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1. Fatal case of sorafenib-associated idiosyncratic hepatotoxicity in the adjuvant treatment of a patient with renal cell carcinoma

Author

Fairfax BP, Pratap S, Roberts ISD, Collier J, Kaplan R, Meade AM, Ritchie AW, Eisen T, Macaulay VM, and Protheroe A

Subjects
Sorafenib, Hepatotoxicity, Adjuvant, SORCE, RCC, DILI, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Sorafenib is an orally available kinase inhibitor with activity at Raf, PDGFβ and VEGF receptors that is licensed for the treatment of advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Current evidence-based post-nephrectomy management of individuals with localized RCC consists of surveillance-based follow up. The SORCE trial is designed to investigate whether treatment with adjuvant sorafenib can reduce recurrence rates in this cohort. Case presentation Here we report an idiosyncratic reaction to sorafenib resulting in fatal hepatotoxicity and associated renal failure in a 62 year-old man treated with sorafenib within the SORCE trial. Conclusion This is the first reported case of sorafenib exposure associated fatal toxicity in the adjuvant setting and highlights the unpredictable adverse effects of novel adjuvant therapies.

Published
2012
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6. MIGHTEE-H i: deep spectral line observations of the COSMOS field.

Author

Heywood, I, Ponomareva, A A, Maddox, N, Jarvis, M J, Frank, B S, Adams, E A K, Baes, M, Bianchetti, A, Collier, J D, Deane, R P, Glowacki, M, Jung, S L, Pan, H, Rajohnson, S H A, Rodighiero, G, Ruffa, I, Santos, M G, Sinigaglia, F, and Vaccari, M

Subjects
SPECTRAL imaging, SPECTRAL lines, RADIO lines, RADIO galaxies, GALAXY formation
Abstract

The MIGHTEE survey utilizes the South African MeerKAT radio telescope to observe four extragalactic deep fields, with the aim of advancing our understanding of the formation and evolution of galaxies across cosmic time. MIGHTEE's frequency coverage encompasses the |$\textrm {H}\scriptstyle \mathrm{I}$|  line to a redshift of z |$\simeq$|  0.58, and OH megamasers to z |$\simeq$|  0.9. We present the MIGHTEE- |$\textrm {H}\scriptstyle \mathrm{I}$|  imaging products for the COSMOS field, using a total of 94.2 h on-target and a close-packed mosaic of 15 individual pointings. The spectral imaging covers two broad, relatively interference-free regions (960–1150 and 1290–1520 MHz) within MeerKAT's L -band, with up to 26 kHz spectral resolution (5.5 km s |$^{-1}$| at z  = 0). The median noise in the highest spectral resolution data is 74 μ Jy beam |$^{-1}$|⁠ , corresponding to a 5 |$\sigma$| |$\textrm {H}\scriptstyle \mathrm{I}$|  mass limit of 10 |$^{8.5}$|  M |$_{\odot }$| for a 300 km s |$^{-1}$| line at z  = 0.07. The mosaics cover |$\gt $| 4 deg |$^{2}$|⁠ , provided at multiple angular resolution / sensitivity pairings, with an angular resolution for |$\textrm {H}\scriptstyle \mathrm{I}$|  at z  = 0 of 12 arcsec. We describe the spectral line processing workflow that will be the basis for future MIGHTEE- |$\textrm {H}\scriptstyle \mathrm{I}$|  products, and validation of, and some early results from, the spectral imaging of the COSMOS field. We find no evidence for line emission at the position of the z  = 0.376 |$\textrm {H}\scriptstyle \mathrm{I}$|  line reported from the CHILES survey at a |$\gt $| 94 per cent confidence level, placing a 3 |$\sigma$| upper limit of 8.1 |$\times$|  10 |$^{9}$|  M |$_{\odot }$| on |$M_{\mathrm{HI}}$| for this galaxy. A public data release accompanies this article. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Accelerated onset of diabetes in non‐obese diabetic mice fed a refined high‐fat diet.

Author

Batdorf, Heidi M., Lawes, Luz de Luna, Cassagne, Gabrielle A., Fontenot, Molly S., Harvey, Innocence C., Richardson, Jeremy T., Burk, David H., Dupuy, Samuel D., Karlstad, Michael D., Salbaum, J. Michael, Staszkiewicz, Jaroslaw, Beyl, Robbie, Ghosh, Sujoy, Burke, Susan J., and Collier, J. Jason

Subjects
HIGH-fat diet, FAT, TYPE 1 diabetes, GLUCOSE intolerance, LOW-fat diet, DIABETES
Abstract

Aim: Type 1 diabetes results from autoimmune events influenced by environmental variables, including changes in diet. This study investigated how feeding refined versus unrefined (aka 'chow') diets affects the onset and progression of hyperglycaemia in non‐obese diabetic (NOD) mice. Methods: Female NOD mice were fed either unrefined diets or matched refined low‐ and high‐fat diets. The onset of hyperglycaemia, glucose tolerance, food intake, energy expenditure, circulating insulin, liver gene expression and microbiome changes were measured for each dietary group. Results: NOD mice consuming unrefined (chow) diets developed hyperglycaemia at similar frequencies. By contrast, mice consuming the defined high‐fat diet had an accelerated onset of hyperglycaemia compared to the matched low‐fat diet. There was no change in food intake, energy expenditure, or physical activity within each respective dietary group. Microbiome changes were driven by diet type, with chow diets clustering similarly, while refined low‐ and high‐fat bacterial diversity also grouped closely. In the defined dietary cohort, liver gene expression changes in high‐fat‐fed mice were consistent with a greater frequency of hyperglycaemia and impaired glucose tolerance. Conclusion: Glucose intolerance is associated with an enhanced frequency of hyperglycaemia in female NOD mice fed a defined high‐fat diet. Using an appropriate matched control diet is an essential experimental variable when studying changes in microbiome composition and diet as a modifier of disease risk. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Channel Expansion in the Ligand-Binding Domain of the Glucocorticoid Receptor Contributes to the Activity of Highly Potent Glucocorticoid Analogues.

