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Cell
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Jun 19, 2014

Volume 157Issue 7p1489-1738
Open Archive
On the cover: Summertime for some heralds the quest for the perfect tan. Others bronze year-round in salons despite the well-known dangers of excessive UV exposure. Several studies have supported an addictive potential of skin tanning, and in this issue, Fell et al. (pp. 1527–1534) show that, in mice, UV-irradiated skin produces the endogenous opioid ß-endorphin in sufficient quantities to cause systemic elevations accompanied by behaviors consistent with opioid dependency. The cover image depicts a mannequin being controlled by rays of sunlight, representing the powerful effects of addiction. Cover artwork created by Arch MacInnes, Massachusetts General Hospital....
On the cover: Summertime for some heralds the quest for the perfect tan. Others bronze year-round in salons despite the well-known dangers of excessive UV exposure. Several studies have supported an addictive potential of skin tanning, and in this issue, Fell et al. (pp. 1527–1534) show that, in mice, UV-irradiated skin produces the endogenous opioid ß-endorphin in sufficient quantities to cause systemic elevations accompanied by behaviors consistent with opioid dependency. The cover image depicts a mannequin being controlled by rays of sunlight, representing the powerful effects of addiction. Cover artwork created by Arch MacInnes, Massachusetts General Hospital.

Leading Edge

In This Issue

Select

  • Nutritious Food for All in a Changing World

    One of the grand challenges for society is global security in food and nutrition. The “perfect storm” metaphor has been used by Sir John Beddington to describe the scenario that we might be heading for, with simultaneous shortages for food, water, and energy within the foreseeable future. This Select highlights the need for a truly multipronged approach across scientific disciplines and country borders, involving policy makers and industry to provide a framework for sustainable food production in a changing world.

Correspondence

  • No Positive Selection for G Allele in a p53 Response Element in Europeans

    • Sudhir Kumar,
    • Li Liu
    In a recent publication, a SNP, rs4590952, in a functional KITLG p53-response element (p53-RE) was claimed to have undergone adaptive evolution in Europeans (Zeron-Medina et al., 2013). This conclusion was based on the experimental finding that the G allele exhibits stronger p53-RE activity than the A allele and that the observation that the G allele is found to be in much higher frequency in Europeans than Africans. This SNP is in high linkage disequilibrium with variants that are strongly associated with cancer risk in genome-wide association studies.

Previews

  • Shedding “UV” Light on Endogenous Opioid Dependence

    • Hugo A. Tejeda,
    • Antonello Bonci
    Excessive sun tanning can result in addictive behavior. In this issue of Cell, Fell et al. utilize a combination of behavioral pharmacology and transgenic mice to demonstrate that chronic UV light exposure recruits p53 signaling in keratinocytes, subsequently increasing β-endorphin signaling at opioid receptors, and produces an endogenous opioid-dependent state.
  • Assembling Cell Ensembles

    • Nelson Spruston
    The way the hippocampus processes information and encodes memories in the form of “cell assemblies” is likely determined in part by how its circuits are wired up during development. In this issue, Xu et al. now provide new insight into how neurons arising from a single common precursor migrate to their final destination and form functionally synchronous ensembles.
  • The Angiotensin II Type 2 Receptor for Pain Control

    • A.H. Jan Danser,
    • Praveen Anand
    All well-known deleterious effects of angiotensin (Ang) II, including vasoconstriction, inflammation, water and salt retention, and vascular remodeling, are mediated via its type 1 (AT1) receptor. This explains why AT1 receptor blockers (ARBs) and inhibitors of Ang II synthesis, such as ACE inhibitors and renin inhibitors, are beneficial for cardiovascular disease. Yet, Ang II has a second receptor, the Ang II type 2 (AT2) receptor, the function of which, even after over 20 years of research, remains largely unknown.
  • Designer Proteins to Trigger Cell Death

    • Wayne J. Fairbrother,
    • Avi Ashkenazi
    Efforts to generate biologically active proteins by de novo computational design have been limited to creating functional sites within pre-existing scaffolds. Procko et al. use an innovative computational design approach coupled with in-vitro-targeted evolution to produce a potent polypeptide inhibitor of a viral Bcl-2-like protein. This novel inhibitor triggers apoptosis of virus-infected cells.

