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  • Humans  (890)
  • Cell Biology  (99)
  • Genetics  (72)
  • Evolution  (68)
  • American Association for the Advancement of Science (AAAS)  (1,129)
  • American Geophysical Union (AGU)
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  • Public Library of Science
  • 2015-2019  (1,129)
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  • 1
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-07-22
    Description: The vast majority of genes in sexually reproducing eukaryotes can recombine during the production of gametes. This reshuffling generates new genotypes that may provide selective advantages. However, reshuffling does not occur among the few genes in the genomes of cytoplasmic organelles (chloroplasts and mitochondria). Instead, these organelles are almost always transmitted through maternal inheritance (1). Why is this phenomenon widespread and how is it achieved? On page 394 of this issue, Zhou et al. (2) solve part of this puzzle by identifying the enzyme that degrades sperm mitochondrial DNA after fertilization. Author: Alexander M. van der Bliek
    Keywords: Genetics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-07-22
    Description: Mutualistic symbiotic relationships are those in which both species benefit; for example, the vivid colors of coral reefs come from symbiotic algae that provide their living coral hosts with nutrients and oxygen through photosynthesis in exchange for protection. A similar mutualistic relationship exists between gut-dwelling bacteria and their animal hosts (1). It remains unclear, however, to what degree symbiosis has shaped host-microbial interactions and coevolution. On page 380 of this issue, Moeller et al. show that gut bacterial strains cospeciated with hominids (apes and humans) over the past 15 million years (2). These findings set the stage for exploring the evolutionary processes that underlie the symbiotic relationship between hominids and their gut-dwelling microbes. Authors: Julia A. Segre, Nick Salafsky
    Keywords: Evolution
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  • 3
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-07-22
    Description: Author: Caroline Ash
    Keywords: Evolution
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  • 4
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-25
    Description: Author: Laura M. Zahn
    Keywords: Genetics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-25
    Description: Several unprecedented videos of gelatinous sea creatures called comb jellies, or ctenophores, now threaten to upend the standard view of the evolution of the so-called through-gut. Comb jellies, jellyfish, sea sponges, and a few other creatures all were thought to lack an anus, which meant they had to eat and defecate through a single hole. These are descendants of some of the first animals to arise, so it has been thought that the through-gut and anus were an innovation that came after those lineages emerged—and perhaps something that drove the diversity of new animal forms. But on 15 March, at the Ctenopolooza meeting in St. Augustine, Florida, evolutionary biologist William Browne of the University of Miami in Florida debuted films of comb jellies pooping—and it wasn't through their mouths. Browne's videos elicited gasps from the audience, who is now rethinking when the through-gut first evolved—and whether it may have emerged more than once. Author: Amy Maxmen
    Keywords: Evolution
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  • 6
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-07-01
    Description: Author: Stella M. Hurtley
    Keywords: Cell Biology
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  • 7
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-08-16
    Description: The major human neurodegenerative diseases, including Alzheimer's, amyotrophic lateral sclerosis, Parkinson's, and Huntington's diseases, are associated with accumulation and aggregation of misfolded proteins. In most cases, the majority of aberrantly aggregated proteins are found in the cell cytoplasm. However, in disorders caused by the expansion of a trinucleotide repeat, including Huntington's disease and spinocerebellar ataxia, the corresponding aggregates of proteins containing the encoded polyglutamine expansions are predominantly nuclear. Whether differences in intracellular location matter for the toxicity generated by such proteins has not been determined. On page 173 of this issue, Woerner et al. (1) report that the location does indeed matter, with toxicity arising from the cytoplasmic accumulation of a pair of artificial proteins designed to mimic the properties of amyloid aggregates. Surprisingly, forcing the same artificial proteins into the nucleus substantially reduces their toxicity. Authors: Sandrine Da Cruz, Don W. Cleveland
    Keywords: Cell Biology
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  • 8
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-17
    Description: "This missing science of heredity … is, in simple truth, ten times more important to humanity than all the chemistry and physics, all the technical and industrial science that ever has been or ever will be discovered," wrote H. G. Wells in 1903. Having dedicated more than 500 pages to the topic in his new book, The Gene, Siddhartha Mukherjee would seem to agree. The book examines human genetics, from its philosophical roots in the work of Aristotle, through Gregor Mendel's garden and Thomas Hunt Morgan's work on fruitflies, and including active work in genome editing. Author: Michael A. Goldman
