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  • Humans  (890)
  • Biochemistry  (146)
  • Immunology  (79)
  • American Association for the Advancement of Science (AAAS)  (1,114)
  • 2015-2019  (1,114)
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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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    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
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernstein, Rachel -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):1506. doi: 10.1126/science.348.6242.1506.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rachel Bernstein is a staff writer for Science Careers. For more on life and careers, visit 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/26113726" target="_blank"〉PubMed〈/a〉
    Keywords: *Biomedical Research ; *Faculty, Medical ; Health Promotion/*methods ; Health Status ; Humans ; Mental Health ; *Research Personnel ; Stress, Psychological/prevention & control
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  • 68
    Publication Date: 2015-05-09
    Description: Technical advances have enabled the collection of genome and transcriptome data sets with single-cell resolution. However, single-cell characterization of the epigenome has remained challenging. Furthermore, because cells must be physically separated before biochemical processing, conventional single-cell preparatory methods scale linearly. We applied combinatorial cellular indexing to measure chromatin accessibility in thousands of single cells per assay, circumventing the need for compartmentalization of individual cells. We report chromatin accessibility profiles from more than 15,000 single cells and use these data to cluster cells on the basis of chromatin accessibility landscapes. We identify modules of coordinately regulated chromatin accessibility at the level of single cells both between and within cell types, with a scalable method that may accelerate progress toward a human cell atlas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cusanovich, Darren A -- Daza, Riza -- Adey, Andrew -- Pliner, Hannah A -- Christiansen, Lena -- Gunderson, Kevin L -- Steemers, Frank J -- Trapnell, Cole -- Shendure, Jay -- 1DP1HG007811/DP/NCCDPHP CDC HHS/ -- New York, N.Y. -- Science. 2015 May 22;348(6237):910-4. doi: 10.1126/science.aab1601. Epub 2015 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Washington, Department of Genome Sciences, Seattle, WA, USA. ; Oregon Health and Science University, Department of Molecular and Medical Genetics, Portland, OR, USA. ; Illumina, Inc., Advanced Research Group, San Diego, CA, USA. ; University of Washington, Department of Genome Sciences, Seattle, WA, USA. shendure@uw.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25953818" target="_blank"〉PubMed〈/a〉
    Keywords: Chromatin/*metabolism ; *Epigenesis, Genetic ; HEK293 Cells ; HL-60 Cells ; Humans ; Single-Cell Analysis/*methods
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  • 69
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-02-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kloor, Keith -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):699. doi: 10.1126/science.347.6223.699.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678635" target="_blank"〉PubMed〈/a〉
    Keywords: *Access to Information ; Agriculture/*legislation & jurisprudence ; Biotechnology/*legislation & jurisprudence ; Commerce ; Food Labeling/*legislation & jurisprudence ; Food, Genetically Modified/*adverse effects ; Humans ; Research Personnel ; United States ; Universities
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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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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kloosterman, Wigard P -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1205-6. doi: 10.1126/science.aac5277.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, 3584CG Utrecht, Netherlands. w.kloosterman@umcutrecht.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068832" target="_blank"〉PubMed〈/a〉
    Keywords: *Chromosome Breakage ; *DNA Damage ; Humans ; *Micronuclei, Chromosome-Defective
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  • 72
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernstein, Rachel -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):269. doi: 10.1126/science.348.6232.269.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883332" target="_blank"〉PubMed〈/a〉
    Keywords: Engineering/*education/manpower ; Faculty/*statistics & numerical data ; Female ; Humans ; Male ; Mathematics/*education/manpower ; Science/*education/manpower ; Sex Factors ; Technology/*education/manpower ; United States ; Women, Working/*statistics & numerical data
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  • 73
