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  • 1
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    Meta-analysis of genome-wide association studies in five cohorts reveals common variants in RBFOX1, a regulator of tissue-specific splicing, associated with refractive error (2013)
    Stambolian, D., Wojciechowski, R., Oexle, K., Pirastu, M., Li, X., Raffel, L. J., Cotch, M. F., Chew, E. Y., Klein, B., Klein, R., Wong, T. Y., Simpson, C. L., Klaver, C. C. W., van Duijn, C. M., Verhoeven, V. J. M., Baird, P. N., Vitart, V., Paterson, A. D., Mitchell, P., Saw, S. M., Fossarello, M., Kazmierkiewicz, K., Murgia, F., Portas, L., Schache, M., Richardson, A., Xie, J., Wang, J. J., Rochtchina, E., DCCT/EDIC Research Group, Viswanathan, A. C., Hayward, C., Wright, A. F., Polasek, O., Campbell, H., Rudan, I., Oostra, B. A., Uitterlinden, A. G., Hofman, A., Rivadeneira, F., Amin, N., Karssen, L. C., Vingerling, J. R., Hosseini, S. M., Doring, A., Bettecken, T., Vatavuk, Z., Gieger, C., Wichmann, H.- E., Wilson, J. F., Fleck, B., Foster, P. J., Topouzis, F., McGuffin, P., Sim, X., Inouye, M., Holliday, E. G., Attia, J., Scott, R. J., Rotter, J. I., Meitinger, T., Bailey-Wilson, J. E.
    Oxford University Press
    Details
    Publication Date: 2013-06-07
    Description: Visual refractive errors (REs) are complex genetic traits with a largely unknown etiology. To date, genome-wide association studies (GWASs) of moderate size have identified several novel risk markers for RE, measured here as mean spherical equivalent (MSE). We performed a GWAS using a total of 7280 samples from five cohorts: the Age-Related Eye Disease Study (AREDS); the KORA study (‘Cooperative Health Research in the Region of Augsburg’); the Framingham Eye Study (FES); the Ogliastra Genetic Park-Talana (OGP-Talana) Study and the Multiethnic Study of Atherosclerosis (MESA). Genotyping was performed on Illumina and Affymetrix platforms with additional markers imputed to the HapMap II reference panel. We identified a new genome-wide significant locus on chromosome 16 (rs10500355, P = 3.9 x 10 –9 ) in a combined discovery and replication set (26 953 samples). This single nucleotide polymorphism (SNP) is located within the RBFOX1 gene which is a neuron-specific splicing factor regulating a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    A systemic study of 14 southern infrared dark clouds with N2H+, HNC, HCO+ and HCN lines (2013)
    Oxford University Press
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    Publication Date: 2013-04-03
    Description: We studied 14 southern infrared dark clouds (IRDCs) using data taken from the Millimetre Astronomy Legacy Team 90 GHz (MALT90) survey and the GLIMPSE and MIPSGAL mid-infrared surveys of the inner Galaxy. The physical and chemical characteristics of the 14 IRDCs were investigated using N 2 H + (1–0), HNC(1–0), HCO + (1–0) and HCN(1–0) molecular lines. We found that the 14 IRDCs are in different evolutionary stages, from ‘starless’ to sources with an ultra-compact H  ii region. Three IRDCs were detected to have star-forming activity. The integrated intensity ratios $I{\rm _{HCO^+/HCN}}$ , $I{\rm _{N_2H^+/HCN}}$ and I HNC/HCN are all ~1.5, which is different from previous measurements, suggesting that the integrated intensity ratios may be affected by the cloud environments. The integrated intensities of HNC, HCO + and HCN show a tight correlation for the 14 IRDCs, implying a close link to the chemical evolution of these three species in the IRDCs.The derived excitation temperature for each IRDC is less than 25 K. We estimated the abundances of the four molecules to be from 10 –11 to 10 –9 , and the average abundance ratios are N HNC / N HCN  = 1.47 ± 0.50, $N_{\rm HNC}/N_{\rm HCO^+}=1.74\pm 0.22$ and $N_{\rm HCN}/N_{\rm HCO^+}=1.21\pm 0.41$ .
