39 results on '"Niazi, U."'
Search Results
2. Effect of microwave plasma treatment on magnetic and photocatalytic response of manganese ferrite nanoparticles for wastewater treatment
- Author
-
Naz, M.Y., primary, Irfan, M., additional, Shukrullah, S., additional, Ahmad, I., additional, Ghaffar, A., additional, Niazi, U. M., additional, Rahman, S., additional, Jalalah, M., additional, Alsaiari, M.A., additional, and Khan, M.K.A., additional
- Published
- 2021
- Full Text
- View/download PDF
3. 128 Transcriptional profiling of Blaschko-linear psoriasis skin highlights mostly shared but occasionally divergent features with psoriasis vulgaris
- Author
-
Onoufriadis, A., primary, Niazi, U., additional, Dimitrakopoulou, K., additional, Reich, J., additional, Ainali, C., additional, Papanikolaou, M., additional, Hsu, C., additional, Saqi, M., additional, McGrath, J.A., additional, and Reich, K., additional
- Published
- 2021
- Full Text
- View/download PDF
4. P083 The transcriptomic signature of IL-23-treated lamina propria mononuclear cells is significantly enriched for genes in the Th17 pathway and is enriched in active UC
- Author
-
Digby-Bell, J, primary, Pavlidis, P, additional, Niazi, U, additional, Kassam, Z, additional, Prescott, N, additional, Perucha, E, additional, Saqi, M, additional, and Powell, N, additional
- Published
- 2019
- Full Text
- View/download PDF
5. DOP60 The interleukin 22 transcriptional programme is activated in human colonic inflammation and associated to anti-TNFα primary non-response in Crohn’s
- Author
-
Pavlidis, P, primary, Tsakmaki, A, additional, Niazi, U, additional, Digby-Bell, J, additional, Lombardi, G, additional, Hayee, B, additional, Bewick, G, additional, and Powell, N, additional
- Published
- 2019
- Full Text
- View/download PDF
6. Stratification of latent tuberculosis infection by cellular immune profiling
- Author
-
Halliday, A, Whitworth, H, Hermagild Kottoor, S, Niazi, U, Menzies, S, Kunst, H, Bremang, S, Badhan, A, Beverley, P, Kon, OM, Lalvani, A, and National Institute for Health Research
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Immunology ,BIOMARKERS ,diagnostic ,risk stratification ,DIAGNOSIS ,Microbiology ,Sensitivity and Specificity ,cellular immune signatures ,Interferon-gamma ,Young Adult ,latent M. tuberculosis infection ,Latent Tuberculosis ,Tuberculosis ,Humans ,ASSAY ,Prospective Studies ,Aged ,RISK ,Science & Technology ,Tumor Necrosis Factor-alpha ,Mycobacterium tuberculosis ,11 Medical And Health Sciences ,ACTIVE TUBERCULOSIS ,GAMMA ,Middle Aged ,06 Biological Sciences ,bacterial infections and mycoses ,Infectious Diseases ,T-CELLS ,Interleukin-2 ,Female ,Life Sciences & Biomedicine - Abstract
Background: Recently-acquired and remotely-acquired latent tuberculosis (TB) infection (LTBI) are clinically indistinguishable, yet recent acquisition of infection is the greatest risk factor for progression to active TB (ATB) in immunocompetent individuals. We aimed to evaluate the ability of cellular immune signatures which differ between ATB and LTBI, to distinguish recently from remotely acquired LTBI. Methods: Fifty-nine individuals were recruited: ATB (n=20); recent LTBI (n=19); remote LTBI (n=20). The proportion of mycobacteria-specific TNFα+IFNγ-IL-2-- secreting CD4+ T cells with a differentiated effector phenotype (TNFα-only TEFF), and the level of CD27 expression on IFNγ-producing CD4+ T cells, were detected by flow-cytometry. Results: The TNFα-only TEFF signature was significantly higher in recent compared to remote LTBI (p
- Published
- 2017
7. Corrigendum: Whole genome analysis of a schistosomiasis-transmitting freshwater snail
- Author
-
Adema, CM, Hillier, LDW, Jones, CS, Loker, ES, Knight, M, Minx, P, Oliveira, G, Raghavan, N, Shedlock, A, do Amaral, LR, Arican-Goktas, HD, Assis, JG, Baba, EH, Baron, OL, Bayne, CJ, Bickham-Wright, U, Biggar, KK, Blouin, M, Bonning, BC, Botka, C, Bridger, JM, Buckley, KM, Buddenborg, SK, Lima Caldeira, R, Carleton, J, Carvalho, OS, Castillo, MG, Chalmers, IW, Christensens, M, Clifton, S, Cosseau, C, Coustau, C, Cripps, RM, Cuesta-Astroz, Y, Cummins, SF, Di Stefano, L, Dinguirard, N, Duval, D, Emrich, S, Feschotte, C, Feyereisen, R, FitzGerald, P, Fronick, C, Fulton, L, Galinier, R, Gava, SG, Geusz, M, Geyer, KK, Giraldo-Calderón, GI, de Souza Gomes, M, Gordy, MA, Gourbal, B, Grunau, C, Hanington, PC, Hoffmann, KF, Hughes, D, Humphries, J, Jackson, DJ, Jannotti-Passos, LK, de Jesus Jeremias, W, Jobling, S, Kamel, B, Kapusta, A, Kaur, S, Koene, JM, Kohn, AB, Lawson, D, Lawton, SP, Liang, D, Limpanont, Y, Liu, S, Lockyer, AE, Lovato, TAL, Ludolf, F, Magrini, V, McManus, DP, Medina, M, Misra, M, Mitta, G, Mkoji, GM, Montague, MJ, Montelongo, C, Moroz, LL, Munoz-Torres, MC, Niazi, U, Noble, LR, Oliveira, FS, Pais, FS, Papenfuss, AT, Peace, R, Pena, JJ, Pila, EA, Quelais, T, Raney, BJ, Rast, JP, Rollinson, D, Rosse, IC, Rotgans, B, Routledge, EJ, and Ryan, KM
- Abstract
This corrects the article DOI: 10.1038/ncomms15451.
