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  • Animals  (743)
  • Biochemistry  (146)
  • Immunology  (79)
  • American Association for the Advancement of Science (AAAS)  (968)
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  • 1
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-07-15
    Description: Author: Leslie K. Ferrarelli
    Keywords: Biochemistry
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  • 2
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-24
    Description: Author: Guy Riddihough
    Keywords: Biochemistry
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  • 3
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-24
    Description: Author: John F. Foley
    Keywords: Immunology
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  • 4
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-27
    Description: Staphylococcus aureus is a Gram-positive bacterium that is a leading cause of life-threatening infections in humans. Knowledge of how this pathogen colonizes the human host and causes disease is crucial for the development of strategies to prevent and treat S. aureus infections (see the image, next page). On page 1105 of this issue, Ghssein et al. report the discovery, isolation, and functional evaluation of staphylopine (see the figure), a compound biosynthesized by S. aureus that captures metal ions from the pathogen's surroundings and thereby enables it to grow (1). Author: Elizabeth M. Nolan
    Keywords: Biochemistry
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  • 5
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-27
    Description: Author: Nicolas S. Wigginton
    Keywords: Biochemistry
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  • 6
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-07-22
    Description: Author: John F. Foley
    Keywords: Immunology
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  • 7
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-07-01
    Description: Autoimmune diseases share a grim similarity with cancer: People's own cells become their enemies. But a study published online in Science reveals a happier parallel, suggesting that a therapy designed to harness the immune system to attack cancer cells may also cull the turncoat immune cells behind certain autoimmune diseases. The approach relies on chimeric antigen receptor T cells, or CAR T cells: immune cells genetically modified to home in on a desired target on cancer cells or—in this case—on rogue B cells, another immune cell type. The new study only gauged the CAR T cells' capabilities in the lab dish and in mouse models of pemphigus vulgaris, an autoimmune condition in which B cells secrete antibodies that attack a protein in skin and mucous membrane. But some scientists are already calling the approach, which specifically targets the errant B cells, a breakthrough. Author: Mitch Leslie
    Keywords: Immunology
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  • 8
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-24
    Description: Effective immune responses rely on balancing lymphocyte stability and plasticity. Lymphocytes have regulatory circuits that control phenotypic and functional identity. Stable circuits maintain homeostasis and prevent autoimmunity. But plasticity is needed to integrate new environmental inputs and generate immune responses that subdue the eliciting agent without damaging tissue. Regulatory T cells (Tregs) are a subset of CD4+ T cells that control effector T cell responses and prevent excessive inflammation and autoimmunity (1, 2). On page 1581 in this issue, Sujino et al. (3) report that intestinal Tregs convert into CD4+ intraepithelial T cells (CD4IELs) to adapt to the local intestinal environment, thus identifying the intestinal epithelium as a compartment that enforces lymphocyte plasticity. Authors: Marco Colonna, Luisa Cervantes-Barragan
    Keywords: Immunology
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  • 9
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-03
    Description: Innate immune cells act as a surveillance system, detecting and responding to pathogens and endogenous danger signals. The complex patterns of signals they receive are detected by a variety of pattern recognition receptors (PRRs). On page 1232 of this issue, Zanoni et al. (1) find that innate immune responses to microbial products do not occur in a vacuum; rather, there is a complex array of danger signals in surrounding damaged tissue that can determine an immune cell type–specific response to pathogens. They describe a host-derived lipid that binds to a PRR to induce a hyperactive innate immune response that enhances long-lived protective immunity against invading microbes. Authors: Brooke A. Napier, Denise M. Monack
    Keywords: Immunology
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  • 10
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-03
    Description: Author: John F. Foley
    Keywords: Immunology
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  • 11
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-03
    Description: Author: Guy Riddihough
    Keywords: Biochemistry
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  • 12
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-10
    Description: Author: Kristen L. Mueller
    Keywords: Immunology
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  • 13
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-30
    Keywords: Immunology
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  • 14
    Publication Date: 2018-11-30
    Description: Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment that controls pyroptosis in macrophages. GSDMD is processed via inflammasome-activated caspase-1 or -11. It is currently unknown whether macrophage GSDMD can be processed by other mechanisms. Here, we describe an additional pathway controlling GSDMD processing. The inhibition of TAK1 or IB kinase (IKK) by the Yersinia effector protein YopJ elicits RIPK1- and caspase-8–dependent cleavage of GSDMD, which subsequently results in cell death. GSDMD processing also contributes to the NLRP3 inflammasome–dependent release of interleukin-1β (IL-1β). Thus, caspase-8 acts as a regulator of GSDMD-driven cell death. Furthermore, this study establishes the importance of TAK1 and IKK activity in the control of GSDMD cleavage and cytotoxicity.
    Keywords: Immunology
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  • 15
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-14
    Keywords: Immunology
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  • 16
    Publication Date: 2018-12-14
    Description: Primordial sequence signatures in modern proteins imply ancestral origins tracing back to simple peptides. Although short peptides seldom adopt unique folds, metal ions might have templated their assembly into higher-order structures in early evolution and imparted useful chemical reactivity. Recapitulating such a biogenetic scenario, we have combined design and laboratory evolution to transform a zinc-binding peptide into a globular enzyme capable of accelerating ester cleavage with exacting enantiospecificity and high catalytic efficiency ( k cat / K M ~ 10 6 M –1 s –1 ). The simultaneous optimization of structure and function in a naïve peptide scaffold not only illustrates a plausible enzyme evolutionary pathway from the distant past to the present but also proffers exciting future opportunities for enzyme design and engineering.
    Keywords: Biochemistry
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  • 17
    Publication Date: 2018-12-14
    Description: Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.
    Keywords: Immunology
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  • 18
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-17
    Description: The binding of DNA to cyclic GMP–AMP synthase (cGAS) leads to the production of the secondary messenger cyclic GMP–AMP (cGAMP), which activates innate immune responses. We have shown that DNA binding to cGAS robustly induced the formation of liquidlike droplets in which cGAS was activated. The disordered and positively charged cGAS N terminus enhanced cGAS-DNA phase separation by increasing the valencies of DNA binding. Long DNA was more efficient in promoting cGAS liquid phase separation and cGAS enzyme activity than short DNA. Moreover, free zinc ions enhanced cGAS enzyme activity both in vitro and in cells by promoting cGAS-DNA phase separation. These results demonstrated that the DNA-induced phase transition of cGAS promotes cGAMP production and innate immune signaling.
    Keywords: Immunology
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  • 19
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-17
    Keywords: Immunology
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  • 20
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-17
    Keywords: Immunology
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  • 21
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-24
    Keywords: Immunology
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  • 22
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-31
    Description: Cryo–electron microscopy, or simply cryo-EM, refers mainly to three very different yet closely related techniques: electron crystallography, single-particle cryo-EM, and electron cryotomography. In the past few years, single-particle cryo-EM in particular has triggered a revolution in structural biology and has become a newly dominant discipline. This Review examines the fascinating story of its start and evolution over the past 40-plus years, delves into how and why the recent technological advances have been so groundbreaking, and briefly considers where the technique may be headed in the future.
    Keywords: Biochemistry
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  • 23
    Publication Date: 2018-08-31
    Description: Riback et al . (Reports, 13 October 2017, p. 238) used small-angle x-ray scattering (SAXS) experiments to infer a degree of compaction for unfolded proteins in water versus chemical denaturant that is highly consistent with the results from Förster resonance energy transfer (FRET) experiments. There is thus no "contradiction" between the two methods, nor evidence to support their claim that commonly used FRET fluorophores cause protein compaction.
    Keywords: Biochemistry
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  • 24
    Publication Date: 2018-08-31
    Description: Best et al . claim that we provide no convincing basis to assert that a discrepancy remains between FRET and SAXS results on the dimensions of disordered proteins under physiological conditions. We maintain that a clear discrepancy is apparent in our and other recent publications, including results shown in the Best et al . comment. A plausible origin is fluorophore interactions in FRET experiments.