Essay

Review

Articles

  • Skin β-Endorphin Mediates Addiction to UV Light

    • Gillian L. Fell,
    • Kathleen C. Robinson,
    • Jianren Mao,
    • Clifford J. Woolf,
    • David E. Fisher
    Exposure to radiation triggers an addiction response mediated by a keratinocyte UV-response pathway and β-endorphin.
  • Natural Neural Projection Dynamics Underlying Social Behavior

    • Lisa A. Gunaydin,
    • Logan Grosenick,
    • Joel C. Finkelstein,
    • Isaac V. Kauvar,
    • Lief E. Fenno,
    • Avishek Adhikari,
    • Stephan Lammel,
    • Julie J. Mirzabekov,
    • Raag D. Airan,
    • Kelly A. Zalocusky,
    • Kay M. Tye,
    • Polina Anikeeva,
    • Robert C. Malenka,
    • Karl Deisseroth
    A new method called fiber photometry allows recording of the natural neuronal activity of neuronal projections in behaving mice. Such recordings in mice partaking in social interactions reveal that the dynamics of a neural projection between the ventral tegmental area (VTA) and nucleus accumbens (NAc) encode and predict key features of social behavior.
  • Distinct Lineage-Dependent Structural and Functional Organization of the Hippocampus

    • Hua-Tai Xu,
    • Zhi Han,
    • Peng Gao,
    • Shuijin He,
    • Zhizhong Li,
    • Wei Shi,
    • Oren Kodish,
    • Wei Shao,
    • Keith N. Brown,
    • Kun Huang,
    • Song-Hai Shi
    Clonally related excitatory neurons in the hippocampus are progressively organized into discrete horizontal clusters and preferentially receive common synaptic inputs from nearby fast-spiking interneurons and exhibit synchronous activity.
  • Mycobacterial Toxin Induces Analgesia in Buruli Ulcer by Targeting the Angiotensin Pathways

    • Estelle Marion,
    • Ok-Ryul Song,
    • Thierry Christophe,
    • Jérémie Babonneau,
    • Denis Fenistein,
    • Joël Eyer,
    • Frank Letournel,
    • Daniel Henrion,
    • Nicolas Clere,
    • Vincent Paille,
    • Nathalie C. Guérineau,
    • Jean-Paul Saint André,
    • Philipp Gersbach,
    • Karl-Heinz Altmann,
    • Timothy Paul Stinear,
    • Yannick Comoglio,
    • Guillaume Sandoz,
    • Laurence Preisser,
    • Yves Delneste,
    • Edouard Yeramian,
    • Laurent Marsollier,
    • Priscille Brodin
    The absence of pain in Buruli ulcer, despite extensive skin lesions, is ensured by the toxin mycolactone secreted by Mycobacterium ulcerans through the triggering of a specific angiotensin (AT2R) pathway.
  • The Diabetes Susceptibility Gene Clec16a Regulates Mitophagy

    • Scott A. Soleimanpour,
    • Aditi Gupta,
    • Marina Bakay,
    • Alana M. Ferrari,
    • David N. Groff,
    • João Fadista,
    • Lynn A. Spruce,
    • Jake A. Kushner,
    • Leif Groop,
    • Steven H. Seeholzer,
    • Brett A. Kaufman,
    • Hakon Hakonarson,
    • Doris A. Stoffers
    The diabetes susceptibility gene Clec16a interacts with the E3 ubiquitin ligase Nrdp1 to regulate Parkin-mediated mitophagy and maintain glucose homeostasis in β cells.
  • Polar Body Genome Transfer for Preventing the Transmission of Inherited Mitochondrial Diseases

    • Tian Wang,
    • Hongying Sha,
    • Dongmei Ji,
    • Helen L. Zhang,
    • Dawei Chen,
    • Yunxia Cao,
    • Jianhong Zhu
    Polar body genome transfer can effectively prevent the transmission of defective mitochondria DNA across generations, indicating the potential of this procedure to treat inherited mitochondrial diseases.
  • Programmed Translational Readthrough Generates Antiangiogenic VEGF-Ax

    • Sandeepa M. Eswarappa,
    • Alka A. Potdar,
    • William J. Koch,
    • Yi Fan,
    • Kommireddy Vasu,
    • Daniel Lindner,
    • Belinda Willard,
    • Linda M. Graham,
    • Paul E. DiCorleto,
    • Paul L. Fox
    VEGF-Ax, an antiangiogenic form of VEGF-A, is generated by translational readthrough programmed by a cis-acting RNA signal element and facilitated by the trans-acting protein hnRNP A2/B1.
  • Programmed –1 Frameshifting by Kinetic Partitioning during Impeded Translocation

    • Neva Caliskan,
    • Vladimir I. Katunin,
    • Riccardo Belardinelli,
    • Frank Peske,
    • Marina V. Rodnina
    Programmed ribosomal frameshifting is an mRNA recoding process that allows cells to maximize gene expression. Kinetic deconstruction of this process reveals that the binding of tRNAs to adjacent slippery sequence codons of the mRNA and the resulting pseudoknot impair movement of the 30S ribosome and slip it to the −1 position into a new translational frame.
  • Structure of the Mammalian Ribosome-Sec61 Complex to 3.4 Å Resolution