- Published
- 2017
8. Deformation and Heat Transfer on Three Sides Protected Beams under Fire Accident
- Author
-
Imran, M, primary, Liew, M S, additional, Garcia, E M, additional, Nasif, M S, additional, Yassin, A Y M, additional, and Niazi, U M, additional
- Published
- 2018
- Full Text
- View/download PDF
9. Whole genome analysis of a schistosomiasis-transmitting freshwater snail
- Author
-
Adema, C.M. (Coen M.), Hillier, L.W. (LaDeana W.), Jones, C.S. (Catherine S.), Loker, E.S. (Eric S.), Knight, M. (Matty), Minx, P. (Patrick), Oliveira, G. (Guilherme), Raghavan, N. (Nithya), Shedlock, A. (Andrew), Do Amaral, L.R. (Laurence Rodrigues), Arican-Goktas, H.D. (Halime D.), Assis, J.G. (Juliana G.), Baba, E.H. (Elio Hideo), Baron, O.L. (Olga L.), Bayne, C.J. (Christopher J.), Bickham-Wright, U. (Utibe), Biggar, K.K. (Kyle K.), Blouin, M. (Michael), Bonning, B.C. (Bryony C.), Botka, C. (Chris), Bridger, J.M. (Joanna M.), Buckley, K.M. (Katherine M.), Buddenborg, S.K. (Sarah K.), Lima Caldeira, R. (Roberta), Carleton, J. (Julia), Carvalho, O.S. (Omar S.), Castillo, M.G. (Maria G.), Chalmers, I.W. (Iain W.), Christensens, M. (Mikkel), Clifton, S. (Sandra), Cosseau, C. (Celine), Coustau, C. (Christine), Cripps, R.M. (Richard M.), Cuesta-Astroz, Y. (Yesid), Cummins, S.F. (Scott F.), DI Stephano, L. (Leon), DInguirard, N. (Nathalie), Duval, D. (David), Emrich, S. (Scott), Feschotte, C. (Cédric), Feyereisen, R. (Rene), Fitzgerald, P. (Peter), Fronick, C. (Catrina), Fulton, L. (Lucinda), Galinier, R. (Richard), Gava, S.G. (Sandra G.), Geusz, M. (Michael), Geyer, K.K. (Kathrin K.), Giraldo-Calderón, G.I. (Gloria I.), De Souza Gomes, M. (Matheus), Gordy, M.A. (Michelle A.), Gourbal, B. (Benjamin), Grunau, C. (Christoph), Hanington, P.C. (Patrick C.), Hoffmann, K.F. (Karl F.), Hughes, D. (Daniel), Humphries, J. (Judith), Jackson, D.J. (Daniel J.), Jannotti-Passos, L.K. (Liana K.), De Jesus Jeremias, W. (Wander), Jobling, S. (Susan), Kamel, B. (Bishoy), Kapusta, A. (Aurélie), Kaur, S. (Satwant), Koene, J.M. (Joris M.), Kohn, A.B. (Andrea B.), Lawson, D. (Dan), Lawton, S.P. (Scott P), Liang, D. (Di), Limpanont, Y. (Yanin), Liu, S. (Sijun), Lockyer, A.E. (Anne E.), Lovato, T.L. (TyAnna L.), Ludolf, F. (Fernanda), Magrini, V. (Vince), McManus, D.P. (Donald P.), Medina, M. (Monica), Misra, M. (Milind), Mitta, G. (Guillaume), Mkoji, G.M. (Gerald M.), Montague, M.J. (Michael J.), Montelongo, C. (Cesar), Moroz, L.L. (Leonid L.), Munoz-Torres, M.C. (Monica C.), Niazi, U. (Umar), Noble, L.R. (Leslie R.), Oliveira, F.S. (Francislon S.), Pais, F.S. (Fabiano S.), Papenfuss, A.T. (Anthony T.), Peace, R. (Rob), Pena, J.J. (Janeth J.), Pila, E.A. (Emmanuel A.), Quelais, T. (Titouan), Raney, B.J. (Brian J.), Rast, J.P. (Jonathan P.), Rollinson, D. (David), Rosse, I.C. (Izinara C.), Rotgans, B. (Bronwyn), Routledge, E.J. (Edwin J.), Ryan, K.M. (Kathryn M.), Scholte, L.L.S. (Larissa L. S.), Storey, K. (Kenneth B.), Swain, M. (Martin), Tennessen, J.A. (Jacob A.), Tomlinson, C. (Chad), Trujillo, D.L. (Damian L.), Volpi, E.V. (Emanuela V.), Walker, A.J. (Anthony J.), Wang, T. (Tianfang), Wannaporn, I. (Ittiprasert), Warren, W.C. (Wesley C.), Wu, X.-J. (Xiao-Jun), Yoshino, T.P. (Timothy P.), Yusuf, M. (Mohammed), Zhang, S.-M. (Si-Ming), Zhao, M. (Min), Wilson, R.K. (Richard K.), Adema, C.M. (Coen M.), Hillier, L.W. (LaDeana W.), Jones, C.S. (Catherine S.), Loker, E.S. (Eric S.), Knight, M. (Matty), Minx, P. (Patrick), Oliveira, G. (Guilherme), Raghavan, N. (Nithya), Shedlock, A. (Andrew), Do Amaral, L.R. (Laurence Rodrigues), Arican-Goktas, H.D. (Halime D.), Assis, J.G. (Juliana G.), Baba, E.H. (Elio Hideo), Baron, O.L. (Olga L.), Bayne, C.J. (Christopher J.), Bickham-Wright, U. (Utibe), Biggar, K.K. (Kyle K.), Blouin, M. (Michael), Bonning, B.C. (Bryony C.), Botka, C. (Chris), Bridger, J.M. (Joanna M.), Buckley, K.M. (Katherine M.), Buddenborg, S.K. (Sarah K.), Lima Caldeira, R. (Roberta), Carleton, J. (Julia), Carvalho, O.S. (Omar S.), Castillo, M.G. (Maria G.), Chalmers, I.W. (Iain W.), Christensens, M. (Mikkel), Clifton, S. (Sandra), Cosseau, C. (Celine), Coustau, C. (Christine), Cripps, R.M. (Richard M.), Cuesta-Astroz, Y. (Yesid), Cummins, S.F. (Scott F.), DI Stephano, L. (Leon), DInguirard, N. (Nathalie), Duval, D. (David), Emrich, S. (Scott), Feschotte, C. (Cédric), Feyereisen, R. (Rene), Fitzgerald, P. (Peter), Fronick, C. (Catrina), Fulton, L. (Lucinda), Galinier, R. (Richard), Gava, S.G. (Sandra G.), Geusz, M. (Michael), Geyer, K.K. (Kathrin K.), Giraldo-Calderón, G.I. (Gloria I.), De Souza Gomes, M. (Matheus), Gordy, M.A. (Michelle A.), Gourbal, B. (Benjamin), Grunau, C. (Christoph), Hanington, P.C. (Patrick C.), Hoffmann, K.F. (Karl F.), Hughes, D. (Daniel), Humphries, J. (Judith), Jackson, D.J. (Daniel J.), Jannotti-Passos, L.K. (Liana K.), De Jesus Jeremias, W. (Wander), Jobling, S. (Susan), Kamel, B. (Bishoy), Kapusta, A. (Aurélie), Kaur, S. (Satwant), Koene, J.M. (Joris M.), Kohn, A.B. (Andrea B.), Lawson, D. (Dan), Lawton, S.P. (Scott P), Liang, D. (Di), Limpanont, Y. (Yanin), Liu, S. (Sijun), Lockyer, A.E. (Anne E.), Lovato, T.L. (TyAnna L.), Ludolf, F. (Fernanda), Magrini, V. (Vince), McManus, D.P. (Donald P.), Medina, M. (Monica), Misra, M. (Milind), Mitta, G. (Guillaume), Mkoji, G.M. (Gerald M.), Montague, M.J. (Michael J.), Montelongo, C. (Cesar), Moroz, L.L. (Leonid L.), Munoz-Torres, M.C. (Monica C.), Niazi, U. (Umar), Noble, L.R. (Leslie R.), Oliveira, F.S. (Francislon S.), Pais, F.S. (Fabiano S.), Papenfuss, A.T. (Anthony T.), Peace, R. (Rob), Pena, J.J. (Janeth J.), Pila, E.A. (Emmanuel A.), Quelais, T. (Titouan), Raney, B.J. (Brian J.), Rast, J.P. (Jonathan P.), Rollinson, D. (David), Rosse, I.C. (Izinara C.), Rotgans, B. (Bronwyn), Routledge, E.J. (Edwin J.), Ryan, K.M. (Kathryn M.), Scholte, L.L.S. (Larissa L. S.), Storey, K. (Kenneth B.), Swain, M. (Martin), Tennessen, J.A. (Jacob A.), Tomlinson, C. (Chad), Trujillo, D.L. (Damian L.), Volpi, E.V. (Emanuela V.), Walker, A.J. (Anthony J.), Wang, T. (Tianfang), Wannaporn, I. (Ittiprasert), Warren, W.C. (Wesley C.), Wu, X.-J. (Xiao-Jun), Yoshino, T.P. (Timothy P.), Yusuf, M. (Mohammed), Zhang, S.-M. (Si-Ming), Zhao, M. (Min), and Wilson, R.K. (Richard K.)
- Abstract
Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis.