Author

Seaton, Wesley B., Burke, Susan J., Fisch, Alexander R., Schilletter, William A., Beck, Mary Grace A., Cassagne, Gabrielle A., Harvey, Innocence, Fontenot, Molly S., Collier, J. Jason, and Campagna, Shawn R.

Subjects
GLUCOCORTICOID receptors, GLUCOCORTICOIDS, ANTI-inflammatory agents, LIGAND binding (Biochemistry), DIABETES complications, GENE expression
Abstract

Glucocorticoids (GCs) act through the glucocorticoid receptor (GR) and are commonly used as anti-inflammatory and immunosuppressant medications. Chronic GC use has been linked with unwanted complications such as steroid-induced diabetes mellitus (SIDM), although the mechanisms for these effects are not completely understood. Modification of six GC parent molecules with 2-mercaptobenzothiazole resulted in consistently less promoter activity in transcriptional activation assays using a 3xGRE reporter construct while constantly reducing inflammatory pathway activity. The most selective candidate, DX1, demonstrated a significant reduction (87%) in transactivation compared to commercially available dexamethasone. DX1 also maintained 90% of the anti-inflammatory potential of dexamethasone while simultaneously displaying a reduced toxicity profile. Additionally, two novel and highly potent compounds, DX4 and PN4, were developed and shown to elicit similar mRNA expression at attomolar concentrations that dexamethasone exhibits at nanomolar dosages. To further explain these results, Molecular Dynamic (MD) simulations were performed to examine structural changes in the ligand-binding domain of the glucocorticoid receptor in response to docking with the top ligands. Differing interactions with the transcriptional activation function 2 (AF-2) region of the GR may be responsible for lower transactivation capacity in DX1. DX4 and PN4 lose contact with Arg611 due to a key interaction changing from a stronger hydrophilic to a weaker hydrophobic one, which leads to the formation of an unoccupied channel at the location of the deacylcortivazol (DAC)-expanded binding pocket. These findings provide insights into the structure–function relationships important for regulating anti-inflammatory activity, which has implications for clinical utility. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Radio spectral properties of star-forming galaxies between 150 and 5000 MHz in the ELAIS-N1 field.

Author

An, Fangxia, Vaccari, M, Best, P N, Ocran, E F, Ishwara-Chandra, C H, Taylor, A R, Leslie, S K, Röttgering, H J A, Kondapally, R, Haskell, Paul, Collier, J D, and Bonato, M

Subjects
GALAXIES, STELLAR mass, THERMAL electrons, GALACTIC evolution, RADIO galaxies, REDSHIFT
Abstract

By combining high-sensitivity LOFAR 150 MHz, uGMRT 400 MHz and 1250 MHz, GMRT 610 MHz, and VLA 5 GHz data in the ELAIS-N1 field, we study the radio spectral properties of radio-detected star-forming galaxies (SFGs) at observer-frame frequencies of 150–5000 MHz. We select ∼3500 SFGs that have both LOFAR 150 MHz and GMRT 610 MHz detections, and obtain a median two-point spectral index of |$\alpha _{150}^{610}=-0.51\pm 0.01$|⁠. The photometric redshift of these SFGs spans z  = 0.01−6.21. We also measure the two-point radio spectral indices at 150–400–610–1250 MHz and 150–610–5000 MHz, respectively, for the GMRT 610-MHz-detected SFGs, and find that, on average, the radio spectrum of SFGs is flatter at low frequency than at high frequency. At observer-frame 150–5000 MHz, we find that the radio spectrum slightly steepens with increasing stellar mass. However, we only find that the radio spectrum flattens with increasing optical depth at V band at |$\nu \lesssim 1$|  GHz. We suggest that spectral ageing due to the energy loss of CR electrons and thermal free–free absorption could be among the possible main physical mechanisms that drive the above two correlations, respectively. In addition, both of these mechanisms could physically explain why the radio spectrum is flatter at low frequency than at high frequency. [ABSTRACT FROM AUTHOR]

Published
2024
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16. MIGHTEE polarization early science fields: the deep polarized sky.

Author

Taylor, A R, Sekhar, S, Heino, L, Scaife, A M M, Stil, J, Bowles, M, Jarvis, M, Heywood, I, and Collier, J D

Subjects
RADIANT intensity, FARADAY effect, ELECTRONIC data processing, DATA science, SPECTRAL imaging
Abstract

The MeerKAT International GigaHertz Tiered Extragalactic Exploration (MIGHTEE) is one of the MeerKAT large survey projects, designed to pathfind SKA key science. MIGHTEE is undertaking deep radio imaging of four well-observed fields (COSMOS, XMM -LSS, ELAIS S1, and CDFS) totaling 20 square degrees to μJy sensitivities. Broad-band imaging observations between 880 and1690 MHz yield total intensity continuum, spectro-polarimetry, and atomic hydrogen spectral imaging. Early science data from MIGHTEE are being released from initial observations of COSMOS and XMM –LSS. This paper describes the spectro-polarimetric observations, the polarization data processing of the MIGHTEE early science fields, and presents polarization data images and catalogues. The catalogues include radio spectral index, redshift information, and Faraday rotation measure synthesis results for 13 267 total intensity radio sources down to a polarized intensity detection limit of ∼20 μJy bm−1. Polarized signals were detected from 324 sources. For the polarized detections, we include a catalogue of Faraday Depth from both Faraday Synthesis and Q, U fitting, as well as total intensity and polarization spectral indices. The distribution of redshift of the total radio sources and detected polarized sources are the same, with median redshifts of 0.86 and 0.82, respectively. Depolarization of the emission at longer-wavelengths is seen to increase with decreasing total-intensity spectral index, implying that depolarization is intrinsic to the radio sources. No evidence is seen for a redshift dependence of the variance of Faraday depth. [ABSTRACT FROM AUTHOR]

Published
2024
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17. MIGHTEE: Multi-wavelength counterparts in the COSMOS field.