    Keywords: Biochemistry
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  • 25
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-28
    Keywords: Biochemistry
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  • 26
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-05
    Keywords: Biochemistry
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  • 27
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-12
    Keywords: Biochemistry
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  • 28
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-21
    Keywords: Biochemistry
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  • 29
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-21
    Keywords: Biochemistry
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  • 30
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-04-22
    Description: Author: Kristen L. Mueller
    Keywords: Immunology
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  • 31
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-18
    Description: Author: Nicholas S. Wigginton
    Keywords: Biochemistry
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  • 32
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-18
    Description: Helminth and protozoan parasites are the most common infectious agents of humans living in developing countries and represent an important disease burden, particularly through their ability to cause physical and intellectual growth retardation in young children (1, 2). Type 2 immune responses promote efficient expulsion of intestinal parasites such as helminths by driving a “weep and sweep” response that involves mucous production, fluid secretion, and increased intestinal motility. These same responses in susceptible individuals cause the symptoms of allergy after exposure to pollens and certain food antigens. The generation of type 2 immunity in response to helminth parasites requires the secretion of cytokines by intestinal epithelial cells, but the source and induction of cytokine secretion have been unclear. Three studies (3–5), including a report by Howitt et al. (5) on page 1329 of this issue, reveal a key role for a rare intestinal cell—the tuft or brush cell—in driving type 2 immunity. Author: Nicola Harris
    Keywords: Immunology
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  • 33
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-18
    Description: The S-adenosylmethionine (SAM) radical enzyme superfamily plays a central role in the biosynthesis of many vitamins, cofactors, and antibiotics. Radical SAM enzymes catalyze challenging chemical reactions such as C-H bond activation (1), ring contraction (2), and molecular skeletal rearrangements (3, 4). They overcome the dif culty of these reactions by forming a highly oxidizing radical species, 5′-deoxyadenosyl (5′-dAdo·), from SAM and a reduced iron-sulfur cluster (5). This radical species can selectively abstract a hydrogen atom from a substrate, enabling complex chemical transformations. There are more than 113,000 radical SAM enzymes, but only a small number are both biochemically and structurally characterized, and many of the reaction mechanisms remain enigmatic. On page 1320 of this issue, Sicoli et al. provide evidence for unexpected radical intermediates in the mechanism of the radical SAM enzyme NosL (6). Authors: Jennifer Bridwell-Rabb, Catherine L. Drennan
    Keywords: Biochemistry
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  • 34
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-18
    Description: Author: L. Bryan Ray
    Keywords: Immunology
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  • 35
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-04
    Description: T helper lymphocytes play essential roles in the adaptive immune system. They come in distinct types defined by unique transcriptional programs that control their development and functions. Among these, T helper 17 (TH17) cells are important in protecting mucosal surfaces against fungal and bacterial infections. In addition, TH17 cells contribute to the pathogenesis of multiple autoimmune diseases (1). A recent study (2) adds yet another layer of complexity to the biology of these complex cells—an RNA helicase and a long noncoding RNA (lncRNA) that act together to control their effector functions. Authors: Maninjay K. Atianand, Katherine A. Fitzgerald
    Keywords: Immunology
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  • 36
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-04
    Description: Author: Kristen L. Mueller
    Keywords: Immunology
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  • 37
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-11
    Description: Author: John F. Foley
    Keywords: Immunology
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  • 38
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-06
    Description: Author: John F. Foley
    Keywords: Immunology
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  • 39
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-20
    Description: About 500 to 600 million metric tons of methane, a potent greenhouse gas, are emitted annually worldwide; ~69% of this methane is produced biologically by anaerobic archaea known as methanogens (1). In some environments, methane emissions are partly offset by anaerobic methane oxidizing archaea (ANME) and aerobic methanotrophic bacteria (1). In methanogens, the methyl-coenzyme M reductase (MCR) enzyme uses a nickel-containing cofactor (F430) to catalyze the final step of methane synthesis (see the figure, panels A and B) (2, 3). The MCR reaction is reversible, and MCR may also catalyze the first step of methane oxidation by ANME (2). The MCR catalytic cycle begins with F430 in the reduced Ni(I) form (4), but what happens next has been unclear. On page 953 of this issue, Wongnate et al. (5) report evidence for a Ni(II)-thiolate intermediate. Authors: Thomas J. Lawton, Amy C. Rosenzweig
    Keywords: Biochemistry
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  • 40
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-04-29
    Description: Most biological oxygen consumption is carried out by membrane-integrated oxidases, which fall into three main classes. The heme-copper oxidases (HCOs) of mitochondria and many bacteria (1) have a binuclear active site that contains a heme and a copper atom. They achieve rapid, virtually complete reduction of oxygen to water. The alternative oxidases (AOXs) found in certain plants, fungi, and bacteria have a heme-free iron-iron reactive site (2) that confers nitric oxide–resistant respiration (3). The last class, the bacterial cytochrome bd–type oxidases (4), are found in many pathogenic bacteria and have a distinctive heme composition consisting of two hemes b and one heme d. On page 583 of this issue, Safarian et al. report the atomic-resolution structure of a cytochrome bd–type oxidase from Geobacillus thermodenitrificans (5). The structure will facilitate targeted and rational drug development against cytochrome bd–type oxidases. Authors: Gregory M. Cook, Robert K. Poole
    Keywords: Biochemistry
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  • 41
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-04-01
    Description: Author: Kristen L. Mueller
    Keywords: Immunology
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  • 42
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-02
    Keywords: Biochemistry
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  • 43
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-14
    Keywords: Biochemistry
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  • 44
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-19
    Keywords: Immunology
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  • 45
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-19
    Keywords: Biochemistry
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  • 46
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-16
    Keywords: Immunology
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  • 47
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-16
    Keywords: Biochemistry
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  • 48
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-30
    Keywords: Biochemistry
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  • 49
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-30
    Keywords: Biochemistry
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  • 50
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-10
    Keywords: Biochemistry
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  • 51
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-10
    Description: The Hedgehog (Hh) pathway involved in development and regeneration is activated by the extracellular binding of Hh to the membrane receptor Patched (Ptch). We report the structures of human Ptch1 alone and in complex with the N-terminal domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 and 3.6 angstroms, respectively, as determined by cryo–electron microscopy. Ptch1 comprises two interacting extracellular domains, ECD1 and ECD2, and 12 transmembrane segments (TMs), with TMs 2 to 6 constituting the sterol-sensing domain (SSD). Two steroid-shaped densities are resolved in both structures, one enclosed by ECD1/2 and the other in the membrane-facing cavity of the SSD. Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dependent. The structure of a steroid binding–deficient Ptch1 mutant displays pronounced conformational rearrangements.
    Keywords: Biochemistry
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  • 52
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-31
    Description: Super-resolution microscopy has overcome a long-held resolution barrier—the diffraction limit—in light microscopy and enabled visualization of previously invisible molecular details in biological systems. Since their conception, super-resolution imaging methods have continually evolved and can now be used to image cellular structures in three dimensions, multiple colors, and living systems with nanometer-scale resolution. These methods have been applied to answer questions involving the organization, interaction, stoichiometry, and dynamics of individual molecular building blocks and their integration into functional machineries in cells and tissues. In this Review, we provide an overview of super-resolution methods, their state-of-the-art capabilities, and their constantly expanding applications to biology, with a focus on the latter. We will also describe the current technical challenges and future advances anticipated in super-resolution imaging.
    Keywords: Biochemistry
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  • 53
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-04-27
    Keywords: Immunology
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  • 54
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-05-11
    Keywords: Biochemistry
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  • 55
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-19
    Keywords: Immunology
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  • 56
    Publication Date: 2018-10-19
    Description: Host injury triggers feedback mechanisms that limit tissue damage. Conventional type 1 dendritic cells (cDC1s) express dendritic cell natural killer lectin group receptor-1 (DNGR-1), encoded by the gene Clec9a , which senses tissue damage and favors cross-presentation of dead-cell material to CD8 + T cells. Here we find that DNGR-1 additionally reduces host-damaging inflammatory responses induced by sterile and infectious tissue injury in mice. DNGR-1 deficiency leads to exacerbated caerulein-induced necrotizing pancreatitis and increased pathology during systemic Candida albicans infection without affecting fungal burden. This effect is B and T cell–independent and attributable to increased neutrophilia in DNGR-1–deficient settings. Mechanistically, DNGR-1 engagement activates SHP-1 and inhibits MIP-2 (encoded by Cxcl2 ) production by cDC1s during Candida infection. This consequently restrains neutrophil recruitment and promotes disease tolerance. Thus, DNGR-1–mediated sensing of injury by cDC1s serves as a rheostat for the control of tissue damage, innate immunity, and immunopathology.
    Keywords: Immunology
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  • 57
    Publication Date: 2018-11-02
    Description: Genomic DNA forms chromatin, in which the nucleosome is the repeating unit. The mechanism by which RNA polymerase II (RNAPII) transcribes the nucleosomal DNA remains unclear. Here we report the cryo–electron microscopy structures of RNAPII-nucleosome complexes in which RNAPII pauses at the superhelical locations SHL(–6), SHL(–5), SHL(–2), and SHL(–1) of the nucleosome. RNAPII pauses at the major histone-DNA contact sites, and the nucleosome interactions with the RNAPII subunits stabilize the pause. These structures reveal snapshots of nucleosomal transcription, in which RNAPII gradually tears DNA from the histone surface while preserving the histone octamer. The nucleosomes in the SHL(–1) complexes are bound to a "foreign" DNA segment, which might explain the histone transfer mechanism. These results provide the foundations for understanding chromatin transcription and epigenetic regulation.
    Keywords: Biochemistry
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  • 58
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-09
    Keywords: Immunology
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  • 59
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-09
    Keywords: Biochemistry
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  • 60
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-09
    Keywords: Immunology
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  • 61
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-09
    Keywords: Immunology
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  • 62
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-09
    Keywords: Biochemistry
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  • 63
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-09
    Keywords: Biochemistry
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  • 64
    Publication Date: 2018-11-09
    Description: We describe a general computational approach to designing self-assembling helical filaments from monomeric proteins and use this approach to design proteins that assemble into micrometer-scale filaments with a wide range of geometries in vivo and in vitro. Cryo–electron microscopy structures of six designs are close to the computational design models. The filament building blocks are idealized repeat proteins, and thus the diameter of the filaments can be systematically tuned by varying the number of repeat units. The assembly and disassembly of the filaments can be controlled by engineered anchor and capping units built from monomers lacking one of the interaction surfaces. The ability to generate dynamic, highly ordered structures that span micrometers from protein monomers opens up possibilities for the fabrication of new multiscale metamaterials.
    Keywords: Biochemistry
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  • 65
    Publication Date: 2018-11-16
    Description: Membrane proteins reside in lipid bilayers and are typically extracted from this environment for study, which often compromises their integrity. In this work, we ejected intact assemblies from membranes, without chemical disruption, and used mass spectrometry to define their composition. From Escherichia coli outer membranes, we identified a chaperone-porin association and lipid interactions in the β-barrel assembly machinery. We observed efflux pumps bridging inner and outer membranes, and from inner membranes we identified a pentameric pore of TonB, as well as the protein-conducting channel SecYEG in association with F 1 F O adenosine triphosphate (ATP) synthase. Intact mitochondrial membranes from Bos taurus yielded respiratory complexes and fatty acid–bound dimers of the ADP (adenosine diphosphate)/ATP translocase (ANT-1). These results highlight the importance of native membrane environments for retaining small-molecule binding, subunit interactions, and associated chaperones of the membrane proteome.
    Keywords: Biochemistry
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  • 66
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-06-29
    Description: The precatalytic spliceosome (B complex) is preceded by the pre-B complex. Here we report the cryo–electron microscopy structures of the Saccharomyces cerevisiae pre-B and B complexes at average resolutions of 3.3 to 4.6 and 3.9 angstroms, respectively. In the pre-B complex, the duplex between the 5' splice site (5'SS) and U1 small nuclear RNA (snRNA) is recognized by Yhc1, Luc7, and the Sm ring. In the B complex, U1 small nuclear ribonucleoprotein is dissociated, the 5'-exon–5'SS sequences are translocated near U6 snRNA, and three B-specific proteins may orient the precursor messenger RNA. In both complexes, U6 snRNA is anchored to loop I of U5 snRNA, and the duplex between the branch point sequence and U2 snRNA is recognized by the SF3b complex. Structural analysis reveals the mechanism of assembly and activation for the yeast spliceosome.