- Published
- 2017
- Full Text
- View/download PDF
10. Whole genome analysis of a schistosomiasis-transmitting freshwater snail
- Author
-
Adema, CM, Hillier, LW, Jones, CS, Loker, ES, Knight, M, Minx, P, Oliveira, G, Raghavan, N, Shedlock, A, do Amaral, LR, Arican-Goktas, HD, Assis, JG, Baba, EH, Baron, OL, Bayne, CJ, Bickham-Wright, U, Biggar, KK, Blouin, M, Bonning, BC, Botka, C, Bridger, JM, Buckley, KM, Buddenborg, SK, Caldeira, RL, Carleton, J, Carvalho, OS, Castillo, MG, Chalmers, IW, Christensens, M, Clifton, S, Cosseau, C, Coustau, C, Cripps, RM, Cuesta-Astroz, Y, Cummins, SF, Di Stephano, L, Dinguirard, N, Duval, D, Emrich, S, Feschotte, C, Feyereisen, R, FitzGerald, P, Fronick, C, Fulton, L, Galinier, R, Gava, SG, Geusz, M, Geyer, KK, Giraldo-Calderon, GI, Gomes, MDS, Gordy, MA, Gourbal, B, Grunau, C, Hanington, PC, Hoffmann, KF, Hughes, D, Humphries, J, Jackson, DJ, Jannotti-Passos, LK, Jeremias, WDJ, Jobling, S, Kamel, B, Kapusta, A, Kaur, S, Koene, JM, Kohn, AB, Lawson, D, Lawton, SP, Liang, D, Limpanont, Y, Liu, S, Lockyer, AE, Lovato, TL, Ludolf, F, Magrini, V, McManus, DP, Medina, M, Misra, M, Mitta, G, Mkoji, GM, Montague, MJ, Montelongo, C, Moroz, LL, Munoz-Torres, MC, Niazi, U, Noble, LR, Oliveira, FS, Pais, FS, Papenfuss, AT, Peace, R, Pena, JJ, Pila, EA, Quelais, T, Raney, BJ, Rast, JP, Rollinson, D, Rosse, IC, Rotgans, B, Routledge, EJ, Ryan, KM, Scholte, LLS, Storey, KB, Swain, M, Tennessen, JA, Tomlinson, C, Trujillo, DL, Volpi, EV, Walker, AJ, Wang, T, Wannaporn, I, Warren, WC, Wu, X-J, Yoshino, TP, Yusuf, M, Zhang, S-M, Zhao, M, Wilson, RK, Adema, CM, Hillier, LW, Jones, CS, Loker, ES, Knight, M, Minx, P, Oliveira, G, Raghavan, N, Shedlock, A, do Amaral, LR, Arican-Goktas, HD, Assis, JG, Baba, EH, Baron, OL, Bayne, CJ, Bickham-Wright, U, Biggar, KK, Blouin, M, Bonning, BC, Botka, C, Bridger, JM, Buckley, KM, Buddenborg, SK, Caldeira, RL, Carleton, J, Carvalho, OS, Castillo, MG, Chalmers, IW, Christensens, M, Clifton, S, Cosseau, C, Coustau, C, Cripps, RM, Cuesta-Astroz, Y, Cummins, SF, Di Stephano, L, Dinguirard, N, Duval, D, Emrich, S, Feschotte, C, Feyereisen, R, FitzGerald, P, Fronick, C, Fulton, L, Galinier, R, Gava, SG, Geusz, M, Geyer, KK, Giraldo-Calderon, GI, Gomes, MDS, Gordy, MA, Gourbal, B, Grunau, C, Hanington, PC, Hoffmann, KF, Hughes, D, Humphries, J, Jackson, DJ, Jannotti-Passos, LK, Jeremias, WDJ, Jobling, S, Kamel, B, Kapusta, A, Kaur, S, Koene, JM, Kohn, AB, Lawson, D, Lawton, SP, Liang, D, Limpanont, Y, Liu, S, Lockyer, AE, Lovato, TL, Ludolf, F, Magrini, V, McManus, DP, Medina, M, Misra, M, Mitta, G, Mkoji, GM, Montague, MJ, Montelongo, C, Moroz, LL, Munoz-Torres, MC, Niazi, U, Noble, LR, Oliveira, FS, Pais, FS, Papenfuss, AT, Peace, R, Pena, JJ, Pila, EA, Quelais, T, Raney, BJ, Rast, JP, Rollinson, D, Rosse, IC, Rotgans, B, Routledge, EJ, Ryan, KM, Scholte, LLS, Storey, KB, Swain, M, Tennessen, JA, Tomlinson, C, Trujillo, DL, Volpi, EV, Walker, AJ, Wang, T, Wannaporn, I, Warren, WC, Wu, X-J, Yoshino, TP, Yusuf, M, Zhang, S-M, Zhao, M, and Wilson, RK
- Abstract
Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis.
- Published
- 2017
11. Structural modeling and analysis of dengue-mediated inhibition of interferon signaling pathway
- Author
-
Aslam, B., primary, Ahmad, J., additional, Ali, A., additional, Paracha, R.Z., additional, Tareen, S.H.K., additional, Khusro, S., additional, Ahmad, T., additional, Muhammad, S.A., additional, Niazi, U., additional, and Azevedo, V., additional
- Published
- 2015
- Full Text
- View/download PDF
12. Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2
- Author
-
Mclaughlin, L. A., primary, Niazi, U., additional, Bibby, J., additional, David, J.-P., additional, Vontas, J., additional, Hemingway, J., additional, Ranson, H., additional, Sutcliffe, M. J., additional, and Paine, M. J. I., additional
- Published
- 2008
- Full Text
- View/download PDF
13. Modeling of pool fire and injury prediction considering different wind speeds and directions in offshore platform
- Author
-
Niazi, U. M., Nasif, M. S., Bin Muhammad, M., and Muhammd Imran
14. ChemInform Abstract: An MC‐SCF Study of the Mechanisms for 1,3‐Dipolar Cycloadditions.
- Author
-
MCDOUALL, J. J. W., primary, ROBB, M. A., additional, NIAZI, U., additional, BERNARDI, F., additional, and SCHLEGEL, H. B., additional
- Published
- 1987
- Full Text
- View/download PDF
15. Interleukin-22 regulates neutrophil recruitment in ulcerative colitis and is associated with resistance to ustekinumab therapy.
- Author
-
Pavlidis P, Tsakmaki A, Pantazi E, Li K, Cozzetto D, Digby-Bell J, Yang F, Lo JW, Alberts E, Sa ACC, Niazi U, Friedman J, Long AK, Ding Y, Carey CD, Lamb C, Saqi M, Madgwick M, Gul L, Treveil A, Korcsmaros T, Macdonald TT, Lord GM, Bewick G, and Powell N
- Subjects
- Chemokines, CXC metabolism, Humans, Interleukin-8 metabolism, Interleukins, Neutrophil Infiltration, Neutrophils metabolism, Receptors, Interleukin-8B metabolism, Ustekinumab pharmacology, Ustekinumab therapeutic use, Interleukin-22, Colitis, Ulcerative drug therapy, Colitis, Ulcerative genetics
- Abstract
The function of interleukin-22 (IL-22) in intestinal barrier homeostasis remains controversial. Here, we map the transcriptional landscape regulated by IL-22 in human colonic epithelial organoids and evaluate the biological, functional and clinical significance of the IL-22 mediated pathways in ulcerative colitis (UC). We show that IL-22 regulated pro-inflammatory pathways are involved in microbial recognition, cancer and immune cell chemotaxis; most prominently those involving CXCR2
+ neutrophils. IL-22-mediated transcriptional regulation of CXC-family neutrophil-active chemokine expression is highly conserved across species, is dependent on STAT3 signaling, and is functionally and pathologically important in the recruitment of CXCR2+ neutrophils into colonic tissue. In UC patients, the magnitude of enrichment of the IL-22 regulated transcripts in colonic biopsies correlates with colonic neutrophil infiltration and is enriched in non-responders to ustekinumab therapy. Our data provide further insights into the biology of IL-22 in human disease and highlight its function in the regulation of pathogenic immune pathways, including neutrophil chemotaxis. The transcriptional networks regulated by IL-22 are functionally and clinically important in UC, impacting patient trajectories and responsiveness to biological intervention., (© 2022. The Author(s).)- Published
- 2022
- Full Text
- View/download PDF
16. Cytokine responsive networks in human colonic epithelial organoids unveil a molecular classification of inflammatory bowel disease.