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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〉Reich, Justin -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):34-5. doi: 10.1126/science.1261627.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉HarvardX, Harvard University, Cambridge, MA 02476, USA. justin_reich@harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554779" target="_blank"〉PubMed〈/a〉
    Keywords: *Access to Information ; Education, Distance/*methods ; Humans ; *Information Dissemination ; Learning ; *Online Systems ; Research Design
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  • 74
    Publication Date: 2015-05-23
    Description: Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with 〉40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing 〉35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that 〉73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sunagawa, Shinichi -- Coelho, Luis Pedro -- Chaffron, Samuel -- Kultima, Jens Roat -- Labadie, Karine -- Salazar, Guillem -- Djahanschiri, Bardya -- Zeller, Georg -- Mende, Daniel R -- Alberti, Adriana -- Cornejo-Castillo, Francisco M -- Costea, Paul I -- Cruaud, Corinne -- d'Ovidio, Francesco -- Engelen, Stefan -- Ferrera, Isabel -- Gasol, Josep M -- Guidi, Lionel -- Hildebrand, Falk -- Kokoszka, Florian -- Lepoivre, Cyrille -- Lima-Mendez, Gipsi -- Poulain, Julie -- Poulos, Bonnie T -- Royo-Llonch, Marta -- Sarmento, Hugo -- Vieira-Silva, Sara -- Dimier, Celine -- Picheral, Marc -- Searson, Sarah -- Kandels-Lewis, Stefanie -- Tara Oceans coordinators -- Bowler, Chris -- de Vargas, Colomban -- Gorsky, Gabriel -- Grimsley, Nigel -- Hingamp, Pascal -- Iudicone, Daniele -- Jaillon, Olivier -- Not, Fabrice -- Ogata, Hiroyuki -- Pesant, Stephane -- Speich, Sabrina -- Stemmann, Lars -- Sullivan, Matthew B -- Weissenbach, Jean -- Wincker, Patrick -- Karsenti, Eric -- Raes, Jeroen -- Acinas, Silvia G -- Bork, Peer -- New York, N.Y. -- Science. 2015 May 22;348(6237):1261359. doi: 10.1126/science.1261359.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium. Department of Applied Biological Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. ; CEA-Institut de Genomique, GENOSCOPE, 2 rue Gaston Cremieux, 91057 Evry, France. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta, 37-49, Barcelona E08003, Spain. ; Sorbonne Universites, UPMC, Universite Paris 06, CNRS-IRD-MNHN, LOCEAN Laboratory, 4 Place Jussieu, 75005 Paris France. ; CNRS, UMR 7093, Laboratoire d'Oceanographie de Villefranche-sur-Mer, Observatoire Oceanologique, F-06230 Villefranche-sur-mer, France. Sorbonne Universites, UPMC Universite Paris 06, UMR 7093, LOV, Observatoire Oceanologique, F-06230 Villefranche-sur-mer, France. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. Laboratoire de Physique des Oceans UBO-IUEM, Place Copernic 29820 Plouzane, France. ; Aix Marseille Universite CNRS IGS UMR 7256, 13288 Marseille, France. ; Department of Ecology and Evolutionary Biology, University of Arizona, 1007 East Lowell Street, Tucson, AZ 85721, USA. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta, 37-49, Barcelona E08003, Spain. Department of Hydrobiology, Federal University of Sao Carlos (UFSCar), Rodovia Washington Luiz, 13565-905 Sao Carlos, Sao Paulo, Brazil. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, UPMC Universite Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Directors' Research, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. ; CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, UPMC Universite Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; CNRS UMR 7232, BIOM, Avenue du Fontaule, 66650 Banyuls-sur-Mer, France. Sorbonne Universites Paris 06, OOB UPMC, Avenue du Fontaule, 66650 Banyuls-sur-Mer, France. ; Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy. ; CEA-Institut de Genomique, GENOSCOPE, 2 rue Gaston Cremieux, 91057 Evry, France. CNRS, UMR 8030, CP5706, Evry, France. Universite d'Evry, UMR 8030, CP5706, Evry, France. ; Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, 611-001, Japan. ; PANGAEA, Data Publisher for Earth and Environmental Science, University of Bremen, Bremen, Germany. MARUM, Center for Marine Environmental Sciences, University of Bremen, Bremen, Germany. ; Department of Geosciences, Laboratoire de Meteorologie Dynamique (LMD), Ecole Normale Superieure, 24 rue Lhomond, 75231 Paris Cedex 05, France. Laboratoire de Physique des Oceans UBO-IUEM, Place Copernic, 29820 Plouzane, France. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. Directors' Research, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium. Department of Applied Biological Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta, 37-49, Barcelona E08003, Spain. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Max-Delbruck-Centre for Molecular Medicine, 13092 Berlin, Germany. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999513" target="_blank"〉PubMed〈/a〉