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    A molecular line study towards massive extended green object clumps in the southern sky: chemical properties (2015)
    Oxford University Press
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    Publication Date: 2015-06-15
    Description: We present a molecular line study towards 31 extended green object (EGO) clumps in the southern sky using data from MALT90 (Millimetre Astronomy Legacy Team 90 GHz). According to previous multiwavelength observations, we divide our sample into two groups: massive young stellar objects (MYSOs) and H ii regions. The most detected lines are N 2 H + ( J  = 1 – 0), HCO + ( J  = 1 – 0), HNC ( J  = 1 – 0), HCN ( J  = 1 – 0), HC 3 N ( J  = 10 – 9), H 13 CO + ( J  = 1 – 0), C 2 H ( N  = 1 – 0) and SiO ( J  = 2 – 1), indicating that most EGOs are indeed associated with dense clumps and recent outflow activities. The velocity widths of the N 2 H + ( J  = 1 – 0), H 13 CO + ( J  = 1 – 0), C 2 H ( N  = 1 – 0) and HC 3 N ( J  = 10 – 9) lines are comparable to each other in MYSOs. However, in H ii regions the velocity widths of the N 2 H + ( J  = 1 – 0) and C 2 H ( N  = 1 – 0) lines tend to be narrower than those of H 13 CO + ( J  = 1 – 0) and HC 3 N ( J  = 10 – 9). Our results seem to support that N 2 H + and C 2 H emissions mainly come from the gas inside quiescent clumps. In addition, we also find that the [N 2 H + ]/[H 13 CO + ] and [C 2 H]/[H 13 CO + ] relative abundance ratios decrease from MYSOs to H ii regions. These results suggest depletion of N 2 H + and C 2 H in the late stages of massive-star formation, probably caused by the formation of H ii regions inside. N 2 H + and C 2 H might be used as chemical clocks for massive-star formation by comparing with other molecules such as H 13 CO + and HC 3 N.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 4
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    The environment and star formation of H II region Sh2-163: a multi-wavelength study (2014)
    Oxford University Press
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    Publication Date: 2014-10-31
    Description: To investigate the environment of H ii region Sh2-163 and search for evidence of triggered star formation in this region, we performed a multi-wavelength study of this H ii region. Most of our data were taken from large-scale surveys: 2MASS, CGPS, MSX and SCUBA. We also made CO molecular line observations, using the 13.7-m telescope. The ionized region of Sh2-163 is detected by both the optical and radio continuum observations. Sh2-163 is partially bordered by an arc-like photodissociation region (PDR), which is coincident with the strongest optical and radio emissions, indicating interactions between the H ii region and the surrounding interstellar medium. Two molecular clouds were discovered on the border of the PDR. The morphology of these two clouds suggests they are compressed by the expansion of Sh2-163. In cloud A, we found two molecular clumps. And it seems star formation in clump A2 is much more active than in clump A1. In cloud B, we found new outflow activities and massive star(s) are forming inside. Using 2MASS photometry, we tried to search for embedded young stellar object (YSO) candidates in this region. The very good agreement between CO emission, infrared shell and YSOs suggest that it is probably a star formation region triggered by the expansion of Sh2-163. We also found the most likely massive protostar related to IRAS 23314+6033.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 5
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    Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract (2014)
    Oxford University Press
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    Publication Date: 2014-10-22