- Author
-
Pavlidis P, Tsakmaki A, Treveil A, Li K, Cozzetto D, Yang F, Niazi U, Hayee BH, Saqi M, Friedman J, Korcsmaros T, Bewick G, and Powell N
- Subjects
- Colon pathology, Cytokines, Humans, Inflammation pathology, Interferon-gamma pharmacology, Interleukin-13, Intestinal Mucosa pathology, Tumor Necrosis Factor-alpha, Inflammatory Bowel Diseases pathology, Organoids pathology
- Abstract
Interactions between the epithelium and the immune system are critical in the pathogenesis of inflammatory bowel disease (IBD). In this study, we mapped the transcriptional landscape of human colonic epithelial organoids in response to different cytokines responsible for mediating canonical mucosal immune responses. By profiling the transcriptome of human colonic organoids treated with the canonical cytokines interferon gamma, interleukin-13, -17A, and tumor necrosis factor alpha with next-generation sequencing, we unveil shared and distinct regulation patterns of epithelial function by different cytokines. An integrative analysis of cytokine responses in diseased tissue from patients with IBD (n = 1,009) reveals a molecular classification of mucosal inflammation defined by gradients of cytokine-responsive transcriptional signatures. Our systems biology approach detected signaling bottlenecks in cytokine-responsive networks and highlighted their translational potential as theragnostic targets in intestinal inflammation., Competing Interests: Declaration of interests K.L., F.Y., and J.F. are/were employees of Janssen Pharmaceuticals., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2022
- Full Text
- View/download PDF
17. Organoids capture tissue-specific innate lymphoid cell development in mice and humans.
- Author
-
Jowett GM, Read E, Roberts LB, Coman D, Vilà González M, Zabinski T, Niazi U, Reis R, Trieu TJ, Danovi D, Gentleman E, Vallier L, Curtis MA, Lord GM, and Neves JF
- Subjects
- Animals, Cell Differentiation, Humans, Immunity, Innate, Immunotherapy, Lymphocytes, Mice, Induced Pluripotent Stem Cells, Organoids
- Abstract
Organoid-based models of murine and human innate lymphoid cell precursor (ILCP) maturation are presented. First, murine intestinal and pulmonary organoids are harnessed to demonstrate that the epithelial niche is sufficient to drive tissue-specific maturation of all innate lymphoid cell (ILC) groups in parallel, without requiring subset-specific cytokine supplementation. Then, more complex human induced pluripotent stem cell (hiPSC)-based gut and lung organoid models are used to demonstrate that human epithelial cells recapitulate maturation of ILC from a stringent systemic human ILCP population, but only when the organoid-associated stromal cells are depleted. These systems offer versatile and reductionist models to dissect the impact of environmental and mucosal niche cues on ILC maturation. In the future, these could provide insight into how ILC activity and development might become dysregulated in chronic inflammatory diseases., Competing Interests: Declaration of interests G.M.J. and J.F.N. are inventors on a patent application related to this work (UK Patent Application No. 2208963.5). The remaining authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
18. Cellular and molecular mechanisms of IMMunE dysfunction and Recovery from SEpsis-related critical illness in adults: An observational cohort study (IMMERSE) protocol paper.
- Author
-
Fish M, Arkless K, Jennings A, Wilson J, Carter MJ, Arbane G, Campos S, Novellas N, Wester R, Petrov N, Niazi U, Sanderson B, Ellis R, Saqi M, Spencer J, Singer M, Martinez-Nunez RT, Pitchford S, Swanson CM, and Shankar-Hari M
- Abstract
Sepsis is a common illness. Immune responses are considered major drivers of sepsis illness and outcomes. However, there are no proven immunomodulator therapies in sepsis. We hypothesised that in-depth characterisation of sepsis-specific immune trajectory may inform immunomodulation in sepsis-related critical illness. We describe the protocol of the IMMERSE study to address this hypothesis. We include critically ill sepsis patients without documented immune comorbidity and age-sex matched cardiac surgical patients as controls. We plan to perform an in-depth biological characterisation of innate and adaptive immune systems, platelet function, humoral components and transcriptional determinants of the immune system responses in sepsis. This will be done at pre-specified time points during their critical illness to generate an illness trajectory. The sample size for each biological assessment is different and is described in detail. In summary, the overall aim of the IMMERSE study is to increase the granularity of longitudinal immunology model of sepsis to inform future immunomodulation trials., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2020.)
- Published
- 2022
- Full Text
- View/download PDF
19. Experimental and Numerical Investigation of Effect of Static and Fatigue Loading on Behavior of Different Double Strap Adhesive Joint Configurations in Fiber Metal Laminates.
- Author
-
Azeem M, Irfan M, Masud M, Rehman GU, Ali H, Ali MU, Zafar A, Muhammad Niazi U, Rahman S, Legutko S, Petrů J, and Kratochvíl J
- Abstract
Double strap lap adhesive joints between metal (AA 6061-T6) and composite (carbon/epoxy) laminates were fabricated and characterized based on strength. Hand layup methods were used to fabricate double strap match lap joints and double strap mismatch lap joints. These joints were compared for their strength under static and fatigue loadings. Fracture toughness (GIIC) was measured experimentally using tensile testing and validated with numerical simulations using the cohesive zone model (CZM) in ABAQUS/Standard. Fatigue life under tension-tension fluctuating sinusoidal loading was determined experimentally. Failure loads for both joints were in close relation, whereas the fatigue life of the double strap mismatch lap joint was longer than that of the double strap match lap joint. A cohesive dominating failure pattern was identified in tensile testing. During fatigue testing, it was observed that inhomogeneity (air bubble) in adhesive plays a negative role while the long time duration between two consecutive cycle spans has a positive effect on the life of joints.
- Published
- 2022
- Full Text
- View/download PDF
20. Transcriptomic Analysis of Blaschko-Linear Psoriasis Reveals Shared and Distinct Features with Psoriasis Vulgaris.
- Author
-
Onoufriadis A, Niazi U, Dimitrakopoulou K, Reich J, Ainali C, Papanikolaou M, Kesidou E, Hsu CK, Saqi M, McGrath JA, and Reich K
- Subjects
- Adult, Female, Gene Expression Profiling, Humans, Male, Protein Interaction Maps genetics, Psoriasis immunology, Psoriasis pathology, Signal Transduction genetics, Signal Transduction immunology, Skin immunology, Skin pathology, Protein Interaction Maps immunology, Psoriasis genetics
- Published
- 2022
- Full Text
- View/download PDF
21. Combining Allergen Components Improves the Accuracy of Peanut Allergy Diagnosis.
- Author
-
Hemmings O, Niazi U, Kwok M, Radulovic S, Du Toit G, Lack G, and Santos AF
- Subjects
- Allergens, Antigens, Plant, Arachis, Bayes Theorem, Humans, Immunoglobulin E, Peanut Hypersensitivity diagnosis
- Abstract
Background: IgE to peanut often occurs in the absence of peanut allergy. Detection of allergen component specific IgE (sIgE) has improved diagnosis and birthed molecular allergen component arrays, in which sensitization to multiple allergen components can be measured simultaneously., Objective: To improve the diagnostic utility of serology for peanut allergy, by mapping interactions of sIgE to multiple components and IgE functional characteristics., Methods: A cohort of 100 children was studied, with a 60-children cohort employed for external validation. Levels of total IgE, sIgE to peanut, and peanut components were measured using singleplex ImmunoCAP and multiplex immuno solid-phase allergen chip (ISAC). Peanut IgE specific activity, avidity, and diversity were determined. Diagnostic modeling was performed using a Bayesian hierarchical model., Results: Sensitization to the 112 allergens on ISAC (model 1) demonstrated the highest accuracy to diagnose peanut allergy (area under the curve [AUC] = 0.92). Sensitization to peanut components on ISAC (model 2) reported an AUC of 0.86 and on singleplex (model 3) an AUC of 0.92, which was greater than that of Ara h 2 sIgE alone (AUC = 0.90). Functional characteristics of peanut sIgE (model 4) reported an AUC of 0.89, which was greater than that of peanut sIgE (AUC = 0.75). Model 3 offered the highest predictive value and the second highest overall diagnostic accuracy., Conclusions: sIgE to a combination of allergen components (Ara h 1, 2, 3, and 6) is highly predictive of peanut allergy and superior to individual markers. Combining the functional characteristics of IgE was superior to peanut sIgE levels alone. These models can be applied in real time during clinical consultations using online calculators., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
22. Peanut diversity and specific activity are the dominant IgE characteristics for effector cell activation in children.