    Keywords: Genetics
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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: For years, scientists have debated where dogs came from. Did wolves first forge their special relationship with humans in Europe, or in Asia? The answer, according to a new study, is yes. Researchers report that genetic analysis of hundreds of canines—including a nearly 5000-year-old dog unearthed on the east coast of Ireland—reveals that dogs may have been domesticated twice, once in Asia and once in Europe or the Near East, although European ancestry has mostly vanished from today's dogs. The findings could resolve a rift that has roiled the canine origins community—but experts say a lot more work needs to be done to confirm them. Author: David Grimm
    Keywords: Evolution
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  • 10
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-10
    Description: Author: Guy Riddihough
    Keywords: Cell Biology
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  • 11
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-09-09
    Description: One of the greatest symbols of the birth of evolutionary biology is Darwin's first sketch of an evolutionary tree, above which he wrote: “I think.” Not only are evolutionary trees central to how scientists conceptualize evolutionary processes, Darwin's words also capture a key aspect of evolutionary science: It is difficult to observe, forcing researchers to rely heavily on inference. In recent decades, studies of fast-growing microorganisms have allowed hypotheses about evolutionary processes to be tested experimentally (1). On page 1147 of this issue, Baym et al. (2) report a device for visualizing evolutionary branching as bacteria grow across a meter-scale agar slab. The results offer important insights into evolutionary dynamics in spatially extended systems. Authors: Luke McNally, Sam P. Brown
    Keywords: Evolution
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  • 12
    Publication Date: 2018-02-16
    Description: Gram-negative bacteria have an outer membrane that serves as a barrier to noxious agents in the environment. This protective function is dependent on lipopolysaccharide, a large glycolipid located in the outer leaflet of the outer membrane. Lipopolysaccharide is synthesized at the cytoplasmic membrane and must be transported to the cell surface. To understand this transport process, we reconstituted membrane-to-membrane movement of lipopolysaccharide by incorporating purified inner and outer membrane transport complexes into separate proteoliposomes. Transport involved stable association between the inner and outer membrane proteoliposomes. Our results support a model in which lipopolysaccharide molecules are pushed one after the other in a PEZ dispenser–like manner across a protein bridge that connects the inner and outer membranes.
    Keywords: Cell Biology
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  • 13
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-02-16
    Keywords: Cell Biology
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  • 14
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-03
    Keywords: Genetics
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  • 15
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-03
    Description: Our textbook image of organelles has changed. Instead of revealing isolated cellular compartments, the picture now emerging shows organelles as largely interdependent structures that can communicate through membrane contact sites (MCSs). MCSs are sites where opposing organelles are tethered but do not fuse. MCSs provide a hybrid location where the tool kits of two different organelles can work together to perform vital cellular functions, such as lipid and ion transfer, signaling, and organelle division. Here, we focus on MCSs involving the endoplasmic reticulum (ER), an organelle forming an extensive network of cisternae and tubules. We highlight how the dynamic ER network regulates a plethora of cellular processes through MCSs with various organelles and with the plasma membrane.
    Keywords: Cell Biology
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  • 16
    Publication Date: 2018-08-10
    Description: Mammals diversified by colonizing drastically different environments, with each transition yielding numerous molecular changes, including losses of protein function. Though not initially deleterious, these losses could subsequently carry deleterious pleiotropic consequences. We have used phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. In one extreme case, Paraoxonase 1 ( PON1 ) accrued lesions in all marine lineages, while remaining intact in all terrestrial mammals. These lesions coincide with PON1 enzymatic activity loss in marine species’ blood plasma. This convergent loss is likely explained by parallel shifts in marine ancestors’ lipid metabolism and/or bloodstream oxidative environment affecting PON1’s role in fatty acid oxidation. PON1 loss also eliminates marine mammals’ main defense against neurotoxicity from specific man-made organophosphorus compounds, implying potential risks in modern environments.
