ALBERT

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiermeier, Quirin -- England -- Nature. 2010 Feb 4;463(7281):596-7. doi: 10.1038/463596a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130621" target="_blank"〉PubMed〈/a〉

Description: Although the notion of an early origin and diversification of life on Earth during the Archaean eon has received increasing support in geochemical, sedimentological and palaeontological evidence, ambiguities and controversies persist regarding the biogenicity and syngeneity of the record older than Late Archaean. Non-biological processes are known to produce morphologies similar to some microfossils, and hydrothermal fluids have the potential to produce abiotic organic compounds with depleted carbon isotope values, making it difficult to establish unambiguous traces of life. Here we report the discovery of a population of large (up to about 300 mum in diameter) carbonaceous spheroidal microstructures in Mesoarchaean shales and siltstones of the Moodies Group, South Africa, the Earth's oldest siliciclastic alluvial to tidal-estuarine deposits. These microstructures are interpreted as organic-walled microfossils on the basis of petrographic and geochemical evidence for their endogenicity and syngeneity, their carbonaceous composition, cellular morphology and ultrastructure, occurrence in populations, taphonomic features of soft wall deformation, and the geological context plausible for life, as well as a lack of abiotic explanation falsifying a biological origin. These are the oldest and largest Archaean organic-walled spheroidal microfossils reported so far. Our observations suggest that relatively large microorganisms cohabited with earlier reported benthic microbial mats in the photic zone of marginal marine siliciclastic environments 3.2 billion years ago.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Javaux, Emmanuelle J -- Marshall, Craig P -- Bekker, Andrey -- England -- Nature. 2010 Feb 18;463(7283):934-8. doi: 10.1038/nature08793. Epub 2010 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology, University of Liege, 17 allee du 6 Aout B18, Liege 4000, Belgium. ej.javaux@ulg.ac.be〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20139963" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Javitt, Gail -- England -- Nature. 2010 Aug 12;466(7308):817-8. doi: 10.1038/466817a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Berman Institute of Bioethics, Johns Hopkins University, USA. gjavitt1@jhu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703288" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Sep 23;467(7314):368. doi: 10.1038/467368a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20864950" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456675/" 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/PMC4456675/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berman, Helen M -- Kleywegt, Gerard J -- Nakamura, Haruki -- Markley, John L -- Burley, Stephen K -- P41 LM005799/LM/NLM NIH HHS/ -- England -- Nature. 2010 Jan 28;463(7280):425. doi: 10.1038/463425c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20110969" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Deborah -- Carter, Philip -- England -- Nature. 2010 Jul 15;466(7304):315. doi: 10.1038/466315a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631779" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsnelson, Alla -- England -- Nature. 2010 Dec 9;468(7325):741. doi: 10.1038/468741a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21150963" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Mar 18;464(7287):325. doi: 10.1038/464325a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237517" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Oct 28;467(7319):1136. doi: 10.1038/4671136a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981104" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lok, Corie -- England -- Nature. 2010 Sep 2;467(7311):18-21. doi: 10.1038/467018a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20811430" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsnelson, Alla -- England -- Nature. 2010 Jun 3;465(7298):537. doi: 10.1038/465537a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20520682" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schrope, Mark -- England -- Nature. 2010 Aug 12;466(7308):802. doi: 10.1038/466802a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703275" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Aug 12;466(7308):797. doi: 10.1038/466797a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703263" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Borrell, Brendan -- England -- Nature. 2010 Feb 18;463(7283):858. doi: 10.1038/463858a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20164888" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Apr 22;464(7292):1103-4. doi: 10.1038/4641103b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20414265" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von Storch, Hans -- Allen, Myles -- England -- Nature. 2010 Jan 7;463(7277):25. doi: 10.1038/463025a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054378" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, Virginia -- England -- Nature. 2010 Mar 18;464(7287):340-2. doi: 10.1038/464340a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237536" target="_blank"〉PubMed〈/a〉

Description: Autophagy, the process by which proteins and organelles are sequestered in autophagosomal vesicles and delivered to the lysosome/vacuole for degradation, provides a primary route for turnover of stable and defective cellular proteins. Defects in this system are linked with numerous human diseases. Although conserved protein kinase, lipid kinase and ubiquitin-like protein conjugation subnetworks controlling autophagosome formation and cargo recruitment have been defined, our understanding of the global organization of this system is limited. Here we report a proteomic analysis of the autophagy interaction network in human cells under conditions of ongoing (basal) autophagy, revealing a network of 751 interactions among 409 candidate interacting proteins with extensive connectivity among subnetworks. Many new autophagy interaction network components have roles in vesicle trafficking, protein or lipid phosphorylation and protein ubiquitination, and affect autophagosome number or flux when depleted by RNA interference. The six ATG8 orthologues in humans (MAP1LC3/GABARAP proteins) interact with a cohort of 67 proteins, with extensive binding partner overlap between family members, and frequent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting regions in partner proteins. These studies provide a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901998/" 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/PMC2901998/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Behrends, Christian -- Sowa, Mathew E -- Gygi, Steven P -- Harper, J Wade -- R01 AG011085/AG/NIA NIH HHS/ -- R01 AG011085-18/AG/NIA NIH HHS/ -- R01 GM054137/GM/NIGMS NIH HHS/ -- R01 GM054137-14/GM/NIGMS NIH HHS/ -- R01 GM054137-14S1/GM/NIGMS NIH HHS/ -- R01 GM054137-15/GM/NIGMS NIH HHS/ -- R01 GM070565/GM/NIGMS NIH HHS/ -- R01 GM070565-05S1/GM/NIGMS NIH HHS/ -- R01 GM095567/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jul 1;466(7302):68-76. doi: 10.1038/nature09204. Epub 2010 Jun 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20562859" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Nov 4;468(7320):6. doi: 10.1038/468006b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048718" target="_blank"〉PubMed〈/a〉

Description: Increased levels of brain amyloid-beta, a secreted peptide cleavage product of amyloid precursor protein (APP), is believed to be critical in the aetiology of Alzheimer's disease. Increased amyloid-beta can cause synaptic depression, reduce the number of spine protrusions (that is, sites of synaptic contacts) and block long-term synaptic potentiation (LTP), a form of synaptic plasticity; however, the receptor through which amyloid-beta produces these synaptic perturbations has remained elusive. Lauren et al. suggested that binding between oligomeric amyloid-beta (a form of amyloid-beta thought to be most active) and the cellular prion protein (PrP(C)) is necessary for synaptic perturbations. Here we show that PrP(C) is not required for amyloid-beta-induced synaptic depression, reduction in spine density, or blockade of LTP; our results indicate that amyloid-beta-mediated synaptic defects do not require PrP(c).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057871/" 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/PMC3057871/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kessels, Helmut W -- Nguyen, Louis N -- Nabavi, Sadegh -- Malinow, Roberto -- R01 AG032132/AG/NIA NIH HHS/ -- R01 AG032132-14/AG/NIA NIH HHS/ -- R01 AG032132-15/AG/NIA NIH HHS/ -- R01 AG032132-17/AG/NIA NIH HHS/ -- R01 AG032132-18/AG/NIA NIH HHS/ -- R01 MH049159/MH/NIMH NIH HHS/ -- R01 MH049159-09/MH/NIMH NIH HHS/ -- R01 MH049159-21/MH/NIMH NIH HHS/ -- R01 MH049159-22/MH/NIMH NIH HHS/ -- England -- Nature. 2010 Aug 12;466(7308):E3-4; discussion E4-5. doi: 10.1038/nature09217.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neural Circuits and Behavior, 9500 Gilman Drive 0634, University of California at San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703260" target="_blank"〉PubMed〈/a〉

Description: Laryngeal echolocation, used by most living bats to form images of their surroundings and to detect and capture flying prey, is considered to be a key innovation for the evolutionary success of bats, and palaeontologists have long sought osteological correlates of echolocation that can be used to infer the behaviour of fossil bats. Veselka et al. argued that the most reliable trait indicating echolocation capabilities in bats is an articulation between the stylohyal bone (part of the hyoid apparatus that supports the throat and larynx) and the tympanic bone, which forms the floor of the middle ear. They examined the oldest and most primitive known bat, Onychonycteris finneyi (early Eocene, USA), and argued that it showed evidence of this stylohyal-tympanic articulation, from which they concluded that O. finneyi may have been capable of echolocation. We disagree with their interpretation of key fossil data and instead argue that O. finneyi was probably not an echolocating bat.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simmons, Nancy B -- Seymour, Kevin L -- Habersetzer, Jorg -- Gunnell, Gregg F -- England -- Nature. 2010 Aug 19;466(7309):E8; discussion E9. doi: 10.1038/nature09219.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉American Museum of Natural History, Central Park West at 79th Street, New York, New York 10024, USA. simmons@amnh.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20724993" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2010 Feb 11;463(7282):724-5. doi: 10.1038/463724a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20148008" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2010 Feb 11;463(7282):718-9. doi: 10.1038/463718a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20148004" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2010 Jun 10;465(7299):672-3. doi: 10.1038/465672a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20535170" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agre, Peter -- England -- Nature. 2010 Oct 14;467(7317):S11. doi: 10.1038/467S11a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944611" target="_blank"〉PubMed〈/a〉

