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Nozawa, Takaya,Yoon, Sung-Chul,Maeda, Keiichi,Kozasa, Takashi,Nomoto, Ken'ichi,Langer, Norbert University of Chicago Press for the American Astro 2014 ASTROPHYSICAL JOURNAL LETTERS - Vol.787 No.2
We investigate the formation of dust in a stellar wind during the red-supergiant (RSG) phase of a very massive Population III star with a zero-age main sequence mass of 500 M-circle dot. We show that, in a carbon-rich wind with a constant velocity, carbon grains can form with a lognormal-like size distribution, and that all of the carbon available for dust formation finally condenses into dust for wide ranges of the mass-loss rate ((0.1-3) x 10(-3) M-circle dot yr(-1)) and wind velocity (1-100 km s(-1)). We also find that the acceleration of the wind, driven by newly formed dust, suppresses the grain growth but still allows more than half of the gas-phase carbon to finally be locked up in dust grains. These results indicate that, at most, 1.7 M-circle dot of carbon grains can form during the RSG phase of 500 M-circle dot Population III stars. Such a high dust yield could place very massive primordial stars as important sources of dust at the very early epoch of the universe if the initial mass function of Population III stars was top-heavy. We also briefly discuss a new formation scenario of carbon-rich ultra-metal-poor stars, considering feedback from very massive Population III stars.
Gene duplication and loss in a MADS box gene transcription factor circuit.
Lee, Hae-Lim,Irish, Vivian F University of Chicago Press 2011 Molecular biology and evolution Vol.28 No.12
<P>Although many models have been proposed that could lead to the maintenance of gene duplicates, the ways in which interacting gene duplicates influence each other's evolution and function remain poorly understood. Here, we focus on duplication and loss of the B class MADS box transcription factor genes in the euasterids I and the ramifications of such changes on paralog evolution and their encoded functions. In core eudicots, the B class genes belong to two paralogous lineages whose products form obligate heterodimers. Based on comparative genomic and phylogenetic analyses, we show that five stepwise B class MADS box gene gain or loss events occurred during the radiation of the euasterids I within core eudicots. Gene loss in one sublineage was correlated with a deficit of other sublineage genes. We also show that the gain or loss of B class MADS box gene paralogs were associated with altered protein-protein interactions among the remaining copies. These altered protein interactions were correlated with asymmetric patterns of sequence diversification and selection, suggesting that compensatory changes were driving the evolution of such genes. Furthermore, these B class MADS box gene gain or loss events were associated with the evolutionary divergence of floral morphology in the euasterids I. Together, these observations point to a cooperative strategy by which gene networks evolve, with selection maintaining the overall logic of a network despite changes in individual components.</P>
Mutations in <i>ATP1A1</i> Cause Dominant Charcot-Marie-Tooth Type 2
Lassuthova, Petra,Rebelo, Adriana P.,Ravenscroft, Gianina,Lamont, Phillipa J.,Davis, Mark R.,Manganelli, Fiore,Feely, Shawna M.,Bacon, Chelsea,Brož,ková,, Dana Š,afka,Haberlova, Jana,M University of Chicago Press [etc.] 2018 American journal of human genetics Vol.102 No.3
<P>Although mutations in more than 90 genes are known to cause CMT, the underlying genetic cause of CMT remains unknown in more than 50% of affected individuals. The discovery of additional genes that harbor CMT2-causing mutations increasingly depends on sharing sequence data on a global level. In this way—by combining data from seven countries on four continents—we were able to define mutations in <I>ATP1A1</I>, which encodes the alpha1 subunit of the Na<SUP>+</SUP>,K<SUP>+</SUP>-ATPase, as a cause of autosomal-dominant CMT2. Seven missense changes were identified that segregated within individual pedigrees: c.143T>G (p.Leu48Arg), c.1775T>C (p.Ile592Thr), c.1789G>A (p.Ala597Thr), c.1801_1802delinsTT (p.Asp601Phe), c.1798C>G (p.Pro600Ala), c.1798C>A (p.Pro600Thr), and c.2432A>C (p.Asp811Ala). Immunostaining peripheral nerve axons localized ATP1A1 to the axolemma of myelinated sensory and motor axons and to Schmidt-Lanterman incisures of myelin sheaths. Two-electrode voltage clamp measurements on <I>Xenopus</I> oocytes demonstrated significant reduction in Na<SUP>+</SUP> current activity in some, but not all, ouabain-insensitive ATP1A1 mutants, suggesting a loss-of-function defect of the Na<SUP>+</SUP>,K<SUP>+</SUP> pump. Five mutants fall into a remarkably narrow motif within the helical linker region that couples the nucleotide-binding and phosphorylation domains. These findings identify a CMT pathway and a potential target for therapy development in degenerative diseases of peripheral nerve axons.</P>
EXPLORING THE X-RAY AND gamma-RAY PROPERTIES OF THE REDBACK MILLISECOND PULSAR PSR J1723-2837
Hui, C. Y.,Tam, P. H. T.,Takata, J.,Kong, A. K. H.,Cheng, K. S.,Wu, J. H. K.,Lin, L. C. C.,Wu, E. M. H. University of Chicago Press for the American Astro 2014 ASTROPHYSICAL JOURNAL LETTERS - Vol.781 No.1
We have investigated the X-ray and gamma-ray properties of the redback millisecond pulsar PSR J1723-2837 with XMM-Newton, Chandra, and Fermi. We have discovered the X-ray orbital modulation of this binary system with a minimum that coincides with the phases of radio eclipse. The X-ray emission is clearly non-thermal in nature, which can be described well by a simple power law with a photon index of similar to 1.2. The phase-averaged luminosity is similar to 9 x 10(31) erg s(-1) in 0.3-10 keV, which consumes similar to 0.2% of the spin-down power. We have detected the gamma-ray emission in 0.1-300 GeV from this system at a significance of similar to 6 sigma for the first time. The gamma-rays in this energy range consume similar to 2% of the spin-down power and can be modeled by a power law with a photon index of similar to 2.6. We discuss the high energy properties of the new redback in the context of an intrabinary shock model.
Use of a Multiethnic Approach to Identify Rheumatoid- Arthritis-Susceptibility Loci, 1p36 and 17q12
CLEAR investigators,Kurreeman, Fina A.S.,Stahl, Eli A.,Okada, Y.,Liao, K.,Diogo, D.,Raychaudhuri, S.,Freudenberg, J.,Kochi, Y.,Patsopoulos, Nikolaos A.,Gupta, N.,Sandor, C.,Bang, S.Y.,Lee, H.S.,Padyuk University of Chicago Press [etc.] 2012 American journal of human genetics Vol.90 No.3
We have previously shown that rheumatoid arthritis (RA) risk alleles overlap between different ethnic groups. Here, we utilize a multiethnic approach to show that we can effectively discover RA risk alleles. Thirteen putatively associated SNPs that had not yet exceeded genome-wide significance (p < 5 x 10<SUP>-8</SUP>) in our previous RA genome-wide association study (GWAS) were analyzed in independent sample sets consisting of 4,366 cases and 17,765 controls of European, African American, and East Asian ancestry. Additionally, we conducted an overall association test across all 65,833 samples (a GWAS meta-analysis plus the replication samples). Of the 13 SNPs investigated, four were significantly below the study-wide Bonferroni corrected p value threshold (p < 0.0038) in the replication samples. Two SNPs (rs3890745 at the 1p36 locus [p = 2.3 x 10<SUP>-12</SUP>] and rs2872507 at the 17q12 locus [p = 1.7 x 10<SUP>-9</SUP>]) surpassed genome-wide significance in all 16,659 RA cases and 49,174 controls combined. We used available GWAS data to fine map these two loci in Europeans and East Asians, and we found that the same allele conferred risk in both ethnic groups. A series of bioinformatic analyses identified TNFRSF14-MMEL1 at the 1p36 locus and IKZF3-ORMDL3-GSDMB at the 17q12 locus as the genes most likely associated with RA. These findings demonstrate empirically that a multiethnic approach is an effective strategy for discovering RA risk loci, and they suggest that combining GWASs across ethnic groups represents an efficient strategy for gaining statistical power.