Author

Whittam, I H, Prescott, M, Hale, C L, Jarvis, M J, Heywood, I, An, Fangxia, Glowacki, M, Maddox, N, Marchetti, L, Morabito, L K, Adams, N J, Bowler, R A A, Hatfield, P W, Varadaraj, R G, Collier, J, Frank, B, Taylor, A R, Santos, M G, Vaccari, M, and Afonso, J

Subjects
ACTIVE galactic nuclei, THERMAL noise, DATA release, RADIO galaxies, GALACTIC evolution
Abstract

In this paper, we combine the Early Science radio continuum data from the MeerKAT International GHz Tiered Extragalactic Exploration (MIGHTEE) Survey, with optical and near-infrared data and release the cross-matched catalogues. The radio data used in this work covers 0.86 deg2 of the COSMOS field, reaches a thermal noise of 1.7  μ Jy beam−1 and contains 6102 radio components. We visually inspect and cross-match the radio sample with optical and near-infrared data from the Hyper Suprime-Cam (HSC) and UltraVISTA surveys. This allows the properties of active galactic nuclei and star-forming populations of galaxies to be probed out to z ≈ 5. Additionally, we use the likelihood ratio method to automatically cross-match the radio and optical catalogues and compare this to the visually cross-matched catalogue. We find that 94 per cent of our radio source catalogue can be matched with this method, with a reliability of 95 per cent. We proceed to show that visual classification will still remain an essential process for the cross-matching of complex and extended radio sources. In the near future, the MIGHTEE survey will be expanded in area to cover a total of ∼20 deg2; thus the combination of automated and visual identification will be critical. We compare the redshift distribution of SFG and AGN to the SKADS and T-RECS simulations and find more AGN than predicted at z ∼ 1. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Cold gas outflows from the Small Magellanic Cloud traced with ASKAP

Author

McClure-Griffiths, N. M., Dénes, H., Dickey, J. M., Stanimirović, S., Staveley-Smith, L., Jameson, Katherine, Di Teodoro, Enrico, Allison, James R., Collier, J. D., Chippendale, A. P., Franzen, T., Gürkan, Gülay, Heald, G., Hotan, A., Kleiner, D., Lee-Waddell, K., McConnell, D., Popping, A., Rhee, Jonghwan, Riseley, C. J., Voronkov, M. A., and Whiting, M.

Published
2018
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21. The dispersion–brightness relation for fast radio bursts from a wide-field survey

Author

Shannon, R. M., Macquart, J.-P., Bannister, K. W., Ekers, R. D., James, C. W., Osłowski, S., Qiu, H., Sammons, M., Hotan, A. W., Voronkov, M. A., Beresford, R. J., Brothers, M., Brown, A. J., Bunton, J. D., Chippendale, A. P., Haskins, C., Leach, M., Marquarding, M., McConnell, D., Pilawa, M. A., Sadler, E. M., Troup, E. R., Tuthill, J., Whiting, M. T., Allison, J. R., Anderson, C. S., Bell, M. E., Collier, J. D., Gürkan, G., Heald, G., and Riseley, C. J.

Published
2018
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23. Radio spectral properties at 150-5000MHz of star-forming galaxies in the ELAIS-N1 field

Author

An, Fangxia, Vaccari, M., Best, P. N., Ocran, E. F., Ishwara-Chandra, C. H., Taylor, A. R., Leslie, S. K., Röttgering, H. J. A., Kondapally, R., Haske, P., Collier, J. D., and Bonato, M.

Subjects
Cosmology and Nongalactic Astrophysics (astro-ph.CO), Astrophysics of Galaxies (astro-ph.GA), FOS: Physical sciences, Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

By combining high-sensitivity LOFAR 150MHz, uGMRT 400MHz, GMRT 610MHz, and JVLA 5GHz data in the ELAIS-N1 field, we study the radio spectral properties of radio-detected star-forming galaxies (SFGs) at observer-frame frequencies of 150-5000MHz. We select ~3,500 SFGs that have both LOFAR 150MHz and GMRT 610MHz detections by removing AGN from the two radio samples, and obtain a median spectral index of $\alpha_{150}^{610}=-0.51\pm0.01$ with a scatter of $\sigma=0.2$. Due to the relatively lower sensitivity of uGMRT 400MHz data, we apply a flux cut of $S_{610}>300\mu$Jy and obtain the median spectral indices of $\alpha_{150}^{385}=-0.42^{+0.03}_{-0.02}$, $\alpha_{385}^{610}=-0.44^{+0.03}_{-0.04}$, and $\alpha_{150}^{610}=-0.42^{+0.02}_{-0.01}$ for the sample of 258 SFGs that have detections at these three radio frequencies. The JVLA 5GHz observations only cover the central 0.1deg$^{2}$, where ~100 SFGs are selected, for which we obtain median $\alpha_{610}^{5000}=-1.14^{+0.04}_{-0.05}$, $\alpha_{385}^{5000}=-1.08^{+0.01}_{-0.02}$ and $\alpha_{150}^{5000}=-0.87\pm0.01$. Overall, the results show that the radio spectrum is flatter if we include a lower frequency dataset when measuring the radio spectral index at 150-5000MHz. We study the correlations between radio spectral index and physical properties of radio-selected SFGs and find that, on average, the radio spectrum slightly steepens with increasing stellar mass. However, we only find that the radio spectrum flattens with increasing optical depth at V-band at $\nu, Comment: 15 pages, 11 figures, 1 table, submitted to MNRAS on 20 Feb 2023

Published
2023

24. NOD mice have distinct metabolic and immunologic profiles when compared with genetically similar MHC-matched ICR mice.