Description: Transporter proteins from the MATE (multidrug and toxic compound extrusion) family are vital in metabolite transport in plants, directly affecting crop yields worldwide. MATE transporters also mediate multiple-drug resistance (MDR) in bacteria and mammals, modulating the efficacy of many pharmaceutical drugs used in the treatment of a variety of diseases. MATE transporters couple substrate transport to electrochemical gradients and are the only remaining class of MDR transporters whose structure has not been determined. Here we report the X-ray structure of the MATE transporter NorM from Vibrio cholerae determined to 3.65 A, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known MDR transporter. We also report a cation-binding site in close proximity to residues previously deemed critical for transport. This conformation probably represents a stage of the transport cycle with high affinity for monovalent cations and low affinity for substrates.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152480/" 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/PMC3152480/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Xiao -- Szewczyk, Paul -- Karyakin, Andrey -- Evin, Mariah -- Hong, Wen-Xu -- Zhang, Qinghai -- Chang, Geoffrey -- GM70480/GM/NIGMS NIH HHS/ -- GM73197/GM/NIGMS NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073197-07/GM/NIGMS NIH HHS/ -- R01 GM070480/GM/NIGMS NIH HHS/ -- R01 GM070480-01A1/GM/NIGMS NIH HHS/ -- R01 GM070480-02/GM/NIGMS NIH HHS/ -- R01 GM070480-03/GM/NIGMS NIH HHS/ -- R01 GM070480-04/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Oct 21;467(7318):991-4. doi: 10.1038/nature09408. Epub 2010 Sep 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20861838" target="_blank"〉PubMed〈/a〉

Description: The longstanding concept that corneal epithelial stem cells reside mainly in the limbus is supported by the absence of major corneal epithelial differentiation markers, that is, K3 and K12 keratins, in limbal basal cells (these markers are expressed, however, in corneal basal cells, thus distinguishing the mode of keratin expression in corneal epithelium from that of all other stratified epithelia), the centripetal migration of corneal epithelial cells, the exclusive location of slow-cycling cells in the limbal basal layer, the superior in vitro proliferative potential of limbal epithelial cells, and the transplanted limbal cells' ability to reconstitute corneal epithelium in vivo (reviewed in refs 1-4). Moreover, previous data indicate that corneal and conjunctival epithelia represent two separate cell lineages (reviewed in refs 1-4). Majo et al. suggested, however, that corneal and conjunctival epithelia are equipotent, and that identical oligopotent stem cells are present throughout the corneal, limbal and conjunctival epithelia. We point out here that these suggestions are inconsistent with many known growth, differentiation and cell migration properties of the anterior ocular epithelia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Tung-Tien -- Tseng, Scheffer C -- Lavker, Robert M -- England -- Nature. 2010 Feb 25;463(7284):E10-1; discussion E11. doi: 10.1038/nature08805.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA. sunt01@nyumc.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182462" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heffernan, Olive -- England -- Nature. 2010 Feb 18;463(7283):860. doi: 10.1038/463860a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20164892" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2010 Oct 28;467(7319):1020. doi: 10.1038/4671020a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981065" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swedlow, Jason R -- Cotta-Ramusino, Cecilia -- Elledge, Stephen J -- England -- Nature. 2010 Apr 1;464(7289):684-5. doi: 10.1038/464684a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360724" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Henrich, Joseph -- Heine, Steven J -- Norenzayan, Ara -- England -- Nature. 2010 Jul 1;466(7302):29. doi: 10.1038/466029a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. joseph.henrich@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20595995" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neufeld, Peter -- Scheck, Barry -- England -- Nature. 2010 Mar 18;464(7287):351. doi: 10.1038/464351a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardozo School of Law, New York, New York 10011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237545" target="_blank"〉PubMed〈/a〉

Description: Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the approximately 21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Phenotypes were scored quantitatively by computational image processing, which allowed us to identify hundreds of human genes involved in diverse biological functions including cell division, migration and survival. As part of the Mitocheck consortium, this study provides an in-depth analysis of cell division phenotypes and makes the entire high-content data set available as a resource to the community.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108885/" 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/PMC3108885/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neumann, Beate -- Walter, Thomas -- Heriche, Jean-Karim -- Bulkescher, Jutta -- Erfle, Holger -- Conrad, Christian -- Rogers, Phill -- Poser, Ina -- Held, Michael -- Liebel, Urban -- Cetin, Cihan -- Sieckmann, Frank -- Pau, Gregoire -- Kabbe, Rolf -- Wunsche, Annelie -- Satagopam, Venkata -- Schmitz, Michael H A -- Chapuis, Catherine -- Gerlich, Daniel W -- Schneider, Reinhard -- Eils, Roland -- Huber, Wolfgang -- Peters, Jan-Michael -- Hyman, Anthony A -- Durbin, Richard -- Pepperkok, Rainer -- Ellenberg, Jan -- 077192/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Apr 1;464(7289):721-7. doi: 10.1038/nature08869.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MitoCheck Project Group, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360735" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taylor, Charles -- Colman, Paul -- England -- Nature. 2010 Apr 29;464(7293):1266-7. doi: 10.1038/4641266c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20428138" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicholson, Francis -- England -- Nature. 2010 Dec 2;468(7324):634. doi: 10.1038/468634b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124437" target="_blank"〉PubMed〈/a〉