    Description: Age-related cataract is a leading cause of blindness worldwide, especially in developing countries where access to cataract surgery remains limited. Previous linkage and candidate gene studies suggested genetic influences on age-related nuclear cataract but few genetic markers have been identified thus far. We conducted genome-wide association studies on 4569 Asians (including 2369 Malays and 2200 Indians), and replicated our analysis in 2481 Chinese from two independent cohorts (1768 Chinese in Singapore and 803 Chinese in Beijing). We confirmed two genome-wide significant loci for nuclear cataract in the combined meta-analysis of four cohorts ( n = 7140). The first locus was at chromosome 3q25.31 in KCNAB1 (rs7615568, fixed-effect P meta = 2.30 x 10 –8 ; random-effect P meta = 1.08 x 10 –8 ) . The second locus was at chromosome 21 in the proximity of CRYAA (rs11911275, fixed-effect P meta = 2.77 x 10 –8 ; random-effect P meta = 1.98 x 10 –9 ), a major protein component of eye lens. The findings were further supported by up-regulation and down-regulation of KCNAB1 and CRYAA in human lens capsule , respectively, as the severity of nuclear cataract increases. The results offer additional insights into the pathogenesis of nuclear cataract in Asians.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    Physical and chemical properties of Red MSX Sources in the southern sky: H II regions (2014)
    Oxford University Press
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    Publication Date: 2014-12-03
    Description: We have studied the physical and chemical properties of 18 southern Red Midcourse Space Experiment Sources (RMSs), using archival data taken from the Atacama Pathfinder Experiment (APEX) Telescope Large Area Survey of the Galaxy, the Australia Telescope Compact Array, and the Millimeter Astronomy Legacy Team Survey at 90 GHz. Most of our sources have simple cometary/unresolved radio emissions at 4.8 and/or 8.6GHz. The large number of Lyman continuum fluxes ( N L ) indicates they are probably massive O- or early B-type star formation regions. Archival IRAS infrared data are used to estimate the dust temperature, which is about 30 K of our sources. Then, the H 2 column densities and the volume-averaged H 2 number densities are estimated using the 870 μm dust emissions. Large-scale infall and ionized accretions may be occurring in G345.4881+00.3148. We also attempt to characterize the chemical properties of these RMSs through molecular line (N 2 H + (1–0) and HCO + (1–0)) observations. Most of the detected N 2 H + and HCO + emissions match well with the dust emission, implying a close link to their chemical evolution in the RMSs. We found that the abundance of N 2 H + is one order of magnitude lower than that in other surveys of infrared dark clouds, and a positive correlation between the abundances of N 2 H + and HCO + . The fractional abundance of N 2 H + with respect to H 2 seems to decrease as a function of N L . These observed trends could be interpreted as an indication of enhanced destruction of N 2 H + , either by CO or through dissociative recombination with electrons produced by central UV photons.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 7
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    ARHGEF12 influences the risk of glaucoma by increasing intraocular pressure (2015)
    Oxford University Press
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    Publication Date: 2015-04-04
    Description: Primary open-angle glaucoma (POAG) is a blinding disease. Two important risk factors for this disease are a positive family history and elevated intraocular pressure (IOP), which is also highly heritable. Genes found to date associated with IOP and POAG are ABCA1 , CAV1/CAV2, GAS7 and TMCO1 . However, these genes explain only a small part of the heritability of IOP and POAG. We performed a genome-wide association study of IOP in the population-based Rotterdam Study I and Rotterdam Study II using single nucleotide polymorphisms (SNPs) imputed to 1000 Genomes. In this discovery cohort ( n = 8105), we identified a new locus associated with IOP. The most significantly associated SNP was rs58073046 ( β = 0.44, P -value = 1.87 x 10 –8 , minor allele frequency = 0.12), within the gene ARHGEF12 . Independent replication in five population-based studies ( n = 7471) resulted in an effect size in the same direction that was significantly associated ( β = 0.16, P -value = 0.04). The SNP was also significantly associated with POAG in two independent case–control studies [ n = 1225 cases and n = 4117 controls; odds ratio (OR) = 1.53, P -value = 1.99 x 10 –8 ], especially with high-tension glaucoma (OR = 1.66, P -value = 2.81 x 10 –9 ; for normal-tension glaucoma OR = 1.29, P -value = 4.23 x 10 –2 ). ARHGEF12 plays an important role in the RhoA/RhoA kinase pathway, which has been implicated in IOP regulation. Furthermore, it binds to ABCA1 and links the ABCA1 , CAV1/CAV2 and GAS7 pathway to Mendelian POAG genes ( MYOC , OPTN , WDR36 ). In conclusion, this study identified a novel association between IOP and ARHGEF12 .