    Keywords: Biochemistry
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  • 67
    Publication Date: 2015-09-01
    Description: Glycerophospholipids, the structural components of cell membranes, have not been considered to be spatial cues for intercellular signaling because of their ubiquitous distribution. We identified lyso-phosphatidyl-beta-D-glucoside (LysoPtdGlc), a hydrophilic glycerophospholipid, and demonstrated its role in modality-specific repulsive guidance of spinal cord sensory axons. LysoPtdGlc is locally synthesized and released by radial glia in a patterned spatial distribution to regulate the targeting of nociceptive but not proprioceptive central axon projections. Library screening identified the G protein-coupled receptor GPR55 as a high-affinity receptor for LysoPtdGlc, and GPR55 deletion or LysoPtdGlc loss of function in vivo caused the misallocation of nociceptive axons into proprioceptive zones. These findings show that LysoPtdGlc/GPR55 is a lipid-based signaling system in glia-neuron communication for neural development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guy, Adam T -- Nagatsuka, Yasuko -- Ooashi, Noriko -- Inoue, Mariko -- Nakata, Asuka -- Greimel, Peter -- Inoue, Asuka -- Nabetani, Takuji -- Murayama, Akiho -- Ohta, Kunihiro -- Ito, Yukishige -- Aoki, Junken -- Hirabayashi, Yoshio -- Kamiguchi, Hiroyuki -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):974-7. doi: 10.1126/science.aab3516.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Lipid Biology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Sendai, Miyagi 980-8578, Japan. Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology (PRESTO), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. ; Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan. ; Synthetic Cellular Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Sendai, Miyagi 980-8578, Japan. Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), 1-7-1 Otemachi, Chiyoda, Tokyo 100-0004, Japan. ; RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. kamiguchi@brain.riken.jp hirabaya@riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315437" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Chick Embryo ; Coculture Techniques ; Ganglia, Spinal/*cytology/physiology ; Gene Knockout Techniques ; Glycerophospholipids/analysis/metabolism/*physiology ; Glycolipids/analysis/*physiology ; Mice ; Nerve Growth Factor/pharmacology ; Neuroglia/*physiology ; Nociceptors/*physiology ; Receptor, trkA/metabolism ; Receptor, trkC/metabolism ; Receptors, Cannabinoid/genetics/*physiology ; Spinal Cord/*cytology/*embryology ; Tissue Culture Techniques
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  • 68
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reczek, Colleen R -- Chandel, Navdeep S -- New York, N.Y. -- Science. 2015 Dec 11;350(6266):1317-8. doi: 10.1126/science.aad8671.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. ; Department of Medicine and Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. nav@northwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26659042" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ascorbic Acid/*therapeutic use ; Colorectal Neoplasms/*drug therapy/*genetics ; Female ; Humans ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins B-raf/*genetics ; ras Proteins/*genetics
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  • 69
    Publication Date: 2015-02-28
    Description: Double-stranded RNAs (dsRNAs) targeted against essential genes can trigger a lethal RNA interference (RNAi) response in insect pests. The application of this concept in plant protection is hampered by the presence of an endogenous plant RNAi pathway that processes dsRNAs into short interfering RNAs. We found that long dsRNAs can be stably produced in chloroplasts, a cellular compartment that appears to lack an RNAi machinery. When expressed from the chloroplast genome, dsRNAs accumulated to as much as 0.4% of the total cellular RNA. Transplastomic potato plants producing dsRNAs targeted against the beta-actin gene of the Colorado potato beetle, a notorious agricultural pest, were protected from herbivory and were lethal to its larvae. Thus, chloroplast expression of long dsRNAs can provide crop protection without chemical pesticides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jiang -- Khan, Sher Afzal -- Hasse, Claudia -- Ruf, Stephanie -- Heckel, David G -- Bock, Ralph -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):991-4. doi: 10.1126/science.1261680.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Molekulare Pflanzenphysiologie, D-14476 Potsdam-Golm, Germany. ; Max-Planck-Institut fur Chemische Okologie, D-07745 Jena, Germany. ; Max-Planck-Institut fur Molekulare Pflanzenphysiologie, D-14476 Potsdam-Golm, Germany. rbock@mpimp-golm.mpg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25722411" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*antagonists & inhibitors/genetics ; Animals ; Beetles/*genetics/pathogenicity ; Crops, Agricultural/genetics/*parasitology ; Genetic Vectors ; Pest Control, Biological/*methods ; Plant Leaves/genetics/parasitology ; Plastids/*genetics ; *RNA Interference ; RNA, Double-Stranded/*genetics ; RNA, Small Interfering/*genetics/metabolism ; Solanum tuberosum/genetics/*parasitology ; Transformation, Genetic
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hackett, Perry -- Carroll, Dana -- P01 HD032652/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1324. doi: 10.1126/science.347.6228.1324.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Cell Biology, and Development, Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. hacke004@umn.edu. ; Department of Biochemistry, School of Medicine, University of Utah, Salt Lake City, UT 84112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792322" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*legislation & jurisprudence ; Animals ; *Government Regulation ; *Organisms, Genetically Modified ; United States
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-11-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dajani, Rana -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1043. doi: 10.1126/science.350.6264.1043-b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Biotechnology, Hashemite University, Zarqa, Jordan. rdajani@hu.edu.jo.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612944" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Art ; Equipment Reuse ; Fibroblasts ; Gloves, Protective ; Jordan ; Laboratories ; Mice ; Recycling/*methods ; United States
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  • 72
    Publication Date: 2015-11-14
    Description: The RNA-guided CRISPR-associated protein Cas9 is used for genome editing, transcriptional modulation, and live-cell imaging. Cas9-guide RNA complexes recognize and cleave double-stranded DNA sequences on the basis of 20-nucleotide RNA-DNA complementarity, but the mechanism of target searching in mammalian cells is unknown. Here, we use single-particle tracking to visualize diffusion and chromatin binding of Cas9 in living cells. We show that three-dimensional diffusion dominates Cas9 searching in vivo, and off-target binding events are, on average, short-lived (〈1 second). Searching is dependent on the local chromatin environment, with less sampling and slower movement within heterochromatin. These results reveal how the bacterial Cas9 protein interrogates mammalian genomes and navigates eukaryotic chromatin structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knight, Spencer C -- Xie, Liangqi -- Deng, Wulan -- Guglielmi, Benjamin -- Witkowsky, Lea B -- Bosanac, Lana -- Zhang, Elisa T -- El Beheiry, Mohamed -- Masson, Jean-Baptiste -- Dahan, Maxime -- Liu, Zhe -- Doudna, Jennifer A -- Tjian, Robert -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Nov 13;350(6262):823-6. doi: 10.1126/science.aac6572.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley, CA, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. ; Laboratoire Physico-Chimie Curie, Institut Curie, Centre National de la Recherche Scientifique UMR 168, Paris, France. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. ; Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Laboratoire Physico-Chimie Curie, Institut Curie, Centre National de la Recherche Scientifique UMR 168, Paris, France. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. liuz11@janelia.hhmi.org doudna@berkeley.edu jmlim@berkeley.edu. ; Department of Chemistry, University of California, Berkeley, CA, USA. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. Innovative Genomics Initiative, University of California, Berkeley, CA, USA. liuz11@janelia.hhmi.org doudna@berkeley.edu jmlim@berkeley.edu. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Li Ka Shing Biomedical and Health Sciences Center, University of California, Berkeley, CA, USA. liuz11@janelia.hhmi.org doudna@berkeley.edu jmlim@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26564855" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Bacterial Proteins/chemistry/*metabolism ; *CRISPR-Cas Systems ; Chromatin/chemistry/*metabolism/ultrastructure ; Clustered Regularly Interspaced Short Palindromic Repeats ; *DNA Cleavage ; Endonucleases/chemistry/*metabolism ; *Genetic Engineering ; Genome ; Mice ; Single-Cell Analysis
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernstein, Rachel -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):686. doi: 10.1126/science.347.6222.686. Epub 2015 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rachel Bernstein is a staf writer for Science Careers. For more on life and careers, visit www.sciencecareers.org. Send your story to SciCareerEditor@aaas.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657252" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Birds ; *Career Choice ; Cooperative Behavior ; Neurobiology/*manpower
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  • 74
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dantzer, Ben -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):822-3. doi: 10.1126/science.aaa6480.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology and Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA. dantzer@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700499" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Competitive Behavior ; *Ecosystem ; Female ; Male ; *Maternal Behavior ; Songbirds/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 75
    Publication Date: 2015-02-14
    Description: A new docodontan mammaliaform from the Middle Jurassic of China has skeletal features for climbing and dental characters indicative of an omnivorous diet that included plant sap. This fossil expands the range of known locomotor adaptations in docodontans to include climbing, in addition to digging and swimming. It further shows that some docodontans had a diet with a substantial herbivorous component, distinctive from the faunivorous diets previously reported in other members of this clade. This reveals a greater ecological diversity in an early mammaliaform clade at a more fundamental taxonomic level not only between major clades as previously thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meng, Qing-Jin -- Ji, Qiang -- Zhang, Yu-Guang -- Liu, Di -- Grossnickle, David M -- Luo, Zhe-Xi -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):764-8. doi: 10.1126/science.1260879.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Beijing Museum of Natural History, Beijing 100050 China. ; Institute of Geology, Chinese Academy of Geological Sciences, Beijing 100037, China. ; Committee on Evolutionary Biology, The University of Chicago, Chicago, IL 60637, USA. ; Committee on Evolutionary Biology, The University of Chicago, Chicago, IL 60637, USA. Department of Organismal Biology and Anatomy, The University of Chicago, Chicago, IL 60637, USA. zxluo@uchicago.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678661" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Feed ; Animals ; *Biodiversity ; China ; Cuspid/anatomy & histology/immunology ; *Dentition ; Forelimb/anatomy & histology/growth & development ; *Herbivory ; Incisor/anatomy & histology/growth & development ; Mammals/anatomy & histology/*classification/*growth & development ; Mandible/anatomy & histology/growth & development ; Phylogeny