Description: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in 〉100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P 〈 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039276/" 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/PMC3039276/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Teslovich, Tanya M -- Musunuru, Kiran -- Smith, Albert V -- Edmondson, Andrew C -- Stylianou, Ioannis M -- Koseki, Masahiro -- Pirruccello, James P -- Ripatti, Samuli -- Chasman, Daniel I -- Willer, Cristen J -- Johansen, Christopher T -- Fouchier, Sigrid W -- Isaacs, Aaron -- Peloso, Gina M -- Barbalic, Maja -- Ricketts, Sally L -- Bis, Joshua C -- Aulchenko, Yurii S -- Thorleifsson, Gudmar -- Feitosa, Mary F -- Chambers, John -- Orho-Melander, Marju -- Melander, Olle -- Johnson, Toby -- Li, Xiaohui -- Guo, Xiuqing -- Li, Mingyao -- Shin Cho, Yoon -- Jin Go, Min -- Jin Kim, Young -- Lee, Jong-Young -- Park, Taesung -- Kim, Kyunga -- Sim, Xueling -- Twee-Hee Ong, Rick -- Croteau-Chonka, Damien C -- Lange, Leslie A -- Smith, Joshua D -- Song, Kijoung -- Hua Zhao, Jing -- Yuan, Xin -- Luan, Jian'an -- Lamina, Claudia -- Ziegler, Andreas -- Zhang, Weihua -- Zee, Robert Y L -- Wright, Alan F -- Witteman, Jacqueline C M -- Wilson, James F -- Willemsen, Gonneke -- Wichmann, H-Erich -- Whitfield, John B -- Waterworth, Dawn M -- Wareham, Nicholas J -- Waeber, Gerard -- Vollenweider, Peter -- Voight, Benjamin F -- Vitart, Veronique -- Uitterlinden, Andre G -- Uda, Manuela -- Tuomilehto, Jaakko -- Thompson, John R -- Tanaka, Toshiko -- Surakka, Ida -- Stringham, Heather M -- Spector, Tim D -- Soranzo, Nicole -- Smit, Johannes H -- Sinisalo, Juha -- Silander, Kaisa -- Sijbrands, Eric J G -- Scuteri, Angelo -- Scott, James -- Schlessinger, David -- Sanna, Serena -- Salomaa, Veikko -- Saharinen, Juha -- Sabatti, Chiara -- Ruokonen, Aimo -- Rudan, Igor -- Rose, Lynda M -- Roberts, Robert -- Rieder, Mark -- Psaty, Bruce M -- Pramstaller, Peter P -- Pichler, Irene -- Perola, Markus -- Penninx, Brenda W J H -- Pedersen, Nancy L -- Pattaro, Cristian -- Parker, Alex N -- Pare, Guillaume -- Oostra, Ben A -- O'Donnell, Christopher J -- Nieminen, Markku S -- Nickerson, Deborah A -- Montgomery, Grant W -- Meitinger, Thomas -- McPherson, Ruth -- McCarthy, Mark I -- McArdle, Wendy -- Masson, David -- Martin, Nicholas G -- Marroni, Fabio -- Mangino, Massimo -- Magnusson, Patrik K E -- Lucas, Gavin -- Luben, Robert -- Loos, Ruth J F -- Lokki, Marja-Liisa -- Lettre, Guillaume -- Langenberg, Claudia -- Launer, Lenore J -- Lakatta, Edward G -- Laaksonen, Reijo -- Kyvik, Kirsten O -- Kronenberg, Florian -- Konig, Inke R -- Khaw, Kay-Tee -- Kaprio, Jaakko -- Kaplan, Lee M -- Johansson, Asa -- Jarvelin, Marjo-Riitta -- Janssens, A Cecile J W -- Ingelsson, Erik -- Igl, Wilmar -- Kees Hovingh, G -- Hottenga, Jouke-Jan -- Hofman, Albert -- Hicks, Andrew A -- Hengstenberg, Christian -- Heid, Iris M -- Hayward, Caroline -- Havulinna, Aki S -- Hastie, Nicholas D -- Harris, Tamara B -- Haritunians, Talin -- Hall, Alistair S -- Gyllensten, Ulf -- Guiducci, Candace -- Groop, Leif C -- Gonzalez, Elena -- Gieger, Christian -- Freimer, Nelson B -- Ferrucci, Luigi -- Erdmann, Jeanette -- Elliott, Paul -- Ejebe, Kenechi G -- Doring, Angela -- Dominiczak, Anna F -- Demissie, Serkalem -- Deloukas, Panagiotis -- de Geus, Eco J C -- de Faire, Ulf -- Crawford, Gabriel -- Collins, Francis S -- Chen, Yii-der I -- Caulfield, Mark J -- Campbell, Harry -- Burtt, Noel P -- Bonnycastle, Lori L -- Boomsma, Dorret I -- Boekholdt, S Matthijs -- Bergman, Richard N -- Barroso, Ines -- Bandinelli, Stefania -- Ballantyne, Christie M -- Assimes, Themistocles L -- Quertermous, Thomas -- Altshuler, David -- Seielstad, Mark -- Wong, Tien Y -- Tai, E-Shyong -- Feranil, Alan B -- Kuzawa, Christopher W -- Adair, Linda S -- Taylor, Herman A Jr -- Borecki, Ingrid B -- Gabriel, Stacey B -- Wilson, James G -- Holm, Hilma -- Thorsteinsdottir, Unnur -- Gudnason, Vilmundur -- Krauss, Ronald M -- Mohlke, Karen L -- Ordovas, Jose M -- Munroe, Patricia B -- Kooner, Jaspal S -- Tall, Alan R -- Hegele, Robert A -- Kastelein, John J P -- Schadt, Eric E -- Rotter, Jerome I -- Boerwinkle, Eric -- Strachan, David P -- Mooser, Vincent -- Stefansson, Kari -- Reilly, Muredach P -- Samani, Nilesh J -- Schunkert, Heribert -- Cupples, L Adrienne -- Sandhu, Manjinder S -- Ridker, Paul M -- Rader, Daniel J -- van Duijn, Cornelia M -- Peltonen, Leena -- Abecasis, Goncalo R -- Boehnke, Michael -- Kathiresan, Sekar -- 068545/Z/02/Wellcome Trust/United Kingdom -- 076113/B/04/Z/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- 1Z01 HG000024/HG/NHGRI NIH HHS/ -- 5R01DK06833603/DK/NIDDK NIH HHS/ -- 5R01DK07568102/DK/NIDDK NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01HL08770003/HL/NHLBI NIH HHS/ -- 5R01HL08821502/HL/NHLBI NIH HHS/ -- CA 047988/CA/NCI NIH HHS/ -- CZB/4/710/Chief Scientist Office/United Kingdom -- DK062370/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK072193/DK/NIDDK NIH HHS/ -- DK078150/DK/NIDDK NIH HHS/ -- DK56350/DK/NIDDK NIH HHS/ -- ES10126/ES/NIEHS NIH HHS/ -- G0000934/Medical Research Council/United Kingdom -- G0401527/Medical Research Council/United Kingdom -- G0601966/Medical Research Council/United Kingdom -- G0700931/Medical Research Council/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G0801566/Medical Research Council/United Kingdom -- G9521010/Medical Research Council/United Kingdom -- G9521010D/Medical Research Council/United Kingdom -- HHSN268200625226C/PHS HHS/ -- HL 04381/HL/NHLBI NIH HHS/ -- HL 080467/HL/NHLBI NIH HHS/ -- HL-54776/HL/NHLBI NIH HHS/ -- HL085144/HL/NHLBI NIH HHS/ -- K99 HL098364/HL/NHLBI NIH HHS/ -- K99 HL098364-01/HL/NHLBI NIH HHS/ -- K99HL094535/HL/NHLBI NIH HHS/ -- M01-RR00425/RR/NCRR NIH HHS/ -- MC_QA137934/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- MC_U127561128/Medical Research Council/United Kingdom -- N01 HC-15103/HC/NHLBI NIH HHS/ -- N01 HC-55222/HC/NHLBI NIH HHS/ -- N01-AG-12100/AG/NIA NIH HHS/ -- N01-HC-25195/HC/NHLBI NIH HHS/ -- N01-HC-35129/HC/NHLBI NIH HHS/ -- N01-HC-45133/HC/NHLBI NIH HHS/ -- N01-HC-55015/HC/NHLBI NIH HHS/ -- N01-HC-55016/HC/NHLBI NIH HHS/ -- N01-HC-55018/HC/NHLBI NIH HHS/ -- N01-HC-55019/HC/NHLBI NIH HHS/ -- N01-HC-55020/HC/NHLBI NIH HHS/ -- N01-HC-55021/HC/NHLBI NIH HHS/ -- N01-HC-55022/HC/NHLBI NIH HHS/ -- N01-HC-75150/HC/NHLBI NIH HHS/ -- N01-HC-85079/HC/NHLBI NIH HHS/ -- N01-HC-85080/HC/NHLBI NIH HHS/ -- N01-HC-85081/HC/NHLBI NIH HHS/ -- N01-HC-85082/HC/NHLBI NIH HHS/ -- N01-HC-85083/HC/NHLBI NIH HHS/ -- N01-HC-85084/HC/NHLBI NIH HHS/ -- N01-HC-85085/HC/NHLBI NIH HHS/ -- N01-HC-85086/HC/NHLBI NIH HHS/ -- N01-HG-65403/HG/NHGRI NIH HHS/ -- N02-HL-6-4278/HL/NHLBI NIH HHS/ -- PG/02/128/British Heart Foundation/United Kingdom -- PG/08/094/British Heart Foundation/United Kingdom -- PG/08/094/26019/British Heart Foundation/United Kingdom -- R01 DK072193/DK/NIDDK NIH HHS/ -- R01 DK078150/DK/NIDDK NIH HHS/ -- R01 HL087647/HL/NHLBI NIH HHS/ -- R01 HL087676/HL/NHLBI NIH HHS/ -- R01 HL089650/HL/NHLBI NIH HHS/ -- R01HL086694/HL/NHLBI NIH HHS/ -- R01HL087641/HL/NHLBI NIH HHS/ -- R01HL087652/HL/NHLBI NIH HHS/ -- R01HL59367/HL/NHLBI NIH HHS/ -- R24 HD050924/HD/NICHD NIH HHS/ -- RC1 HL099634/HL/NHLBI NIH HHS/ -- RC1 HL099634-02/HL/NHLBI NIH HHS/ -- RC1 HL099793/HL/NHLBI NIH HHS/ -- RC2 HL101864,/HL/NHLBI NIH HHS/ -- RC2 HL102419/HL/NHLBI NIH HHS/ -- RG/07/005/23633/British Heart Foundation/United Kingdom -- RR20649/RR/NCRR NIH HHS/ -- SP/08/005/25115/British Heart Foundation/United Kingdom -- T32 GM007092/GM/NIGMS NIH HHS/ -- T32 HG00040/HG/NHGRI NIH HHS/ -- T32HL007208/HL/NHLBI NIH HHS/ -- TW05596/TW/FIC NIH HHS/ -- U01 DK062370/DK/NIDDK NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 HL069757/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01HG004402/HG/NHGRI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1RR025005/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):707-13. doi: 10.1038/nature09270.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686565" target="_blank"〉PubMed〈/a〉

Description: Universal common ancestry (UCA) is a central pillar of modern evolutionary theory. As first suggested by Darwin, the theory of UCA posits that all extant terrestrial organisms share a common genetic heritage, each being the genealogical descendant of a single species from the distant past. The classic evidence for UCA, although massive, is largely restricted to 'local' common ancestry-for example, of specific phyla rather than the entirety of life-and has yet to fully integrate the recent advances from modern phylogenetics and probability theory. Although UCA is widely assumed, it has rarely been subjected to formal quantitative testing, and this has led to critical commentary emphasizing the intrinsic technical difficulties in empirically evaluating a theory of such broad scope. Furthermore, several researchers have proposed that early life was characterized by rampant horizontal gene transfer, leading some to question the monophyly of life. Here I provide the first, to my knowledge, formal, fundamental test of UCA, without assuming that sequence similarity implies genetic kinship. I test UCA by applying model selection theory to molecular phylogenies, focusing on a set of ubiquitously conserved proteins that are proposed to be orthologous. Among a wide range of biological models involving the independent ancestry of major taxonomic groups, the model selection tests are found to overwhelmingly support UCA irrespective of the presence of horizontal gene transfer and symbiotic fusion events. These results provide powerful statistical evidence corroborating the monophyly of all known life.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Theobald, Douglas L -- England -- Nature. 2010 May 13;465(7295):219-22. doi: 10.1038/nature09014.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Brandeis University, Waltham, Massachusetts 01778, USA. dtheobald@brandeis.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463738" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baggerly, Keith -- England -- Nature. 2010 Sep 23;467(7314):401. doi: 10.1038/467401b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20864982" target="_blank"〉PubMed〈/a〉

