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41.
Côté M Misasi J Ren T Bruchez A Lee K Filone CM Hensley L Li Q Ory D Chandran K Cunningham J 《Nature》2011,477(7364):344-348
Ebola virus (EboV) is a highly pathogenic enveloped virus that causes outbreaks of zoonotic infection in Africa. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines in response to infection and in many outbreaks, mortality exceeds 75%. The unpredictable onset, ease of transmission, rapid progression of disease, high mortality and lack of effective vaccine or therapy have created a high level of public concern about EboV. Here we report the identification of a novel benzylpiperazine adamantane diamide-derived compound that inhibits EboV infection. Using mutant cell lines and informative derivatives of the lead compound, we show that the target of the inhibitor is the endosomal membrane protein Niemann-Pick C1 (NPC1). We find that NPC1 is essential for infection, that it binds to the virus glycoprotein (GP), and that antiviral compounds interfere with GP binding to NPC1. Combined with the results of previous studies of GP structure and function, our findings support a model of EboV infection in which cleavage of the GP1 subunit by endosomal cathepsin proteases removes heavily glycosylated domains to expose the amino-terminal domain, which is a ligand for NPC1 and regulates membrane fusion by the GP2 subunit. Thus, NPC1 is essential for EboV entry and a target for antiviral therapy. 相似文献
42.
Vacic V McCarthy S Malhotra D Murray F Chou HH Peoples A Makarov V Yoon S Bhandari A Corominas R Iakoucheva LM Krastoshevsky O Krause V Larach-Walters V Welsh DK Craig D Kelsoe JR Gershon ES Leal SM Dell Aquila M Morris DW Gill M Corvin A Insel PA McClellan J King MC Karayiorgou M Levy DL DeLisi LE Sebat J 《Nature》2011,471(7339):499-503
43.
M. Novak 《Cellular and molecular life sciences : CMLS》1983,39(4):414-414
Summary Gerbils kept at high (35°C) temperature harbored a significantly largerEchinococcus multilocularis cyst biomass than those kept at room (21°C) and low (5°C) temperature. Parasite induced adrenomegaly was observed in all temperature groups.Acknowledgments. I am indebted to Miss Marianne Hardy and Mr Terry Durham for their excellent technical assistance. 相似文献
44.
45.
Mutagenicity of melanin from human red hair 总被引:1,自引:0,他引:1
Z. P. Harsanyl P. W. Post Jeannie P. Brinkmann M. R. Chedekel Rose Marie Deibel 《Cellular and molecular life sciences : CMLS》1980,36(3):291-292
Summary TheSalmonella typhimurium histidine reversion test of Ames et al. was used to demonstrate that pheomelanin, the red-brown polymeric pigment produced in human skin and hair, becomes mutagenic after exposure to long wave-length UV-light; a finding consistent with the UV-induced somatic mutation hypothesis for the origin of freckles and the high susceptibility of redheads and blonds to sunlight-induced skin cancers.Acknowledgments.S. typhimurium strains were kindly provided by Dr Bruce N. Ames. Z. Harzanyi was supported by NIEHS grant 00675-03 and an Andrew W. Mellon Teacher-Scientist Award. M. Chedekel thanks The Ohio State University Graduate School for financial assistance. 相似文献
46.
Summary The addition of L-serine to short-term cultures of rat thymocytes stimulated the incorporation of3H-deoxycytidine into DNA, but simultaneously depressed the incorporation of3H-thymidine into DNA.This investigation was supported by NIH grants No. CA-10291 and T12CA8021 from the National Cancer Institute. 相似文献
47.
