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  • 1
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    Spontaneous Dock2 mutation in Irf5-/- mice [Immunology] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-04-11
    Description: Genome-wide studies have identified associations between polymorphisms in the IFN regulatory factor-5 (Irf5) gene and a variety of human autoimmune diseases. Its functional role in disease pathogenesis, however, remains unclear, as studies in Irf5−/− mice have reached disparate conclusions regarding the importance of this transcription factor in type I IFN production and antibody responses. We identified a spontaneous genomic duplication and frameshift mutation in the guanine exchange factor dedicator of cytokinesis 2 (Dock2) that has arisen in at least a subset of circulating Irf5−/− mice and inadvertently been bred to homozygosity. Retroviral expression of DOCK2, but not IRF-5, rescued defects in plasmacytoid dendritic cell and B-cell development, and Irf5−/− mice lacking the mutation in Dock2 exhibited normal plasmacytoid dendritic cell and B-cell development, largely intact type I IFN responses, and relatively normal antibody responses to viral infection. Thus, confirmation of the normal Dock2 genotype in circulating Irf5−/− mice is warranted, and our data may partly explain conflicting results in this field.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    Behavioral study of whisker-mediated vibration sensation in rats [Neuroscience] (2012)
    National Academy of Sciences
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    Publication Date: 2012-01-18
    Description: Rats use their vibrissal sensory system to collect information about the nearby environment. They can accurately and rapidly identify object location, shape, and surface texture. Which features of whisker motion does the sensory system extract to construct sensations? We addressed this question by training rats to make discriminations between sinusoidal vibrations simultaneously presented to the left and right whiskers. One set of rats learned to reliably identify which of two vibrations had higher frequency (f1 vs. f2) when amplitudes were equal. Another set of rats learned to reliably identify which of two vibrations had higher amplitude (A1 vs. A2) when frequencies were equal. Although these results indicate that both elemental features contribute to the rats’ sensation, a further test found that the capacity to discriminate A and f was reduced to chance when the difference in one feature was counterbalanced by the difference in the other feature: Rats could not discriminate amplitude or frequency whenever A1f1 = A2f2. Thus, vibrations were sensed as the product Af rather than as separable elemental features, A and f. The product Af is proportional to a physical entity, the mean speed. Analysis of performance revealed that rats extracted more information about differences in Af than predicted by the sum of the information in elemental differences. These behavioral experiments support the predictions of earlier physiological studies by demonstrating that rats are “blind” to the elemental features present in a sinusoidal whisker vibration; instead, they perceive a composite feature, the speed of whisker motion.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Tau seeding predicts tauopathy in vivo [Neuroscience] (2014)
    National Academy of Sciences
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    Publication Date: 2014-10-15
    Description: Transcellular propagation of protein aggregates, or proteopathic seeds, may drive the progression of neurodegenerative diseases in a prion-like manner. In tauopathies such as Alzheimer’s disease, this model predicts that tau seeds propagate pathology through the brain via cell–cell transfer in neural networks. The critical role of tau seeding activity is...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 4
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    Searching for Light Dark Matter with the SLAC Millicharge Experiment (2013)
    American Physical Society (APS)
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    Publication Date: 2013-11-28
    Description: Author(s): M. Diamond and P. Schuster New sub-GeV gauge forces (“dark photons”) that kinetically mix with the photon provide a promising scenario for MeV–GeV dark matter and are the subject of a program of searches at fixed-target and collider facilities around the world. In such models, dark photons produced in collisions may decay inv... [Phys. Rev. Lett. 111, 221803] Published Wed Nov 27, 2013