    Keywords: Databases, Genetic ; Ecosystem ; Gastrointestinal Tract/microbiology ; Genetic Variation ; Humans ; Metagenome ; Microbiota/*genetics ; Oceans and Seas ; Plankton/*classification/genetics/isolation & purification ; Seawater/*microbiology
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  • 75
    Publication Date: 2015-06-13
    Description: Jan et al. (Research Articles, 7 November 2014, p. 716) propose that ribosomes translating secretome messenger RNAs (mRNAs) traffic from the cytosol to the endoplasmic reticulum (ER) upon emergence of the signal peptide and return to the cytosol after termination. An accounting of controls demonstrates that mRNAs initiate translation on ER-bound ribosomes and that ribosomes are retained on the ER through many cycles of translation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reid, David W -- Nicchitta, Christopher V -- GM101533/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1217. doi: 10.1126/science.aaa7257. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, Singapore 169857, Singapore. ; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. christopher.nicchitta@duke.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068841" target="_blank"〉PubMed〈/a〉
    Keywords: Cells/*metabolism ; Endoplasmic Reticulum/*metabolism ; Humans ; Mitochondria/*metabolism ; *Protein Biosynthesis ; Ribosomes/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 76
    Publication Date: 2015-02-24
    Description: According to the disease module hypothesis, the cellular components associated with a disease segregate in the same neighborhood of the human interactome, the map of biologically relevant molecular interactions. Yet, given the incompleteness of the interactome and the limited knowledge of disease-associated genes, it is not obvious if the available data have sufficient coverage to map out modules associated with each disease. Here we derive mathematical conditions for the identifiability of disease modules and show that the network-based location of each disease module determines its pathobiological relationship to other diseases. For example, diseases with overlapping network modules show significant coexpression patterns, symptom similarity, and comorbidity, whereas diseases residing in separated network neighborhoods are phenotypically distinct. These tools represent an interactome-based platform to predict molecular commonalities between phenotypically related diseases, even if they do not share primary disease genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435741/" 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/PMC4435741/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Menche, Jorg -- Sharma, Amitabh -- Kitsak, Maksim -- Ghiassian, Susan Dina -- Vidal, Marc -- Loscalzo, Joseph -- Barabasi, Albert-Laszlo -- P01-HL083069/HL/NHLBI NIH HHS/ -- P50 HG004233/HG/NHGRI NIH HHS/ -- P50-HG004233/HG/NHGRI NIH HHS/ -- R37 HL061795/HL/NHLBI NIH HHS/ -- R37-HL061795/HL/NHLBI NIH HHS/ -- RC2-HL101543/HL/NHLBI NIH HHS/ -- U01 HG001715/HG/NHGRI NIH HHS/ -- U01 HG007690/HG/NHGRI NIH HHS/ -- U01 HL108630/HL/NHLBI NIH HHS/ -- U01-HG001715/HG/NHGRI NIH HHS/ -- U01-HG007690/HG/NHGRI NIH HHS/ -- U01-HL108630/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):1257601. doi: 10.1126/science.1257601.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Complex Networks Research and Department of Physics, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115, USA. Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Center for Network Science, Central European University, Nador u. 9, 1051 Budapest, Hungary. ; Center for Complex Networks Research and Department of Physics, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115, USA. Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. ; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. ; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. ; Center for Complex Networks Research and Department of Physics, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115, USA. Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Center for Network Science, Central European University, Nador u. 9, 1051 Budapest, Hungary. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. alb@neu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700523" target="_blank"〉PubMed〈/a〉
    Keywords: Comorbidity ; Disease/*etiology/genetics ; *Genetic Predisposition to Disease ; Humans ; *Information Services ; *Protein Interaction Maps
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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sundquist, Wesley I -- Ullman, Katharine S -- P50 GM082545/GM/NIGMS NIH HHS/ -- R01 AI051174/AI/NIAID NIH HHS/ -- R01 GM112080/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 19;348(6241):1314-5. doi: 10.1126/science.aac7083.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA. wes@biochem.utah.edu katharine.ullman@hci.utah.edu. ; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112-5650, USA. wes@biochem.utah.edu katharine.ullman@hci.utah.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089496" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/*metabolism ; Endosomal Sorting Complexes Required for Transport/*metabolism ; Humans ; *Membrane Fusion ; Nuclear Envelope/*metabolism ; Spindle Apparatus/*metabolism
