set of factors called autophagy-related (Atg) proteins. The Atg proteins assemble to organize the preautophagosomal structure (PAS), at which a...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1806727115
      Issue No: Vol. 115, No. 41 (2018)
  • Nebulin stiffens the thin filament and augments cross-bridge interaction
           in skeletal muscle [Cell Biology]
    • Authors: Balazs Kiss; Eun–Jeong Lee, Weikang Ma, Frank W. Li, Paola Tonino, Srbolȷub M. Miȷailovich, Thomas C. Irving, Henk L. Granzier
      Pages: 10369 - 10374
      Abstract: Nebulin is a giant sarcomeric protein that spans along the actin filament in skeletal muscle, from the Z-disk to near the thin filament pointed end. Mutations in nebulin cause muscle weakness in nemaline myopathy patients, suggesting that nebulin plays important roles in force generation, yet little is known about nebulin’s...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1804726115
      Issue No: Vol. 115, No. 41 (2018)
  • Mechanics of mouse blastocyst hatching revealed by a hydrogel-based
           microdeformation assay [Mathematics]
    • Authors: Karolis Leonavicius; Christophe Royer, Chris Preece, Benjamin Davies, John S. Biggins, Shankar Srinivas
      Pages: 10375 - 10380
      Abstract: Mammalian embryos are surrounded by an acellular shell, the zona pellucida. Hatching out of the zona is crucial for implantation and continued development of the embryo. Clinically, problems in hatching can contribute to failure in assisted reproductive intervention. Although hatching is fundamentally a mechanical process, due to limitations in methodology...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1719930115
      Issue No: Vol. 115, No. 41 (2018)
  • Corepressor SMRT is required to maintain Hox transcriptional memory during
           somitogenesis [Developmental Biology]
    • Authors: Suk–Hyun Hong; Sungsoon Fang, Benson C. Lu, Russell Nofsinger, Yasuhiko Kawakami, Glenda L. Castro, Yunqiang Yin, Chengqi Lin, Ruth T. Yu, Michael Downes, Juan Carlos Izpisua Belmonte, Ali Shilatifard, Ronald M. Evans
      Pages: 10381 - 10386
      Abstract: Nuclear hormone receptors (NRs), such as retinoic acid receptors (RARs), play critical roles in vertebrate development and homeostasis by regulating target gene transcription. Their activity is controlled by ligand-dependent release of corepressors and subsequent recruitment of coactivators, but how these individual receptor modes contribute to development are unknown. Here, we...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809480115
      Issue No: Vol. 115, No. 41 (2018)
  • Role of transcription complexes in the formation of the basal methylation
           pattern in early development [Developmental Biology]
    • Authors: Razi Greenfield; Amalia Tabib, Ilana Keshet, Joshua Moss, Ofra Sabag, Alon Goren, Howard Cedar
      Pages: 10387 - 10391
      Abstract: Following erasure in the blastocyst, the entire genome undergoes de novo methylation at the time of implantation, with CpG islands being protected from this process. This bimodal pattern is then preserved throughout development and the lifetime of the organism. Using mouse embryonic stem cells as a model system, we demonstrate...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1804755115
      Issue No: Vol. 115, No. 41 (2018)
  • Contrasting dynamics and trait controls in first-order root compared with
           leaf litter decomposition [Ecology]
    • Authors: Tao Sun; Sarah E. Hobbie, Bȷorn Berg, Hongguang Zhang, Qingkui Wang, Zhengwen Wang, Stephan Hattenschwiler
      Pages: 10392 - 10397
      Abstract: Decomposition is a key component of the global carbon (C) cycle, yet current ecosystem C models do not adequately represent the contributions of plant roots and their mycorrhizae to this process. The understanding of decomposition dynamics and their control by traits is particularly limited for the most distal first-order roots....