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  • 76
    Publication Date: 2015-05-23
    Description: Sex determination in the mosquito Aedes aegypti is governed by a dominant male-determining factor (M factor) located within a Y chromosome-like region called the M locus. Here, we show that an M-locus gene, Nix, functions as an M factor in A. aegypti. Nix exhibits persistent M linkage and early embryonic expression, two characteristics required of an M factor. Nix knockout with clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 resulted in largely feminized genetic males and the production of female isoforms of two key regulators of sexual differentiation: doublesex and fruitless. Ectopic expression of Nix resulted in genetic females with nearly complete male genitalia. Thus, Nix is both required and sufficient to initiate male development. This study provides a foundation for mosquito control strategies that convert female mosquitoes into harmless males.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hall, Andrew Brantley -- Basu, Sanjay -- Jiang, Xiaofang -- Qi, Yumin -- Timoshevskiy, Vladimir A -- Biedler, James K -- Sharakhova, Maria V -- Elahi, Rubayet -- Anderson, Michelle A E -- Chen, Xiao-Guang -- Sharakhov, Igor V -- Adelman, Zach N -- Tu, Zhijian -- AI113643/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1268-70. doi: 10.1126/science.aaa2850. Epub 2015 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. ; Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. Department of Entomology, Virginia Tech, Blacksburg, VA, USA. ; Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. ; Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. ; School of Public Health and Tropical Medicine, Southern Medical University, Guangdong, People's Republic of China. ; Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. Department of Entomology, Virginia Tech, Blacksburg, VA, USA. ; Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. Department of Entomology, Virginia Tech, Blacksburg, VA, USA. jaketu@vt.edu zachadel@vt.edu. ; Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. jaketu@vt.edu zachadel@vt.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999371" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/*genetics/*growth & development ; Animals ; Caspase 9 ; Clustered Regularly Interspaced Short Palindromic Repeats ; Female ; Gene Knockout Techniques ; *Genes, Insect ; *Genetic Loci ; Male ; Molecular Sequence Data ; Mosquito Control/methods ; Sex Determination Processes/*genetics
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  • 77
    Publication Date: 2015-03-07
    Description: Human higher cognition is attributed to the evolutionary expansion and elaboration of the human cerebral cortex. However, the genetic mechanisms contributing to these developmental changes are poorly understood. We used comparative epigenetic profiling of human, rhesus macaque, and mouse corticogenesis to identify promoters and enhancers that have gained activity in humans. These gains are significantly enriched in modules of coexpressed genes in the cortex that function in neuronal proliferation, migration, and cortical-map organization. Gain-enriched modules also showed correlated gene expression patterns and similar transcription factor binding site enrichments in promoters and enhancers, suggesting that they are connected by common regulatory mechanisms. Our results reveal coordinated patterns of potential regulatory changes associated with conserved developmental processes during corticogenesis, providing insight into human cortical evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426903/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426903/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reilly, Steven K -- Yin, Jun -- Ayoub, Albert E -- Emera, Deena -- Leng, Jing -- Cotney, Justin -- Sarro, Richard -- Rakic, Pasko -- Noonan, James P -- 099175/Z/12/Z/Wellcome Trust/United Kingdom -- DA023999/DA/NIDA NIH HHS/ -- F32 GM106628/GM/NIGMS NIH HHS/ -- GM094780/GM/NIGMS NIH HHS/ -- NS014841/NS/NINDS NIH HHS/ -- P30 CA016359/CA/NCI NIH HHS/ -- R01 DA023999/DA/NIDA NIH HHS/ -- R01 GM094780/GM/NIGMS NIH HHS/ -- T32 GM007223/GM/NIGMS NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1155-9. doi: 10.1126/science.1260943.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. ; Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA. ; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. ; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. james.noonan@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745175" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/*growth & development ; Enhancer Elements, Genetic/*genetics ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Humans ; Macaca mulatta ; Mice ; Organogenesis/*genetics ; Promoter Regions, Genetic/*genetics ; Rats
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  • 78
    Publication Date: 2015-08-22
    Description: Paradigms of sustainable exploitation focus on population dynamics of prey and yields to humanity but ignore the behavior of humans as predators. We compared patterns of predation by contemporary hunters and fishers with those of other predators that compete over shared prey (terrestrial mammals and marine fishes). Our global survey (2125 estimates of annual finite exploitation rate) revealed that humans kill adult prey, the reproductive capital of populations, at much higher median rates than other predators (up to 14 times higher), with particularly intense exploitation of terrestrial carnivores and fishes. Given this competitive dominance, impacts on predators, and other unique predatory behavior, we suggest that humans function as an unsustainable "super predator," which-unless additionally constrained by managers-will continue to alter ecological and evolutionary processes globally.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Darimont, Chris T -- Fox, Caroline H -- Bryan, Heather M -- Reimchen, Thomas E -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):858-60. doi: 10.1126/science.aac4249.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geography, University of Victoria, Post Office Box 1700, Station CSC, Victoria, British Columbia V8W 2Y2, Canada. Raincoast Conservation Foundation, Post Office Box 2429, Sidney, British Columbia V8L 3Y3, Canada. Hakai Institute, Post Office Box 309, Heriot Bay, British Columbia V0P 1H0, Canada. darimont@uvic.ca. ; Department of Geography, University of Victoria, Post Office Box 1700, Station CSC, Victoria, British Columbia V8W 2Y2, Canada. Raincoast Conservation Foundation, Post Office Box 2429, Sidney, British Columbia V8L 3Y3, Canada. ; Department of Geography, University of Victoria, Post Office Box 1700, Station CSC, Victoria, British Columbia V8W 2Y2, Canada. Raincoast Conservation Foundation, Post Office Box 2429, Sidney, British Columbia V8L 3Y3, Canada. Hakai Institute, Post Office Box 309, Heriot Bay, British Columbia V0P 1H0, Canada. ; Department of Biology, University of Victoria, Post Office Box 3060, Station CSC, Victoria, British Columbia V8W 2Y2, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293961" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; *Consumer Behavior ; Ecology ; Fishes ; Humans ; Mammals/psychology ; Population Dynamics ; *Predatory Behavior ; Reproduction
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  • 79
    Publication Date: 2015-01-03
    Description: Adipocytes have been suggested to be immunologically active, but their role in host defense is unclear. We observed rapid proliferation of preadipocytes and expansion of the dermal fat layer after infection of the skin by Staphylococcus aureus. Impaired adipogenesis resulted in increased infection as seen in Zfp423(nur12) mice or in mice given inhibitors of peroxisome proliferator-activated receptor gamma. This host defense function was mediated through the production of cathelicidin antimicrobial peptide from adipocytes because cathelicidin expression was decreased by inhibition of adipogenesis, and adipocytes from Camp(-/-) mice lost the capacity to inhibit bacterial growth. Together, these findings show that the production of an antimicrobial peptide by adipocytes is an important element for protection against S. aureus infection of the skin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318537/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318537/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ling-juan -- Guerrero-Juarez, Christian F -- Hata, Tissa -- Bapat, Sagar P -- Ramos, Raul -- Plikus, Maksim V -- Gallo, Richard L -- AR052728/AR/NIAMS NIH HHS/ -- DK096828/DK/NIDDK NIH HHS/ -- GM055246/GM/NIGMS NIH HHS/ -- HHSN272201000020C/PHS HHS/ -- P01 HL107150/HL/NHLBI NIH HHS/ -- R01 AI052453/AI/NIAID NIH HHS/ -- R01 AI083358/AI/NIAID NIH HHS/ -- R01 AI116576/AI/NIAID NIH HHS/ -- R01 AR064781/AR/NIAMS NIH HHS/ -- R01 AR067273/AR/NIAMS NIH HHS/ -- R01-AR067273/AR/NIAMS NIH HHS/ -- R01AI052453/AI/NIAID NIH HHS/ -- R25 GM055246/GM/NIGMS NIH HHS/ -- T32 GM007198/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):67-71. doi: 10.1126/science.1260972.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Dermatology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA. ; Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA. Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA. ; Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, San Diego, La Jolla, CA 92037, USA. ; Division of Dermatology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA. rgallo@ucsd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554785" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Adipocytes/*immunology/microbiology ; Adipogenesis/immunology ; Animals ; Antimicrobial Cationic Peptides/immunology ; Cathelicidins/genetics/*immunology ; DNA-Binding Proteins/genetics/immunology ; Dermis/*immunology/microbiology ; Host-Pathogen Interactions/immunology ; Mice ; Mice, Mutant Strains ; Staphylococcal Skin Infections/*immunology ; Staphylococcus aureus/*immunology ; Transcription Factors/genetics/immunology
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  • 80
    Publication Date: 2015-04-11