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  • 78
    Publication Date: 2015-05-09
    Description: Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes-which is most clearly seen in blood-though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547472/" 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/PMC4547472/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mele, Marta -- Ferreira, Pedro G -- Reverter, Ferran -- DeLuca, David S -- Monlong, Jean -- Sammeth, Michael -- Young, Taylor R -- Goldmann, Jakob M -- Pervouchine, Dmitri D -- Sullivan, Timothy J -- Johnson, Rory -- Segre, Ayellet V -- Djebali, Sarah -- Niarchou, Anastasia -- GTEx Consortium -- Wright, Fred A -- Lappalainen, Tuuli -- Calvo, Miquel -- Getz, Gad -- Dermitzakis, Emmanouil T -- Ardlie, Kristin G -- Guigo, Roderic -- HHSN261200800001E/PHS HHS/ -- HHSN268201000029C/HL/NHLBI NIH HHS/ -- HHSN268201000029C/PHS HHS/ -- R01 DA006227-17/DA/NIDA NIH HHS/ -- R01 MH090936/MH/NIMH NIH HHS/ -- R01 MH090941/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2015 May 8;348(6235):660-5. doi: 10.1126/science.aaa0355.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Harvard Department of stem cell and regenerative biology, Harvard University, Cambridge, MA, USA. ; Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. Swiss Institute of Bioinformatics, Geneva, Switzerland. ; Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. ; Broad Institute of MIT and Harvard, Cambridge, MA, USA. ; Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. McGill University, Montreal, Canada. ; Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. National Institute for Scientific Computing (LNCC), Petropolis, Rio de Janeiro, Brazil. ; Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. Radboud University, Nijmegen, Netherlands. ; Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. Faculty of Bioengineering and Bioinformatics, Moscow State University, Leninskie Gory 1-73, 119992 Moscow, Russia. ; Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. ; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. Swiss Institute of Bioinformatics, Geneva, Switzerland. ; Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Harvard Department of stem cell and regenerative biology, Harvard University, Cambridge, MA, USA. Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. Swiss Institute of Bioinformatics, Geneva, Switzerland. Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. Broad Institute of MIT and Harvard, Cambridge, MA, USA. McGill University, Montreal, Canada. National Institute for Scientific Computing (LNCC), Petropolis, Rio de Janeiro, Brazil. Radboud University, Nijmegen, Netherlands. Faculty of Bioengineering and Bioinformatics, Moscow State University, Leninskie Gory 1-73, 119992 Moscow, Russia. North Carolina State University, Raleigh, NC, USA. New York Genome Center, New York, NY, USA. Department of Systems Biology, Columbia University, New York, NY, USA. Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. Institut Hospital del Mar d'Investigacions Mediques (IMIM), Barcelona, Catalonia, Spain. Joint CRG-Barcelona Super Computing Center (BSC)-Institut de Recerca Biomedica (IRB) Program in Computational Biology, Barcelona, Catalonia, Spain. ; North Carolina State University, Raleigh, NC, USA. ; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. Swiss Institute of Bioinformatics, Geneva, Switzerland. New York Genome Center, New York, NY, USA. Department of Systems Biology, Columbia University, New York, NY, USA. ; Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Catalonia, Spain. ; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA, USA. kardlie@broadinstitute.org roderic.guigo@crg.cat. ; Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. Institut Hospital del Mar d'Investigacions Mediques (IMIM), Barcelona, Catalonia, Spain. Joint CRG-Barcelona Super Computing Center (BSC)-Institut de Recerca Biomedica (IRB) Program in Computational Biology, Barcelona, Catalonia, Spain. kardlie@broadinstitute.org roderic.guigo@crg.cat.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25954002" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Female ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome, Human/*genetics ; Humans ; Male ; Organ Specificity/genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Sequence Analysis, RNA ; Sex Factors ; *Transcriptome
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  • 79
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haddad, Nick M -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1166-7. doi: 10.1126/science.aad5072.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Ecology, North Carolina State University, Raleigh, NC 27695, USA. nick_haddad@ncsu.ed.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785459" target="_blank"〉PubMed〈/a〉