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1716595115
      Issue No: Vol. 115, No. 41 (2018)
  • Genomic responses to selection for tame/aggressive behaviors in the silver
           fox (Vulpes vulpes) [Evolution]
    • Authors: Xu Wang; Lenore Pipes, Lyudmila N. Trut, Yury Herbeck, Anastasiya V. Vladimirova, Rimma G. Gulevich, Anastasiya V. Kharlamova, Jennifer L. Johnson, Gregory M. Acland, Anna V. Kukekova, Andrew G. Clark
      Pages: 10398 - 10403
      Abstract: Animal domestication efforts have led to a shared spectrum of striking behavioral and morphological changes. To recapitulate this process, silver foxes have been selectively bred for tame and aggressive behaviors for more than 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. To understand the genetic basis...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1800889115
      Issue No: Vol. 115, No. 41 (2018)
  • MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic
           phenotype [Immunology and Inflammation]
    • Authors: Emilie Plantamura; Amiran Dzutsev, Mathias Chamaillard, Sophia Dȷebali, Lyvia Moudombi, Lilia Boucinha, Morgan Grau, Claire Macari, David Bauche, Oana Dumitrescu, Jean–Philippe Rasigade, Saskia Lippens, Michelina Plateroti, Elsa Kress, Annabelle Cesaro, Clovis Bondu, Ulrike Rothermel, Mathias Heikenwalder, Gerard Lina, Azzak Bentaher–Belaaouaȷ, Julien C. Marie, Christophe Caux, Giorgio Trinchieri, Jacqueline Marvel, Marie–Cecile Michallet
      Pages: 10404 - 10409
      Abstract: Prominent changes in the gut microbiota (referred to as “dysbiosis”) play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1722372115
      Issue No: Vol. 115, No. 41 (2018)
  • Siglec-7 engagement by GBS {beta}-protein suppresses pyroptotic cell death
           of natural killer cells [Immunology and Inflammation]
    • Authors: Jerry J. Fong; Chih-Ming Tsai, Sudeshna Saha, Victor Nizet, Ajit Varki, Jack D. Bui
      Pages: 10410 - 10415
      Abstract: Natural killer (NK) cells are innate immune lymphocytes that recognize and destroy abnormal host cells, such as tumor cells or those infected by viral pathogens. To safely accomplish these functions, NK cells display activating receptors that detect stress molecules or viral ligands displayed at the cell surface, balanced by inhibitory...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1804108115
      Issue No: Vol. 115, No. 41 (2018)
  • Optimal protection against Salmonella infection requires noncirculating
           memory [Immunology and Inflammation]
    • Authors: Joseph M. Benoun; Newton G. Peres, Nancy Wang, Oanh H. Pham, Victoria L. Rudisill, Zachary N. Fogassy, Paul G. Whitney, Daniel Fernandez-Ruiz, Thomas Gebhardt, Quynh-Mai Pham, Lynn Puddington, Sammy Bedoui, Richard A. Strugnell, Stephen J. McSorley
      Pages: 10416 - 10421
      Abstract: While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against Salmonella infection. Using an epitope-tagged vaccine strain of Salmonella, we found that effective protection correlated with expanded Salmonella-specific memory CD4 T cells in circulation and nonlymphoid tissues. However, naive...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1808339115
      Issue No: Vol. 115, No. 41 (2018)
  • Genomic blueprint of a relapsing fever pathogen in 15th century
           Scandinavia [Microbiology]
    • Authors: Meriam Guellil; Oliver Kersten, Amine Namouchi, Egil L. Bauer, Michael Derrick, Anne O. Jensen, Nils C. Stenseth, Barbara Bramanti
      Pages: 10422 - 10427
      Abstract: Louse-borne relapsing fever (LBRF) is known to have killed millions of people over the course of European history and remains a major cause of mortality in parts of the world. Its pathogen, Borrelia recurrentis, shares a common vector with global killers such as typhus and plague and is known for...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1807266115
      Issue No: Vol. 115, No. 41 (2018)
  • Comparative immunogenicity and efficacy of equivalent outer membrane
           vesicle and glycoconjugate vaccines against nontyphoidal Salmonella
    • Authors: Francesca Micoli; Simona Rondini, Renzo Alfini, Luisa Lanzilao, Francesca Necchi, Aurel Negrea, Omar Rossi, Cornelia Brandt, Simon Clare, Pietro Mastroeni, Rino Rappuoli, Allan Saul, Calman A. MacLennan