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 8
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    Molecular line study of massive star-forming regions from the Red MSX Source survey (2014)
    Oxford University Press
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    Publication Date: 2014-04-15
    Description: In this paper, we have selected a sample of massive star-forming regions from the Red MSX Source survey, in order to study star formation activities (mainly outflow and inflow signatures). We have focused on three molecular lines from the Millimeter Astronomy Legacy Team Survey at 90 GHz: HCO + (1–0), H 13 CO + (1–0) and SiO(2–1). According to previous observations, our sources can be divided into two groups: nine massive young stellar object candidates (radio-quiet) and 10 H ii regions (which have spherical or unresolved radio emissions). Outflow activities have been found in 11 sources, while only three show inflow signatures in all. The high outflow detection rate means that outflows are common in massive star-forming regions. The inflow detection rate was relatively low. We suggest that this was because of the beam dilution of the telescope. All three inflow candidates have outflow(s). The outward radiation and thermal pressure from the central massive star(s) do not seem to be strong enough to halt accretion in G345.0034–00.2240. Our simple model of G318.9480–00.1969 shows that it has an infall velocity of about 1.8 km s –1 . The spectral energy distribution analysis agrees our sources are massive and intermediate–massive star formation regions.
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    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 9
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    Kinematics and chemistry of the hot core in G20.08-0.14N (2013)
    Oxford University Press
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    Publication Date: 2013-04-26
    Description: We present Submillimeter Array (SMA) observations of the the massive star-forming region G20.08–0.14N at 335 and 345 GHz. With the SMA data, 41 molecular transitions were detected related to 11 molecular species and their isotopologues, including SO 2 , SO, C 34 S, NS, C 17 O, SiO, CH 3 OH, HC 3 N, H 13 CO + , HCOOCH 3 and NH 2 CHO. In G20.08–0.14N, 10 transition lines out of the 41 detected belong to SO 2 , which dominates the appearance of the submillimetre-wave spectrum. To obtain the spatial kinematic distribution of molecules in G20.08–0.14N, we chose the strongest and unblended lines for the channel maps. The channel maps of C 34 S and SiO, together with their position–velocity diagrams, show that there are two accretion flows in G20.08–0.14N. Additionally, SiO emission shows a collimated outflow in the north-east–south-west direction. The direction of the outflow is revealed for the first time. The rotational temperature and column density of CH 3 OH are 105 K and 3.1  x 10 17  cm –2 , respectively. Our results confirm that a hot core is associated with G20.08–0.14N. The hot core is heated by a protostar radiation at its centre, not by external excitation from shocks. Images of the spatial distribution of different species have shown that the different molecules are located at different positions of the hot core. By comparing the spatial distributions and abundances of molecules, we discuss possible chemical processes for producing the complex sulphur-bearing, nitrogen-bearing and oxygen-bearing molecules in G20.08–0.14N.
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    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 10
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    The connection of protein O-mannosyltransferase family to the biocontrol potential of Beauveria bassiana, a fungal entomopathogen (2014)
    Oxford University Press
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    Publication Date: 2014-05-30
    Description: O -Mannosylation dependent on the protein O -mannosyltransferase (Pmt) family is an essential post-translational modification process in eukaryotes, but their connection to the biocontrol potential of a filamentous entomopathogen against arthropod pests is not understood. Here, we characterized the functions of three Pmt orthologues (Pmt1, Pmt2 and Pmt4) in the Pmt family of Beauveria bassiana and found that they were positive, but differential, regulators of the fungal growth, conidiation, multi-stress tolerance and virulence. Three Pmt2 knockdown mutants ( Pmt2 was lethal), Pmt1 and Pmt4 grew 20–79% slower on nutrition-rich and limited media. Their conidial yields on a standard medium were reduced by 17–62%, accompanied with delayed germination. All the mutants became significantly less tolerant to most stresses of cell wall perturbation, high osmolarity, oxidation, wet heat and UV-B irradiation during colony growth and conidial germination and lost virulence by 53–62% via cuticle infection, although their virulence via hemocoel injection was not affected. Strikingly, these phenotypic defects were accompanied with remarkable cell wall damage, including thinner cell wall, lower conidial hydrophobicity and altered cell wall composition. All the changes were well restored to wild-type levels by targeted Pmt1 or Pmt4 complementation. Our results indicate for the first time that Pmt1, Pmt2 and Pmt4 are all required for the full biocontrol potential of B. bassiana despite differential contributions.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
    Published by Oxford University Press
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