Author

Batdorf, Heidi M., Lawes, Luz de Luna, Richardson, Jeremy T., Burk, David H., Dupuy, Samuel D., Karlstad, Michael D., Noland, Robert C., Burke, Susan J., and Collier, J. Jason

Subjects
MICE, LABORATORY mice, TYPE 1 diabetes, MAJOR histocompatibility complex, ISLANDS of Langerhans
Abstract

Nonobese diabetic (NOD) mice are the most commonly used rodent model to study mechanisms relevant to the autoimmunity and immunology of type 1 diabetes. Although many different strains of mice have been used as controls for studies comparing nondiabetic lines to the NOD strain, we hypothesized that the parental strain that gave rise to the NOD line might be one of the best options. Therefore, we compared female ICR and NOD mice, which are matched at key major histocompatibility complex (MHC) loci, to understand their metabolic and immunologic similarities and differences. Several novel observations emerged: 1) NOD mice have greater circulating proinsulin when compared with ICR mice. 2) NOD mice display CD3þ and IBA1þ cell infiltration into and near pancreatic islets before hyperglycemia. 3) NOD mice show increased expression of the Il1b and Cxcl11 genes in islets when compared with islets from age-matched ICR mice. 4) NOD mice have a greater abundance of STAT1 and ICAM-1 protein in islets when compared with ICR mice. These data show that ICR mice, which are genetically similar to NOD mice, do not retain the same immunologic outcomes. Thus, ICR mice are an excellent choice as a genetically similar and MHC-matched control for NOD mice in studies designed to understand mechanisms relevant to autoimmune-mediated diabetes onset as well as novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Published
2023
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27. Utility of a buccal swab point-of-care test for the IFNL4 genotype in the era of direct acting antivirals for hepatitis C virus

Author

Sy, A, McCabe, L, Hudson, E, Ansari, AM, Pedergnana, V, Lin, S-K, Santana, S, Fiorino, M, Ala, A, Stone, B, Smith, M, Nelson, M, Barclay, ST, McPherson, S, Ryder, SD, Collier, J, Barnes, E, Walker, AS, Pett, SL, Cooke, G, STOP-HCV-1 trial team, and team, STOP-HCV-1 trial

Subjects
Multidisciplinary
Abstract

Background The CC genotype of the IFNL4 gene is known to be associated with increased Hepatitis C (HCV) cure rates with interferon-based therapy and may contribute to cure with direct acting antivirals. The Genedrive® IFNL4 is a CE marked Point of Care (PoC) molecular diagnostic test, designed for in vitro diagnostic use to provide rapid, real-time detection of IFNL4 genotype status for SNP rs12979860. Methods 120 Participants were consented to a substudy comparing IFNL4 genotyping results from a buccal swab analysed on the Genedrive® platform with results generated using the Affymetix UK Biobank array considered to be the gold standard. Results Buccal swabs were taken from 120 participants for PoC IFNL4 testing and a whole blood sample for genetic sequencing. Whole blood genotyping vs. buccal swab PoC testing identified 40 (33%), 65 (54%), and 15 (13%) had CC, CT and TT IFNL4 genotype respectively. The Buccal swab PoC identified 38 (32%) CC, 64 (53%) CT and 18 (15%) TT IFNL4 genotype respectively. The sensitivity and specificity of the buccal swab test to detect CC vs non-CC was 90% (95% CI 76–97%) and 98% (95% CI 91–100%) respectively. Conclusions The buccal swab test was better at correctly identifying non-CC genotypes than CC genotypes. The high specificity of the Genedrive® assay prevents CT/TT genotypes being mistaken for CC, and could avoid patients being identified as potentially ‘good responders’ to interferon-based therapy.

Published
2023

30. MIGHTEE: the nature of the radio-loud AGN population:the nature of the radio-loud AGN population

Author

Whittam, I. H., Jarvis, M. J., Hale, C. L., Prescott, M., Morabito, L. K., Heywood, I., Adams, N. J., Afonso, J., An, Fangxia, Ao, Y., Bowler, R. A. A., Collier, J. D., Deane, R. P., Delhaize, J., Frank, B., Glowacki, M., Hatfield, P. W., Maddox, N., Marchetti, L., Matthews, A. M., Prandoni, I., Randriamampandry, S., Randriamanakoto, Z., Smith, D. J. B., Taylor, A. R., Thomas, N. L., and Vaccari, M.

Subjects
astro-ph.GA, astro-ph.CO
Abstract

We study the nature of the faint radio source population detected in the MeerKAT International GHz Tiered Extragalactic Exploration (MIGHTEE) Early Science data in the COSMOS field, focusing on the properties of the radio-loud active galactic nuclei (AGNs). Using the extensive multiwavelength data available in the field, we are able to classify 88 per cent of the 5223 radio sources in the field with host galaxy identifications as AGNs (35 per cent) or star-forming galaxies (54 per cent). We select a sample of radio-loud AGNs with redshifts out to z ∼ 6 and radio luminosities 1020 < L1.4 GHz/W Hz−1 < 1027 and classify them as high-excitation and low-excitation radio galaxies (HERGs and LERGs). The classification catalogue is released with this work. We find no significant difference in the host galaxy properties of the HERGs and LERGs in our sample. In contrast to previous work, we find that the HERGs and LERGs have very similar Eddington-scaled accretion rates; in particular we identify a population of very slowly accreting AGNs that are formally classified as HERGs at these low radio luminosities, where separating into HERGs and LERGs possibly becomes redundant. We investigate how black hole mass affects jet power, and find that a black hole mass ≳ 107.8 M⊙ is required to power a jet with mechanical power greater than the radiative luminosity of the AGN (Lmech/Lbol > 1). We discuss that both a high black hole mass and black hole spin may be necessary to launch and sustain a dominant radio jet.