    Keywords: Brazil ; *Conservation of Natural Resources ; Humans ; *Transportation
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  • 80
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernstein, Rachel -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1282. doi: 10.1126/science.347.6227.1282.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rachel Bernstein is a staf writer for Science Careers. For more on life and careers, visit 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/25766239" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; Drug Discovery/*organization & administration ; *Entrepreneurship ; Humans ; Rare Diseases/*drug therapy
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  • 81
    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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  • 82
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hall, Stephen S -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1274-8. doi: 10.1126/science.349.6254.1274.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383933" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*drug effects ; Humans ; Hypoglycemic Agents/*pharmacology ; Liver/drug effects ; Metformin/*pharmacology ; Mitochondria/drug effects ; Neoplasms/epidemiology/mortality/prevention & control
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  • 83
    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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  • 84
    Publication Date: 2015-10-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Merrigan, Kathleen -- Griffin, Timothy -- Wilde, Parke -- Robien, Kimberly -- Goldberg, Jeanne -- Dietz, William -- New York, N.Y. -- Science. 2015 Oct 9;350(6257):165-6. doi: 10.1126/science.aab2031. Epub 2015 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Trachtenberg School of Public Policy and Public Administration, the George Washington University, Washington, DC 20052, USA. kmerrigan@gwu.edu. ; Friedman School of Nutrition Science and Policy, Tufts University, Medford, MA 02155, USA. ; Milken Institute School of Public Health, the George Washington University, Washington, DC 20052, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26429883" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Diet/*standards ; Food Assistance ; Food Technology/*standards ; Humans ; *Nutrition Policy ; United States
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  • 85
    Publication Date: 2015-07-15
    Description: Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Despite their physiological importance, the structural information on Insigs remains limited. Here we report the high-resolution structures of MvINS, an Insig homolog from Mycobacterium vanbaalenii. MvINS exists as a homotrimer. Each protomer comprises six transmembrane segments (TMs), with TM3 and TM4 contributing to homotrimerization. The six TMs enclose a V-shaped cavity that can accommodate a diacylglycerol molecule. A homology-based structural model of human Insig-2, together with biochemical characterizations, suggest that the central cavity of Insig-2 accommodates 25-hydroxycholesterol, whereas TM3 and TM4 engage in Scap binding. These analyses provide an important framework for further functional and mechanistic understanding of Insig proteins and the sterol regulatory element-binding protein pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704858/" 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/PMC4704858/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ren, Ruobing -- Zhou, Xinhui -- He, Yuan -- Ke, Meng -- Wu, Jianping -- Liu, Xiaohui -- Yan, Chuangye -- Wu, Yixuan -- Gong, Xin -- Lei, Xiaoguang -- Yan, S Frank -- Radhakrishnan, Arun -- Yan, Nieng -- HL-20948/HL/NHLBI NIH HHS/ -- P01 HL020948/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):187-91. doi: 10.1126/science.aab1091.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. Center for Structural Biology, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China. ; National Institute of Biological Sciences, Beijing 102206, China. ; Molecular Design and Chemical Biology, Therapeutic Modalities, Roche Pharma Research and Early Development, Roche Innovation Center Shanghai, Shanghai 201203, China. ; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160948" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry ; Crystallography, X-Ray ; Diglycerides/chemistry ; Humans ; Hydroxycholesterols/chemistry/*metabolism ; Intracellular Signaling Peptides and Proteins/*chemistry ; Membrane Proteins/*chemistry ; Mycobacterium/*metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Sterol Regulatory Element Binding Proteins/*chemistry
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  • 86