    Description: Protein phosphorylation regulates virtually all biological processes. Although protein kinases are popular drug targets, targeting protein phosphatases remains a challenge. Here, we describe Sephin1 (selective inhibitor of a holophosphatase), a small molecule that safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo. Sephin1 selectively bound and inhibited the stress-induced PPP1R15A, but not the related and constitutive PPP1R15B, to prolong the benefit of an adaptive phospho-signaling pathway, protecting cells from otherwise lethal protein misfolding stress. In vivo, Sephin1 safely prevented the motor, morphological, and molecular defects of two otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B, and amyotrophic lateral sclerosis. Thus, regulatory subunits of phosphatases are drug targets, a property exploited here to safely prevent two protein misfolding diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490275/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490275/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Das, Indrajit -- Krzyzosiak, Agnieszka -- Schneider, Kim -- Wrabetz, Lawrence -- D'Antonio, Maurizio -- Barry, Nicholas -- Sigurdardottir, Anna -- Bertolotti, Anne -- 309516/European Research Council/International -- MC_U105185860/Medical Research Council/United Kingdom -- R01-NS55256/NS/NINDS NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Apr 10;348(6231):239-42. doi: 10.1126/science.aaa4484.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. ; Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy. ; Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. aberto@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25859045" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Animals ; Cells, Cultured ; Charcot-Marie-Tooth Disease/drug therapy/metabolism/pathology ; Disease Models, Animal ; Endoplasmic Reticulum Stress/drug effects ; Enzyme Inhibitors/metabolism/pharmacokinetics/*pharmacology/toxicity ; Guanabenz/*analogs & derivatives/chemical ; synthesis/metabolism/pharmacology/toxicity ; HeLa Cells ; Humans ; Mice ; Mice, Transgenic ; Molecular Targeted Therapy ; Phosphorylation ; Protein Folding ; Protein Phosphatase 1/*antagonists & inhibitors ; Proteostasis Deficiencies/*drug therapy/*prevention & control ; Signal Transduction
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  • 81
    Publication Date: 2015-08-01
    Description: Jumping on water is a unique locomotion mode found in semi-aquatic arthropods, such as water striders. To reproduce this feat in a surface tension-dominant jumping robot, we elucidated the hydrodynamics involved and applied them to develop a bio-inspired impulsive mechanism that maximizes momentum transfer to water. We found that water striders rotate the curved tips of their legs inward at a relatively low descending velocity with a force just below that required to break the water surface (144 millinewtons/meter). We built a 68-milligram at-scale jumping robotic insect and verified that it jumps on water with maximum momentum transfer. The results suggest an understanding of the hydrodynamic phenomena used by semi-aquatic arthropods during water jumping and prescribe a method for reproducing these capabilities in artificial systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koh, Je-Sung -- Yang, Eunjin -- Jung, Gwang-Pil -- Jung, Sun-Pill -- Son, Jae Hak -- Lee, Sang-Im -- Jablonski, Piotr G -- Wood, Robert J -- Kim, Ho-Young -- Cho, Kyu-Jin -- New York, N.Y. -- Science. 2015 Jul 31;349(6247):517-21. doi: 10.1126/science.aab1637. Epub 2015 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biorobotics Laboratory, Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-744, Korea. School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA. hyk@snu.ac.kr kjcho@snu.ac.kr. ; Micro Fluid Mechanics Laboratory, Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-744, Korea. hyk@snu.ac.kr kjcho@snu.ac.kr. ; Biorobotics Laboratory, Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-744, Korea. ; Laboratory of Behavioral Ecology and Evolution, School of Biological Sciences, Seoul National University, Seoul 151-742, Korea. ; Laboratory of Behavioral Ecology and Evolution, School of Biological Sciences, Seoul National University, Seoul 151-742, Korea. Institute of Advanced Machines and Design, Seoul National University, Seoul 151-744, Korea. ; Laboratory of Behavioral Ecology and Evolution, School of Biological Sciences, Seoul National University, Seoul 151-742, Korea. Museum and Institute of Zoology, Polish Academy of Sciences, Warsaw 00-679, Poland. ; School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA. ; Micro Fluid Mechanics Laboratory, Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-744, Korea. Institute of Advanced Machines and Design, Seoul National University, Seoul 151-744, Korea. ; Biorobotics Laboratory, Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-744, Korea. Institute of Advanced Machines and Design, Seoul National University, Seoul 151-744, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26228144" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Extremities/physiology ; Heteroptera/*physiology ; Hydrodynamics ; *Locomotion ; Robotics ; Rotation ; Surface Tension ; *Water
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  • 82
    Publication Date: 2015-05-02
    Description: Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1alpha and nuclear lamina-heterochromatin anchoring protein LAP2beta. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494668/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494668/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Weiqi -- Li, Jingyi -- Suzuki, Keiichiro -- Qu, Jing -- Wang, Ping -- Zhou, Junzhi -- Liu, Xiaomeng -- Ren, Ruotong -- Xu, Xiuling -- Ocampo, Alejandro -- Yuan, Tingting -- Yang, Jiping -- Li, Ying -- Shi, Liang -- Guan, Dee -- Pan, Huize -- Duan, Shunlei -- Ding, Zhichao -- Li, Mo -- Yi, Fei -- Bai, Ruijun -- Wang, Yayu -- Chen, Chang -- Yang, Fuquan -- Li, Xiaoyu -- Wang, Zimei -- Aizawa, Emi -- Goebl, April -- Soligalla, Rupa Devi -- Reddy, Pradeep -- Esteban, Concepcion Rodriguez -- Tang, Fuchou -- Liu, Guang-Hui -- Belmonte, Juan Carlos Izpisua -- F32 AG047770/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1160-3. doi: 10.1126/science.aaa1356. Epub 2015 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ; State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ; Diagnosis and Treatment Center for Oral Disease, the 306th Hospital of the PLA, Beijing, China. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; College of Life Sciences, Peking University, Beijing 100871, China. ; The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Universidad Catolica San Antonio de Murcia, Campus de los Jeronimos s/n, 30107 Guadalupe, Murcia, Spain. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu. ; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Beijing Institute for Brain Disorders, Beijing 100069, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931448" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics/*metabolism ; Animals ; *Cell Aging ; Cell Differentiation ; Centromere/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; DNA-Binding Proteins/metabolism ; Epigenesis, Genetic ; Exodeoxyribonucleases/genetics/*metabolism ; Gene Knockout Techniques ; HEK293 Cells ; Heterochromatin/chemistry/*metabolism ; Humans ; Membrane Proteins/metabolism ; Mesenchymal Stromal Cells/*metabolism ; Methyltransferases/genetics/metabolism ; Mice ; Models, Biological ; RecQ Helicases/genetics/*metabolism ; Repressor Proteins/genetics/metabolism ; Werner Syndrome/genetics/*metabolism
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  • 83
    Publication Date: 2015-06-27
    Description: Bone morphogenetic proteins (BMPs) act in dose-dependent fashion to regulate cell fate choices in a myriad of developmental contexts. In early vertebrate and invertebrate embryos, BMPs and their antagonists establish epidermal versus central nervous system domains. In this highly conserved system, BMP antagonists mediate the neural-inductive activities proposed by Hans Spemann and Hilde Mangold nearly a century ago. BMPs distributed in gradients subsequently function as morphogens to subdivide the three germ layers into distinct territories and act to organize body axes, regulate growth, maintain stem cell niches, or signal inductively across germ layers. In this Review, we summarize the variety of mechanisms that contribute to generating reliable developmental responses to BMP gradients and other morphogen systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bier, Ethan -- De Robertis, Edward M -- NS29870/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):aaa5838. doi: 10.1126/science.aaa5838.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92095-0349, USA. ebier@ucsd.edu ederobertis@mednet.ucla.edu. ; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095-1662, USA. Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095-1662, USA. ebier@ucsd.edu ederobertis@mednet.ucla.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113727" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Body Patterning ; Bone Morphogenetic Proteins/*metabolism ; Drosophila melanogaster/embryology ; Ectoderm/embryology ; Epidermis/embryology ; Feedback, Physiological ; Neural Tube/embryology ; Xenopus/embryology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 84
    Publication Date: 2015-11-14
    Description: Climate change impacts on vertebrates have consequences for marine ecosystem structures and services. We review marine fish, mammal, turtle, and seabird responses to climate change and discuss their potential for adaptation. Direct and indirect responses are demonstrated from every ocean. Because of variation in research foci, observed responses differ among taxonomic groups (redistributions for fish, phenology for seabirds). Mechanisms of change are (i) direct physiological responses and (ii) climate-mediated predator-prey interactions. Regional-scale variation in climate-demographic functions makes range-wide population dynamics challenging to predict. The nexus of metabolism relative to ecosystem productivity and food webs appears key to predicting future effects on marine vertebrates. Integration of climate, oceanographic, ecosystem, and population models that incorporate evolutionary processes is needed to prioritize the climate-related conservation needs for these species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sydeman, William J -- Poloczanska, Elvira -- Reed, Thomas E -- Thompson, Sarah Ann -- New York, N.Y. -- Science. 2015 Nov 13;350(6262):772-7. doi: 10.1126/science.aac9874.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Farallon Institute for Advanced Ecosystem Research, Petaluma, CA 94952, USA. Bodega Marine Laboratory/University of California Davis, Bodega Bay, CA 94923, USA. wsydeman@faralloninstitute.org. ; Commonwealth Scientific and Industrial Research Organisation, Ecosciences Precinct, Brisbane QLD 4102, Australia. Global Change Institute, University of Queensland, St Lucia, Brisbane QLD 4072, Australia. ; School of Biological, Earth and Environmental Sciences, University College Cork, Cork, Ireland. ; Farallon Institute for Advanced Ecosystem Research, Petaluma, CA 94952, USA. Climate Impacts Group, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26564847" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquatic Organisms ; Birds/*classification ; *Climate Change ; *Endangered Species ; Extinction, Biological ; Fishes/*classification ; Mammals/*classification ; Phylogeny ; Population Dynamics ; Seawater ; Turtles/*classification
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  • 85
    Publication Date: 2015-03-21