      Pages: 10428 - 10433
      Abstract: Nontyphoidal Salmonellae cause a devastating burden of invasive disease in sub-Saharan Africa with high levels of antimicrobial resistance. Vaccination has potential for a major global health impact, but no licensed vaccine is available. The lack of commercial incentive makes simple, affordable technologies the preferred route for vaccine development. Here we...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1807655115
      Issue No: Vol. 115, No. 41 (2018)
  • Human Endogenous Retrovirus-K HML-2 integration within RASGRF2 is
           associated with intravenous drug abuse and modulates transcription in a
           cell-line model [Microbiology]
    • Authors: Timokratis Karamitros; Tara Hurst, Emanuele Marchi, Eirini Karamichali, Urania Georgopoulou, Andreas Mentis, Joey Riepsaame, Audrey Lin, Dimitrios Paraskevis, Angelos Hatzakis, John McLauchlan, Aris Katzourakis, Gkikas Magiorkinis
      Pages: 10434 - 10439
      Abstract: HERV-K HML-2 (HK2) has been proliferating in the germ line of humans at least as recently as 250,000 years ago, with some integrations that remain polymorphic in the modern human population. One of the solitary HK2 LTR polymorphic integrations lies between exons 17 and 18 of RASGRF2, a gene that...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1811940115
      Issue No: Vol. 115, No. 41 (2018)
  • TRIM21 mediates antibody inhibition of adenovirus-based gene delivery and
           vaccination [Microbiology]
    • Authors: Maria Bottermann; Stian Foss, Laurens M. van Tienen, Marina Vaysburd, James Cruickshank, Kevin O’Connell, Jessica Clark, Keith Mayes, Katie Higginson, Jack C. Hirst, Martin B. McAdam, Greg Slodkowicz, Edward Hutchinson, Patrycȷa Kozik, Jan Terȷe Andersen, Leo C. James
      Pages: 10440 - 10445
      Abstract: Adenovirus has enormous potential as a gene-therapy vector, but preexisting immunity limits its widespread application. What is responsible for this immune block is unclear because antibodies potently inhibit transgene expression without impeding gene transfer into target cells. Here we show that antibody prevention of adenoviral gene delivery in vivo is...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1806314115
      Issue No: Vol. 115, No. 41 (2018)
  • Neural basis of location-specific pupil luminance modulation
           [Psychological and Cognitive Sciences]
    • Authors: Chin-An Wang; Douglas P. Munoz
      Pages: 10446 - 10451
      Abstract: Spatial attention enables us to focus visual processing toward specific locations or stimuli before the next fixation. Recent evidence has suggested that local luminance at the spatial locus of attention or saccade preparation influences pupil size independent of global luminance levels. However, it remains to be determined which neural pathways...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809668115
      Issue No: Vol. 115, No. 41 (2018)
  • Movement kinematics drive chain selection toward intention detection
           [Psychological and Cognitive Sciences]
    • Authors: Marco Soriano; Andrea Cavallo, Alessandro D’Ausilio, Cristina Becchio, Luciano Fadiga
      Pages: 10452 - 10457
      Abstract: The ability to understand intentions based on another’s movements is crucial for human interaction. This ability has been ascribed to the so-called motor chaining mechanism: anytime a motor chain is activated (e.g., grasp-to-drink), the observer attributes to the agent the corresponding intention (i.e., to drink) from the first motor act...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809825115
      Issue No: Vol. 115, No. 41 (2018)
  • A single phosphorylation site of SIK3 regulates daily sleep amounts and
           sleep need in mice [Neuroscience]
    • Authors: Takato Honda; Tomoyuki Fujiyama, Chika Miyoshi, Aya Ikkyu, Noriko Hotta-Hirashima, Satomi Kanno, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
      Pages: 10458 - 10463
      Abstract: Sleep is an evolutionally conserved behavior from vertebrates to invertebrates. The molecular mechanisms that determine daily sleep amounts and the neuronal substrates for homeostatic sleep need remain unknown. Through a large-scale forward genetic screen of sleep behaviors in mice, we previously demonstrated that the Sleepy mutant allele of the Sik3...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1810823115