    Keywords: Elementary Particles and Fields
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
    Published by American Physical Society (APS)
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  • 5
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    Integrative genomics identifies LMO1 as a neuroblastoma oncogene (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-12-03
    Description: Neuroblastoma is a childhood cancer of the sympathetic nervous system that accounts for approximately 10% of all paediatric oncology deaths. To identify genetic risk factors for neuroblastoma, we performed a genome-wide association study (GWAS) on 2,251 patients and 6,097 control subjects of European ancestry from four case series. Here we report a significant association within LIM domain only 1 (LMO1) at 11p15.4 (rs110419, combined P = 5.2 x 10(-16), odds ratio of risk allele = 1.34 (95% confidence interval 1.25-1.44)). The signal was enriched in the subset of patients with the most aggressive form of the disease. LMO1 encodes a cysteine-rich transcriptional regulator, and its paralogues (LMO2, LMO3 and LMO4) have each been previously implicated in cancer. In parallel, we analysed genome-wide DNA copy number alterations in 701 primary tumours. We found that the LMO1 locus was aberrant in 12.4% through a duplication event, and that this event was associated with more advanced disease (P 〈 0.0001) and survival (P = 0.041). The germline single nucleotide polymorphism (SNP) risk alleles and somatic copy number gains were associated with increased LMO1 expression in neuroblastoma cell lines and primary tumours, consistent with a gain-of-function role in tumorigenesis. Short hairpin RNA (shRNA)-mediated depletion of LMO1 inhibited growth of neuroblastoma cells with high LMO1 expression, whereas forced expression of LMO1 in neuroblastoma cells with low LMO1 expression enhanced proliferation. These data show that common polymorphisms at the LMO1 locus are strongly associated with susceptibility to developing neuroblastoma, but also may influence the likelihood of further somatic alterations at this locus, leading to malignant progression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320515/" 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/PMC3320515/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Kai -- Diskin, Sharon J -- Zhang, Haitao -- Attiyeh, Edward F -- Winter, Cynthia -- Hou, Cuiping -- Schnepp, Robert W -- Diamond, Maura -- Bosse, Kristopher -- Mayes, Patrick A -- Glessner, Joseph -- Kim, Cecilia -- Frackelton, Edward -- Garris, Maria -- Wang, Qun -- Glaberson, Wendy -- Chiavacci, Rosetta -- Nguyen, Le -- Jagannathan, Jayanti -- Saeki, Norihisa -- Sasaki, Hiroki -- Grant, Struan F A -- Iolascon, Achille -- Mosse, Yael P -- Cole, Kristina A -- Li, Hongzhe -- Devoto, Marcella -- McGrady, Patrick W -- London, Wendy B -- Capasso, Mario -- Rahman, Nazneen -- Hakonarson, Hakon -- Maris, John M -- 9024/Cancer Research UK/United Kingdom -- R00 CA151869/CA/NCI NIH HHS/ -- R01 CA124709/CA/NCI NIH HHS/ -- R01 CA124709-05/CA/NCI NIH HHS/ -- R01-CA124709/CA/NCI NIH HHS/ -- U10-CA98413/CA/NCI NIH HHS/ -- U10-CA98543/CA/NCI NIH HHS/ -- UL1-RR024134-03/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Jan 13;469(7329):216-20. doi: 10.1038/nature09609. Epub 2010 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124317" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cell Line, Tumor ; Cell Proliferation ; Chromosomes, Human, Pair 11/genetics ; DNA Copy Number Variations/genetics ; DNA-Binding Proteins/*genetics ; Disease Progression ; Europe/ethnology ; Gene Duplication/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; *Genome-Wide Association Study ; Genomics ; Genotype ; Humans ; LIM Domain Proteins ; Neuroblastoma/*genetics/pathology ; Odds Ratio ; Oncogenes/*genetics ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Survival Rate ; Transcription Factors/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 6
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    Stellar feedback as the origin of an extended molecular outflow in a starburst galaxy (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-12-05