    Description: Analysis of single molecules in living cells has provided quantitative insights into the kinetics of fundamental biological processes; however, the dynamics of messenger RNA (mRNA) translation have yet to be addressed. We have developed a fluorescence microscopy technique that reports on the first translation events of individual mRNA molecules. This allowed us to examine the spatiotemporal regulation of translation during normal growth and stress and during Drosophila oocyte development. We have shown that mRNAs are not translated in the nucleus but translate within minutes after export, that sequestration within P-bodies regulates translation, and that oskar mRNA is not translated until it reaches the posterior pole of the oocyte. This methodology provides a framework for studying initiation of protein synthesis on single mRNAs in living cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451088/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451088/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Halstead, James M -- Lionnet, Timothee -- Wilbertz, Johannes H -- Wippich, Frank -- Ephrussi, Anne -- Singer, Robert H -- Chao, Jeffrey A -- EB013571/EB/NIBIB NIH HHS/ -- GM57071/GM/NIGMS NIH HHS/ -- NS83085/NS/NINDS NIH HHS/ -- R01 EB013571/EB/NIBIB NIH HHS/ -- R01 GM057071/GM/NIGMS NIH HHS/ -- R01 NS083085/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1367-671. doi: 10.1126/science.aaa3380.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland. ; Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Transcription Imaging Consortium, Howard Hughes Medical Institute Janelia Farm Research Campus, Ashburn, VA 20147, USA. ; Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland. University of Basel, CH-4003 Basel, Switzerland. ; Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany. ; Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany. ephrussi@embl.de robert.singer@einstein.yu.edu jeffrey.chao@fmi.ch. ; Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Transcription Imaging Consortium, Howard Hughes Medical Institute Janelia Farm Research Campus, Ashburn, VA 20147, USA. ephrussi@embl.de robert.singer@einstein.yu.edu jeffrey.chao@fmi.ch. ; Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. ephrussi@embl.de robert.singer@einstein.yu.edu jeffrey.chao@fmi.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792328" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Transport ; *Biosensing Techniques ; Cell Nucleus/metabolism ; Cytosol/metabolism ; Drosophila Proteins/biosynthesis/genetics ; Drosophila melanogaster/cytology/growth & development/metabolism ; Microscopy, Fluorescence/methods ; Molecular Imaging/*methods ; Oocytes/growth & development/metabolism ; *Peptide Chain Initiation, Translational ; RNA, Messenger/*chemistry/*metabolism
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  • 86
    Publication Date: 2015-06-13
    Description: Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481126/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Yongyou -- Desai, Amar -- Yang, Sung Yeun -- Bae, Ki Beom -- Antczak, Monika I -- Fink, Stephen P -- Tiwari, Shruti -- Willis, Joseph E -- Williams, Noelle S -- Dawson, Dawn M -- Wald, David -- Chen, Wei-Dong -- Wang, Zhenghe -- Kasturi, Lakshmi -- Larusch, Gretchen A -- He, Lucy -- Cominelli, Fabio -- Di Martino, Luca -- Djuric, Zora -- Milne, Ginger L -- Chance, Mark -- Sanabria, Juan -- Dealwis, Chris -- Mikkola, Debra -- Naidoo, Jacinth -- Wei, Shuguang -- Tai, Hsin-Hsiung -- Gerson, Stanton L -- Ready, Joseph M -- Posner, Bruce -- Willson, James K V -- Markowitz, Sanford D -- 1P01CA95471-09/CA/NCI NIH HHS/ -- 5P30 CA142543-03/CA/NCI NIH HHS/ -- P01 CA095471/CA/NCI NIH HHS/ -- P30 CA043703/CA/NCI NIH HHS/ -- P30 CA142543/CA/NCI NIH HHS/ -- P30 DK020572/DK/NIDDK NIH HHS/ -- P30 DK097948/DK/NIDDK NIH HHS/ -- P50 CA130810/CA/NCI NIH HHS/ -- P50 CA150964/CA/NCI NIH HHS/ -- R01 CA127590/CA/NCI NIH HHS/ -- R25 CA148052/CA/NCI NIH HHS/ -- R25CA148052/CA/NCI NIH HHS/ -- U54 HL119810/HL/NHLBI NIH HHS/ -- U54HL119810/HL/NHLBI NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):aaa2340. doi: 10.1126/science.aaa2340.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Gastroenterology, Haeundae Paik Hospital, Inje University, Busan 612896, South Korea. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Surgery, Busan Paik Hospital, and Paik Institute of Clinical Research and Ocular Neovascular Research Center, Inje University, Busan, South Korea. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Family Medicine, University of Michigan, Ann Arbor MI 48109, USA. ; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA. ; Proteomics Center, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA. ; College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068857" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Transplantation ; Colitis/enzymology/prevention & control ; Dinoprostone/metabolism ; Enzyme Inhibitors/chemistry/pharmacology ; Hematopoiesis/drug effects ; Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors/genetics/*physiology ; Liver Regeneration/drug effects ; Mice ; Mice, Knockout ; Prostaglandins/*metabolism ; Pyridines/chemistry/pharmacology ; Regeneration/drug effects/genetics/*physiology ; Thiophenes/chemistry/pharmacology
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  • 87
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bilbe, Graeme -- New York, N.Y. -- Science. 2015 May 29;348(6238):974-6. doi: 10.1126/science.aaa3683. Epub 2015 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Drugs for Neglected Diseases Initiative, 15 Chemin Louis Dunant, 1202 Geneva, Switzerland. gbilbe@dndi.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26023124" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiprotozoal Agents/adverse effects/*chemistry/therapeutic use ; Chagas Disease/drug therapy/transmission ; Disease Models, Animal ; *Drug Design ; Euglenozoa Infections/*drug therapy/transmission ; Humans ; Kinetoplastida/*drug effects ; Leishmaniasis/drug therapy/transmission ; Mice ; Neglected Diseases/*drug therapy ; Trypanosoma cruzi/drug effects ; Trypanosomiasis, African/drug therapy/transmission
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  • 88
    Publication Date: 2015-06-13
    Description: During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richiardi, Jonas -- Altmann, Andre -- Milazzo, Anna-Clare -- Chang, Catie -- Chakravarty, M Mallar -- Banaschewski, Tobias -- Barker, Gareth J -- Bokde, Arun L W -- Bromberg, Uli -- Buchel, Christian -- Conrod, Patricia -- Fauth-Buhler, Mira -- Flor, Herta -- Frouin, Vincent -- Gallinat, Jurgen -- Garavan, Hugh -- Gowland, Penny -- Heinz, Andreas -- Lemaitre, Herve -- Mann, Karl F -- Martinot, Jean-Luc -- Nees, Frauke -- Paus, Tomas -- Pausova, Zdenka -- Rietschel, Marcella -- Robbins, Trevor W -- Smolka, Michael N -- Spanagel, Rainer -- Strohle, Andreas -- Schumann, Gunter -- Hawrylycz, Mike -- Poline, Jean-Baptiste -- Greicius, Michael D -- IMAGEN consortium -- 93558/Medical Research Council/United Kingdom -- R01 MH085772-01A1/MH/NIMH NIH HHS/ -- R01NS073498/NS/NINDS NIH HHS/ -- U54 EB020403/EB/NIBIB NIH HHS/ -- Department of Health/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1241-4. doi: 10.1126/science.1255905. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. Laboratory of Neurology and Imaging of Cognition, Department of Neuroscience, University of Geneva, Geneva, Switzerland. jonas.richiardi@unige.ch greicius@stanford.edu. ; Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. ; The War Related Illness and Injury Study Center, VA Palo Alto Health Care System, Palo Alto, CA, USA. Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. ; Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. ; Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada. Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Canada. ; Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. ; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. ; Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Department of Psychiatry, Universite de Montreal, Centre Hospitalier Universitaire (CHU) Ste Justine Hospital, Montreal, Canada. ; Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Neurospin, Commissariat a l'Energie Atomique et aux Energies Alternatives, Paris, France. ; Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin, Berlin, Germany. ; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA. ; School of Physics and Astronomy, University of Nottingham, Nottingham, UK. ; Institut National de la Sante et de la Recherche Medicale, INSERM Unit 1000 "Neuroimaging and Psychiatry," University Paris Sud, Orsay, France. INSERM Unit 1000 at Maison de Solenn, Assistance Publique Hopitaux de Paris (APHP), Cochin Hospital, University Paris Descartes, Sorbonne Paris Cite, Paris, France. ; Rotman Research Institute, University of Toronto, Toronto, Canada. School of Psychology, University of Nottingham, Nottingham, UK. ; The Hospital for Sick Children, University of Toronto, Toronto, Canada. ; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK. ; Department of Psychiatry and Psychotherapy, and Neuroimaging Center, Technische Universitat Dresden, Dresden, Germany. ; Department of Psychopharmacology, Central Institute of Mental Health, Faculty of Clinical Medicine Mannheim, Mannheim, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, UK. ; Allen Institute for Brain Science, Seattle, WA, USA. ; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA. ; Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. jonas.richiardi@unige.ch greicius@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068849" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Animals ; Brain/metabolism/*physiology ; Female ; Gene Expression ; Humans ; Ion Channels/*genetics ; Magnetic Resonance Imaging ; Male ; Mice ; Nerve Net/metabolism/*physiology ; Neural Pathways/metabolism/physiology ; Polymorphism, Genetic ; Rest/*physiology ; Synapses/metabolism/physiology ; *Transcriptome ; Young Adult
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  • 89
    Publication Date: 2015-01-17
    Description: The physiological and biomechanical requirements of flight at high altitude have been the subject of much interest. Here, we uncover a steep relation between heart rate and wingbeat frequency (raised to the exponent 3.5) and estimated metabolic power and wingbeat frequency (exponent 7) of migratory bar-headed geese. Flight costs increase more rapidly than anticipated as air density declines, which overturns prevailing expectations that this species should maintain high-altitude flight when traversing the Himalayas. Instead, a "roller coaster" strategy, of tracking the underlying terrain and discarding large altitude gains only to recoup them later in the flight with occasional benefits from orographic lift, is shown to be energetically advantageous for flights over the Himalayas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bishop, C M -- Spivey, R J -- Hawkes, L A -- Batbayar, N -- Chua, B -- Frappell, P B -- Milsom, W K -- Natsagdorj, T -- Newman, S H -- Scott, G R -- Takekawa, J Y -- Wikelski, M -- Butler, P J -- BB/FO15615/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):250-4. doi: 10.1126/science.1258732.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, Bangor University, Bangor, Gwynedd, UK. ; School of Biological Sciences, Bangor University, Bangor, Gwynedd, UK. c.bishop@bangor.ac.uk l.hawkes@exeter.ac.uk. ; Wildlife Science and Conservation Center of Mongolia, Ulaanbataar, Mongolia. ; Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada. ; Office of the Dean of Graduate Research, University of Tasmania, Tasmania, Australia. ; Mongolian Academy of Sciences, Ulaanbataar, Mongolia. ; Emergency Prevention System(EMPRES) Wildlife and Ecology Unit, Food and Agriculture Organization of the United Nations (FAO), Rome, Italy. ; Department of Biology, McMaster University, Ontario, Ontario, Canada. ; San Francisco Bay Estuary Field Station, Western Ecological Research Center, U.S. Geological Survey, Vallejo, CA 94592 USA. ; Max Planck Institut fur Ornithologie, Radolfzell, Germany. Department of Biology, University of Konstanz, Konstanz, Germany. ; School of Biosciences, University of Birmingham, Birmingham, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25593180" target="_blank"〉PubMed〈/a〉
    Keywords: *Altitude ; *Animal Migration ; Animals ; Biomechanical Phenomena ; Body Temperature ; Body Weight ; *Energy Metabolism ; Flight, Animal/*physiology ; Geese/*physiology ; Heart Rate ; Tibet ; Wings, Animal/*physiology
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  • 90