Bowler C Allen AE Badger JH Grimwood J Jabbari K Kuo A Maheswari U Martens C Maumus F Otillar RP Rayko E Salamov A Vandepoele K Beszteri B Gruber A Heijde M Katinka M Mock T Valentin K Verret F Berges JA Brownlee C Cadoret JP Chiovitti A Choi CJ Coesel S De Martino A Detter JC Durkin C Falciatore A Fournet J Haruta M Huysman MJ Jenkins BD Jiroutova K Jorgensen RE Joubert Y Kaplan A Kröger N Kroth PG La Roche J Lindquist E Lommer M Martin-Jézéquel V Lopez PJ Lucas S Mangogna M McGinnis K 《Nature》2008,456(7219):239-244
Diatoms are photosynthetic secondary endosymbionts found throughout marine and freshwater environments, and are believed to be responsible for around one-fifth of the primary productivity on Earth. The genome sequence of the marine centric diatom Thalassiosira pseudonana was recently reported, revealing a wealth of information about diatom biology. Here we report the complete genome sequence of the pennate diatom Phaeodactylum tricornutum and compare it with that of T. pseudonana to clarify evolutionary origins, functional significance and ubiquity of these features throughout diatoms. In spite of the fact that the pennate and centric lineages have only been diverging for 90 million years, their genome structures are dramatically different and a substantial fraction of genes ( approximately 40%) are not shared by these representatives of the two lineages. Analysis of molecular divergence compared with yeasts and metazoans reveals rapid rates of gene diversification in diatoms. Contributing factors include selective gene family expansions, differential losses and gains of genes and introns, and differential mobilization of transposable elements. Most significantly, we document the presence of hundreds of genes from bacteria. More than 300 of these gene transfers are found in both diatoms, attesting to their ancient origins, and many are likely to provide novel possibilities for metabolite management and for perception of environmental signals. These findings go a long way towards explaining the incredible diversity and success of the diatoms in contemporary oceans. 相似文献
48.
Aposematism is an anti-predator defence, dependent on a predator's ability to associate unprofitable prey with a prey-borne signal. Multimodal signals should vary in efficacy according to the sensory systems of different predators; however, until now, the impact of multiple predator classes on the evolution of these signals had not been investigated. Here, using a community-level molecular phylogeny to generate phylogenetically independent contrasts, we show that warning signals of tiger moths vary according to the seasonal and daily activity patterns of birds and bats-predators with divergent sensory capacities. Many tiger moths advertise chemical defence using conspicuous colouration and/or ultrasonic clicks. During spring, when birds are active and bats less so, we found that tiger moths did not produce ultrasonic clicks. Throughout both spring and summer, tiger moths most active during the day were visually conspicuous. Those species emerging later in the season produced ultrasonic clicks; those that were most nocturnal were visually cryptic. Our results indicate that selective pressures from multiple predator classes have distinct roles in the evolution of multimodal warning displays now effective against a single predator class. We also suggest that the evolution of acoustic warning signals may lack the theoretical difficulties associated with the origination of conspicuous colouration. 相似文献
49.
Ichimura A Hirasawa A Poulain-Godefroy O Bonnefond A Hara T Yengo L Kimura I Leloire A Liu N Iida K Choquet H Besnard P Lecoeur C Vivequin S Ayukawa K Takeuchi M Ozawa K Tauber M Maffeis C Morandi A Buzzetti R Elliott P Pouta A Jarvelin MR Körner A Kiess W Pigeyre M Caiazzo R Van Hul W Van Gaal L Horber F Balkau B Lévy-Marchal C Rouskas K Kouvatsi A Hebebrand J Hinney A Scherag A Pattou F Meyre D Koshimizu TA Wolowczuk I Tsujimoto G Froguel P 《Nature》2012,483(7389):350-354
Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents. 相似文献
50.
Marie Morelato Mark Barash Lucas Blanes Scott Chadwick Jessirie Dilag Unnikrishnan Kuzhiumparambil Katie D. Nizio Xanthe Spindler Sebastien Moret 《Foundations of Science》2017,22(4):799-825
Forensic science and its influence on policing and the criminal justice system have increased since the beginning of the twentieth century. While the philosophies of the forensic science pioneers remain the pillar of modern practice, rapid advances in technology and the underpinning sciences have seen an explosion in the number of disciplines and tools. Consequently, the way in which we exploit and interpret the remnant of criminal activity are adapting to this changing environment. In order to best exploit the trace, an interdisciplinary approach to both research and investigation is required. In this paper, nine postdoctoral research fellows from a multidisciplinary team discuss their vision for the future of forensic science at the crime scene, in the laboratory and beyond. This paper does not pretend to be exhaustive of all fields of forensic science, but describes a portion of the postdoctoral fellows’ interests and skills. 相似文献