    Keywords: Evolution
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  • 17
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-10
    Description: The turbulent surfaces of rivers and streams are natural hotspots of biogeochemical exchange with the atmosphere. At the global scale, the total river-atmosphere flux of trace gasses such as carbon dioxide depends on the proportion of Earth’s surface that is covered by the fluvial network, yet the total surface area of rivers and streams is poorly constrained. We used a global database of planform river hydromorphology and a statistical approach to show that global river and stream surface area at mean annual discharge is 773,000 ± 79,000 square kilometers (0.58 ± 0.06%) of Earth’s nonglaciated land surface, an area 44 ± 15% larger than previous spatial estimates. We found that rivers and streams likely play a greater role in controlling land-atmosphere fluxes than is currently represented in global carbon budgets.
    Keywords: Evolution
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  • 18
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-17
    Keywords: Genetics
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  • 19
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-28
    Description: Developmental enhancers mediate on/off patterns of gene expression in specific cell types at particular stages during metazoan embryogenesis. They typically integrate multiple signals and regulatory determinants to achieve precise spatiotemporal expression. Such enhancers can map quite far—one megabase or more—from the genes they regulate. How remote enhancers relay regulatory information to their target promoters is one of the central mysteries of genome organization and function. A variety of contrasting mechanisms have been proposed over the years, including enhancer tracking, linking, looping, and mobilization to transcription factories. We argue that extreme versions of these mechanisms cannot account for the transcriptional dynamics and precision seen in living cells, tissues, and embryos. We describe emerging evidence for dynamic three-dimensional hubs that combine different elements of the classical models.
    Keywords: Genetics
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  • 20
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-28
    Keywords: Genetics
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  • 21
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-28
    Description: The classical model of cytosine DNA methylation (the presence of 5-methylcytosine, 5mC) regulation depicts this covalent modification as a stable repressive regulator of promoter activity. However, whole-genome analysis of 5mC reveals widespread tissue- and cell type–specific patterns and pervasive dynamics during mammalian development. Here we review recent findings that delineate 5mC functions in developmental stages and diverse genomic compartments as well as discuss the molecular mechanisms that connect transcriptional regulation and 5mC. Beyond the newly appreciated dynamics, regulatory roles for 5mC have been suggested in new biological contexts, such as learning and memory or aging. The use of new single-cell measurement techniques and precise editing tools will enable functional analyses of 5mC in gene expression, clarifying its role in various biological processes.
    Keywords: Genetics
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  • 22
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-28
    Description: During development and throughout life, a variety of specialized cells must be generated to ensure the proper function of each tissue and organ. Chromatin plays a key role in determining cellular state, whether totipotent, pluripotent, multipotent, or differentiated. We highlight chromatin dynamics involved in the generation of pluripotent stem cells as well as their influence on cell fate decision and reprogramming. We focus on the capacity of histone variants, chaperones, modifications, and heterochromatin factors to influence cell identity and its plasticity. Recent technological advances have provided tools to elucidate the underlying chromatin dynamics for a better understanding of normal development and pathological conditions, with avenues for potential therapeutic application.