- Author
-
Hemmings O, Niazi U, Kwok M, James LK, Lack G, and Santos AF
- Subjects
- Adolescent, Child, Child, Preschool, Female, Flow Cytometry, Humans, Infant, Male, Antigens, Plant immunology, Arachis immunology, Basophils immunology, Basophils metabolism, Immunoglobulin E blood, Immunoglobulin E immunology, Mast Cells immunology, Mast Cells metabolism, Peanut Hypersensitivity blood, Peanut Hypersensitivity immunology
- Abstract
Background: IgE mediates allergic reactions to peanut; however, peanut-specific IgE (sIgE) levels do not always equate to clinical peanut allergy. Qualitative differences between sIgE of peanut-sensitized but tolerant (PS) and peanut-allergic (PA) individuals may be important., Objective: We sought to assess the influence of IgE characteristics on effector cell activation in peanut allergy., Methods: A cohort of 100 children was studied. The levels of IgE to peanut and peanut components were measured. Specific activity (SA) was estimated as the ratio of allergen-sIgE to total IgE. Avidity was measured by ImmunoCAP with sodium thiocyanate. IgE diversity was calculated on the basis of ImmunoCAP-Immuno Solid-phase Allergen Chip assays for 112 allergens or for 6 peanut allergens. Whole-blood basophils and mast cell line Laboratory of Allergic Diseases 2 sensitized with patients' plasma were stimulated with peanut or controls and assessed by flow cytometry., Results: SA to peanut (P < .001), Ara h 1 (P = .004), Ara h 2 (P < .001), Ara h 3 (P = .02), and Ara h 6 (P < .001) and the avidity of peanut-sIgE (P < .001) were higher in PA than in PS individuals. Diversity for peanut allergens was greater in PA individuals (P < .001). All IgE characteristics were correlated with basophil and mast cell activation. Peanut SA (R = 0.447) and peanut diversity (R = 0.440) had the highest standardized β-coefficients in combined multivariable regression models (0.447 and 0.440, respectively)., Conclusions: IgE specificity, SA, avidity, and peanut diversity were greater in PA than in PS individuals. IgE peanut SA and peanut diversity had the greatest influence on effector cell activation and could be used clinically., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
23. Synthesis, Surface Nitriding and Characterization of Ti-Nb Modified 316L Stainless Steel Alloy Using Powder Metallurgy.
- Author
-
Ali S, Irfan M, Muhammad Niazi U, Rani AMA, Shah I, Legutko S, Rahman S, Jalalah M, Alsaiari MA, Glowacz A, and AlKahtani FS
- Abstract
The powder metallurgy (PM) technique has been widely used for producing different alloy compositions by the addition of suitable reinforcements. PM is also capable of producing desireable mechanical and physical properties of the material by varying process parameters. This research investigates the addition of titanium and niobium in a 316L stainless steel matrix for potential use in the biomedical field. The increase of sintering dwell time resulted in simultaneous sintering and surface nitriding of compositions, using nitrogen as the sintering atmosphere. The developed alloy compositions were characterized using OM, FESEM, XRD and XPS techniques for quantification of the surface nitride layer and the nitrogen absorbed during sintering. The corrosion resistance and cytotoxicity assessments of the developed compositions were carried out in artificial saliva solution and human oral fibroblast cell culture, respectively. The results indicated that the nitride layer produced during sintering increased the corrosion resistance of the alloy and the developed compositions are non-cytotoxic. This newly developed alloy composition and processing technique is expected to provide a low-cost solution to implant manufacturing.
- Published
- 2021
- Full Text
- View/download PDF
24. SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care.
- Author
-
Gutmann C, Takov K, Burnap SA, Singh B, Ali H, Theofilatos K, Reed E, Hasman M, Nabeebaccus A, Fish M, McPhail MJ, O'Gallagher K, Schmidt LE, Cassel C, Rienks M, Yin X, Auzinger G, Napoli S, Mujib SF, Trovato F, Sanderson B, Merrick B, Niazi U, Saqi M, Dimitrakopoulou K, Fernández-Leiro R, Braun S, Kronstein-Wiedemann R, Doores KJ, Edgeworth JD, Shah AM, Bornstein SR, Tonn T, Hayday AC, Giacca M, Shankar-Hari M, and Mayr M
- Subjects
- Adult, Animals, Antibodies, Neutralizing immunology, Antigens, Neoplasm metabolism, Biomarkers, Tumor metabolism, C-Reactive Protein metabolism, COVID-19 metabolism, COVID-19 virology, Female, HEK293 Cells, Humans, Kaplan-Meier Estimate, Male, Middle Aged, RNA, Viral blood, SARS-CoV-2 metabolism, SARS-CoV-2 physiology, Serum Amyloid P-Component metabolism, Spike Glycoprotein, Coronavirus immunology, Spike Glycoprotein, Coronavirus metabolism, Viral Load immunology, COVID-19 prevention & control, Critical Care statistics & numerical data, Proteomics methods, RNA, Viral genetics, SARS-CoV-2 genetics
- Abstract
Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia is associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22-2.77] adjusted for age and sex). RNAemia is comparable in performance to the best protein predictors. Mannose binding lectin 2 and pentraxin-3 (PTX3), two activators of the complement pathway of the innate immune system, are positively associated with mortality. Machine learning identified 'Age, RNAemia' and 'Age, PTX3' as the best binary signatures associated with 28-day ICU mortality. In longitudinal comparisons, COVID-19 ICU patients have a distinct proteomic trajectory associated with mortality, with recovery of many liver-derived proteins indicating survival. Finally, proteins of the complement system and galectin-3-binding protein (LGALS3BP) are identified as interaction partners of SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake and spike-induced cell-cell fusion in vitro.
- Published
- 2021
- Full Text
- View/download PDF
25. MicroRNA-142 Critically Regulates Group 2 Innate Lymphoid Cell Homeostasis and Function.
- Author
-
Roberts LB, Jowett GM, Read E, Zabinski T, Berkachy R, Selkirk ME, Jackson I, Niazi U, Anandagoda N, Araki M, Araki K, Kasturiarachchi J, James C, Enver T, Nimmo R, Reis R, Howard JK, Neves JF, and Lord GM
- Subjects
- Animals, HEK293 Cells, Homeostasis, Humans, Immunity, Innate immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs genetics, Lymphocytes immunology, MicroRNAs immunology
- Abstract
Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor-biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following Nippostrongylus brasiliensis infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, Socs1 and Gfi1 expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions., (Copyright © 2021 The Authors.)
- Published
- 2021
- Full Text
- View/download PDF
26. Transcriptomic signatures for diagnosing tuberculosis in clinical practice: a prospective, multicentre cohort study.
- Author
-
Hoang LT, Jain P, Pillay TD, Tolosa-Wright M, Niazi U, Takwoingi Y, Halliday A, Berrocal-Almanza LC, Deeks JJ, Beverley P, Kon OM, and Lalvani A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Diagnostic Tests, Routine, England, Female, Humans, Male, Middle Aged, Prospective Studies, ROC Curve, Sensitivity and Specificity, Tuberculosis microbiology, Young Adult, Biomarkers blood, Mycobacterium tuberculosis genetics, Transcription Factors blood, Tuberculosis diagnosis
- Abstract
Background: Blood transcriptomic signatures for diagnosis of tuberculosis have shown promise in case-control studies, but none have been prospectively designed or validated in adults presenting with the full clinical spectrum of suspected tuberculosis, including extrapulmonary tuberculosis and common differential diagnoses that clinically resemble tuberculosis. We aimed to evaluate the diagnostic accuracy of transcriptomic signatures in patients presenting with clinically suspected tuberculosis in routine practice., Methods: The Validation of New Technologies for Diagnostic Evaluation of Tuberculosis (VANTDET) study was nested within a prospective, multicentre cohort study in secondary care in England (IDEA 11/H0722/8). Patients (aged ≥16 years) suspected of having tuberculosis in the routine clinical inpatient and outpatient setting were recruited at ten National Health Service hospitals in England for IDEA and were included in VANTDET if they provided consent for genomic analysis. Patients had whole blood taken for microarray analysis to measure abundance of transcripts and were followed up for 6-12 months to determine final diagnoses on the basis of predefined diagnostic criteria. The diagnostic accuracy of six signatures derived from the cohort and three previously published transcriptomic signatures with potentially high diagnostic performance were assessed by calculating area under the receiver-operating characteristic curves (AUC-ROCs), sensitivities, and specificities., Findings: Between Nov 25, 2011, and Dec 31, 2013, 1162 participants were enrolled. 628 participants (aged ≥16 years) were included in the analysis, of whom 212 (34%) had culture-confirmed tuberculosis, 89 (14%) had highly probable tuberculosis, and 327 (52%) had tuberculosis excluded. The novel signature with highest performance for identifying all active tuberculosis gave an AUC-ROC of 0·87 (95% CI 0·81-0·92), sensitivity of 77% (66-87), and specificity of 84% (74-91). The best-performing published signature gave an AUC-ROC of 0·83 (0·80-0·86), sensitivity of 78% (73-83), and specificity of 76% (70-80). For detecting highly probable tuberculosis, the best novel signature yielded results of 0·86 (0·71-0·95), 77% (56-94%), and 77% (57-95%). None of the relevant cohort-derived or previously published signatures achieved the WHO-defined targets of paired sensitivity and specificity for a non-sputum-based diagnostic test., Interpretation: In a clinically representative cohort in routine practice in a low-incidence setting, transcriptomic signatures did not have adequate accuracy for diagnosis of tuberculosis, including in patients with highly probable tuberculosis where the unmet need is greatest. These findings suggest that transcriptomic signatures have little clinical utility for diagnostic assessment of suspected tuberculosis., Funding: National Institute for Health Research., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