Published
2022

31. Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581] (Journal of Hepatology (2021) 75(3) (572–581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))

Author

Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byun, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. A., O'Donnell, S., Picciotto, A., Portincasa, P., Rigamonti, C., Ronca, V., Rosina, F., Spinzi, G., Strazzabosco, M., Tarocchi, M., Tiribelli, C., Toniutto, P., Valenti, L., Vinci, M., Zuin, M., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Migita, K., Ohira, H., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Tanaka, A., Takikawa, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Kawata, K., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., H, E., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Chalasani, N., Luketic, V., Odin, J., Chopra, K., Abecasis, G., Cantor, M., Coppola, G., Economides, A., Lotta, L. A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. R., Williams, S., Tidbury, J., Lim, G., Cheent, K., Levi, S., Mansour, D., Beckley, M., Hollywood, C., Wong, T., Marley, R., Ramage, J., Gordon, H. M., Ridpath, J., Ngatchu, T., Bob Grover, V. P., Shidrawi, R. G., Abouda, G., Corless, L., Narain, M., Rees, I., Brown, A., Taylor-Robinson, S., Wilkins, J., Grellier, L., Banim, P., Das, D., Heneghan, M. A., Curtis, H., Matthews, H. C., Mohammed, F., Aldersley, M., Srirajaskanthan, R., Walker, G., Mcnair, A., Sharif, A., Sen, S., Bird, G., Prince, M. I., Prasad, G., Kitchen, P., Barnardo, A., Oza, C., Sivaramakrishnan, N. N., Gupta, P., Shah, A., Evans, C. D., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Barclay, S. T., Mcdonald, N., Bathgate, A. J., Palmer, K., Dillon, J. F., Rushbrook, S. M., Przemioslo, R., Mcdonald, C., Millar, A., Tai, C., Mitchell, S., Metcalf, J., Shaukat, S., Ninkovic, M., Shmueli, U., Davis, A., Naqvi, A., Lee, T. J., Ryder, S., Collier, J., Klass, H., Cramp, M. E., Sharer, N., Aspinall, R., Ghosh, D., Douds, A. C., Booth, J., Williams, E., Hussaini, H., Christie, J., Mann, S., Thorburn, D., Marshall, A., Patanwala, I., Ala, A., Maltby, J., Matthew, R., Corbett, C., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Mitchison, H., Panter, S., Shearman, J., Bray, G., Roberts, M., Butcher, G., Forton, D., Mahmood, Z., Cowan, M., Ch'Ng, C. L., Rahman, M., Whatley, G. C. A., Wesley, E., Mandal, A., Jain, S., Pereira, S. P., Wright, M., Trivedi, P., Gordon, F. H., Unitt, E., Palejwala, A., Austin, A., Vemala, V., Grant, A., Higham, A. D., Brind, A., Mathew, R., Cox, M., Ramakrishnan, S., King, A., Whalley, S., Fraser, J., Thomson, S. J., Bell, A., Wong, V. S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byun J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M.C., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V.J., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D.J., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J.W., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., and Millson C.

Subjects
PBC
Abstract

It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled ‘Jinyoung Byan’; the correct spelling is ‘Jinyoung Byun’ as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused.

Published
2022

32. Author Correction: Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease (Nature Communications, (2020), 11, 1, (995), 10.1038/s41467-019-14275-y)