    Keywords: Cell Biology
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  • 23
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-28
    Keywords: Genetics
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  • 24
    Publication Date: 2018-09-28
    Description: Although we can increasingly measure transcription, chromatin, methylation, and other aspects of molecular biology at single-cell resolution, most assays survey only one aspect of cellular biology. Here we describe sci-CAR, a combinatorial indexing–based coassay that jointly profiles chromatin accessibility and mRNA (CAR) in each of thousands of single cells. As a proof of concept, we apply sci-CAR to 4825 cells, including a time series of dexamethasone treatment, as well as to 11,296 cells from the adult mouse kidney. With the resulting data, we compare the pseudotemporal dynamics of chromatin accessibility and gene expression, reconstruct the chromatin accessibility profiles of cell types defined by RNA profiles, and link cis-regulatory sites to their target genes on the basis of the covariance of chromatin accessibility and transcription across large numbers of single cells.
    Keywords: Genetics
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  • 25
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-05
    Keywords: Evolution
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  • 26
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-12
    Keywords: Cell Biology
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  • 27
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-21
    Keywords: Cell Biology
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  • 28
    Publication Date: 2018-12-21
    Description: The endosomal sorting complexes required for transport (ESCRTs) catalyze reverse-topology scission from the inner face of membrane necks in HIV budding, multivesicular endosome biogenesis, cytokinesis, and other pathways. We encapsulated ESCRT-III subunits Snf7, Vps24, and Vps2 and the AAA+ ATPase (adenosine triphosphatase) Vps4 in giant vesicles from which membrane nanotubes reflecting the correct topology of scission could be pulled. Upon ATP release by photo-uncaging, this system generated forces within the nanotubes that led to membrane scission in a manner dependent upon Vps4 catalytic activity and Vps4 coupling to the ESCRT-III proteins. Imaging of scission revealed Snf7 and Vps4 puncta within nanotubes whose presence followed ATP release, correlated with force generation and nanotube constriction, and preceded scission. These observations directly verify long-standing predictions that ATP-hydrolyzing assemblies of ESCRT-III and Vps4 sever membranes.
    Keywords: Cell Biology
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  • 29
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-13
    Description: Author: Stella M. Hurtley
    Keywords: Cell Biology
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  • 30
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-13
    Description: The field of molecular evolution is concerned with evolutionary changes in genes and genomes and the underlying driving forces behind those changes. Current studies in molecular evolution are almost entirely retrospective, with a focus on the mutations that were fixed during evolution, and the conclusions are often explanatory, offering no predictive insights. Because only a tiny fraction of all mutations that have ever occurred during evolution have been fixed, the “successes” that we see today provide an incomplete or even biased understanding of the evolutionary process. One way to circumvent this problem is to obtain the whole fitness landscape of a gene to understand, prospectively, chance and necessity in evolution (see the figure). Two studies in this issue, by Li et al. on page 837 (1) and Puchta et al. on page 840 (2), each take on this challenge by characterizing the in vivo fitness landscape of two RNA genes. Authors: Xionglei He, Li Liu
    Keywords: Evolution
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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: Sacha Vignieri
    Keywords: Evolution
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  • 32
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-04
    Description: Changes in gene regulatory networks (GRNs) underlie many phenotypic differences between species. However, the mechanisms of GRN evolution are still being debated (1–5). Explaining how GRNs originate, diversify, and maintain their identities despite regulatory element turnover is essential for developing mechanistic explanations for the origin, diversification, and conservation of homologous characters between species. Among the major outstanding questions in GRN evolution is whether individual cis-regulatory elements arise de novo through the gradual accumulation of mutations that increase the regulatory potential of existing DNA or whether cis-regulatory elements originate more rapidly through concerted processes. On page 1083 of this issue, Chuong et al. provide evidence that concerted processes, involving endogenous retroviruses (ERVs), which are remarkably abundant in mammalian genomes, have contributed to the evolution of the regulatory systems that control the mammalian immune system (6). Author: Vincent J. Lynch
    Keywords: Genetics
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  • 33
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-04
    Description: Author: Wei Wong
    Keywords: Cell Biology
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  • 34
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-06
    Description: Author: Stella M. Hurtley
    Keywords: Cell Biology
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  • 35
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-20