27. ILC1 drive intestinal epithelial and matrix remodelling.
- Author
-
Jowett GM, Norman MDA, Yu TTL, Rosell Arévalo P, Hoogland D, Lust ST, Read E, Hamrud E, Walters NJ, Niazi U, Chung MWH, Marciano D, Omer OS, Zabinski T, Danovi D, Lord GM, Hilborn J, Evans ND, Dreiss CA, Bozec L, Oommen OP, Lorenz CD, da Silva RMP, Neves JF, and Gentleman E
- Subjects
- Animals, Female, Humans, Intestinal Mucosa cytology, Lymphocytes cytology, Matrix Metalloproteinase 9 metabolism, Mice, Organoids cytology, Transforming Growth Factor beta1 metabolism, Extracellular Matrix metabolism, Intestinal Mucosa metabolism, Lymphocytes metabolism, Organoids metabolism
- Abstract
Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6
+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.- Published
- 2021
- Full Text
- View/download PDF
28. Time Series Integrative Analysis of RNA Sequencing and MicroRNA Expression Data Reveals Key Biologic Wound Healing Pathways in Keloid-Prone Individuals.
- Author
-
Onoufriadis A, Hsu CK, Ainali C, Ung CY, Rashidghamat E, Yang HS, Huang HY, Niazi U, Tziotzios C, Yang JC, Nuamah R, Tang MJ, Saxena A, de Rinaldis E, and McGrath JA
- Subjects
- Adult, Disease Susceptibility, Female, Humans, Keloid diagnosis, MAP Kinase Signaling System, Male, Middle Aged, Pedigree, Receptors, Notch genetics, Sequence Analysis, RNA, Thailand, Toll-Like Receptors genetics, Transcriptome, Young Adult, Keloid genetics, MicroRNAs genetics, Signal Transduction genetics, Wound Healing genetics
- Published
- 2018
- Full Text
- View/download PDF
29. Corrigendum: Whole genome analysis of a schistosomiasis-transmitting freshwater snail.
- Author
-
Adema CM, Hillier LW, Jones CS, Loker ES, Knight M, Minx P, Oliveira G, Raghavan N, Shedlock A, do Amaral LR, Arican-Goktas HD, Assis JG, Baba EH, Baron OL, Bayne CJ, Bickham-Wright U, Biggar KK, Blouin M, Bonning BC, Botka C, Bridger JM, Buckley KM, Buddenborg SK, Lima Caldeira R, Carleton J, Carvalho OS, Castillo MG, Chalmers IW, Christensens M, Clifton S, Cosseau C, Coustau C, Cripps RM, Cuesta-Astroz Y, Cummins SF, Di Stefano L, Dinguirard N, Duval D, Emrich S, Feschotte C, Feyereisen R, FitzGerald P, Fronick C, Fulton L, Galinier R, Gava SG, Geusz M, Geyer KK, Giraldo-Calderón GI, de Souza Gomes M, Gordy MA, Gourbal B, Grunau C, Hanington PC, Hoffmann KF, Hughes D, Humphries J, Jackson DJ, Jannotti-Passos LK, de Jesus Jeremias W, Jobling S, Kamel B, Kapusta A, Kaur S, Koene JM, Kohn AB, Lawson D, Lawton SP, Liang D, Limpanont Y, Liu S, Lockyer AE, Lovato TAL, Ludolf F, Magrini V, McManus DP, Medina M, Misra M, Mitta G, Mkoji GM, Montague MJ, Montelongo C, Moroz LL, Munoz-Torres MC, Niazi U, Noble LR, Oliveira FS, Pais FS, Papenfuss AT, Peace R, Pena JJ, Pila EA, Quelais T, Raney BJ, Rast JP, Rollinson D, Rosse IC, Rotgans B, Routledge EJ, Ryan KM, Scholte LLS, Storey KB, Swain M, Tennessen JA, Tomlinson C, Trujillo DL, Volpi EV, Walker AJ, Wang T, Wannaporn I, Warren WC, Wu XJ, Yoshino TP, Yusuf M, Zhang SM, Zhao M, and Wilson RK
- Abstract
This corrects the article DOI: 10.1038/ncomms15451.
- Published
- 2017
- Full Text
- View/download PDF
30. Whole genome analysis of a schistosomiasis-transmitting freshwater snail.
- Author
-
Adema CM, Hillier LW, Jones CS, Loker ES, Knight M, Minx P, Oliveira G, Raghavan N, Shedlock A, do Amaral LR, Arican-Goktas HD, Assis JG, Baba EH, Baron OL, Bayne CJ, Bickham-Wright U, Biggar KK, Blouin M, Bonning BC, Botka C, Bridger JM, Buckley KM, Buddenborg SK, Lima Caldeira R, Carleton J, Carvalho OS, Castillo MG, Chalmers IW, Christensens M, Clifton S, Cosseau C, Coustau C, Cripps RM, Cuesta-Astroz Y, Cummins SF, di Stephano L, Dinguirard N, Duval D, Emrich S, Feschotte C, Feyereisen R, FitzGerald P, Fronick C, Fulton L, Galinier R, Gava SG, Geusz M, Geyer KK, Giraldo-Calderón GI, de Souza Gomes M, Gordy MA, Gourbal B, Grunau C, Hanington PC, Hoffmann KF, Hughes D, Humphries J, Jackson DJ, Jannotti-Passos LK, de Jesus Jeremias W, Jobling S, Kamel B, Kapusta A, Kaur S, Koene JM, Kohn AB, Lawson D, Lawton SP, Liang D, Limpanont Y, Liu S, Lockyer AE, Lovato TL, Ludolf F, Magrini V, McManus DP, Medina M, Misra M, Mitta G, Mkoji GM, Montague MJ, Montelongo C, Moroz LL, Munoz-Torres MC, Niazi U, Noble LR, Oliveira FS, Pais FS, Papenfuss AT, Peace R, Pena JJ, Pila EA, Quelais T, Raney BJ, Rast JP, Rollinson D, Rosse IC, Rotgans B, Routledge EJ, Ryan KM, Scholte LLS, Storey KB, Swain M, Tennessen JA, Tomlinson C, Trujillo DL, Volpi EV, Walker AJ, Wang T, Wannaporn I, Warren WC, Wu XJ, Yoshino TP, Yusuf M, Zhang SM, Zhao M, and Wilson RK
- Subjects
- Animal Communication, Animals, Biomphalaria immunology, DNA Transposable Elements, Evolution, Molecular, Fresh Water, Gene Expression Regulation, Host-Parasite Interactions, Pheromones, Proteome, Schistosoma mansoni, Sequence Analysis, DNA, Stress, Physiological, Biomphalaria genetics, Biomphalaria parasitology, Genome, Schistosomiasis mansoni transmission
- Abstract
Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis.
- Published
- 2017
- Full Text
- View/download PDF
31. Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling.