Author

Serra E. G., Schwerd T., Moutsianas L., Cavounidis A., Fachal L., Pandey S., Kammermeier J., Croft N. M., Posovszky C., Rodrigues A., Russell R. K., Barakat F., Auth M. K. H., Heuschkel R., Zilbauer M., Fyderek K., Braegger C., Travis S. P., Satsangi J., Parkes M., Thapar N., Ferry H., Matte J. C., Gilmour K. C., Wedrychowicz A., Sullivan P., Moore C., Sambrook J., Ouwehand W., Roberts D., Danesh J., Baeumler T. A., Fulga T. A., Carrami E. M., Ahmed A., Wilson R., Barrett J. C., Elkadri A., Griffiths A. M., Zurek M., Strisciuglio C., Elawad M., Lo B., Arancibia-Carcamo C., Bailey A., Barnes E., Bird-Lieberman E. L., Brain O., Braden B., Collier J., East J., Howarth L., Keshav S., Klenerman P., Leedham S., Palmer R., Powrie F., Simmons A., Walker M., Tolkien Z., Kaptoge S., Allen D., Mehenny S., Mant J., Di Angelantonio E., Thompson S. G., Yilmaz B., Juillerat P., Geuking M., Wiest R., Macpherson A. J., Bravo F. D., Brugger L., Carstens O., Bigler U. G., Heimgartner B., Rusticeanu M., Schmid-Uebelhart S., Strebel B., Tatu A., Tutuian R., Oyas O., Ramon C., Stelling J., Franc Y., Fournier N., Pittet V. E. H., Burnand B., Egger M., Golay D., Marot A., Musso L., Rossel J. -B., Seematter V., Sommer J., Vulliamy R., Michetti P., Maillard M. H., Keller C., Nydegger A., Schoepfe A., Archanioti E., Ezri J., Fraga M., Schoepfer A., Muller C., Rogler G., Biedermann L., Blattmann M., Burk S., Dora B., Fried M., Misselwitz B., Mullhaupt B., Obialo N., Pohl D., Raschle N., Scharl M., Vavricka S., Von Kanel R., Zeitz J., Abdelrahman K., Ademi G., Borovicka J., Brand S., Frei R., Haarer J., Knellwolf-Grieger C., Krieger-Grubel C., Kunzler P., Meyenberger C., Meyer P., Rohrich N., Sawatzki M., Schelling M., Semadeni G. -M., Sulz M., Zimmermann D., Aepli P., Criblez D. H., Hess C., Richterich J. -P., Spalinger J., Staudenmann D., Stulz A., Wohrle S., Thomas A., Anderegg C., Kohler H., Kusche R., Antonino A. -T., Arrigoni E., Bengoa J. M., Cunningham S., de Saussure P., Girard L., de Jong D. B., Basturk P., Brunner S., Degen L., Hruz P., Bakker C. K. -D., Niess J., Balsiger B., Haldemann J., Saner G., Seibold F., Bauerfeind P., Becocci A., Belli D., Binek J., Hengstler P., Boehm S., Boldanov T., Buhr P., Koller R., Rueger V., Senning A., Burri E., Buyse S., Cao D. -T., D'Angelo F., Delarive J., Doerig C., Hessler R., Preissler C., Rentsch R., Risti B., Ritz M. A., Steuerwald M., Vogtlin J., Sagmeister M., Sauter B., Schibli S., Sokollik C., Schlauri H., Schnegg J. -F., Seirafi M., Spangenberger H., Stadler P., Staub P., Stenz V., Tempia-Caliera M., Thorens J., Truninger K., Urfer P., Viani F., Vouillamoz D., Zander S., Wyli T., Jostins L., Kennedy N. A., Ahmad T., Lamb C. A., Edwards C., Hart A., Hawkey C., Mansfield J. C., Mowat C., Newman W. G., Tremelling M., Lee J. C., Prescott N. J., Mathew C. G., Lees C. W., McGovern D. P. B., Targan S. R., Botwin G., Mengesha E., Fleshner P., Landers C., Li D., Rioux J. D., Bitton A., Cote-Daigneault J., Daly M. J., Xavier R., Morris K., Boucher G., Cho J. H., Abraham C., Merad M., Sands B., Peter I., Hao K., Itan Y., Duerr R. H., Konnikova L., Schwartz M. B., Proksell S., Johnston E., Miladinova V., Chen W., Brant S. R., Datta L., Silverberg M. S., Schumm L. P., Birch S., Giri M., Gettler K., Sharma Y., Stevens C., Lazarev M., Haritunians T., Snapper S. B., Shah N., Muise A. M., Wilson D. C., Uhlig H. H., Anderson C. A., Serra, E. G., Schwerd, T., Moutsianas, L., Cavounidis, A., Fachal, L., Pandey, S., Kammermeier, J., Croft, N. M., Posovszky, C., Rodrigues, A., Russell, R. K., Barakat, F., Auth, M. K. H., Heuschkel, R., Zilbauer, M., Fyderek, K., Braegger, C., Travis, S. P., Satsangi, J., Parkes, M., Thapar, N., Ferry, H., Matte, J. C., Gilmour, K. C., Wedrychowicz, A., Sullivan, P., Moore, C., Sambrook, J., Ouwehand, W., Roberts, D., Danesh, J., Baeumler, T. A., Fulga, T. A., Carrami, E. M., Ahmed, A., Wilson, R., Barrett, J. C., Elkadri, A., Griffiths, A. M., Zurek, M., Strisciuglio, C., Elawad, M., Lo, B., Arancibia-Carcamo, C., Bailey, A., Barnes, E., Bird-Lieberman, E. L., Brain, O., Braden, B., Collier, J., East, J., Howarth, L., Keshav, S., Klenerman, P., Leedham, S., Palmer, R., Powrie, F., Simmons, A., Walker, M., Tolkien, Z., Kaptoge, S., Allen, D., Mehenny, S., Mant, J., Di Angelantonio, E., Thompson, S. G., Yilmaz, B., Juillerat, P., Geuking, M., Wiest, R., Macpherson, A. J., Bravo, F. D., Brugger, L., Carstens, O., Bigler, U. G., Heimgartner, B., Rusticeanu, M., Schmid-Uebelhart, S., Strebel, B., Tatu, A., Tutuian, R., Oyas, O., Ramon, C., Stelling, J., Franc, Y., Fournier, N., Pittet, V. E. H., Burnand, B., Egger, M., Golay, D., Marot, A., Musso, L., Rossel, J. -B., Seematter, V., Sommer, J., Vulliamy, R., Michetti, P., Maillard, M. H., Keller, C., Nydegger, A., Schoepfe, A., Archanioti, E., Ezri, J., Fraga, M., Schoepfer, A., Muller, C., Rogler, G., Biedermann, L., Blattmann, M., Burk, S., Dora, B., Fried, M., Misselwitz, B., Mullhaupt, B., Obialo, N., Pohl, D., Raschle, N., Scharl, M., Vavricka, S., Von Kanel, R., Zeitz, J., Abdelrahman, K., Ademi, G., Borovicka, J., Brand, S., Frei, R., Haarer, J., Knellwolf-Grieger, C., Krieger-Grubel, C., Kunzler, P., Meyenberger, C., Meyer, P., Rohrich, N., Sawatzki, M., Schelling, M., Semadeni, G. -M., Sulz, M., Zimmermann, D., Aepli, P., Criblez, D. H., Hess, C., Richterich, J. -P., Spalinger, J., Staudenmann, D., Stulz, A., Wohrle, S., Thomas, A., Anderegg, C., Kohler, H., Kusche, R., Antonino, A. -T., Arrigoni, E., Bengoa, J. M., Cunningham, S., de Saussure, P., Girard, L., de Jong, D. B., Basturk, P., Brunner, S., Degen, L., Hruz, P., Bakker, C. K. -D., Niess, J., Balsiger, B., Haldemann, J., Saner, G., Seibold, F., Bauerfeind, P., Becocci, A., Belli, D., Binek, J., Hengstler, P., Boehm, S., Boldanov, T., Buhr, P., Koller, R., Rueger, V., Senning, A., Burri, E., Buyse, S., Cao, D. -T., D'Angelo, F., Delarive, J., Doerig, C., Hessler, R., Preissler, C., Rentsch, R., Risti, B., Ritz, M. A., Steuerwald, M., Vogtlin, J., Sagmeister, M., Sauter, B., Schibli, S., Sokollik, C., Schlauri, H., Schnegg, J. -F., Seirafi, M., Spangenberger, H., Stadler, P., Staub, P., Stenz, V., Tempia-Caliera, M., Thorens, J., Truninger, K., Urfer, P., Viani, F., Vouillamoz, D., Zander, S., Wyli, T., Jostins, L., Kennedy, N. A., Ahmad, T., Lamb, C. A., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Tremelling, M., Lee, J. C., Prescott, N. J., Mathew, C. G., Lees, C. W., Mcgovern, D. P. B., Targan, S. R., Botwin, G., Mengesha, E., Fleshner, P., Landers, C., Li, D., Rioux, J. D., Bitton, A., Cote-Daigneault, J., Daly, M. J., Xavier, R., Morris, K., Boucher, G., Cho, J. H., Abraham, C., Merad, M., Sands, B., Peter, I., Hao, K., Itan, Y., Duerr, R. H., Konnikova, L., Schwartz, M. B., Proksell, S., Johnston, E., Miladinova, V., Chen, W., Brant, S. R., Datta, L., Silverberg, M. S., Schumm, L. P., Birch, S., Giri, M., Gettler, K., Sharma, Y., Stevens, C., Lazarev, M., Haritunians, T., Snapper, S. B., Shah, N., Muise, A. M., Wilson, D. C., Uhlig, H. H., and Anderson, C. A.