    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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  • 87
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-07-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kohane, Isaac S -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):37-8. doi: 10.1126/science.aab1328. Epub 2015 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. isaac_kohane@harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138968" target="_blank"〉PubMed〈/a〉
    Keywords: *Evidence-Based Medicine ; Genomics/trends ; *Health Policy ; Humans ; Medical Record Linkage ; Reproducibility of Results ; United States
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  • 88
    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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  • 89
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):896. doi: 10.1126/science.350.6263.896.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26586739" target="_blank"〉PubMed〈/a〉
    Keywords: *African Americans ; Biomedical Research/economics ; Biotechnology/*economics/*manpower ; Financial Support ; Government Programs ; Humans ; Laboratory Personnel/*economics ; National Institutes of Health (U.S.)/*economics ; Small Business/economics/trends ; United States
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  • 90
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    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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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Komander, David -- New York, N.Y. -- Science. 2015 Apr 10;348(6231):183-4. doi: 10.1126/science.aab0931.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. dk@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25859031" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase-Promoting Complex-Cyclosome/*metabolism ; Humans ; Proteasome Endopeptidase Complex/*metabolism ; *Proteolysis ; Ubiquitin/*metabolism ; Ubiquitinated Proteins/*metabolism
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  • 92
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, Mark M -- U19 AI057229/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):371-2. doi: 10.1126/science.aaa5082.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Institute for Immunity, Transplantation and Infection, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. mmdavis@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25613876" target="_blank"〉PubMed〈/a〉
    Keywords: CD4-Positive T-Lymphocytes/*immunology ; Candida albicans/*immunology ; Host-Pathogen Interactions/*immunology ; Humans ; *Immunologic Memory ; Mycobacterium tuberculosis/*immunology ; T-Lymphocyte Subsets/*immunology ; Vaccines/*immunology
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  • 93
    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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  • 94
    Publication Date: 2016-01-20
    Description: Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type-specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blackburn, Elizabeth H -- Epel, Elissa S -- Lin, Jue -- CA096840/CA/NCI NIH HHS/ -- GM026259/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1193-8. doi: 10.1126/science.aab3389.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA. elizabeth.blackburn@ucsf.edu. ; Department of Psychiatry, University of California, San Francisco, CA 94143, USA. ; Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785477" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*genetics ; Cell Division/genetics ; Disease/*genetics ; *Genetic Predisposition to Disease ; Humans ; Life Style ; Neoplasms/genetics ; Stress, Physiological ; Telomerase/metabolism ; Telomere/chemistry/*physiology/ultrastructure ; Telomere Homeostasis/*genetics
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  • 95
    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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  • 96
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Sep 25;349(6255):1440. doi: 10.1126/science.349.6255.1440.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26404808" target="_blank"〉PubMed〈/a〉
    Keywords: *Environmental Monitoring ; *Homicide ; Humans ; Puerto Rico
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  • 97
    Publication Date: 2015-08-01
