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Cell
This journal offers authors two options (open access or subscription) to publish research

May 19, 2016

Volume 165Issue 5p1029-1294
Open Archive
On the cover: RNA structures and interactions are fundamental to the various functions of RNA molecules but very difficult to determine in living cells. In this issue, Lu et al. (1267–1279) describe a new method called PARIS (psoralen analysis of RNA interactions and structures) that directly determines RNA helices in vivo with near base-pair resolution and single-molecule accuracy. The cover image depicts the city skyline of PARIS at night, highlighting the Eiffel tower made of RNA structures. The light beams represent the UV light used to crosslink RNA helices and reverse them. Artwork by Yuva Oz....
On the cover: RNA structures and interactions are fundamental to the various functions of RNA molecules but very difficult to determine in living cells. In this issue, Lu et al. (1267–1279) describe a new method called PARIS (psoralen analysis of RNA interactions and structures) that directly determines RNA helices in vivo with near base-pair resolution and single-molecule accuracy. The cover image depicts the city skyline of PARIS at night, highlighting the Eiffel tower made of RNA structures. The light beams represent the UV light used to crosslink RNA helices and reverse them. Artwork by Yuva Oz.

Leading Edge

Editorial

  • Publishing Science in the Time of Zika

    • Mirna Kvajo,
    • João Monteiro
    On February 1, 2016, the World Health Organization declared that the spread of the Zika virus (ZIKV) was an international emergency of public health concern. The virus, identified in the late ‘40s, was introduced into Brazil from the Pacific Islands and spread quickly through the Americas in the short span of 1 year. Beyond the damaging effect of the infection in healthy adults, ZIKV infection has become the first major infectious disease to be associated with birth defects in over 50 years, creating a concern that the burden of the current outbreak may extend to the next generation.

Correspondence

  • Lack of Evidence that CYTH2/ARNO Functions as a Direct Intracellular EGFR Activator

    • Sergio Anastasi,
    • Su-Jie Zhu,
    • Costanza Ballarò,
    • Sonia Manca,
    • Dante Lamberti,
    • Li-Jun Wang,
    • Stefano Alemà,
    • Cai-Hong Yun,
    • Oreste Segatto
    The EGFR instructs complex cellular programs by generating robust signals of defined strength and duration. To preserve signal identity and guard cells against the oncogenic risk generated by unabated signaling, it is imperative that EGFR be tightly regulated. In this framework, the ligand-dependent transition of EGFR from an inactive state to a catalytically competent one is regarded as a key control step. In absence of ligand, the EGFR adopts a default auto-inhibited conformation that is relieved by EGF binding and attendant stabilization of EGFR dimers.

Book Review

  • Universal Rules of Regulation

    • Pavel Tomancak
    The latest book by the accomplished evolutionist and molecular biologist Sean B. Carroll was born during two trips to African natural reserves—Serengeti in Tanzania and the recovering Gorongosa National Park in Mozambique. Carroll is well known for his influential popular books on evolution and the science of evo-devo; however, writing in the background of Earth’s most impressive ecosystems has turned his attention to ecology. The Serengeti Rules shows that the rules governing the behavior of ecosystems are no different from the molecular rules that regulate processes in our cells.

Bench to Bedside

  • PCSK9 Inhibitors

    • Pradeep Natarajan,
    • Sekar Kathiresan
    Alirocumab and evolocumab are monoclonal antibodies that block proprotein convertase subtilisin/kexin type 9 (PCSK9), a circulating protein that degrades low-density lipoprotein (LDL) receptors. These therapies increase LDL receptors on the cell surface and reduce plasma LDL cholesterol. Both therapies are approved to lower LDL cholesterol, a causative agent for atherosclerotic cardiovascular disease.

Conversations

  • On a Quest for Principles, Big Data in Hand

    Cell editor Karen Carniol discusses the excitement and challenges of the “big data” era and how quantitative approaches reveal important biological principles with Galit Lahav, Gürol Süel, and Olga Troyanskaya. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.

Voices

  • iPSCs: 10 Years and Counting

    Embryos, fetuses, and neonates form perfectly functional tissues and organs every day. Despite fevered efforts over the past 30 years, there has been very modest progress toward achieving the bewitching goal of organ replacement with embryonic or iPSCs. What is the basis of this humbling status quo? Surely one reason is our enduring ignorance of mechanisms governing development in any organ or cell. For organs like pancreatic islets, developmental studies have revealed dozens of crucial conditions or factors required to create a functional islet.

Commentary

  • Lessons from a Recovering Academic

    • Michael D. Ehlers
    The conversion of basic biology into new therapeutics requires scientific activities in both academia and industry. Successful drug discovery projects span disciplines, sectors, and institutions and tightly couple laboratory and clinical experiments. Here, Ehlers describes conceptions and misconceptions about how science is conducted in industry versus academia.