Published
2022

33. GDF15 Mediates the Effect of Skeletal Muscle Contraction on Glucose-Stimulated Insulin Secretion.

Author

Zhang, Hui, Mulya, Anny, Nieuwoudt, Stephan, Vandanmagsar, Bolormaa, McDowell, Ruth, Heintz, Elizabeth C., Zunica, Elizabeth R.M., Collier, J. Jason, Bozadjieva-Kramer, Nadejda, Seeley, Randy J., Axelrod, Christopher L., and Kirwan, John P.

Subjects
SKELETAL muscle, GROWTH differentiation factors, MUSCLE contraction, SECRETION, INSULIN, MICROBIAL exopolysaccharides
Abstract

Exercise is a first-line treatment for type 2 diabetes and preserves β-cell function by hitherto unknown mechanisms. We postulated that proteins from contracting skeletal muscle may act as cellular signals to regulate pancreatic β-cell function. We used electric pulse stimulation (EPS) to induce contraction in C2C12 myotubes and found that treatment of β-cells with EPS-conditioned medium enhanced glucose-stimulated insulin secretion (GSIS). Transcriptomics and subsequent targeted validation revealed growth differentiation factor 15 (GDF15) as a central component of the skeletal muscle secretome. Exposure to recombinant GDF15 enhanced GSIS in cells, islets, and mice. GDF15 enhanced GSIS by upregulating the insulin secretion pathway in β-cells, which was abrogated in the presence of a GDF15 neutralizing antibody. The effect of GDF15 on GSIS was also observed in islets from GFRAL-deficient mice. Circulating GDF15 was incrementally elevated in patients with pre- and type 2 diabetes and positively associated with C-peptide in humans with overweight or obesity. Six weeks of high-intensity exercise training increased circulating GDF15 concentrations, which positively correlated with improvements in β-cell function in patients with type 2 diabetes. Taken together, GDF15 can function as a contraction-induced protein that enhances GSIS through activating the canonical signaling pathway in a GFRAL-independent manner. Article Highlights: Exercise improves glucose-stimulated insulin secretion through direct interorgan communication. Contracting skeletal muscle releases growth differentiation factor 15 (GDF15), which is required to synergistically enhance glucose-stimulated insulin secretion. GDF15 enhances glucose-stimulated insulin secretion by activating the canonical insulin release pathway. Increased levels of circulating GDF15 after exercise training are related to improvements in β-cell function in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
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42. Multivalent antigen presentation increases the antibody binding breadth and neutralizing potency upon the immunization with a self-assembling HIV env vaccine

Author

Fries, C., Dennis, M., Eudailey, J., Moody, A., Permar, S., Collier, J., and Fouda, G.

Subjects
Antigen-antibody reactions -- Observations, Viral antigens -- Health aspects, AIDS (Disease) -- Research, AIDS research, AIDS vaccines -- Testing, Health
Abstract

Background: Although previous studies have demonstrated that antigen valency is important to diversify the B cell repertoire, the ability of multivalent HIV vaccines to increase the breadth of vaccine-elicited antibodies and to promote neutralization remain unclear. Herein, we utilized a novel nanomaterial platform (Q11) to evaluate the influence of antigen valency on the HIV vaccine-elicited antibody responses. Methods: Self-assembly of the fiber-like nanoscale structure of Q11 was triggered by increasing the solvent ionic strength, followed by conjugation of HIV Envelope gycoprotein120 of clade C strains. We constructed vaccines with distinct valency by changing the concentration of antigen in the conjugation. Mice and rabbits were immunized with 15 [micro]g of gp120 or Q11-conjugated gp120 vaccine (gp120-Q11) along with a TLR7/8 and 9 agonist adjuvant STR8SC. A bead-based multiplex assay was used to measure antibody binding to heterologous Envs of subtypes B, C, and CRF_AE, and the TZM-bl cell assay was used to measure neutralization. Results: Mice immunized with gp120-Q11 demonstrated higher antibody titers against the autologous Env (p =0.027) after three immunizations; and higher binding to the 4 heterologous Env after each immunization than mice immunized with gp120 (Figure 1). The increased magnitude and breadth were only observed in mice immunized gp120-Q11 with 3 to 4 antigens on each fiber but not with gp120-Q11 with lower valency, suggesting that multivalent antigen presentation on Q11 contributed to the enhanced response. Immunization of rabbits indicated that Q11-gp120 also induced higher neutralization titer against the autologous tier 1 virus than gp120 (p =0.0285). Conclusions: We demonstrated that increasing the antigen valency by Q11 conjugation enhanced the humoral response in two distinct animal models, showing the potential of such nanomaterial in vaccine delivery. As a more clinically relevant model is required to further assess this platform, we plan to conjugate SOSIP trimer to Q11 and assess its immunogenicity in non-human primates., OA18.05LB J.-L. Chen (1); C. Fries (2); M. Dennis (3); J. Eudailey (3); A. Moody (3); S. Permar (3); J. Collier (2) and G. Fouda (3) (1) Duke University, Molecular [...]