    Publication Date: 2015-06-06
    Description: Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbalpha, a transcription factor (TF) that functions both as a core repressive component of the cell-autonomous clock and as a regulator of metabolic genes. Here, we show that Rev-erbalpha modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbalpha to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbalpha regulates metabolic genes primarily by recruiting the HDAC3 co-repressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erbalpha and ROR TFs provides a universal mechanism for self-sustained control of the molecular clock across all tissues, whereas Rev-erbalpha uses lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613749/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613749/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Yuxiang -- Fang, Bin -- Emmett, Matthew J -- Damle, Manashree -- Sun, Zheng -- Feng, Dan -- Armour, Sean M -- Remsberg, Jarrett R -- Jager, Jennifer -- Soccio, Raymond E -- Steger, David J -- Lazar, Mitchell A -- F30 DK104513/DK/NIDDK NIH HHS/ -- F32 DK102284/DK/NIDDK NIH HHS/ -- K08 DK094968/DK/NIDDK NIH HHS/ -- P30 DK019525/DK/NIDDK NIH HHS/ -- P30 DK050306/DK/NIDDK NIH HHS/ -- P30 DK19525/DK/NIDDK NIH HHS/ -- R00 DK099443/DK/NIDDK NIH HHS/ -- R01 DK045586/DK/NIDDK NIH HHS/ -- R01 DK098542/DK/NIDDK NIH HHS/ -- R01 DK45586/DK/NIDDK NIH HHS/ -- T32 GM0008275/GM/NIGMS NIH HHS/ -- T32 GM008275/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):1488-92. doi: 10.1126/science.aab3021. Epub 2015 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Molecular and Cellular Biology, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. ; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. lazar@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26044300" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CLOCK Proteins/*genetics ; Circadian Clocks/*genetics ; Circadian Rhythm/*genetics ; *Gene Expression Regulation ; Hepatocyte Nuclear Factor 6/metabolism ; Histone Deacetylases/*metabolism ; Lipid Metabolism/genetics ; Liver/metabolism ; Male ; Metabolism/*genetics ; Mice, Inbred C57BL ; Mice, Knockout ; Nuclear Receptor Subfamily 1, Group D, Member 1/genetics/*metabolism ; Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism ; Organ Specificity ; Protein Binding ; Tissue Distribution
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  • 91
    Publication Date: 2015-09-01
    Description: The global biogeography of microorganisms remains largely unknown, in contrast to the well-studied diversity patterns of macroorganisms. We used arbuscular mycorrhizal (AM) fungus DNA from 1014 plant-root samples collected worldwide to determine the global distribution of these plant symbionts. We found that AM fungal communities reflected local environmental conditions and the spatial distance between sites. However, despite AM fungi apparently possessing limited dispersal ability, we found 93% of taxa on multiple continents and 34% on all six continents surveyed. This contrasts with the high spatial turnover of other fungal taxa and with the endemism displayed by plants at the global scale. We suggest that the biogeography of AM fungi is driven by unexpectedly efficient dispersal, probably via both abiotic and biotic vectors, including humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davison, J -- Moora, M -- Opik, M -- Adholeya, A -- Ainsaar, L -- Ba, A -- Burla, S -- Diedhiou, A G -- Hiiesalu, I -- Jairus, T -- Johnson, N C -- Kane, A -- Koorem, K -- Kochar, M -- Ndiaye, C -- Partel, M -- Reier, U -- Saks, U -- Singh, R -- Vasar, M -- Zobel, M -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):970-3. doi: 10.1126/science.aab1161.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Ecology and Earth Sciences, University of Tartu, Lai 40, Tartu 51005, Estonia. ; Centre for Mycorrhizal Research, The Energy and Resources Institute (TERI), India Habitat Centre, Lodhi Road, New Delhi 110 003, India. ; Laboratoire des Symbioses Tropicales et Mediterraneennes, Unite Mixte de Recherche 113, Laboratoire de Biologie et Physiologie Vegetales, Faculte des Sciences Exactes et Naturelles, Universite des Antilles, BP 592, 97159, Pointe-a-Pitre, Guadeloupe (French West Indies). ; Laboratoire Commun de Microbiologie de l'Institut de Recherche pour le Developpement-Institut Senegalais de Recherches Agricoles-Universite Cheikh Anta Diop (UCAD), Departement de Biologie Vegetale, UCAD, BP 5005 Dakar, Senegal. ; Institute of Ecology and Earth Sciences, University of Tartu, Lai 40, Tartu 51005, Estonia. Institute of Botany, Czech Academy of Sciences, Dukelska 135, 379 01 Trebon, Czech Republic. ; School of Earth Sciences and Environmental Sustainability, Northern Arizona University, Flagstaff, AZ 86011-5694, USA. ; Institute of Ecology and Earth Sciences, University of Tartu, Lai 40, Tartu 51005, Estonia. Netherlands Institute of Ecology, Droevendaalsesteeg 10, 6708 PB Wageningen, Netherlands. ; TERI-Deakin Nano Biotechnology Centre, Biotechnology and Management of Bioresources Division, TERI, India Habitat Centre, Lodhi Road, New Delhi 110 003, India.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315436" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; DNA, Fungal/analysis ; *Ecosystem ; Environment ; Humans ; *Mycorrhizae/genetics/isolation & purification/physiology ; Phylogeny ; Phylogeography ; Plant Roots/*microbiology ; *Symbiosis ; Water ; Wind
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  • 92
    Publication Date: 2015-05-16
    Description: PIWI-interacting RNAs (piRNAs) protect the animal germ line by silencing transposons. Primary piRNAs, generated from transcripts of genomic transposon "junkyards" (piRNA clusters), are amplified by the "ping-pong" pathway, yielding secondary piRNAs. We report that secondary piRNAs, bound to the PIWI protein Ago3, can initiate primary piRNA production from cleaved transposon RNAs. The first ~26 nucleotides (nt) of each cleaved RNA becomes a secondary piRNA, but the subsequent ~26 nt become the first in a series of phased primary piRNAs that bind Piwi, allowing piRNAs to spread beyond the site of RNA cleavage. The ping-pong pathway increases only the abundance of piRNAs, whereas production of phased primary piRNAs from cleaved transposon RNAs adds sequence diversity to the piRNA pool, allowing adaptation to changes in transposon sequence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545291/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545291/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Bo W -- Wang, Wei -- Li, Chengjian -- Weng, Zhiping -- Zamore, Phillip D -- GM62862/GM/NIGMS NIH HHS/ -- GM65236/GM/NIGMS NIH HHS/ -- HG007000/HG/NHGRI NIH HHS/ -- R01 GM065236/GM/NIGMS NIH HHS/ -- R37 GM062862/GM/NIGMS NIH HHS/ -- U41 HG007000/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 May 15;348(6236):817-21. doi: 10.1126/science.aaa1264.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. ; RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. ; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. zhiping.weng@umassmed.edu phillip.zamore@umassmed.edu. ; RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. zhiping.weng@umassmed.edu phillip.zamore@umassmed.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25977554" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins/genetics/*metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics/*metabolism ; Endoribonucleases/genetics/*metabolism ; Female ; Germ Cells/metabolism ; Male ; Metabolic Networks and Pathways ; Mice ; Ovary/metabolism ; Peptide Initiation Factors/genetics/*metabolism ; *RNA Cleavage ; RNA, Guide/*metabolism ; RNA, Small Interfering/biosynthesis/*metabolism ; *Retroelements ; Testis/metabolism
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  • 93
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Shuo -- Brunet, Anne -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):32-3. doi: 10.1126/science.aaa4565.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University, Stanford, CA 94035, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554778" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*physiology ; Caenorhabditis elegans Proteins/*metabolism ; Longevity/*physiology ; Lysosomes/*metabolism ; Molecular Chaperones/*metabolism
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  • 94
    Publication Date: 2015-08-15
    Description: Human vocal development occurs through two parallel interactive processes that transform infant cries into more mature vocalizations, such as cooing sounds and babbling. First, natural categories of sounds change as the vocal apparatus matures. Second, parental vocal feedback sensitizes infants to certain features of those sounds, and the sounds are modified accordingly. Paradoxically, our closest living ancestors, nonhuman primates, are thought to undergo few or no production-related acoustic changes during development, and any such changes are thought to be impervious to social feedback. Using early and dense sampling, quantitative tracking of acoustic changes, and biomechanical modeling, we showed that vocalizations in infant marmoset monkeys undergo dramatic changes that cannot be solely attributed to simple consequences of growth. Using parental interaction experiments, we found that contingent parental feedback influences the rate of vocal development. These findings overturn decades-old ideas about primate vocalizations and show that marmoset monkeys are a compelling model system for early vocal development in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, D Y -- Fenley, A R -- Teramoto, Y -- Narayanan, D Z -- Borjon, J I -- Holmes, P -- Ghazanfar, A A -- New York, N.Y. -- Science. 2015 Aug 14;349(6249):734-8. doi: 10.1126/science.aab1058.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA. Department of Psychology, Princeton University, Princeton, NJ 08544, USA. ; Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA. ; Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA. Department of Mechanical and Aerospace Engineering and Program in Applied and Computational Mathematics, Princeton University, Princeton, NJ 08544, USA. ; Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA. Department of Psychology, Princeton University, Princeton, NJ 08544, USA. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26273055" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustics ; Animals ; Biomechanical Phenomena ; Callithrix/*growth & development/physiology/psychology ; Female ; Male ; Models, Biological ; Muscle Tonus ; Vocal Cords/growth & development/physiology ; *Vocalization, Animal
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  • 95
    Publication Date: 2015-11-21