Description: Variation in transcriptional regulation is thought to be a major cause of phenotypic diversity. Although widespread differences in gene expression among individuals of a species have been observed, studies to examine the variability of transcription factor binding on a global scale have not been performed, and thus the extent and underlying genetic basis of transcription factor binding diversity is unknown. By mapping differences in transcription factor binding among individuals, here we present the genetic basis of such variation on a genome-wide scale. Whole-genome Ste12-binding profiles were determined using chromatin immunoprecipitation coupled with DNA sequencing in pheromone-treated cells of 43 segregants of a cross between two highly diverged yeast strains and their parental lines. We identified extensive Ste12-binding variation among individuals, and mapped underlying cis- and trans-acting loci responsible for such variation. We showed that most transcription factor binding variation is cis-linked, and that many variations are associated with polymorphisms residing in the binding motifs of Ste12 as well as those of several proposed Ste12 cofactors. We also identified two trans-factors, AMN1 and FLO8, that modulate Ste12 binding to promoters of more than ten genes under alpha-factor treatment. Neither of these two genes was previously known to regulate Ste12, and we suggest that they may be mediators of gene activity and phenotypic diversity. Ste12 binding strongly correlates with gene expression for more than 200 genes, indicating that binding variation is functional. Many of the variable-bound genes are involved in cell wall organization and biogenesis. Overall, these studies identified genetic regulators of molecular diversity among individuals and provide new insights into mechanisms of gene regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941147/" 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/PMC2941147/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Wei -- Zhao, Hongyu -- Mancera, Eugenio -- Steinmetz, Lars M -- Snyder, Michael -- P01 HG000205/HG/NHGRI NIH HHS/ -- P01 HG000205-10/HG/NHGRI NIH HHS/ -- R01 CA077808/CA/NCI NIH HHS/ -- R01 CA077808-09/CA/NCI NIH HHS/ -- R01 GM059507-09/GM/NIGMS NIH HHS/ -- R01 GM068717/GM/NIGMS NIH HHS/ -- R01 GM068717-08/GM/NIGMS NIH HHS/ -- RR19895/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Apr 22;464(7292):1187-91. doi: 10.1038/nature08934. Epub 2010 Mar 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237471" target="_blank"〉PubMed〈/a〉

Description: Recently, Brinster et al. suggested that type II fatty-acid biosynthesis (FASII) is not a suitable antibacterial target for Gram-positive pathogens because they use fatty acids directly from host serum rather than de novo synthesis. Their findings, if confirmed, are relevant for further scientific and financial investments in the development of new drugs targeting FASII. We present here in vitro and in vivo data demonstrating that their observations do not hold for Staphylococcus aureus, a major Gram-positive pathogen causing several human infections. The observed differences among Gram-positive pathogens in FASII reflects heterogeneity either in fatty-acid synthesis or in the capacity for fatty-acid uptake from the environment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balemans, Wendy -- Lounis, Nacer -- Gilissen, Ron -- Guillemont, Jerome -- Simmen, Kenny -- Andries, Koen -- Koul, Anil -- England -- Nature. 2010 Jan 21;463(7279):E3; discussion E4. doi: 10.1038/nature08667.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Antimicrobial Research, Tibotec BVBA, Johnson & Johnson, Turnhoutseweg 30, B-2340 Beerse, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20090698" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Dec 16;468(7326):867. doi: 10.1038/468867a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164433" target="_blank"〉PubMed〈/a〉

Description: A popular hypothesis in the social sciences is that humans have social preferences to reduce inequality in outcome distributions because it has a negative impact on their experienced reward. Although there is a large body of behavioural and anthropological evidence consistent with the predictions of these theories, there is no direct neural evidence for the existence of inequality-averse preferences. Such evidence would be especially useful because some behaviours that are consistent with a dislike for unequal outcomes could also be explained by concerns for social image or reciprocity, which do not require a direct aversion towards inequality. Here we use functional MRI to test directly for the existence of inequality-averse social preferences in the human brain. Inequality was created by recruiting pairs of subjects and giving one of them a large monetary endowment. While both subjects evaluated further monetary transfers from the experimenter to themselves and to the other participant, we measured neural responses in the ventral striatum and ventromedial prefrontal cortex, two areas that have been shown to be involved in the valuation of monetary and primary rewards in both social and non-social contexts. Consistent with inequality-averse models of social preferences, we find that activity in these areas was more responsive to transfers to others than to self in the 'high-pay' subject, whereas the activity of the 'low-pay' subject showed the opposite pattern. These results provide direct evidence for the validity of this class of models, and also show that the brain's reward circuitry is sensitive to both advantageous and disadvantageous inequality.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tricomi, Elizabeth -- Rangel, Antonio -- Camerer, Colin F -- O'Doherty, John P -- England -- Nature. 2010 Feb 25;463(7284):1089-91. doi: 10.1038/nature08785.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Psychology Department, Rutgers University, Newark, New Jersey 07102, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182511" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- England -- Nature. 2010 Jul 1;466(7302):24-6. doi: 10.1038/466024a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20595989" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, David R -- England -- Nature. 2010 Jan 7;463(7277):25. doi: 10.1038/463025b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054375" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilbert, Natasha -- England -- Nature. 2010 Mar 18;464(7287):347-8. doi: 10.1038/464347a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237538" target="_blank"〉PubMed〈/a〉

Description: Alternative splicing has a crucial role in the generation of biological complexity, and its misregulation is often involved in human disease. Here we describe the assembly of a 'splicing code', which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons. The code determines new classes of splicing patterns, identifies distinct regulatory programs in different tissues, and identifies mutation-verified regulatory sequences. Widespread regulatory strategies are revealed, including the use of unexpectedly large combinations of features, the establishment of low exon inclusion levels that are overcome by features in specific tissues, the appearance of features deeper into introns than previously appreciated, and the modulation of splice variant levels by transcript structure characteristics. The code detected a class of exons whose inclusion silences expression in adult tissues by activating nonsense-mediated messenger RNA decay, but whose exclusion promotes expression during embryogenesis. The code facilitates the discovery and detailed characterization of regulated alternative splicing events on a genome-wide scale.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barash, Yoseph -- Calarco, John A -- Gao, Weijun -- Pan, Qun -- Wang, Xinchen -- Shai, Ofer -- Blencowe, Benjamin J -- Frey, Brendan J -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 May 6;465(7294):53-9. doi: 10.1038/nature09000.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomedical Engineering, Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Road, Toronto M5S 3G4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20445623" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crutzen, Paul J -- England -- Nature. 2010 Oct 14;467(7317):S10. doi: 10.1038/467S10a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944610" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilbert, Natasha -- England -- Nature. 2010 Jan 14;463(7278):142-3. doi: 10.1038/463142b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075888" target="_blank"〉PubMed〈/a〉

Description: The Southern Ocean, with its large surface area and vigorous overturning circulation, is potentially a substantial sink of anthropogenic CO(2) (refs 1-4). Despite its importance, the mechanism and pathways of anthropogenic CO(2) uptake and transport are poorly understood. Regulation of the Southern Ocean carbon sink by the wind-driven Ekman flow, mesoscale eddies and their interaction is under debate. Here we use a high-resolution ocean circulation and carbon cycle model to address the mechanisms controlling the Southern Ocean sink of anthropogenic CO(2). The focus of our study is on the intra-annual variability in anthropogenic CO(2) over a two-year time period. We show that the pattern of carbon uptake is correlated with the oceanic vertical exchange. Zonally integrated carbon uptake peaks at the Antarctic polar front. The carbon is then advected away from the uptake regions by the circulation of the Southern Ocean, which is controlled by the interplay among Ekman flow, ocean eddies and subduction of water masses. Although lateral carbon fluxes are locally dominated by the imprint of mesoscale eddies, the Ekman transport is the primary mechanism for the zonally integrated, cross-frontal transport of anthropogenic CO(2). Intra-annual variability of the cross-frontal transport is dominated by the Ekman flow with little compensation from eddies. A budget analysis in the density coordinate highlights the importance of wind-driven transport across the polar front and subduction at the subtropical front. Our results suggest intimate connections between oceanic carbon uptake and climate variability through the temporal variability of Ekman transport.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, T -- Woloszyn, M -- Mazloff, M -- England -- Nature. 2010 Jan 7;463(7277):80-3. doi: 10.1038/nature08687.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atmospheric Science, Colorado State University, 1371 Campus Delivery, Fort Collins, Colorado 80523-1371, USA. ito@atmos.colostate.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054394" target="_blank"〉PubMed〈/a〉

