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  • 1
    Publication Date: 2013-11-29
    Description: Bacterial pathogens use an injectisome to deliver virulence proteins into eukaryotic host cells. The bacterial flagellum and injectisome export their component proteins for self-assembly. These two systems show high structural similarities and are classified as the type III secretion system, but it remains elusive how similar they are in situ because the structures of these complexes isolated from cells and visualized by electron cryomicroscopy have shown only the export channel and housing for the export apparatus. Here we report in situ structures of Salmonella injectisome and flagellum by electron cryotomography. The injectisome lacks the flagellar basal body C-ring, but a wing-like disc and a globular density corresponding to the export gate platform and ATPase hexamer ring, respectively, are stably attached through thin connectors, revealing yet unidentified common architectures of the two systems. The ATPase ring is far from the disc, suggesting that both apparatuses are observed in an export-off state. Scientific Reports 3 doi: 10.1038/srep03369
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 2
    Publication Date: 2013-09-13
    Description: Established infections with the human and simian immunodeficiency viruses (HIV and SIV, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral therapies only able to control, but not clear, these infections. Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that approximately 50% of rhesus macaques (RM; Macaca mulatta) vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviraemic control of infection with the highly pathogenic strain SIVmac239 (ref. 5). Here we show that regardless of the route of challenge, RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable lymphatic and haematogenous viral dissemination, and that replication-competent SIV persists in several sites for weeks to months. Over time, however, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma- or tissue-associated virus using ultrasensitive assays, and a loss of T-cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive quantitative PCR and quantitative PCR with reverse transcription analyses of tissues from RhCMV/SIV vector-protected RM necropsied 69-172 weeks after challenge did not detect SIV RNA or DNA sequences above background levels, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells to naive RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T-cell-mediated immune surveillance elicited and maintained by cytomegalovirus vectors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849456/" 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/PMC3849456/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, Scott G -- Piatak, Michael Jr -- Ventura, Abigail B -- Hughes, Colette M -- Gilbride, Roxanne M -- Ford, Julia C -- Oswald, Kelli -- Shoemaker, Rebecca -- Li, Yuan -- Lewis, Matthew S -- Gilliam, Awbrey N -- Xu, Guangwu -- Whizin, Nathan -- Burwitz, Benjamin J -- Planer, Shannon L -- Turner, John M -- Legasse, Alfred W -- Axthelm, Michael K -- Nelson, Jay A -- Fruh, Klaus -- Sacha, Jonah B -- Estes, Jacob D -- Keele, Brandon F -- Edlefsen, Paul T -- Lifson, Jeffrey D -- Picker, Louis J -- HHSN261200800001E/PHS HHS/ -- P01 AI094417/AI/NIAID NIH HHS/ -- P51OD011092/OD/NIH HHS/ -- R01 AI060392/AI/NIAID NIH HHS/ -- R01 DE021291/DE/NIDCR NIH HHS/ -- R37 AI054292/AI/NIAID NIH HHS/ -- U19 AI095985/AI/NIAID NIH HHS/ -- U19 AI096109/AI/NIAID NIH HHS/ -- U24 OD010850/OD/NIH HHS/ -- U42 OD010426/OD/NIH HHS/ -- England -- Nature. 2013 Oct 3;502(7469):100-4. doi: 10.1038/nature12519. Epub 2013 Sep 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24025770" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytomegalovirus/genetics/immunology ; Female ; Macaca mulatta ; Male ; Molecular Sequence Data ; SAIDS Vaccines/*immunology ; Simian Acquired Immunodeficiency Syndrome/*prevention & control/virology ; Simian Immunodeficiency Virus/*immunology ; Time Factors ; Vaccines, Attenuated/immunology ; Viral Load ; Virus Replication/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-07-13
    Description: RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence. The motifs that we identify in vitro correlate well with in vivo RNA-binding data. Moreover, we can associate them with distinct functional roles in diverse types of post-transcriptional regulation, enabling new insights into the functions of RNA-binding proteins both in normal physiology and in human disease. These data provide an unprecedented overview of RNA-binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929597/" 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/PMC3929597/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ray, Debashish -- Kazan, Hilal -- Cook, Kate B -- Weirauch, Matthew T -- Najafabadi, Hamed S -- Li, Xiao -- Gueroussov, Serge -- Albu, Mihai -- Zheng, Hong -- Yang, Ally -- Na, Hong -- Irimia, Manuel -- Matzat, Leah H -- Dale, Ryan K -- Smith, Sarah A -- Yarosh, Christopher A -- Kelly, Seth M -- Nabet, Behnam -- Mecenas, Desirea -- Li, Weimin -- Laishram, Rakesh S -- Qiao, Mei -- Lipshitz, Howard D -- Piano, Fabio -- Corbett, Anita H -- Carstens, Russ P -- Frey, Brendan J -- Anderson, Richard A -- Lynch, Kristen W -- Penalva, Luiz O F -- Lei, Elissa P -- Fraser, Andrew G -- Blencowe, Benjamin J -- Morris, Quaid D -- Hughes, Timothy R -- 1R01HG00570/HG/NHGRI NIH HHS/ -- DK015602-05/DK/NIDDK NIH HHS/ -- MOP-125894/Canadian Institutes of Health Research/Canada -- MOP-14409/Canadian Institutes of Health Research/Canada -- MOP-49451/Canadian Institutes of Health Research/Canada -- MOP-67011/Canadian Institutes of Health Research/Canada -- MOP-93671/Canadian Institutes of Health Research/Canada -- P30 CA014520/CA/NCI NIH HHS/ -- R01 CA104708/CA/NCI NIH HHS/ -- R01 GM051968/GM/NIGMS NIH HHS/ -- R01 GM084034/GM/NIGMS NIH HHS/ -- R01 HG005700/HG/NHGRI NIH HHS/ -- R01GM084034/GM/NIGMS NIH HHS/ -- T32 GM008061/GM/NIGMS NIH HHS/ -- Z01 DK015602-01/Intramural NIH HHS/ -- England -- Nature. 