    Description: Metagenomic sequencing increased our understanding of the role of the microbiome in health and disease, yet it only provides a snapshot of a highly dynamic ecosystem. Here, we show that the pattern of metagenomic sequencing read coverage for different microbial genomes contains a single trough and a single peak, the latter coinciding with the bacterial origin of replication. Furthermore, the ratio of sequencing coverage between the peak and trough provides a quantitative measure of a species' growth rate. We demonstrate this in vitro and in vivo, under different growth conditions, and in complex bacterial communities. For several bacterial species, peak-to-trough coverage ratios, but not relative abundances, correlated with the manifestation of inflammatory bowel disease and type II diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korem, Tal -- Zeevi, David -- Suez, Jotham -- Weinberger, Adina -- Avnit-Sagi, Tali -- Pompan-Lotan, Maya -- Matot, Elad -- Jona, Ghil -- Harmelin, Alon -- Cohen, Nadav -- Sirota-Madi, Alexandra -- Thaiss, Christoph A -- Pevsner-Fischer, Meirav -- Sorek, Rotem -- Xavier, Ramnik J -- Elinav, Eran -- Segal, Eran -- New York, N.Y. -- Science. 2015 Sep 4;349(6252):1101-6. doi: 10.1126/science.aac4812. Epub 2015 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. ; Immunology Department, Weizmann Institute of Science, Rehovot, Israel. ; Department of Biological services, Weizmann Institute of Science, Rehovot, Israel. ; Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel. ; Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School and Broad Institute, Cambridge, MA, USA. ; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. ; Immunology Department, Weizmann Institute of Science, Rehovot, Israel. eran.elinav@weizmann.ac.il eran.segal@weizmann.ac.il. ; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. eran.elinav@weizmann.ac.il eran.segal@weizmann.ac.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26229116" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/classification/genetics/*growth & development ; Diabetes Mellitus, Type 2/*microbiology ; Gastrointestinal Tract/*microbiology ; Genome, Bacterial ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Metagenome ; Metagenomics ; Microbiota/genetics/*physiology
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  • 98
    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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  • 99
    Publication Date: 2015-03-15
    Description: The Ebola epidemic in West Africa has caused substantial morbidity and mortality. The outbreak has also disrupted health care services, including childhood vaccinations, creating a second public health crisis. We project that after 6 to 18 months of disruptions, a large connected cluster of children unvaccinated for measles will accumulate across Guinea, Liberia, and Sierra Leone. This pool of susceptibility increases the expected size of a regional measles outbreak from 127,000 to 227,000 cases after 18 months, resulting in 2000 to 16,000 additional deaths (comparable to the numbers of Ebola deaths reported thus far). There is a clear path to avoiding outbreaks of childhood vaccine-preventable diseases once the threat of Ebola begins to recede: an aggressive regional vaccination campaign aimed at age groups left unprotected because of health care disruptions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691345/" 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/PMC4691345/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, Saki -- Metcalf, C Jessica E -- Ferrari, Matthew J -- Moss, William J -- Truelove, Shaun A -- Tatem, Andrew J -- Grenfell, Bryan T -- Lessler, Justin -- R01 AI102939/AI/NIAID NIH HHS/ -- U19AI089674/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1240-2. doi: 10.1126/science.aaa3438.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. ; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. Woodrow Wilson School, Princeton University, Princeton, NJ 08544, USA. ; Centre for Infectious Disease Dynamics, Pennsylvania State University, State College, PA 16801, USA. ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. ; Department of Geography and Environment, University of Southampton, Southampton SO17 1BJ, UK. Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. Flowminder Foundation, 17177 Stockholm, Sweden. ; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. justin@jhu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766232" target="_blank"〉PubMed〈/a〉
    Keywords: Child, Preschool ; Disease Outbreaks/prevention & control/*statistics & numerical data ; Disease Susceptibility ; Guinea/epidemiology ; Hemorrhagic Fever, Ebola/*epidemiology ; Humans ; Immunization Programs/*statistics & numerical data ; Infant ; Liberia/epidemiology ; Measles/*epidemiology/mortality/*prevention & control ; *Measles Vaccine ; Sierra Leone/epidemiology ; Vaccination/*statistics & numerical data
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  • 100
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1268. doi: 10.1126/science.349.6254.1268.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383927" target="_blank"〉PubMed〈/a〉
    Keywords: Air/*standards ; Asthma/*epidemiology ; Child ; Humans ; Ozone/*standards ; Politics ; Prevalence ; Public Health/trends ; Smog/*prevention & control ; United States/epidemiology ; United States Environmental Protection Agency/*legislation & jurisprudence
    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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