    Description: Recent observations have revealed that starburst galaxies can drive molecular gas outflows through stellar radiation pressure. Molecular gas is the phase of the interstellar medium from which stars form, so these outflows curtail stellar mass growth in galaxies. Previously known outflows, however, involve small fractions of the total molecular gas content and have typical scales of less than a kiloparsec. In at least some cases, input from active galactic nuclei is dynamically important, so pure stellar feedback (the momentum return into the interstellar medium) has been considered incapable of rapidly terminating star formation on galactic scales. Molecular gas has been detected outside the galactic plane of the archetypal starburst galaxy M82 (refs 4 and 5), but so far there has been no evidence that starbursts can propel substantial quantities of cold molecular gas to the same galactocentric radius (about 10 kiloparsecs) as the warmer gas that has been traced by metal ion absorbers in the circumgalactic medium. Here we report observations of molecular gas in a compact (effective radius 100 parsecs) massive starburst galaxy at redshift 0.7, which is known to drive a fast outflow of ionized gas. We find that 35 per cent of the total molecular gas extends approximately 10 kiloparsecs, and one-third of this extended gas has a velocity of up to 1,000 kilometres per second. The kinetic energy associated with this high-velocity component is consistent with the momentum flux available from stellar radiation pressure. This demonstrates that nuclear bursts of star formation are capable of ejecting large amounts of cold gas from the central regions of galaxies, thereby strongly affecting their evolution by truncating star formation and redistributing matter.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geach, J E -- Hickox, R C -- Diamond-Stanic, A M -- Krips, M -- Rudnick, G H -- Tremonti, C A -- Sell, P H -- Coil, A L -- Moustakas, J -- England -- Nature. 2014 Dec 4;516(7529):68-70. doi: 10.1038/nature14012.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Astrophysics Research, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, UK. ; Department of Physics and Astronomy, Dartmouth College, Hanover, New Hampshire 03755, USA. ; Department of Astronomy, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. ; Institut de Radioastronomie Millimetrique, 300 rue de la Piscine, F-38406 Saint Martin d'Heres, France. ; 1] Department of Physics and Astronomy, University of Kansas, Lawrence, Kansas 66045, USA [2] Max Planck Institute for Astronomy, Konigstuhl 17, D-69117 Heidelberg, Germany. ; Department of Physics, Texas Tech University, Lubbock, Texas 79409-1051, USA. ; Center for Astrophysics and Space Sciences, University of California, San Diego, La Jolla, California 92093, USA. ; Department of Physics and Astronomy, Siena College, 515 Loudon Road, Loudonville, New York 12211, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25471881" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    Band structure of ^{235}U (2012)
    American Physical Society (APS)
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    Publication Date: 2012-12-22
    Description: Author(s): D. Ward, A. O. Macchiavelli, R. M. Clark, D. Cline, M. Cromaz, M. A. Deleplanque, R. M. Diamond, P. Fallon, A. Görgen, A. B. Hayes, G. J. Lane, I.-Y. Lee, T. Nakatsukasa, G. Schmidt, F. S. Stephens, C. E. Svensson, R. Teng, K. Vetter, and C. Y. Wu Over a period of several years we have performed three separate experiments at Lawrence Berkeley National Laboratory's 88-Inch Cyclotron in which 235 U (thick target) was Coulomb-excited. The program involved stand-alone experiments with Gammmasphere and with the 8pi Spectrometer using 136 Xe beams at... [Phys. Rev. C 86, 064319] Published Fri Dec 21, 2012
    Keywords: Nuclear Structure
    Print ISSN: 0556-2813
    Electronic ISSN: 1089-490X
    Topics: Physics
    Published by American Physical Society (APS)
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  • 8
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    Spontaneous mutation of the Dock2 gene in Irf5-/- mice complicates interpretation of type I interferon production and antibody responses (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-03-19
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
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    Behavioral study of whisker-mediated vibration sensation in rats (2012)
    National Academy of Sciences
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    Publication Date: 2012-01-04
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 10
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    Monoclonal antibody produced in plants efficiently treats West Nile virus infection in mice (2010)
    National Academy of Sciences
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    Publication Date: 2010-02-01
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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