    Description: Cells of all kingdoms form a rigid but dynamic cytoskeleton that is essential for cell shape and growth. Microtubules and actin filaments build the eukaryotic cytoskeleton, and although they serve distinct functions, cooperation and indirect connections between these systems exist (1). On page 1004 of this issue, Henty-Ridilla et al. (2) report how a protein that accumulates at the growing tips of microtubules also elongates actin filaments, revealing an unexpected interaction between the two cytoskeletal systems. Author: Klemens Rottner
    Keywords: Cell Biology
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  • 36
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-04-22
    Description: For many evolutionary biologists, nothing gets their dander up faster than suggesting evolution is anything other than the process of natural selection, acting on random mutations. So some are uneasy that the John Templeton Foundation has awarded $8.7 million to U.K., Swedish, and U.S. researchers for experimental and theoretical work intended to put a revisionist view of evolution, the so-called extended evolutionary synthesis, on a sounder footing. Using a variety of plants, animals, and microbes, the researchers will study the possibility that organisms can influence their own evolution and that inheritance can take place through routes other than the genetic material. Critics are against evolutionary biologists accepting this money and argue that evolutionary theory already embraces the best of these ideas. But others are pleased as the money should help clarify the importance of different aspects of the extended synthesis. Author: Elizabeth Pennisi
    Keywords: Evolution
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-04-15
    Description: By enclosing chromosomes within a nuclear envelope (NE), eukaryotic cells are able to segregate transcription and translation, key activities involved in gene expression (1). The implication is that maintenance of the NE as a selective barrier represents an essential aspect of normal cellular physiology. However, it also presents the cell with the predicament of how to accommodate a membrane-limited organelle that might occupy a substantial portion of the cell volume. On pages 353 and 359 of this issue, Denais et al. (2) and Raab et al. (3), respectively, report that the physical size and mechanical properties of the nucleus may have dramatic effects on the behavior of motile cells. Author: Brian Burke
    Keywords: Cell Biology
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-04-15
    Description: Author: Stella M. Hurtley
    Keywords: Cell Biology
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  • 39
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-23
    Keywords: Cell Biology
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-23
    Keywords: Cell Biology
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-14
    Keywords: Evolution
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  • 42
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-26
    Keywords: Evolution
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  • 43
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-26
    Keywords: Evolution
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  • 44
    Publication Date: 2018-10-26
    Description: The color patterns of African cichlid fishes provide notable examples of phenotypic convergence. Across the more than 1200 East African rift lake species, melanic horizontal stripes have evolved numerous times. We discovered that regulatory changes of the gene agouti-related peptide 2 ( agrp2 ) act as molecular switches controlling this evolutionarily labile phenotype. Reduced agrp2 expression is convergently associated with the presence of stripe patterns across species flocks. However, cis-regulatory mutations are not predictive of stripes across radiations, suggesting independent regulatory mechanisms. Genetic mapping confirms the link between the agrp2 locus and stripe patterns. The crucial role of agrp2 is further supported by a CRISPR-Cas9 knockout that reconstitutes stripes in a nonstriped cichlid. Thus, we unveil how a single gene affects the convergent evolution of a complex color pattern.
    Keywords: Evolution
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  • 45
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-16
    Keywords: Cell Biology
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-16
    Keywords: Cell Biology
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-30
    Keywords: Evolution
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-10
    Keywords: Genetics
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  • 49
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-10
    Keywords: Cell Biology
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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: Evolution
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  • 51
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-10
    Keywords: Evolution
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  • 52
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-10
    Keywords: Evolution
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  • 53
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-10
    Description: Apoptosis is an evolutionarily conserved form of programmed cell death critical for development and tissue homeostasis in animals. The apoptotic control network includes several positive feedback loops that may allow apoptosis to spread through the cytoplasm in self-regenerating trigger waves. We tested this possibility in cell-free Xenopus laevis egg extracts and observed apoptotic trigger waves with speeds of ~30 micrometers per minute. Fractionation and inhibitor studies implicated multiple feedback loops in generating the waves. Apoptotic oocytes and eggs exhibited surface waves with speeds of ~30 micrometers per minute, which were tightly correlated with caspase activation. Thus, apoptosis spreads through trigger waves in both extracts and intact cells. Our findings show how apoptosis can spread over large distances within a cell and emphasize the general importance of trigger waves in cell signaling.