Description: Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) 〉or= 40 kg m(-2) or BMI standard deviation score 〉or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880448/" 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/PMC2880448/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walters, R G -- Jacquemont, S -- Valsesia, A -- de Smith, A J -- Martinet, D -- Andersson, J -- Falchi, M -- Chen, F -- Andrieux, J -- Lobbens, S -- Delobel, B -- Stutzmann, F -- El-Sayed Moustafa, J S -- Chevre, J-C -- Lecoeur, C -- Vatin, V -- Bouquillon, S -- Buxton, J L -- Boute, O -- Holder-Espinasse, M -- Cuisset, J-M -- Lemaitre, M-P -- Ambresin, A-E -- Brioschi, A -- Gaillard, M -- Giusti, V -- Fellmann, F -- Ferrarini, A -- Hadjikhani, N -- Campion, D -- Guilmatre, A -- Goldenberg, A -- Calmels, N -- Mandel, J-L -- Le Caignec, C -- David, A -- Isidor, B -- Cordier, M-P -- Dupuis-Girod, S -- Labalme, A -- Sanlaville, D -- Beri-Dexheimer, M -- Jonveaux, P -- Leheup, B -- Ounap, K -- Bochukova, E G -- Henning, E -- Keogh, J -- Ellis, R J -- Macdermot, K D -- van Haelst, M M -- Vincent-Delorme, C -- Plessis, G -- Touraine, R -- Philippe, A -- Malan, V -- Mathieu-Dramard, M -- Chiesa, J -- Blaumeiser, B -- Kooy, R F -- Caiazzo, R -- Pigeyre, M -- Balkau, B -- Sladek, R -- Bergmann, S -- Mooser, V -- Waterworth, D -- Reymond, A -- Vollenweider, P -- Waeber, G -- Kurg, A -- Palta, P -- Esko, T -- Metspalu, A -- Nelis, M -- Elliott, P -- Hartikainen, A-L -- McCarthy, M I -- Peltonen, L -- Carlsson, L -- Jacobson, P -- Sjostrom, L -- Huang, N -- Hurles, M E -- O'Rahilly, S -- Farooqi, I S -- Mannik, K -- Jarvelin, M-R -- Pattou, F -- Meyre, D -- Walley, A J -- Coin, L J M -- Blakemore, A I F -- Froguel, P -- Beckmann, J S -- 077014/Wellcome Trust/United Kingdom -- 079534/Wellcome Trust/United Kingdom -- 082390/Wellcome Trust/United Kingdom -- 089061/Wellcome Trust/United Kingdom -- 1RL1MH083268-01/MH/NIMH NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01MH63706:02/MH/NIMH NIH HHS/ -- G0500539/Medical Research Council/United Kingdom -- G0600331/Medical Research Council/United Kingdom -- G0600331(77796)/Medical Research Council/United Kingdom -- G0900554/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Feb 4;463(7281):671-5. doi: 10.1038/nature08727.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Genomic Medicine, Imperial College London, London W12 0NN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130649" target="_blank"〉PubMed〈/a〉

Description: Malaria caused by Plasmodium falciparum is a disease that is responsible for 880,000 deaths per year worldwide. Vaccine development has proved difficult and resistance has emerged for most antimalarial drugs. To discover new antimalarial chemotypes, we have used a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library-many of which showed potent in vitro activity against drug-resistant P. falciparum strains-and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in several organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Our findings provide the scientific community with new starting points for malaria drug discovery.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874979/" 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/PMC2874979/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guiguemde, W Armand -- Shelat, Anang A -- Bouck, David -- Duffy, Sandra -- Crowther, Gregory J -- Davis, Paul H -- Smithson, David C -- Connelly, Michele -- Clark, Julie -- Zhu, Fangyi -- Jimenez-Diaz, Maria B -- Martinez, Maria S -- Wilson, Emily B -- Tripathi, Abhai K -- Gut, Jiri -- Sharlow, Elizabeth R -- Bathurst, Ian -- El Mazouni, Farah -- Fowble, Joseph W -- Forquer, Isaac -- McGinley, Paula L -- Castro, Steve -- Angulo-Barturen, Inigo -- Ferrer, Santiago -- Rosenthal, Philip J -- Derisi, Joseph L -- Sullivan, David J -- Lazo, John S -- Roos, David S -- Riscoe, Michael K -- Phillips, Margaret A -- Rathod, Pradipsinh K -- Van Voorhis, Wesley C -- Avery, Vicky M -- Guy, R Kiplin -- AI045774/AI/NIAID NIH HHS/ -- AI053680/AI/NIAID NIH HHS/ -- AI067921/AI/NIAID NIH HHS/ -- AI075517/AI/NIAID NIH HHS/ -- AI075594/AI/NIAID NIH HHS/ -- AI080625/AI/NIAID NIH HHS/ -- AI082617/AI/NIAID NIH HHS/ -- AI28724/AI/NIAID NIH HHS/ -- AI35707/AI/NIAID NIH HHS/ -- AI53862/AI/NIAID NIH HHS/ -- AI772682/AI/NIAID NIH HHS/ -- CA78039/CA/NCI NIH HHS/ -- F32 AI077268/AI/NIAID NIH HHS/ -- F32 AI077268-03/AI/NIAID NIH HHS/ -- P01 AI035707/AI/NIAID NIH HHS/ -- P01 AI035707-140007/AI/NIAID NIH HHS/ -- P01 CA078039-10/CA/NCI NIH HHS/ -- P41 RR001614/RR/NCRR NIH HHS/ -- P41 RR001614-246970/RR/NCRR NIH HHS/ -- R01 AI045774/AI/NIAID NIH HHS/ -- R01 AI045774-09/AI/NIAID NIH HHS/ -- R37 AI028724/AI/NIAID NIH HHS/ -- R37 AI028724-17/AI/NIAID NIH HHS/ -- R56 AI082617/AI/NIAID NIH HHS/ -- R56 AI082617-01/AI/NIAID NIH HHS/ -- U01 AI053862/AI/NIAID NIH HHS/ -- U01 AI053862-05/AI/NIAID NIH HHS/ -- U01 AI075594-03/AI/NIAID NIH HHS/ -- UL1 TR000005/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 May 20;465(7296):311-5. doi: 10.1038/nature09099.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Biology and Therapeutics, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485428" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 Jan 21;463(7279):269. doi: 10.1038/463269a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20090704" target="_blank"〉PubMed〈/a〉

Description: Models derived from human pluripotent stem cells that accurately recapitulate neural development in vitro and allow for the generation of specific neuronal subtypes are of major interest to the stem cell and biomedical community. Notch signalling, particularly through the Notch effector HES5, is a major pathway critical for the onset and maintenance of neural progenitor cells in the embryonic and adult nervous system. Here we report the transcriptional and epigenomic analysis of six consecutive neural progenitor cell stages derived from a HES5::eGFP reporter human embryonic stem cell line. Using this system, we aimed to model cell-fate decisions including specification, expansion and patterning during the ontogeny of cortical neural stem and progenitor cells. In order to dissect regulatory mechanisms that orchestrate the stage-specific differentiation process, we developed a computational framework to infer key regulators of each cell-state transition based on the progressive remodelling of the epigenetic landscape and then validated these through a pooled short hairpin RNA screen. We were also able to refine our previous observations on epigenetic priming at transcription factor binding sites and suggest here that they are mediated by combinations of core and stage-specific factors. Taken together, we demonstrate the utility of our system and outline a general framework, not limited to the context of the neural lineage, to dissect regulatory circuits of differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336237/" 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/PMC4336237/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ziller, Michael J -- Edri, Reuven -- Yaffe, Yakey -- Donaghey, Julie -- Pop, Ramona -- Mallard, William -- Issner, Robbyn -- Gifford, Casey A -- Goren, Alon -- Xing, Jeffrey -- Gu, Hongcang -- Cacchiarelli, Davide -- Tsankov, Alexander M -- Epstein, Charles -- Rinn, John L -- Mikkelsen, Tarjei S -- Kohlbacher, Oliver -- Gnirke, Andreas -- Bernstein, Bradley E -- Elkabetz, Yechiel -- Meissner, Alexander -- F32 DK095537/DK/NIDDK NIH HHS/ -- HG006911/HG/NHGRI NIH HHS/ -- P01 GM099117/GM/NIGMS NIH HHS/ -- P01GM099117/GM/NIGMS NIH HHS/ -- U01 ES017155/ES/NIEHS NIH HHS/ -- U01ES017155/ES/NIEHS NIH HHS/ -- U54 HG006991/HG/NHGRI NIH HHS/ -- England -- Nature. 2015 Feb 19;518(7539):355-9. doi: 10.1038/nature13990. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 6997801, Israel. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA [3] Center for Systems Biology and Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Applied Bioinformatics, Center for Bioinformatics and Quantitative Biology Center, University of Tubingen, Tubingen 72076, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533951" target="_blank"〉PubMed〈/a〉