Yang, Hyungjun,Ko, Hyun-Jeong,Yang, Jin-Young,Kim, Jae-Jin,Seo, Sang-Uk,Park, Seung Gu,Choi, Sun Shim,Seong, Je Kyung,Kweon, Mi-Na University of Chicago Press 2013 The Journal of infectious diseases Vol.207 No.1
<P>Interleukin (IL)-1 is a well-known cytokine for the initiation of innate immunity in bacterial infection. However, the underlying mechanism of IL-1 on the respiratory infection is not fully elucidated. We studied how IL-1 contributes to the host defense against Streptococcus pneumoniae. IL-1R(-/-) mice showed high mortality, local cytokine storm, and substantial infiltrates in the lower respiratory tract after intratracheal challenge with S. pneumoniae. The IL-1-deficient condition did not suppress the propagation of bacteria in the lung, although the recruitment and the bacteria-killing ability of neutrophils (CD11b(+)Ly6C(+)Ly6G(+)) were not defective compared with wild-type mice. Unexpectedly, we found that the transcription of fibrinogen alpha and gamma genes were highly activated in the lungs of wild-type mice after the infection, whereas no significant changes were found in IL-1R(-/-) mice. Of note, synthesis of fibrinogen was dependent on the IL-1-IL-6-Stat3 cascade. Treatment with recombinant fibrinogen improved survival and bacterial propagation in the IL-1R(-/-) mice and blockade of the coagulation increased the susceptibility of wild-type mice to pneumococcal pneumonia. Our findings suggest that IL-1 signaling leads to the synthesis of fibrinogen in the lung after pneumococcus infection and is followed by coagulation, which contributes to the control of bacterial infection in the pulmonary tract.</P>
Antiviral activity of coxsackievirus B3 3C protease inhibitor in experimental murine myocarditis.
Yun, Soo-Hyeon,Lee, Won Gil,Kim, Yong-Chul,Ju, Eun-Seon,Lim, Byung-Kwan,Choi, Jin-Oh,Kim, Duk-Kyung,Jeon, Eun-Seok University of Chicago Press 2012 The Journal of infectious diseases Vol.205 No.3
<P>We investigated the efficacy of a 3C protease inhibitor (3CPI) in a murine coxsackievirus B3 (CVB3) myocarditis model. CVB3 is a primary cause of viral myocarditis. The CVB3 genome encodes a single polyprotein that undergoes a series of proteolytic events to produce several viral proteins. Most of this proteolysis is catalyzed by the 3C protease (3CP).</P>
What Is the Significance of Difference in Phenotypic Variability across SNP Genotypes?
Sun, X.,Elston, R.,Morris, N.,Zhu, X. University of Chicago Press [etc.] 2013 American journal of human genetics Vol.93 No.2
We studied the general problem of interpreting and detecting differences in phenotypic variability among the genotypes at a locus, from both a biological and a statistical point of view. The scales on which we measure interval-scale quantitative traits are man-made and have little intrinsic biological relevance. Before claiming a biological interpretation for genotype differences in variance, we should be sure that no monotonic transformation of the data can reduce or eliminate these differences. We show theoretically that for an autosomal diallelic SNP, when the three corresponding means are distinct so that the variance can be expressed as a quadratic function of the mean, there implicitly exists a transformation that will tend to equalize the three variances; we also demonstrate how to find a transformation that will do this. We investigate the validity of Bartlett's test, Box's modification of it, and a modified Levene's test to test for differences in variances when normality does not hold. We find that, although they may detect differences in variability, these tests do not necessarily detect differences in variance. The same is true for permutation tests that use these three statistics.
CHANDRA DETECTION OF A NEW DIFFUSE X-RAY COMPONENT FROM THE GLOBULAR CLUSTER 47 TUCANAE
Wu, E. M. H.,Hui, C. Y.,Kong, A. K. H.,Tam, P. H. T.,Cheng, K. S.,Dogiel, V. A. University of Chicago Press for the American Astro 2014 ASTROPHYSICAL JOURNAL LETTERS - Vol.788 No.2
In re-analyzing the archival Chandra data of the globular cluster 47 Tucanae, we have detected a new diffuse X-ray emission feature within the half-mass radius of the cluster. The spectrum of the diffuse emission can be described by a power-law model plus a plasma component with photon index Gamma similar to 1.0 and plasma temperature kT similar to 0.2 keV. While the thermal component is apparently uniform, the non-thermal contribution falls off exponentially from the core. The observed properties could possibly be explained in the context of multiple shocks resulting from the collisions among the stellar wind in the cluster and the inverse Compton scattering between the pulsar wind and the relic photons.
Na, Ha-Na,Nam, Jae-Hwan University of Chicago Press 2012 The Journal of Infectious Diseases Vol.205 No.6
<P>Although it is well known that adenovirus 36 (Ad36) is associated with obesity in humans as well as in animals, the detailed cellular mechanism is unclear.</P>