    • Rebecca M. Voorhees,
    • Israel S. Fernández,
    • Sjors H.W. Scheres,
    • Ramanujan S. Hegde
    High-resolution structures of the cotranslational translocation complex in two states containing either an idle or actively translating ribosome provide an unprecedented view of the mammalian ribosome, the translocation channel, and molecular details of how they are coupled.
  • A Computationally Designed Inhibitor of an Epstein-Barr Viral Bcl-2 Protein Induces Apoptosis in Infected Cells

    • Erik Procko,
    • Geoffrey Y. Berguig,
    • Betty W. Shen,
    • Yifan Song,
    • Shani Frayo,
    • Anthony J. Convertine,
    • Daciana Margineantu,
    • Garrett Booth,
    • Bruno E. Correia,
    • Yuanhua Cheng,
    • William R. Schief,
    • David M. Hockenbery,
    • Oliver W. Press,
    • Barry L. Stoddard,
    • Patrick S. Stayton,
    • David Baker
    A novel computationally designed protein, called BINDI, binds to Epstein-Barr virus Bcl-2 protein with picomolar affinity. BINDI initiates apoptosis in EBV-infected cancer lines, can suppress tumor growth, and extends survival in a xenograft disease model of EBV-positive human lymphoma.
  • Conservation of Ca2+/Calmodulin Regulation across Na and Ca2+ Channels

    • Manu Ben-Johny,
    • Philemon S. Yang,
    • Jacqueline Niu,
    • Wanjun Yang,
    • Rosy Joshi-Mukherjee,
    • David T. Yue
    Na and Ca2+ ion channels have distinct biological roles and biophysical properties. However, our data reveal that Ca2+ regulation of Na channels is strikingly similar to that of Ca2+ channels, with consequences for understanding the function of these channels in health and disease.
  • Structure of a RING E3 Trapped in Action Reveals Ligation Mechanism for the Ubiquitin-like Protein NEDD8

    • Daniel C. Scott,
    • Vladislav O. Sviderskiy,
    • Julie K. Monda,
    • John R. Lydeard,
    • Shein Ei Cho,
    • J. Wade Harper,
    • Brenda A. Schulman
    Scott et al. report the structure of a trapped RING E3-E2∼UBL-target intermediate to reveal the mechanism of NEDD8 ligation. NEDD8 itself and CUL1 (its target) regulate the catalytic machinery by positioning the active site, licensing the target’s acceptor lysine, and influencing E2 reactivity.
  • Glucocorticoid Receptor Function Regulated by Coordinated Action of the Hsp90 and Hsp70 Chaperone Cycles

    • Elaine Kirschke,
    • Devrishi Goswami,
    • Daniel Southworth,
    • Patrick R. Griffin,
    • David A. Agard
    Hsp90 activation of the glucocorticoid receptor (GR) is intimately tied to GR’s interaction with Hsp70, which drives GR inactivation through partial unfolding. Hsp90 then utilizes ATP hydrolysis to reverse the Hsp70 inactivation and protects GR as it folds to a highly active state.
  • RNA Clamping by Vasa Assembles a piRNA Amplifier Complex on Transposon Transcripts

    • Jordi Xiol,
    • Pietro Spinelli,
    • Maike A. Laussmann,
    • David Homolka,
    • Zhaolin Yang,
    • Elisa Cora,
    • Yohann Couté,
    • Simon Conn,
    • Jan Kadlec,
    • Ravi Sachidanandam,
    • Marko Kaksonen,
    • Stephen Cusack,
    • Anne Ephrussi,
    • Ramesh S. Pillai
    A point mutation in the RNA helicase Vasa is used to uncover a transient complex that amplifies germline small RNAs for protecting the genome against transposons.
  • A Chromatin-Based Mechanism for Limiting Divergent Noncoding Transcription

    • Sebastian Marquardt,
    • Renan Escalante-Chong,
    • Nam Pho,
    • Jue Wang,
    • L. Stirling Churchman,
    • Michael Springer,
    • Stephen Buratowski
    An unbiased genetic screen in yeast reveals that CAF-I and other chromatin assembly factors suppress transcription in the noncoding RNA direction of divergent promoters.

Resource

Correction

Erratum

SnapShot

  • SnapShot: Receptor Dynamics at Plastic Synapses

    • Matthias Kneussel,
    • Antoine Triller,
    • Daniel Choquet
    The dynamic synapse is represented by the constant mobility and exchange of components at both the cell surface and at intracellular sites. This includes thermally powered Brownian diffusion movement, followed by reversible trapping through receptor-scaffold interactions and active transport of cargo vesicles through cytoskeletal motors.
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