    Description: Infection with intestinal helminths results in immunological changes that influence co-infections, and might influence fecundity by inducing immunological states affecting conception and pregnancy. We investigated associations between intestinal helminths and fertility in women, using 9 years of longitudinal data from 986 Bolivian forager-horticulturalists, experiencing natural fertility and 70% helminth prevalence. We found that different species of helminth are associated with contrasting effects on fecundity. Infection with roundworm (Ascaris lumbricoides) is associated with earlier first births and shortened interbirth intervals, whereas infection with hookworm is associated with delayed first pregnancy and extended interbirth intervals. Thus, helminths may have important effects on human fertility that reflect physiological and immunological consequences of infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blackwell, Aaron D -- Tamayo, Marilyne A -- Beheim, Bret -- Trumble, Benjamin C -- Stieglitz, Jonathan -- Hooper, Paul L -- Martin, Melanie -- Kaplan, Hillard -- Gurven, Michael -- P01AG022500/AG/NIA NIH HHS/ -- R01AG024119/AG/NIA NIH HHS/ -- R56AG024119/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):970-2. doi: 10.1126/science.aac7902.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anthropology, University of California Santa Barbara, CA 93106, USA. Tsimane Health and Life History Project, San Borja, Bolivia. Broom Center for Demography, University of California Santa Barbara, CA 93106, USA. blackwell@anth.ucsb.edu. ; Department of Anthropology, University of Missouri, Columbia, MO 65211, USA. ; Tsimane Health and Life History Project, San Borja, Bolivia. Department of Anthropology, University of New Mexico, Albuquerque, NM 87131, USA. ; Department of Anthropology, University of California Santa Barbara, CA 93106, USA. Tsimane Health and Life History Project, San Borja, Bolivia. Broom Center for Demography, University of California Santa Barbara, CA 93106, USA. Center for Evolutionary Medicine, Arizona State University, Tempe, AZ 85287, USA. School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA. ; Tsimane Health and Life History Project, San Borja, Bolivia. Department of Anthropology, University of New Mexico, Albuquerque, NM 87131, USA. Institute for Advanced Study in Toulouse, Toulouse, France. ; Tsimane Health and Life History Project, San Borja, Bolivia. Department of Anthropology, Emory University, Atlanta, GA 30322, USA. ; Department of Anthropology, University of California Santa Barbara, CA 93106, USA. Tsimane Health and Life History Project, San Borja, Bolivia. Broom Center for Demography, University of California Santa Barbara, CA 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26586763" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Animals ; Ascariasis/epidemiology/immunology ; Ascaris lumbricoides/immunology ; Bolivia/epidemiology ; Coinfection ; Female ; Fertility/*immunology/physiology ; Gravidity/*immunology/physiology ; Helminthiasis/*immunology ; Humans ; Intestinal Diseases, Parasitic/epidemiology/*immunology ; Pregnancy ; Prevalence ; Young Adult
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  • 96
    Publication Date: 2015-04-18
    Description: Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate that a single fibroblast lineage is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation. Lineage-specific cell ablation leads to diminished connective tissue deposition in wounds and reduces melanoma growth. Using flow cytometry, we identify CD26/DPP4 as a surface marker that allows isolation of this lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. Identification and isolation of these lineages hold promise for translational medicine aimed at in vivo modulation of fibrogenic behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rinkevich, Yuval -- Walmsley, Graham G -- Hu, Michael S -- Maan, Zeshaan N -- Newman, Aaron M -- Drukker, Micha -- Januszyk, Michael -- Krampitz, Geoffrey W -- Gurtner, Geoffrey C -- Lorenz, H Peter -- Weissman, Irving L -- Longaker, Michael T -- GM07365/GM/NIGMS NIH HHS/ -- R01 GM087609/GM/NIGMS NIH HHS/ -- U01 HL099776/HL/NHLBI NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):aaa2151. doi: 10.1126/science.aaa2151.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. ryuval@stanford.edu irv@stanford.edu longaker@stanford.edu. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Ludwig Center for Cancer Stem Cell Biology and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. ryuval@stanford.edu irv@stanford.edu longaker@stanford.edu. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. ryuval@stanford.edu irv@stanford.edu longaker@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883361" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage/genetics ; Cell Separation/*methods ; Cicatrix/metabolism/*pathology ; Disease Models, Animal ; Embryonic Development ; Embryonic Stem Cells/cytology ; Fibroblasts/cytology/pathology/*physiology ; Gene Expression ; Homeodomain Proteins/genetics ; Mice ; Mouth/injuries/pathology/surgery ; Skin/injuries/*pathology ; Translational Medical Research ; *Wound Healing
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  • 97
    Publication Date: 2015-11-07
    Description: The sense of smell allows chemicals to be perceived as diverse scents. We used single-neuron RNA sequencing to explore the developmental mechanisms that shape this ability as nasal olfactory neurons mature in mice. Most mature neurons expressed only one of the ~1000 odorant receptor genes (Olfrs) available, and at a high level. However, many immature neurons expressed low levels of multiple Olfrs. Coexpressed Olfrs localized to overlapping zones of the nasal epithelium, suggesting regional biases, but not to single genomic loci. A single immature neuron could express Olfrs from up to seven different chromosomes. The mature state in which expression of Olfr genes is restricted to one per neuron emerges over a developmental progression that appears to be independent of neuronal activity involving sensory transduction molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanchate, Naresh K -- Kondoh, Kunio -- Lu, Zhonghua -- Kuang, Donghui -- Ye, Xiaolan -- Qiu, Xiaojie -- Pachter, Lior -- Trapnell, Cole -- Buck, Linda B -- DP2 HD088158/DP/NCCDPHP CDC HHS/ -- R01 DC009324/DC/NIDCD NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1251-5. doi: 10.1126/science.aad2456. Epub 2015 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98115, USA. Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98115, USA. ; Departments of Mathematics, Molecular and Cell Biology, and Electrical Engineering and Computer Sciences, University of California-Berkeley, Berkeley, CA 94720, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98115, USA. coletrap@uw.edu lbuck@fhcrc.org. ; Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. coletrap@uw.edu lbuck@fhcrc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26541607" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cyclic Nucleotide-Gated Cation Channels/genetics ; *Gene Expression Regulation, Developmental ; Genetic Loci ; Genetic Markers ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/*metabolism ; Neurogenesis/*genetics ; Olfactory Mucosa/innervation ; Olfactory Receptor Neurons/*metabolism ; Receptors, Odorant/*genetics ; Sequence Analysis, RNA ; Single-Cell Analysis ; Smell/*genetics ; Transcriptome
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  • 98
    Publication Date: 2015-08-22
    Description: Plasma membrane depolarization can trigger cell proliferation, but how membrane potential influences mitogenic signaling is uncertain. Here, we show that plasma membrane depolarization induces nanoscale reorganization of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate but not other anionic phospholipids. K-Ras, which is targeted to the plasma membrane by electrostatic interactions with phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization-induced changes in phosphatidylserine and K-Ras plasma membrane organization occur in fibroblasts, excitable neuroblastoma cells, and Drosophila neurons in vivo and robustly amplify K-Ras-dependent mitogen-activated protein kinase (MAPK) signaling. Conversely, plasma membrane repolarization disrupts K-Ras nanoclustering and inhibits MAPK signaling. By responding to voltage-induced changes in phosphatidylserine spatiotemporal dynamics, K-Ras nanoclusters set up the plasma membrane as a biological field-effect transistor, allowing membrane potential to control the gain in mitogenic signaling circuits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687752/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687752/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Yong -- Wong, Ching-On -- Cho, Kwang-jin -- van der Hoeven, Dharini -- Liang, Hong -- Thakur, Dhananiay P -- Luo, Jialie -- Babic, Milos -- Zinsmaier, Konrad E -- Zhu, Michael X -- Hu, Hongzhen -- Venkatachalam, Kartik -- Hancock, John F -- R01 NS081301/NS/NINDS NIH HHS/ -- R01NS081301/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):873-6. doi: 10.1126/science.aaa5619.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. ; Department of Diagnostic and Biomedical Sciences, Dental School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA. ; Department of Neuroscience, University of Arizona, Tucson, AZ 85721, USA. ; Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Program in Cell and Regulatory Biology, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA. ; Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Program in Cell and Regulatory Biology, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA. john.f.hancock@uth.tmc.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293964" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Membrane/metabolism/*physiology ; Cricetinae ; Drosophila melanogaster ; Fibroblasts ; *Membrane Potentials ; Mice ; Neurons ; Phosphatidylinositol 4,5-Diphosphate/*metabolism ; Phosphatidylserines/*metabolism ; Signal Transduction ; ras Proteins/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-05-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanaka, Atsushi -- Sakaguchi, Shimon -- New York, N.Y. -- Science. 2015 May 1;348(6234):506-7. doi: 10.1126/science.aab2998. Epub 2015 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. ; Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. shimon@ifrec.osaka-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931543" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Self Tolerance/*genetics ; T-Lymphocytes, Regulatory/*immunology ; Transcription Factors/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2016-01-20
    Description: The final identity and functional properties of a neuron are specified by terminal differentiation genes, which are controlled by specific motifs in compact regulatory regions. To determine how these sequences integrate inputs from transcription factors that specify cell types, we compared the regulatory mechanism of Drosophila Rhodopsin genes that are expressed in subsets of photoreceptors to that of phototransduction genes that are expressed broadly, in all photoreceptors. Both sets of genes share an 11-base pair (bp) activator motif. Broadly expressed genes contain a palindromic version that mediates expression in all photoreceptors. In contrast, each Rhodopsin exhibits characteristic single-bp substitutions that break the symmetry of the palindrome and generate activator or repressor motifs critical for restricting expression to photoreceptor subsets. Sensory neuron subtypes can therefore evolve through single-bp changes in short regulatory motifs, allowing the discrimination of a wide spectrum of stimuli.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rister, Jens -- Razzaq, Ansa -- Boodram, Pamela -- Desai, Nisha -- Tsanis, Cleopatra -- Chen, Hongtao -- Jukam, David -- Desplan, Claude -- K99EY023995/EY/NEI NIH HHS/ -- R01 EY13010/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1258-61. doi: 10.1126/science.aab3417.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003-6688, USA. ; Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003-6688, USA. cd38@nyu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785491" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Pairing ; Drosophila Proteins/*genetics ; Drosophila melanogaster/genetics/growth & development ; *Gene Expression Regulation, Developmental ; Mutation ; Photoreceptor Cells, Invertebrate/*physiology ; Promoter Regions, Genetic/*genetics ; Rhodopsin/*genetics ; Transcription Factors/metabolism ; Vision, Ocular/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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