Description: Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts. We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. A gene expression signature based on the top screening hits correlated with markers of BRAF inhibitor resistance in cell lines and patient-derived samples. These results collectively demonstrate the potential of Cas9-based activators as a powerful genetic perturbation technology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420636/" 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/PMC4420636/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Konermann, Silvana -- Brigham, Mark D -- Trevino, Alexandro E -- Joung, Julia -- Abudayyeh, Omar O -- Barcena, Clea -- Hsu, Patrick D -- Habib, Naomi -- Gootenberg, Jonathan S -- Nishimasu, Hiroshi -- Nureki, Osamu -- Zhang, Feng -- DP1 MH100706/MH/NIMH NIH HHS/ -- DP1-MH100706/DP/NCCDPHP CDC HHS/ -- R01 NS062849/NS/NINDS NIH HHS/ -- R01 NS073124/NS/NINDS NIH HHS/ -- R01-NS07312401/NS/NINDS NIH HHS/ -- England -- Nature. 2015 Jan 29;517(7536):583-8. doi: 10.1038/nature14136. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, Massachusetts 02142, USA [2] McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [3] Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, Massachusetts 02142, USA [2] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, Massachusetts 02142, USA [2] McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [3] Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [5] Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi Bunkyo, Tokyo 113-0032, Japan [2] JST, PRESTO 2-11-16 Yayoi Bunkyo, Tokyo 113-0032, Japan. ; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi Bunkyo, Tokyo 113-0032, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25494202" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rennison, Andrew -- England -- Nature. 2010 May 13;465(7295):157. doi: 10.1038/465157c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463716" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spinney, Laura -- England -- Nature. 2010 Mar 18;464(7287):344-6. doi: 10.1038/464344a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237537" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2010 Jul 29;466(7306):540-1. doi: 10.1038/466540b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671680" target="_blank"〉PubMed〈/a〉

Description: The conserved Polycomb repressive complex 2 (PRC2) generates trimethylation of histone 3 lysine 27 (H3K27me3), a modification associated with stable epigenetic silencing. Much is known about PRC2-induced silencing but key questions remain concerning its nucleation and stability. Vernalization, the perception and memory of winter in plants, is a classic epigenetic process that, in Arabidopsis, involves PRC2-based silencing of the floral repressor FLC. The slow dynamics of vernalization, taking place over weeks in the cold, generate a level of stable silencing of FLC in the subsequent warm that depends quantitatively on the length of the prior cold. These features make vernalization an ideal experimental system to investigate both the maintenance of epigenetic states and the switching between them. Here, using mathematical modelling, chromatin immunoprecipitation and an FLC:GUS reporter assay, we show that the quantitative nature of vernalization is generated by H3K27me3-mediated FLC silencing in the warm in a subpopulation of cells whose number depends on the length of the prior cold. During the cold, H3K27me3 levels progressively increase at a tightly localized nucleation region within FLC. At the end of the cold, numerical simulations predict that such a nucleation region is capable of switching the bistable epigenetic state of an individual locus, with the probability of overall FLC coverage by silencing H3K27me3 marks depending on the length of cold exposure. Thus, the model predicts a bistable pattern of FLC gene expression in individual cells, a prediction we verify using the FLC:GUS reporter system. Our proposed switching mechanism, involving the local nucleation of an opposing histone modification, is likely to be widely relevant in epigenetic reprogramming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Angel, Andrew -- Song, Jie -- Dean, Caroline -- Howard, Martin -- England -- Nature. 2011 Jul 24;476(7358):105-8. doi: 10.1038/nature10241.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computational and Systems Biology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21785438" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steel, Mike -- Penny, David -- England -- Nature. 2010 May 13;465(7295):168-9. doi: 10.1038/465168a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463725" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Onslow, Mark -- Packman, Ann -- England -- Nature. 2011 Feb 24;470(7335):465; author reply 465. doi: 10.1038/470465b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21350470" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2010 Oct 28;467(7319):1015. doi: 10.1038/4671015a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20981062" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adam, David -- England -- Nature. 2010 Nov 18;468(7322):362-4. doi: 10.1038/468362a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21085150" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Legg, David A -- Ma, Xiaoya -- Wolfe, Joanna M -- Ortega-Hernandez, Javier -- Edgecombe, Gregory D -- Sutton, Mark D -- England -- Nature. 2011 Aug 10;476(7359):E2-3; discussion E3-4. doi: 10.1038/nature10267.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth Science and Engineering, Imperial College London, London SW7 2AZ UK. d.legg10@imperial.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21833046" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lehn, Jean-Marie -- England -- Nature. 2011 Oct 12;478(7368):S8-9. doi: 10.1038/478S8a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21993827" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmidhuber, Jurgen -- England -- Nature. 2011 Jan 6;469(7328):34. doi: 10.1038/469034b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21209647" target="_blank"〉PubMed〈/a〉

Description: Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide has successfully identified specific subtypes of regulatory elements. In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements, chromatin states, transcription factor binding sites, RNA polymerase II regulation and insulator elements; however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179250/" 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/PMC3179250/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Negre, Nicolas -- Brown, Christopher D -- Ma, Lijia -- Bristow, Christopher Aaron -- Miller, Steven W -- Wagner, Ulrich -- Kheradpour, Pouya -- Eaton, Matthew L -- Loriaux, Paul -- Sealfon, Rachel -- Li, Zirong -- Ishii, Haruhiko -- Spokony, Rebecca F -- Chen, Jia -- Hwang, Lindsay -- Cheng, Chao -- Auburn, Richard P -- Davis, Melissa B -- Domanus, Marc -- Shah, Parantu K -- Morrison, Carolyn A -- Zieba, Jennifer -- Suchy, Sarah -- Senderowicz, Lionel -- Victorsen, Alec -- Bild, Nicholas A -- Grundstad, A Jason -- Hanley, David -- MacAlpine, David M -- Mannervik, Mattias -- Venken, Koen -- Bellen, Hugo -- White, Robert -- Gerstein, Mark -- Russell, Steven -- Grossman, Robert L -- Ren, Bing -- Posakony, James W -- Kellis, Manolis -- White, Kevin P -- F32 GM074364/GM/NIGMS NIH HHS/ -- F32 GM074364-01/GM/NIGMS NIH HHS/ -- F32 GM074364-02/GM/NIGMS NIH HHS/ -- P50 GM081892/GM/NIGMS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG004037-04/HG/NHGRI NIH HHS/ -- RC2 HG005639/HG/NHGRI NIH HHS/ -- RC2 HG005639-02/HG/NHGRI NIH HHS/ -- U01 HG004264/HG/NHGRI NIH HHS/ -- U01 HG004279/HG/NHGRI NIH HHS/ -- U01HG004264/HG/NHGRI NIH HHS/ -- England -- Nature. 2011 Mar 24;471(7339):527-31. doi: 10.1038/nature09990.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Genomics and Systems Biology, Department of Human Genetics, The University of Chicago, 900 East 57th Street, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21430782" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jonietz, Erika -- England -- Nature. 2011 Mar 24;471(7339):S20-1. doi: 10.1038/471S20a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21430717" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schooler, Jonathan -- England -- Nature. 2011 Feb 24;470(7335):437. doi: 10.1038/470437a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, Santa Barbara, USA. schooler@psych.ucsb.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21350443" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Noorden, Richard -- England -- Nature. 2011 Apr 21;472(7343):270-1. doi: 10.1038/472270a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21512544" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Neil -- Lux, Thomas -- England -- Nature. 2011 Jan 20;469(7330):302-3. doi: 10.1038/469302a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21248829" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shelton, James -- England -- Nature. 2011 Nov 2;479(7371):7. doi: 10.1038/479007a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bureau for Global Health, US Agency for International Development, Washington DC, USA. jshelton@usaid.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22051636" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maxmen, Amy -- England -- Nature. 2011 Feb 10;470(7333):161-2. doi: 10.1038/470161a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21307912" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poste, George -- England -- Nature. 2011 Jan 13;469(7329):156-7. doi: 10.1038/469156a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Complex Adaptive Systems Initiative, Arizona State University, Scottsdale, Arizona 85257, USA. george.poste@asu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21228852" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2011 Feb 17;470(7334):305-6. doi: 10.1038/470305b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21330998" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2011 Jun 22;474(7352):419. doi: 10.1038/474419a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21697903" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kutschera, U -- England -- Nature. 2011 Mar 3;471(7336):37. doi: 10.1038/471037c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21368813" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kwok, Roberta -- England -- Nature. 2011 May 26;473(7348):436-8. doi: 10.1038/473436a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21614053" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2011 Mar 17;471(7338):266. doi: 10.1038/471266a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21412289" target="_blank"〉PubMed〈/a〉