2013 Jul 11;499(7457):172-7. doi: 10.1038/nature12311.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23846655" target="_blank"〉PubMed〈/a〉
    Keywords: Autistic Disorder/genetics ; Base Sequence ; Binding Sites/genetics ; Conserved Sequence/genetics ; Eukaryotic Cells/metabolism ; Gene Expression Regulation/*genetics ; Humans ; Molecular Sequence Data ; Nucleotide Motifs/*genetics ; Protein Structure, Tertiary/genetics ; RNA Stability/genetics ; RNA-Binding Proteins/chemistry/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2013-01-04
    Description: The formation of gaseous giant planets is thought to occur in the first few million years after stellar birth. Models predict that the process produces a deep gap in the dust component (shallower in the gas). Infrared observations of the disk around the young star HD 142527 (at a distance of about 140 parsecs from Earth) found an inner disk about 10 astronomical units (AU) in radius (1 AU is the Earth-Sun distance), surrounded by a particularly large gap and a disrupted outer disk beyond 140 AU. This disruption is indicative of a perturbing planetary-mass body at about 90 AU. Radio observations indicate that the bulk mass is molecular and lies in the outer disk, whose continuum emission has a horseshoe morphology. The high stellar accretion rate would deplete the inner disk in less than one year, and to sustain the observed accretion matter must therefore flow from the outer disk and cross the gap. In dynamical models, the putative protoplanets channel outer-disk material into gap-crossing bridges that feed stellar accretion through the inner disk. Here we report observations of diffuse CO gas inside the gap, with denser HCO(+) gas along gap-crossing filaments. The estimated flow rate of the gas is in the range of 7 x 10(-9) to 2 x 10(-7) solar masses per year, which is sufficient to maintain accretion onto the star at the present rate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Casassus, Simon -- van der Plas, Gerrit -- Sebastian Perez, M -- Dent, William R F -- Fomalont, Ed -- Hagelberg, Janis -- Hales, Antonio -- Jordan, Andres -- Mawet, Dimitri -- Menard, Francois -- Wootten, Al -- Wilner, David -- Hughes, A Meredith -- Schreiber, Matthias R -- Girard, Julien H -- Ercolano, Barbara -- Canovas, Hector -- Roman, Pablo E -- Salinas, Vachail -- England -- Nature. 2013 Jan 10;493(7431):191-4. doi: 10.1038/nature11769. Epub 2013 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departamento de Astronomia, Universidad de Chile, Casilla 36-D, Santiago, Chile. scasassus@u.uchile.cl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23283173" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2013-11-01
    Description: To understand the processes that maintain genetic diversity is a long-standing challenge in evolutionary biology, with implications for predicting disease resistance, response to environmental change, and population persistence. Simple population genetic models are not sufficient to explain the high levels of genetic diversity sometimes observed in ecologically important traits. In guppies (Poecilia reticulata), male colour pattern is both diverse and heritable, and is arguably one of the most extreme examples of morphological polymorphism known. Negative frequency-dependent selection (NFDS), a form of selection in which genotypes are favoured when they are rare, can potentially maintain such extensive polymorphism, but few experimental studies have confirmed its operation in nature. Here we use highly replicated experimental manipulations of natural populations to show that males with rare colour patterns have higher reproductive fitness, demonstrating NFDS mediated by sexual selection. Rare males acquired more mates and sired more offspring compared to common males and, as previously reported, had higher rates of survival. Orange colour, implicated in other studies of sexual selection in guppies, did predict male reproductive success, but only in one of three populations. These data support the hypothesis that NFDS maintains diversity in the colour patterns of male guppies through two selective agents, mates and predators. Similar field-based manipulations of genotype frequencies could provide a powerful approach to reveal the underlying ecological and behavioural mechanisms that maintain genetic and phenotypic diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, Kimberly A -- Houde, Anne E -- Price, Anna C -- Rodd, F Helen -- England -- Nature. 2013 Nov 7;503(7474):108-10. doi: 10.1038/nature12717. Epub 2013 Oct 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Science, 319 Stadium Drive, Florida State University, Tallahassee, Florida 32306, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24172904" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Wild/genetics/*physiology ; Female ; Fertility/genetics/physiology ; Genetic Fitness/genetics/*physiology ; Genetic Variation/genetics ; Male ; Mating Preference, Animal/*physiology ; Models, Animal ; Phenotype ; Pigmentation/genetics/physiology ; Poecilia/genetics/*physiology ; Predatory Behavior ; Rivers ; Selection, Genetic/genetics/physiology ; Survival Rate