- Author
-
Halliday A, Whitworth H, Kottoor SH, Niazi U, Menzies S, Kunst H, Bremang S, Badhan A, Beverley P, Kon OM, and Lalvani A
- Subjects
- Adult, Aged, Biomarkers blood, CD4-Positive T-Lymphocytes immunology, Female, Humans, Interferon-gamma blood, Interleukin-2 blood, Latent Tuberculosis diagnosis, Male, Middle Aged, Prospective Studies, Sensitivity and Specificity, Tumor Necrosis Factor-alpha blood, Young Adult, Latent Tuberculosis epidemiology, Latent Tuberculosis immunology, Mycobacterium tuberculosis immunology
- Abstract
Background: Recently acquired and remotely acquired latent Mycobacterium tuberculosis infection (LTBI) are clinically indistinguishable, yet recent acquisition of infection is the greatest risk factor for progression to tuberculosis in immunocompetent individuals. We aimed to evaluate the ability of cellular immune signatures that differ between active tuberculosis and LTBI to distinguish recently from remotely acquired LTBI., Methods: Fifty-nine individuals were recruited: 20 had active tuberculosis, 19 had recently acquired LTBI, and 20 had remotely acquired LTBI. The proportion of mycobacteria-specific CD4+ T cells secreting tumor necrosis factor α (TNF-α) but not interferon γ or interleukin 2 which had a differentiated effector phenotype (TNF-α-only TEFF), and the level of CD27 expression on IFN-γ-producing CD4+ T cells, were detected by flow cytometry., Results: The TNF-α-only TEFF signature was significantly higher in the group with recently acquired LTBI, compared with the group with remotely acquired LTBI (P < .0001), and it discriminated between these groups with high sensitivity and specificity, with an area under the curve of 0.87. Two signatures incorporating CD27 expression did not distinguish between recently and remotely acquired LTBI. Interestingly, the TNF-α-only TEFF signature in participants with recently acquired LTBI was more similar to that in participants with tuberculosis than that in participants with remotely acquired LTBI, suggesting that recently acquired LTBI is immunologically more similar to tuberculosis than remotely acquired LTBI., Conclusions: These findings reveal marked biological heterogeneity underlying the clinically homogeneous phenotype of LTBI, providing a rationale for immunological risk stratification to improve targeting of LTBI treatment., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Published
- 2017
- Full Text
- View/download PDF
32. DISMISS: detection of stranded methylation in MeDIP-Seq data.
- Author
-
Niazi U, Geyer KK, Vickers MJ, Hoffmann KF, and Swain MT
- Subjects
- Animals, Base Sequence, Bees metabolism, Databases, Nucleic Acid, Immunoprecipitation, Oligonucleotide Array Sequence Analysis methods, Sequence Analysis, DNA, Software, Bees genetics, DNA Methylation, Genomics methods
- Abstract
Background: DNA methylation is an important regulator of gene expression and chromatin structure. Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) is commonly used to identify regions of DNA methylation in eukaryotic genomes. Within MeDIP-Seq libraries, methylated cytosines can be found in both double-stranded (symmetric) and single-stranded (asymmetric) genomic contexts. While symmetric CG methylation has been relatively well-studied, asymmetric methylation in any dinucleotide context has received less attention. Importantly, no currently available software for processing MeDIP-Seq reads is able to resolve these strand-specific DNA methylation signals. Here we introduce DISMISS, a new software package that detects strand-associated DNA methylation from existing MeDIP-Seq analyses., Results: Using MeDIP-Seq datasets derived from Apis mellifera (honeybee), an invertebrate species that contains more asymmetric- than symmetric- DNA methylation, we demonstrate that DISMISS can identify strand-specific DNA methylation signals with similar accuracy as bisulfite sequencing (BS-Seq; single nucleotide resolution methodology). Specifically, DISMISS is able to confidently predict where DNA methylation predominates (plus or minus DNA strands - asymmetric DNA methylation; plus and minus DNA stands - symmetric DNA methylation) in MeDIP-Seq datasets derived from A. mellifera samples. When compared to DNA methylation data derived from BS-Seq analysis of A. mellifera worker larva, DISMISS-mediated identification of strand-specific methylated cytosines is 80 % accurate. Furthermore, DISMISS can correctly (p <0.0001) detect the origin (sense vs antisense DNA strands) of DNA methylation at splice site junctions in A. mellifera MeDIP-Seq datasets with a precision close to BS-Seq analysis. Finally, DISMISS-mediated identification of DNA methylation signals associated with upstream, exonic, intronic and downstream genomic loci from A. mellifera MeDIP-Seq datasets outperforms MACS2 (Model-based Analysis of ChIP-Seq2; a commonly used MeDIP-Seq analysis software) and closely approaches the results achieved by BS-Seq., Conclusions: While asymmetric DNA methylation is increasingly being found in growing numbers of eukaryotic species and is the predominant pattern observed in some invertebrate genomes, it has been difficult to detect in MeDIP-Seq datasets using existing software. DISMISS now enables more sensitive examinations of MeDIP-Seq datasets and will be especially useful for the study of genomes containing either low levels of DNA methylation or for genomes containing relatively high amounts of asymmetric methylation.
- Published
- 2016
- Full Text
- View/download PDF
33. Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni.
- Author
-
Nowacki FC, Swain MT, Klychnikov OI, Niazi U, Ivens A, Quintana JF, Hensbergen PJ, Hokke CH, Buck AH, and Hoffmann KF
- Abstract
Background: Penetration of skin, migration through tissues and establishment of long-lived intravascular partners require Schistosoma parasites to successfully manipulate definitive host defences. While previous studies of larval schistosomula have postulated a function for excreted/secreted (E/S) products in initiating these host-modulatory events, the role of extracellular vesicles (EVs) has yet to be considered. Here, using preparatory ultracentrifugation as well as methodologies to globally analyse both proteins and small non-coding RNAs (sncRNAs), we conducted the first characterization of Schistosoma mansoni schistosomula EVs and their potential host-regulatory cargos., Results: Transmission electron microscopy analysis of EVs isolated from schistosomula in vitro cultures revealed the presence of numerous, 30-100 nm sized exosome-like vesicles. Proteomic analysis of these vesicles revealed a core set of 109 proteins, including homologs to those previously found enriched in other eukaryotic EVs, as well as hypothetical proteins of high abundance and currently unknown function. Characterization of E/S sncRNAs found within and outside of schistosomula EVs additionally identified the presence of potential gene-regulatory miRNAs (35 known and 170 potentially novel miRNAs) and tRNA-derived small RNAs (tsRNAs; nineteen 5' tsRNAs and fourteen 3' tsRNAs)., Conclusions: The identification of S. mansoni EVs and the combinatorial protein/sncRNA characterization of their cargo signifies that an important new participant in the complex biology underpinning schistosome/host interactions has now been discovered. Further work defining the role of these schistosomula EVs and the function/stability of intra- and extra-vesicular sncRNA components presents tremendous opportunities for developing novel schistosomiasis diagnostics or interventions.
- Published
- 2015
- Full Text
- View/download PDF
34. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.
- Author
-
Ashraf Z, Bais A, Manir MM, and Niazi U
- Subjects
- Amino Acid Sequence, Anti-Infective Agents chemical synthesis, Anti-Infective Agents pharmacology, Molecular Sequence Data, Penicillin-Binding Proteins metabolism, Penicillins chemical synthesis, Penicillins pharmacology, Anti-Infective Agents chemistry, Molecular Docking Simulation, Penicillin-Binding Proteins chemistry, Penicillins chemistry, Quantitative Structure-Activity Relationship
- Abstract
A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.
- Published
- 2015
- Full Text
- View/download PDF
35. On the modelling and analysis of the regulatory network of dengue virus pathogenesis and clearance.
- Author
-
Aslam B, Ahmad J, Ali A, Zafar Paracha R, Tareen SH, Niazi U, and Saeed T
- Abstract
Dengue virus can ignite both protective and pathogenic responses in human. The pathogenesis is related with modified functioning of our immune system during infection. Pattern recognition receptors like Toll like receptor 3 is vital for the induction of innate immunity in case of Dengue infection. Toll like receptor 3 induces TRIF mediated activation of Type 1 interferons and Fc receptor mediated induction of cytokines. Interferons have been related with clearance of Dengue virus but it has adopted modified regulatory mechanisms to counter this effect. SOCS protein is also induced due to the interferon and cytokine mediated signalling which can subsequently play its part in the regulation of interferon and cytokine production. Our hypothesis in this study relates the pathogenesis of Dengue virus with the SOCS mediated inhibition of our innate immunity. We used the qualitative formalism of René Thomas to model the biological regulatory network of Toll like receptor 3 mediated signalling pathway in an association with pathogenesis of dengue. Logical parameters for the qualitative modelling were inferred using a model checking approach implemented in SMBioNet. A linear hybrid model, parametric linear hybrid automaton, was constructed to incorporate the activation and inhibition time delays in the qualitative model. The qualitative model captured all the possible expression dynamics of the proteins in the form of paths, some of which were observed as abstract cycles (representing homoeostasis) and diverging paths towards stable states. The analysis of the qualitative model highlighted the importance of SOCS protein in elevating propagation of dengue virus through inhibition of type 1 interferons. Detailed qualitative analysis of regulatory network endorses our hypothesis that elevated levels of cytokine subsequently induce SOCS expression which in turn results into the continuous down-regulation of Toll like receptor 3 and interferon. This may result into the Dengue pathogenesis during the stage of immunosuppression. Further analysis with HyTech (HYbrid TECHnology) tool provided us with the real-time constraints (delay constraints) of the proteins involved in the cyclic paths of the regulatory network backing the evidence provided by the qualitative analysis. The HyTech results also suggest that the role of SOCS is vital in homoeostasis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
36. Formal modelling of toll like receptor 4 and JAK/STAT signalling pathways: insight into the roles of SOCS-1, interferon-β and proinflammatory cytokines in sepsis.