      Issue No: Vol. 115, No. 41 (2018)
  • Axonal plasticity associated with perceptual learning in adult macaque
           primary visual cortex [Neuroscience]
    • Authors: Timo van Kerkoerle; Sally A. Marik, Stephan Meyer zum Alten Borgloh, Charles D. Gilbert
      Pages: 10464 - 10469
      Abstract: Perceptual learning is associated with changes in the functional properties of neurons even in primary sensory areas. In macaque monkeys trained to perform a contour detection task, we have observed changes in contour-related facilitation of neuronal responses in primary visual cortex that track their improvement in performance on a contour...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1812932115
      Issue No: Vol. 115, No. 41 (2018)
  • Desert ants possess distinct memories for food and nest odors
    • Authors: Roman Huber; Markus Knaden
      Pages: 10470 - 10474
      Abstract: The desert ant Cataglyphis fortis inhabits the North African saltpans where it individually forages for dead arthropods. Homing ants rely mainly on path integration, i.e., the processing of directional information from a skylight compass and distance information from an odometer. Due to the far-reaching foraging runs, path integration is error-prone...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809433115
      Issue No: Vol. 115, No. 41 (2018)
  • Stimulation of AMPK prevents degeneration of photoreceptors and the
           retinal pigment epithelium [Neuroscience]
    • Authors: Lei Xu; Li Kong, Jiangang Wang, John D. Ash
      Pages: 10475 - 10480
      Abstract: Retinal degenerative diseases are generally characterized by a permanent loss of light-sensitive retinal neurons known as photoreceptors, or their support cells, the retinal pigmented epithelium (RPE). Metabolic dysfunction has been implicated as a common mechanism of degeneration. In this study, we used the drug metformin in a gain-of-function approach to...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1802724115
      Issue No: Vol. 115, No. 41 (2018)
  • Small molecule inhibits {alpha}-synuclein aggregation, disrupts amyloid
    • Authors: Jordi Puȷols; Samuel Pena–Diaz, Diana F. Lazaro, Francesca Peccati, Francisca Pinheiro, Danilo Gonzalez, Anita Cariȷa, Susanna Navarro, Maria Conde–Gimenez, Jesus Garcia, Salvador Guardiola, Ernest Giralt, Xavier Salvatella, Javier Sancho, Mariona Sodupe, Tiago Fleming Outeiro, Esther Dalfo, Salvador Ventura
      Pages: 10481 - 10486
      Abstract: Parkinson’s disease (PD) is characterized by a progressive loss of dopaminergic neurons, a process that current therapeutic approaches cannot prevent. In PD, the typical pathological hallmark is the accumulation of intracellular protein inclusions, known as Lewy bodies and Lewy neurites, which are mainly composed of α-synuclein. Here, we exploited a...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1804198115
      Issue No: Vol. 115, No. 41 (2018)
  • Rapid stimulation of human dentate gyrus function with acute mild exercise
    • Authors: Kazuya Suwabe; Kyeongho Byun, Kazuki Hyodo, Zachariah M. Reagh, Jared M. Roberts, Akira Matsushita, Kousaku Saotome, Genta Ochi, Takemune Fukuie, Kenji Suzuki, Yoshiyuki Sankai, Michael A. Yassa, Hideaki Soya
      Pages: 10487 - 10492
      Abstract: Physical exercise has beneficial effects on neurocognitive function, including hippocampus-dependent episodic memory. Exercise intensity level can be assessed according to whether it induces a stress response; the most effective exercise for improving hippocampal function remains unclear. Our prior work using a special treadmill running model in animals has shown that...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1805668115
      Issue No: Vol. 115, No. 41 (2018)
  • Striatal dopamine 2 receptor upregulation during development predisposes
           to diet-induced obesity by reducing energy output in mice [Neuroscience]
    • Authors: Marie A. Labouesse; Andrea M. Sartori, Oliver Weinmann, Eleanor H. Simpson, Christoph Kellendonk, Ulrike Weber-Stadlbauer