Description: Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Nowak et al. argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836173/" 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/PMC3836173/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbot, Patrick -- Abe, Jun -- Alcock, John -- Alizon, Samuel -- Alpedrinha, Joao A C -- Andersson, Malte -- Andre, Jean-Baptiste -- van Baalen, Minus -- Balloux, Francois -- Balshine, Sigal -- Barton, Nick -- Beukeboom, Leo W -- Biernaskie, Jay M -- Bilde, Trine -- Borgia, Gerald -- Breed, Michael -- Brown, Sam -- Bshary, Redouan -- Buckling, Angus -- Burley, Nancy T -- Burton-Chellew, Max N -- Cant, Michael A -- Chapuisat, Michel -- Charnov, Eric L -- Clutton-Brock, Tim -- Cockburn, Andrew -- Cole, Blaine J -- Colegrave, Nick -- Cosmides, Leda -- Couzin, Iain D -- Coyne, Jerry A -- Creel, Scott -- Crespi, Bernard -- Curry, Robert L -- Dall, Sasha R X -- Day, Troy -- Dickinson, Janis L -- Dugatkin, Lee Alan -- El Mouden, Claire -- Emlen, Stephen T -- Evans, Jay -- Ferriere, Regis -- Field, Jeremy -- Foitzik, Susanne -- Foster, Kevin -- Foster, William A -- Fox, Charles W -- Gadau, Juergen -- Gandon, Sylvain -- Gardner, Andy -- Gardner, Michael G -- Getty, Thomas -- Goodisman, Michael A D -- Grafen, Alan -- Grosberg, Rick -- Grozinger, Christina M -- Gouyon, Pierre-Henri -- Gwynne, Darryl -- Harvey, Paul H -- Hatchwell, Ben J -- Heinze, Jurgen -- Helantera, Heikki -- Helms, Ken R -- Hill, Kim -- Jiricny, Natalie -- Johnstone, Rufus A -- Kacelnik, Alex -- Kiers, E Toby -- Kokko, Hanna -- Komdeur, Jan -- Korb, Judith -- Kronauer, Daniel -- Kummerli, Rolf -- Lehmann, Laurent -- Linksvayer, Timothy A -- Lion, Sebastien -- Lyon, Bruce -- Marshall, James A R -- McElreath, Richard -- Michalakis, Yannis -- Michod, Richard E -- Mock, Douglas -- Monnin, Thibaud -- Montgomerie, Robert -- Moore, Allen J -- Mueller, Ulrich G -- Noe, Ronald -- Okasha, Samir -- Pamilo, Pekka -- Parker, Geoff A -- Pedersen, Jes S -- Pen, Ido -- Pfennig, David -- Queller, David C -- Rankin, Daniel J -- Reece, Sarah E -- Reeve, Hudson K -- Reuter, Max -- Roberts, Gilbert -- Robson, Simon K A -- Roze, Denis -- Rousset, Francois -- Rueppell, Olav -- Sachs, Joel L -- Santorelli, Lorenzo -- Schmid-Hempel, Paul -- Schwarz, Michael P -- Scott-Phillips, Tom -- Shellmann-Sherman, Janet -- Sherman, Paul W -- Shuker, David M -- Smith, Jeff -- Spagna, Joseph C -- Strassmann, Beverly -- Suarez, Andrew V -- Sundstrom, Liselotte -- Taborsky, Michael -- Taylor, Peter -- Thompson, Graham -- Tooby, John -- Tsutsui, Neil D -- Tsuji, Kazuki -- Turillazzi, Stefano -- Ubeda, Francisco -- Vargo, Edward L -- Voelkl, Bernard -- Wenseleers, Tom -- West, Stuart A -- West-Eberhard, Mary Jane -- Westneat, David F -- Wiernasz, Diane C -- Wild, Geoff -- Wrangham, Richard -- Young, Andrew J -- Zeh, David W -- Zeh, Jeanne A -- Zink, Andrew -- BB/H022716/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2011 Mar 24;471(7339):E1-4; author reply E9-10. doi: 10.1038/nature09831.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21430721" target="_blank"〉PubMed〈/a〉

Description: Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088773/" 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/PMC3088773/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ernst, Jason -- Kheradpour, Pouya -- Mikkelsen, Tarjei S -- Shoresh, Noam -- Ward, Lucas D -- Epstein, Charles B -- Zhang, Xiaolan -- Wang, Li -- Issner, Robbyn -- Coyne, Michael -- Ku, Manching -- Durham, Timothy -- Kellis, Manolis -- Bernstein, Bradley E -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01HG004037/HG/NHGRI NIH HHS/ -- RC1HG005334/HG/NHGRI NIH HHS/ -- U54 HG004570/HG/NHGRI NIH HHS/ -- U54 HG004570-01/HG/NHGRI NIH HHS/ -- U54 HG004570-02/HG/NHGRI NIH HHS/ -- U54 HG004570-02S1/HG/NHGRI NIH HHS/ -- U54 HG004570-03/HG/NHGRI NIH HHS/ -- U54 HG004570-03S1/HG/NHGRI NIH HHS/ -- U54 HG004570-04/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 May 5;473(7345):43-9. doi: 10.1038/nature09906. Epub 2011 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21441907" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mounce, Ross C P -- Wills, Matthew A -- England -- Nature. 2011 Aug 10;476(7359):E1; discussion E3-4. doi: 10.1038/nature10266.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK. rcpm20@bath.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21833044" target="_blank"〉PubMed〈/a〉

Description: Arising from W. Wiltschko et al. 419, 467-470 (2002); Wiltschko et al. replyThe magnetic compass of migratory birds is embedded in the visual system and it has been reported by Wiltschko et al. that European Robins, Erithacus rubecula, cannot show magnetic compass orientation using their left eye only. This has led to the notion that the magnetic compass should be located only in the right eye of birds. However, a complete right lateralization of the magnetic compass would be very surprising, and functional neuroanatomical data have questioned this notion. Here we show that the results of Wiltschko et al. could not be independently confirmed using double-blind protocols. European Robins can perform magnetic compass orientation with both eyes open, with the left eye open only, and with the right eye open only. No clear lateralization is observed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hein, Christine Maira -- Engels, Svenja -- Kishkinev, Dmitry -- Mouritsen, Henrik -- England -- Nature. 2011 Mar 31;471(7340):E11-2; discussion E12-3. doi: 10.1038/nature09875.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉AG Neurosensorik/Animal Navigation, IBU, University of Oldenburg, D-26111 Oldenburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21455128" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Snowdon, Rod -- Friedt, Wolfgang -- England -- Nature. 2012 Oct 4;490(7418):37. doi: 10.1038/490037d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23038458" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Dec 20;492(7429):311.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23281497" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayden, Erika Check -- England -- Nature. 2012 Apr 25;484(7395):428. doi: 10.1038/484428a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22538578" target="_blank"〉PubMed〈/a〉

Description: Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored. Here we use genetically engineered mouse models to conduct a 'co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors, markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385933/" 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/PMC3385933/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Zhao -- Cheng, Katherine -- Walton, Zandra -- Wang, Yuchuan -- Ebi, Hiromichi -- Shimamura, Takeshi -- Liu, Yan -- Tupper, Tanya -- Ouyang, Jing -- Li, Jie -- Gao, Peng -- Woo, Michele S -- Xu, Chunxiao -- Yanagita, Masahiko -- Altabef, Abigail -- Wang, Shumei -- Lee, Charles -- Nakada, Yuji -- Pena, Christopher G -- Sun, Yanping -- Franchetti, Yoko -- Yao, Catherine -- Saur, Amy -- Cameron, Michael D -- Nishino, Mizuki -- Hayes, D Neil -- Wilkerson, Matthew D -- Roberts, Patrick J -- Lee, Carrie B -- Bardeesy, Nabeel -- Butaney, Mohit -- Chirieac, Lucian R -- Costa, Daniel B -- Jackman, David -- Sharpless, Norman E -- Castrillon, Diego H -- Demetri, George D -- Janne, Pasi A -- Pandolfi, Pier Paolo -- Cantley, Lewis C -- Kung, Andrew L -- Engelman, Jeffrey A -- Wong, Kwok-Kin -- 1U01CA141576/CA/NCI NIH HHS/ -- CA122794/CA/NCI NIH HHS/ -- CA137008/CA/NCI NIH HHS/ -- CA137008-01/CA/NCI NIH HHS/ -- CA137181/CA/NCI NIH HHS/ -- CA140594/CA/NCI NIH HHS/ -- CA147940/CA/NCI NIH HHS/ -- K23 CA157631/CA/NCI NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- P30 CA016086/CA/NCI NIH HHS/ -- P50 CA090578/CA/NCI NIH HHS/ -- P50 CA090578-06/CA/NCI NIH HHS/ -- P50CA090578/CA/NCI NIH HHS/ -- R01 CA122794/CA/NCI NIH HHS/ -- R01 CA122794-01/CA/NCI NIH HHS/ -- R01 CA137008/CA/NCI NIH HHS/ -- R01 CA137008-01/CA/NCI NIH HHS/ -- R01 CA137181/CA/NCI NIH HHS/ -- R01 CA137181-01A2/CA/NCI NIH HHS/ -- R01 CA140594/CA/NCI NIH HHS/ -- R01 CA140594-01/CA/NCI NIH HHS/ -- R01 CA163896/CA/NCI NIH HHS/ -- RC2 CA147940/CA/NCI NIH HHS/ -- RC2 CA147940-01/CA/NCI NIH HHS/ -- U01 CA141576/CA/NCI NIH HHS/ -- U01 CA141576-01/CA/NCI NIH HHS/ -- England -- Nature. 2012 Mar 18;483(7391):613-7. doi: 10.1038/nature10937.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22425996" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Sep 20;489(7416):335-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23002452" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baumgartner, Holger -- England -- Nature. 2012 Apr 4;484(7392):37. doi: 10.1038/484037d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22481345" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sarewitz, Daniel -- England -- Nature. 2012 May 9;485(7397):149. doi: 10.1038/485149a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Consortium for Science, Policy and Outcomes, Arizona State University, USA. dsarewitz@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22575922" target="_blank"〉PubMed〈/a〉