- Author
-
Paracha RZ, Ahmad J, Ali A, Hussain R, Niazi U, Tareen SH, and Aslam B
- Subjects
- Algorithms, Cytokines metabolism, Humans, Inflammation Mediators metabolism, Interferon-beta metabolism, NF-kappa B metabolism, Sepsis metabolism, Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling Proteins metabolism, Janus Kinases metabolism, Models, Biological, STAT Transcription Factors metabolism, Signal Transduction, Toll-Like Receptor 4 metabolism
- Abstract
Sepsis is one of the major causes of human morbidity and results in a considerable number of deaths each year. Lipopolysaccharide-induced sepsis has been associated with TLR4 signalling pathway which in collaboration with the JAK/STAT signalling regulate endotoxemia and inflammation. However, during sepsis our immune system cannot maintain a balance of cytokine levels and results in multiple organ damage and eventual death. Different opinions have been made in previous studies about the expression patterns and the role of proinflammatory cytokines in sepsis that attracted our attention towards qualitative properties of TLR4 and JAK/STAT signalling pathways using computer-aided studies. René Thomas' formalism was used to model septic and non-septic dynamics of TLR4 and JAK/STAT signalling. Comparisons among dynamics were made by intervening or removing the specific interactions among entities. Among our predictions, recurrent induction of proinflammatory cytokines with subsequent downregulation was found as the basic characteristic of septic model. This characteristic was found in agreement with previous experimental studies, which implicate that inflammation is followed by immunomodulation in septic patients. Moreover, intervention in downregulation of proinflammatory cytokines by SOCS-1 was found desirable to boost the immune responses. On the other hand, interventions either in TLR4 or transcriptional elements such as NFκB and STAT were found effective in the downregulation of immune responses. Whereas, IFN-β and SOCS-1 mediated downregulation at different levels of signalling were found to be associated with variations in the levels of proinflammatory cytokines. However, these predictions need to be further validated using wet laboratory experimental studies to further explore the roles of inhibitors such as SOCS-1 and IFN-β, which may alter the levels of proinflammatory cytokines at different stages of sepsis.
- Published
- 2014
- Full Text
- View/download PDF
37. Structural evaluation of BTK and PKCδ mediated phosphorylation of MAL at positions Tyr86 and Tyr106.
- Author
-
Paracha RZ, Ali A, Ahmad J, Hussain R, Niazi U, and Muhammad SA
- Subjects
- Agammaglobulinaemia Tyrosine Kinase, Amino Acid Motifs, Binding Sites, Gene Expression Regulation, Humans, Molecular Dynamics Simulation, Molecular Sequence Data, Myelin and Lymphocyte-Associated Proteolipid Proteins genetics, Myelin and Lymphocyte-Associated Proteolipid Proteins metabolism, Myeloid Differentiation Factor 88 chemistry, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 metabolism, Phosphorylation, Protein Binding, Protein Kinase C-delta genetics, Protein Kinase C-delta metabolism, Protein Structure, Tertiary, Protein-Tyrosine Kinases genetics, Protein-Tyrosine Kinases metabolism, Signal Transduction, Static Electricity, Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling Proteins chemistry, Suppressor of Cytokine Signaling Proteins genetics, Suppressor of Cytokine Signaling Proteins metabolism, Thermodynamics, Toll-Like Receptor 2 chemistry, Toll-Like Receptor 2 genetics, Toll-Like Receptor 2 metabolism, Toll-Like Receptor 4 chemistry, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Tyrosine metabolism, Molecular Docking Simulation, Myelin and Lymphocyte-Associated Proteolipid Proteins chemistry, Protein Kinase C-delta chemistry, Protein-Tyrosine Kinases chemistry, Tyrosine chemistry
- Abstract
A number of diseases including sepsis, rheumatoid arthritis, diabetes, cardiovascular diseases and hyperinflammatory immune disorders have been associated with Toll like receptor (TLR) 2 and TLR4. Endogenous adaptor protein known as MyD88 adapter-like protein (MAL) bind exclusively to the cytosolic portions of TLR2 and TLR4 to initiate downstream signalling. Brutons tyrosine kinase (BTK) and protein kinase C delta (PKCδ) have been implicated to phosphorylate MAL and activate it to initiate downstream signalling. BTK has been associated with phosphorylation at positions Tyr86 and Tyr106, necessary for the activation of MAL but definite residual target of PKCδ in MAL is still to be explored. To produce a better understanding of the functional domains involved in the formation of MAL-kinase complexes, computer-aided studies were used to characterize the protein-protein interactions (PPIs) of phosphorylated BTK and PKCδ with MAL. Docking and physicochemical studies indicated that BTK was involved in close contact with Tyr86 and Tyr106 of MAL whereas PKCδ may phosphorylate Tyr106 only. Moreover, the electrostatics charge distribution of binding interfaces of BTK and PKCδ were distinct but compatible with respective regions of MAL. Our results implicate that position of Tyr86 is specifically phosphorylated by BTK whereas Tyr106 can be phosphorylated by competitive action of both BTK and PKCδ. Additionally, the residues of MAL which are necessary for interaction with TLR2, TLR4, MyD88 and SOCS-1 also play their roles in maintaining interaction with kinases and can be targeted in future to reduce TLR2 and TLR4 induced pathological responses., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
38. Formal modeling and analysis of the MAL-associated biological regulatory network: insight into cerebral malaria.
- Author
-
Ahmad J, Niazi U, Mansoor S, Siddique U, and Bibby J
- Subjects
- Humans, Toll-Like Receptor 2 metabolism, Toll-Like Receptor 4 metabolism, Computational Biology methods, Malaria, Cerebral metabolism, Membrane Glycoproteins metabolism, Models, Biological, Receptors, Interleukin-1 metabolism, Signal Transduction
- Abstract
The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs). This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous) modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL)--a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM) are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK) remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis.
- Published
- 2012
- Full Text
- View/download PDF
39. Inhibition of CYP1A1 by Quassinoids found in Picrasma excelsa.
- Author
-
Shields M, Niazi U, Badal S, Yee T, Sutcliffe MJ, and Delgoda R
- Subjects
- Humans, Molecular Structure, Plant Bark, Plant Extracts chemistry, Plant Leaves, Quassins chemistry, Quassins isolation & purification, Structure-Activity Relationship, Wood, Cytochrome P-450 CYP1A1 antagonists & inhibitors, Picrasma chemistry, Plant Extracts pharmacology, Quassins pharmacology
- Abstract
Infusions of the plant Picrasma excelsa, known as Jamaican bitterwood tea, are commonly consumed to lower blood sugar levels in diabetics who are already on prescription medicines. We therefore investigated the inhibition properties of this tea against a panel of cytochrome P450 (CYP) enzymes, which are primarily responsible for the metabolism of a majority of drugs on the market. The two major ingredients, quassin and neoquassin, were then isolated and used for further characterization. Inhibition of the activities of heterologously expressed CYP microsomes (CYPs 2D6, 3A4, 1A1, 1A2, 2C9, and 2C19) was monitored, and the most potent inhibition was found to be against CYP1A1, with IC (50) values of 9.2 microM and 11.9 microM for quassin and neoquassin, respectively. The moderate inhibition against the CYP1A1 isoform by quassin and neoquassin displayed partial competitive inhibition kinetics, with inhibition constants ( K(i)) of 10.8 +/- 1.6 microM, for quassin and competitive inhibition kinetics, with a K(i) of 11.3 +/- 0.9 microM, for neoquassin. We then docked these two inhibitors into the active site of a model of CYP1A1, which provided insight at the atomic level into the structure-activity relationship of quassinoids with respect to this important CYP isoform known to be an activator of carcinogens, thus providing a useful basis for the search for more potent inhibitors of CYP1A1 that may have implications in chemoprotection.
- Published
- 2009
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.