Previews

  • Tension-Time Integrals and Genetic Cardiomyopathy: The Force Is with You

    • Gerald W. Dorn II
    Hundreds of different mutations in genes encoding a few dozen sarcomeric proteins cause two reciprocal human disease phenotypes, hypertrophic or dilated cardiomyopathy. How molecular dysfunction evokes different patterns of cardiac remodeling is unclear. Davis et al. describe a biophysical metric of cardiomyocyte function, the force-time integral, which predicts disease phenotype.
  • Swollen Nuclei Signal from the Grave

    • Wakam Chang,
    • Gregg G. Gundersen
    Eicosanoid signaling plays key pro-inflammatory roles during tissue damage. Now, Enyedi et al. show that swelling of nuclei in cell corpses activates eicosanoid signaling to recruit leukocytes to sites of tissue damage. The enhanced membrane tension in swollen nuclei directly promotes calcium-dependent translocation and activation of enzymes involved in eicosanoid biosynthesis.
  • Mitochondria: Masters of Epigenetics

    • Marc Tatar,
    • John M. Sedivy
    Accumulating evidence argues that aging exerts a profound influence on epigenetics, and vice versa. A pair of studies by Merkwirth et al. and Tian et al now provide insights on how mitochondrial stress experienced by C. elegans larvae propagates a specific and persistent epigenetic response that protects adult cells and extends lifespan.

Perspectives

Articles

Resources

  • Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure

    • Xuyu Qian,
    • Ha Nam Nguyen,
    • Mingxi M. Song,
    • Christopher Hadiono,
    • Sarah C. Ogden,
    • Christy Hammack,
    • Bing Yao,
    • Gregory R. Hamersky,
    • Fadi Jacob,
    • Chun Zhong,
    • Ki-jun Yoon,
    • William Jeang,
    • Li Lin,
    • Yujing Li,
    • Jai Thakor,
    • Daniel A. Berg,
    • Ce Zhang,
    • Eunchai Kang,
    • Michael Chickering,
    • David Nauen,
    • Cheng-Ying Ho,
    • Zhexing Wen,
    • Kimberly M. Christian,
    • Pei-Yong Shi,
    • Brady J. Maher,
    • Hao Wu,
    • Peng Jin,
    • Hengli Tang,
    • Hongjun Song,
    • Guo-li Ming
    Zika virus preferentially infects neural progenitors in early stage cortical organoids generated using cost-effective miniaturized spinning bioreactors, resulting in suppressed proliferation, increased cell death, and macroscopic features resembling microcephaly.
  • Featured Article
  • Rapid, Low-Cost Detection of Zika Virus Using Programmable Biomolecular Components

    • Keith Pardee,
    • Alexander A. Green,
    • Melissa K. Takahashi,
    • Dana Braff,
    • Guillaume Lambert,
    • Jeong Wook Lee,
    • Tom Ferrante,
    • Duo Ma,
    • Nina Donghia,
    • Melina Fan,
    • Nichole M. Daringer,
    • Irene Bosch,
    • Dawn M. Dudley,
    • David H. O’Connor,
    • Lee Gehrke,
    • James J. Collins
    A diagnostic platform utilizing biomolecular sensors and CRISPR-based technology allows rapid, specific, and low-cost detection of the Zika virus at clinically relevant concentrations.
  • RNA Duplex Map in Living Cells Reveals Higher-Order Transcriptome Structure

    • Zhipeng Lu,
    • Qiangfeng Cliff Zhang,
    • Byron Lee,
    • Ryan A. Flynn,
    • Martin A. Smith,
    • James T. Robinson,
    • Chen Davidovich,
    • Anne R. Gooding,
    • Karen J. Goodrich,
    • John S. Mattick,
    • Jill P. Mesirov,
    • Thomas R. Cech,
    • Howard Y. Chang
    A method for global mapping of RNA duplexes in living cells with near base-pair resolution, called PARIS, reveals extensive long-range structures, higher-order architectures, alternative structures, and RNA-RNA interactions across the transcriptome and uncovers a unique architecture of Xist and its specific interaction with a key silencing factor.
  • Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape

    • Ronan C. O’Malley,
    • Shao-shan Carol Huang,
    • Liang Song,
    • Mathew G. Lewsey,
    • Anna Bartlett,
    • Joseph R. Nery,
    • Mary Galli,
    • Andrea Gallavotti,
    • Joseph R. Ecker
    A new method for pinpointing transcription factor binding sites in the Arabidopsis genome and their responsiveness to DNA methylation demonstrates the impact of tissue-specific DNA chemical modifications on gene regulation, potentially for any organism.

Retraction

SnapShot

  • SnapShot: Microglia in Disease

    • Simon Beggs,
    • Michael W. Salter
    The development and maintenance of the central nervous system is dependent upon regulated, homeostatic actions of microglia, which sculpt and refine neuronal circuitry. By contrast, dysregulation of microglia contributes to the pathology of neurodevelopmental disorders such as autism spectrum disorders; neurodegenerative disorders such as Alzheimer’s disease; and schizophrenia and chronic neuropathic pain.
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