    Keywords: Cell Biology
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  • 54
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-14
    Keywords: Genetics
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  • 55
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-04-20
    Keywords: Genetics
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-04-20
    Keywords: Genetics
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  • 57
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-04-20
    Keywords: Genetics
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  • 58
    Publication Date: 2018-05-25
    Description: RNA promotes liquid-liquid phase separation (LLPS) to build membraneless compartments in cells. How distinct molecular compositions are established and maintained in these liquid compartments is unknown. Here, we report that secondary structure allows messenger RNAs (mRNAs) to self-associate and determines whether an mRNA is recruited to or excluded from liquid compartments. The polyQ-protein Whi3 induces conformational changes in RNA structure and generates distinct molecular fluctuations depending on the RNA sequence. These data support a model in which structure-based, RNA-RNA interactions promote assembly of distinct droplets and protein-driven, conformational dynamics of the RNA maintain this identity. Thus, the shape of RNA can promote the formation and coexistence of the diverse array of RNA-rich liquid compartments found in a single cell.
    Keywords: Cell Biology
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-05-25
    Keywords: Cell Biology
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  • 60
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-06-01
    Keywords: Genetics
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-06-01
    Keywords: Cell Biology
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  • 62
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-19
    Keywords: Cell Biology
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-26
    Keywords: Genetics
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  • 64
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-26
    Keywords: Evolution
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  • 65
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-09
    Keywords: Genetics
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  • 66
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-09
    Keywords: Evolution
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  • 67
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-09
    Description: Consumer genomics databases have reached the scale of millions of individuals. Recently, law enforcement authorities have exploited some of these databases to identify suspects via distant familial relatives. Using genomic data of 1.28 million individuals tested with consumer genomics, we investigated the power of this technique. We project that about 60% of the searches for individuals of European descent will result in a third-cousin or closer match, which theoretically allows their identification using demographic identifiers. Moreover, the technique could implicate nearly any U.S. individual of European descent in the near future. We demonstrate that the technique can also identify research participants of a public sequencing project. On the basis of these results, we propose a potential mitigation strategy and policy implications for human subject research.
    Keywords: Genetics
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  • 68
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-23
    Keywords: Cell Biology
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  • 69
    Publication Date: 2018-07-06
    Description: Current genetic data are equivocal as to whether goat domestication occurred multiple times or was a singular process. We generated genomic data from 83 ancient goats (51 with genome-wide coverage) from Paleolithic to Medieval contexts throughout the Near East. Our findings demonstrate that multiple divergent ancient wild goat sources were domesticated in a dispersed process that resulted in genetically and geographically distinct Neolithic goat populations, echoing contemporaneous human divergence across the region. These early goat populations contributed differently to modern goats in Asia, Africa, and Europe. We also detect early selection for pigmentation, stature, reproduction, milking, and response to dietary change, providing 8000-year-old evidence for human agency in molding genome variation within a partner species.
    Keywords: Genetics
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  • 70
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-07-13
    Keywords: Evolution
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  • 71
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-06-08
    Keywords: Genetics
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  • 72
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-06-22
    Keywords: Evolution
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  • 73
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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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  • 74
    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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  • 75
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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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  • 77
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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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  • 78
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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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 79
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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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 80
    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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  • 81
    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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  • 82
    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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  • 83
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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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  • 84
    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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  • 85
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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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  • 86
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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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  • 87
    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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  • 88
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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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  • 89
    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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  • 90
    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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  • 91
    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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  • 92
    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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  • 93
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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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  • 94
    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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  • 95
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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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  • 96
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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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  • 97
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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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  • 98
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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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  • 99
    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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2016-01-20
    Description: 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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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