Description: Antiviral responses must be tightly regulated to defend rapidly against infection while minimizing inflammatory damage. Type 1 interferons (IFN-I) are crucial mediators of antiviral responses and their transcription is regulated by a variety of transcription factors; principal among these is the family of interferon regulatory factors (IRFs). The IRF gene regulatory networks are complex and contain multiple feedback loops. The tools of systems biology are well suited to elucidate the complex interactions that give rise to precise coordination of the interferon response. Here we have used an unbiased systems approach to predict that a member of the forkhead family of transcription factors, FOXO3, is a negative regulator of a subset of antiviral genes. This prediction was validated using macrophages isolated from Foxo3-null mice. Genome-wide location analysis combined with gene deletion studies identified the Irf7 gene as a critical target of FOXO3. FOXO3 was identified as a negative regulator of Irf7 transcription and we have further demonstrated that FOXO3, IRF7 and IFN-I form a coherent feed-forward regulatory circuit. Our data suggest that the FOXO3-IRF7 regulatory circuit represents a novel mechanism for establishing the requisite set points in the interferon pathway that balances the beneficial effects and deleterious sequelae of the antiviral response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556990/" 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/PMC3556990/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Litvak, Vladimir -- Ratushny, Alexander V -- Lampano, Aaron E -- Schmitz, Frank -- Huang, Albert C -- Raman, Ayush -- Rust, Alistair G -- Bergthaler, Andreas -- Aitchison, John D -- Aderem, Alan -- HHSN272200700038C/AI/NIAID NIH HHS/ -- HHSN272200700038C/PHS HHS/ -- HHSN272200800058C/AI/NIAID NIH HHS/ -- HSN272200800058C/PHS HHS/ -- R01 AI025032/AI/NIAID NIH HHS/ -- R01 AI032972/AI/NIAID NIH HHS/ -- R01AI025032/AI/NIAID NIH HHS/ -- R01AI032972/AI/NIAID NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- U54 GM103511/GM/NIGMS NIH HHS/ -- U54 RR022220/RR/NCRR NIH HHS/ -- U54GM103511/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Oct 18;490(7420):421-5. doi: 10.1038/nature11428. Epub 2012 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22982991" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bolker, Jessica -- England -- Nature. 2012 Nov 1;491(7422):31-3. doi: 10.1038/491031a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of New Hampshire, Durham 03824, New Hampshire, USA. jessica.bolker@unh.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23128209" target="_blank"〉PubMed〈/a〉

Description: Scientific communication relies on evidence that cannot be entirely included in publications, but the rise of computational science has added a new layer of inaccessibility. Although it is now accepted that data should be made available on request, the current regulations regarding the availability of software are inconsistent. We argue that, with some exceptions, anything less than the release of source programs is intolerable for results that depend on computation. The vagaries of hardware, software and natural language will always ensure that exact reproducibility remains uncertain, but withholding code increases the chances that efforts to reproduce results will fail.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ince, Darrel C -- Hatton, Leslie -- Graham-Cumming, John -- England -- Nature. 2012 Feb 22;482(7386):485-8. doi: 10.1038/nature10836.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computing Open University, Walton Hall, Milton Keynes MK7 6AA, UK. d.c.ince@open.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358837" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bourzac, Katherine -- England -- Nature. 2012 Dec 6;492(7427):S18-20. doi: 10.1038/492S18a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222670" target="_blank"〉PubMed〈/a〉

Description: Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with approximately 40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310911/" 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/PMC3310911/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jager, Stefanie -- Cimermancic, Peter -- Gulbahce, Natali -- Johnson, Jeffrey R -- McGovern, Kathryn E -- Clarke, Starlynn C -- Shales, Michael -- Mercenne, Gaelle -- Pache, Lars -- Li, Kathy -- Hernandez, Hilda -- Jang, Gwendolyn M -- Roth, Shoshannah L -- Akiva, Eyal -- Marlett, John -- Stephens, Melanie -- D'Orso, Ivan -- Fernandes, Jason -- Fahey, Marie -- Mahon, Cathal -- O'Donoghue, Anthony J -- Todorovic, Aleksandar -- Morris, John H -- Maltby, David A -- Alber, Tom -- Cagney, Gerard -- Bushman, Frederic D -- Young, John A -- Chanda, Sumit K -- Sundquist, Wesley I -- Kortemme, Tanja -- Hernandez, Ryan D -- Craik, Charles S -- Burlingame, Alma -- Sali, Andrej -- Frankel, Alan D -- Krogan, Nevan J -- P01 AI090935/AI/NIAID NIH HHS/ -- P01 AI090935-02/AI/NIAID NIH HHS/ -- P01 GM073732-05/GM/NIGMS NIH HHS/ -- P41 GM103481/GM/NIGMS NIH HHS/ -- P41 RR001081/RR/NCRR NIH HHS/ -- P41RR001614/RR/NCRR NIH HHS/ -- P50 GM081879/GM/NIGMS NIH HHS/ -- P50 GM081879-02/GM/NIGMS NIH HHS/ -- P50 GM082250/GM/NIGMS NIH HHS/ -- P50 GM082250-05/GM/NIGMS NIH HHS/ -- P50GM081879/GM/NIGMS NIH HHS/ -- P50GM082545/GM/NIGMS NIH HHS/ -- U54 RR022220/RR/NCRR NIH HHS/ -- England -- Nature. 2011 Dec 21;481(7381):365-70. doi: 10.1038/nature10719.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22190034" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- England -- Nature. 2012 May 9;485(7397):164-6. doi: 10.1038/485164a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22575940" target="_blank"〉PubMed〈/a〉

Description: The clinical efficacy and safety of a drug is determined by its activity profile across many proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to design drugs rationally a priori against profiles of several proteins would have immense value in drug discovery. Here we describe a new approach for the automated design of ligands against profiles of multiple drug targets. The method is demonstrated by the evolution of an approved acetylcholinesterase inhibitor drug into brain-penetrable ligands with either specific polypharmacology or exquisite selectivity profiles for G-protein-coupled receptors. Overall, 800 ligand-target predictions of prospectively designed ligands were tested experimentally, of which 75% were confirmed to be correct. We also demonstrate target engagement in vivo. The approach can be a useful source of drug leads when multi-target profiles are required to achieve either selectivity over other drug targets or a desired polypharmacology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653568/" 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/PMC3653568/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Besnard, Jeremy -- Ruda, Gian Filippo -- Setola, Vincent -- Abecassis, Keren -- Rodriguiz, Ramona M -- Huang, Xi-Ping -- Norval, Suzanne -- Sassano, Maria F -- Shin, Antony I -- Webster, Lauren A -- Simeons, Frederick R C -- Stojanovski, Laste -- Prat, Annik -- Seidah, Nabil G -- Constam, Daniel B -- Bickerton, G Richard -- Read, Kevin D -- Wetsel, William C -- Gilbert, Ian H -- Roth, Bryan L -- Hopkins, Andrew L -- 083481/Wellcome Trust/United Kingdom -- BB/FOF/PF/15/09/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J010510/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MH082441/MH/NIMH NIH HHS/ -- R01 DA017204/DA/NIDA NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- WT 083481/Wellcome Trust/United Kingdom -- England -- Nature. 2012 Dec 13;492(7428):215-20. doi: 10.1038/nature11691.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235874" target="_blank"〉PubMed〈/a〉