Published
2021
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43. MIGHTEE: deep 1.4 GHz source counts and the sky temperature contribution of star-forming galaxies and active galactic nuclei.

Author

Hale, C L, Whittam, I H, Jarvis, M J, Best, P N, Thomas, N L, Heywood, I, Prescott, M, Adams, N, Afonso, J, An, Fangxia, Bowler, R A A, Collier, J D, Cook, R H W, Davé, R, Frank, B S, Glowacki, M, Hatfield, P W, Kolwa, S, Lovell, C C, and Maddox, N

Subjects
ACTIVE galactic nuclei, ACTIVE galaxies, DATA release, SKY
Abstract

We present deep 1.4 GHz source counts from ∼5 deg2 of the continuum Early Science data release of the MeerKAT International Gigahertz Tiered Extragalactic Exploration survey down to S 1.4GHz ∼15 |$\mu$| Jy. Using observations over two extragalactic fields (COSMOS and XMM-LSS), we provide a comprehensive investigation into correcting the incompleteness of the raw source counts within the survey to understand the true underlying source count population. We use a variety of simulations that account for: errors in source detection and characterization, clustering, and variations in the assumed source model used to simulate sources within the field and characterize source count incompleteness. We present these deep source count distributions and use them to investigate the contribution of extragalactic sources to the sky background temperature at 1.4 GHz using a relatively large sky area. We then use the wealth of ancillary data covering a subset of the COSMOS field to investigate the specific contributions from both active galactic nuclei (AGN) and star-forming galaxies (SFGs) to the source counts and sky background temperature. We find, similar to previous deep studies, that we are unable to reconcile the sky temperature observed by the ARCADE 2 experiment. We show that AGN provide the majority contribution to the sky temperature contribution from radio sources, but the relative contribution of SFGs rises sharply below 1 mJy, reaching an approximate 15–25 per cent contribution to the total sky background temperature (Tb ∼100 mK) at ∼15 |$\mu$| Jy. [ABSTRACT FROM AUTHOR]

Published
2023
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45. Imaging slab-transported fluids and their deep dehydration from seismic velocity tomography in the Lesser Antilles subduction zone

Author

Bie, L., Hicks, S., Rietbrock, A., Goes, S., Collier, J., Rychert, C., Harmon, N., Maunder, B., Consortium, The VoiLA, and Natural Environment Research Council (NERC)

Subjects
Geochemistry & Geophysics, Lesser Antilles, 02 Physical Sciences, slab, Physics, 04 Earth Sciences, seismic velocity, mantle wedge, Geophysics, Space and Planetary Science, Geochemistry and Petrology, Earth and Planetary Sciences (miscellaneous), ddc:530, fluids, subduction
Abstract

Volatiles play a pivotal role in subduction zone evolution, yet their pathways remain poorly constrained. Studying the Lesser Antilles subduction zone can yield new constraints, where old oceanic lithosphere formed by slow-spreading subducts slowly. Here we use local earthquakes recorded by the temporary VoiLA (Volatile recycling in the Lesser Antilles) deployment of ocean-bottom seismometers in the fore- and back-arc to characterize the 3-D seismic structure of the north-central Lesser Antilles subduction zone. Along the slab top, mapped based on seismicity, we find low Vp extending to 130–150 km depth, deeper than expected for magmatic oceanic crust. The slab's most prominent, elevated Vp/Vs anomalies are beneath the fore- and back-arc offshore Guadeloupe and Dominica, where two subducted fracture zones lie with the obliquely subducting boundary between Proto-Caribbean and Equatorial Atlantic lithosphere. These structures, therefore, enhance hydration of the oceanic lithosphere as it forms and evolves and the subsequent dehydration of mantle serpentinite when subducted. Above the slab, we image the asthenosphere wedge as a high Vp/Vs and moderate Vp feature, indicating slab-dehydrated fluids rising through the overlying cold boundary layer that might induce melting further to the west. Our results provide new evidence for the impact of spatially-variable oceanic plate formation processes on slab dehydration and mantle wedge volatile transfer that ultimately impact volcanic processes at the surface, such as the relatively high magmatic output observed on the north-central islands in the Lesser Antilles.

Published
2022
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46. Simulations of the 2004 North American Monsoon : NAMAP2

Author

Gutzler, D. S., Long, L. N., Schemm, J., Roy, S. Baidya, Bosilovich, M., Collier, J. C., Kanamitsu, M., Kelly, P., Lawrence, D., Lee, M.-I., Sánchez, R. Lobato, Mapes, B., Mo, K., Nunes, A., Ritchie, E. A., Roads, J., Schubert, S., Wei, H., and Zhang, G. J.

Published
2009

50. Cyber security assemblages: the theory and practice of diffuse security provision

Author

Collier, J

Subjects
Non-state actors (International relations), Computer security, Politics and government
Abstract

Cyber security is typically provided by a highly complex and diffuse network of actors. Public, private, global, and local security providers operate within the same structures. The relationships between these actors are highly varied – cooperation, coordination and even conflict exist within these cyber security assemblages. Furthermore, the distinctions between actors are often blurred as hybrid structures emerge. This thesis explores the implications of these trends on cyber security outputs and international relations. Three case studies examine the cyber security of critical national infrastructure in the UK, encryption in the US, and digital society in Estonia. The type of actors providing cyber security (including their incentive structures and resources), the relationships between actors, power dynamics, and levels of fusion are all found to have an influential bearing on the nature of cyber security provision. In developing these ideas, it is argued that examining security actors is an important, yet often neglected component of cyber insecurity. While much attention is paid towards threat actors and the structure of cyber conflict, an examination of who provides cyber security and the dynamics discussed above remains comparatively underexplored. This thesis therefore seeks to develop theoretical, conceptual and empirical findings that emphasise the importance of thinking about security provision.

Published
2021

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