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Nature Publishing Group (NPG)
    Publication Date: 2013-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, Virginia -- England -- Nature. 2013 May 23;497(7450):428-30. doi: 10.1038/497428a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23698426" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Body Mass Index ; Cause of Death ; Confounding Factors (Epidemiology) ; Humans ; *Life Expectancy ; Longevity/physiology ; Meta-Analysis as Topic ; Overweight/*mortality ; Public Health/*statistics & numerical data ; Reproducibility of Results ; Sex Factors ; Smoking/epidemiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2013-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, Virginia -- England -- Nature. 2013 Jan 24;493(7433):466-8. doi: 10.1038/493466a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23344340" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/physiology ; Animals ; Brain/*cytology/growth & development/*physiology ; Brain Mapping/*methods ; Calcium Signaling ; Connectome ; Feedback, Physiological ; Habenula/cytology/physiology ; Humans ; Larva/cytology/growth & development/physiology ; *Models, Animal ; *Neural Pathways ; Neurons/physiology ; Neurosciences/*methods ; Psychomotor Performance/physiology ; Swimming/physiology ; Zebrafish/genetics/growth & development/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2013-09-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ursin, Rupert -- Hughes, Richard -- England -- Nature. 2013 Sep 5;501(7465):37-8. doi: 10.1038/501037a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24005408" target="_blank"〉PubMed〈/a〉
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2013-11-12
    Description: Bacteria swim by means of long flagella extending from the cell surface. These are assembled from thousands of protein subunits translocated across the cell membrane by an export machinery at the base of each flagellum. Unfolded subunits then transit through a narrow channel at the core of the growing flagellum to the tip, where they crystallize into the nascent structure. As the flagellum lengthens outside the cell, the rate of flagellum growth does not change. The mystery is how subunit transit is maintained at a constant rate without a discernible energy source in the channel of the external flagellum. We present evidence for a simple physical mechanism for flagellum growth that harnesses the entropic force of the unfolded subunits themselves. We show that a subunit docked at the export machinery can be captured by a free subunit through head-to-tail linkage of juxtaposed amino (N)- and carboxy (C)-terminal helices. We propose that sequential rounds of linkage would generate a multisubunit chain that pulls successive subunits into and through the channel to the flagellum tip, and by isolating filaments growing on bacterial cells we reveal the predicted chain of head-to-tail linked subunits in the transit channel of flagella. Thermodynamic analysis confirms that links in the subunit chain can withstand the pulling force generated by rounds of subunit crystallization at the flagellum tip, and polymer theory predicts that as the N terminus of each unfolded subunit crystallizes, the entropic force at the subunit C terminus would increase, rapidly overcoming the threshold required to pull the next subunit from the export machinery. This pulling force would adjust automatically over the increasing length of the growing flagellum, maintaining a constant rate of subunit delivery to the tip.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864836/" 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/PMC3864836/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Evans, Lewis D B -- Poulter, Simon -- Terentjev, Eugene M -- Hughes, Colin -- Fraser, Gillian M -- 082895/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2013 Dec 12;504(7479):287-90. doi: 10.1038/nature12682. Epub 2013 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. ; Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 OHE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24213633" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallization ; Entropy ; Flagella/*chemistry/*metabolism ; Intrinsically Disordered Proteins/chemistry/metabolism/secretion ; Protein Folding ; Protein Subunits/*chemistry/*metabolism/secretion ; Protein Transport ; Salmonella typhimurium/*cytology
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2013-02-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, J David -- England -- Nature. 2013 Feb 21;494(7437):307-8. doi: 10.1038/494307a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Post Carbon Institute, Santa Rosa, California 95404, USA. davehughes@twincomm.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23426309" target="_blank"〉PubMed〈/a〉
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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