      Pages: 10493 - 10498
      Abstract: Dopaminergic signaling in the striatum, particularly at dopamine 2 receptors (D2R), has been a topic of active investigation in obesity research in the past decades. However, it still remains unclear whether variations in striatal D2Rs modulate the risk for obesity and if so in which direction. Human studies have yielded...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1800171115
      Issue No: Vol. 115, No. 41 (2018)
  • Bottom-up saliency and top-down learning in the primary visual cortex of
           monkeys [Neuroscience]
    • Authors: Yin Yan; Li Zhaoping, Wu Li
      Pages: 10499 - 10504
      Abstract: Early sensory cortex is better known for representing sensory inputs but less for the effect of its responses on behavior. Here we explore the behavioral correlates of neuronal responses in primary visual cortex (V1) in a task to detect a uniquely oriented bar—the orientation singleton—in a background of uniformly oriented...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1803854115
      Issue No: Vol. 115, No. 41 (2018)
  • Functionally specific optogenetic modulation in primate visual cortex
    • Authors: Mykyta M. Chernov; Robert M. Friedman, Gang Chen, Gene R. Stoner, Anna Wang Roe
      Pages: 10505 - 10510
      Abstract: In primates, visual perception is mediated by brain circuits composed of submillimeter nodes linked together in specific networks that process different types of information, such as eye specificity and contour orientation. We hypothesized that optogenetic stimulation targeted to cortical nodes could selectively activate such cortical networks. We used viral transfection...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1802018115
      Issue No: Vol. 115, No. 41 (2018)
  • l-Serine-modified polyamidoamine dendrimer as a highly potent renal
           targeting drug carrier [Pharmacology]
    • Authors: Satoru Matsuura; Hidemasa Katsumi, Hiroe Suzuki, Natsuko Hirai, Hidetaka Hayashi, Kazuhiro Koshino, Takahiro Higuchi, Yusuke Yagi, Hiroyuki Kimura, Toshiyasu Sakane, Akira Yamamoto
      Pages: 10511 - 10516
      Abstract: Effective delivery of drug carriers selectively to the kidney is challenging because of their uptake by the reticuloendothelial system in the liver and spleen, which limits effective treatment of kidney diseases and results in side effects. To address this issue, we synthesized l-serine (Ser)–modified polyamidoamine dendrimer (PAMAM) as a potent...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1808168115
      Issue No: Vol. 115, No. 41 (2018)
  • Structure of a PSI-LHCI-cyt b6f supercomplex in Chlamydomonas reinhardtii
    • Authors: Janina Steinbeck; Ian L. Ross, Rosalba Rothnagel, Philipp Gabelein, Stefan Schulze, Nichole Giles, Rubbiya Ali, Rohan Drysdale, Emma Sierecki, Yann Gambin, Henning Stahlberg, Yuichiro Takahashi, Michael Hippler, Ben Hankamer
      Pages: 10517 - 10522
      Abstract: Photosynthetic linear electron flow (LEF) produces ATP and NADPH, while cyclic electron flow (CEF) exclusively drives photophosphorylation to supply extra ATP. The fine-tuning of linear and cyclic electron transport levels allows photosynthetic organisms to balance light energy absorption with cellular energy requirements under constantly changing light conditions. As LEF and...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1809973115
      Issue No: Vol. 115, No. 41 (2018)
  • Dawn and photoperiod sensing by phytochrome A [Plant Biology]
    • Authors: Daniel D. Seaton; Gabriela Toledo-Ortiz, Ashwin Ganpudi, Akane Kubota, Takato Imaizumi, Karen J. Halliday
      Pages: 10523 - 10528
      Abstract: In plants, light receptors play a pivotal role in photoperiod sensing, enabling them to track seasonal progression. Photoperiod sensing arises from an interaction between the plant’s endogenous circadian oscillator and external light cues. Here, we characterize the role of phytochrome A (phyA) in photoperiod sensing. Our metaanalysis of functional genomic...
      PubDate: 2018-10-09T09:01:57-07:00
      DOI: 10.1073/pnas.1803398115
      Issue No: Vol. 115, No. 41 (2018)
School of Mathematical and Computer Sciences
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