97 results on '"Eichinger F"'
Search Results
2. Isotope diffusive exchange experiments for deriving porewater isotope composition in low-permeability rocks – Improvements in experimental procedure and data processing
- Author
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Aschwanden, L., primary, Waber, H.N., additional, Eichinger, F., additional, and Gimmi, T., additional
- Published
- 2023
- Full Text
- View/download PDF
3. Helium in Porewater and Rocks of Crystalline Bedrock from the Fennoscandian Shield, Olkiluoto (Finland)
- Author
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Rufer, D., Waber, H.N., Eichinger, F., and Pitkänen, P.
- Published
- 2017
- Full Text
- View/download PDF
4. Hydrogen sulfide removal from geothermal fluids by Fe(III)-based additives
- Author
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Regenspurg, S., Iannotta, J., Feldbusch, E., Zimmermann, F. J., and Eichinger, F.
- Published
- 2020
- Full Text
- View/download PDF
5. WCN23-1158 A TRANSLATIONAL APPROACH TO IDENTIFY NON-INVASIVE SURROGATES AS PREDICTORS OF RESPONSE TO mFT011 IN KIDNEY DISEASE
- Author
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Eddy PhD, S., primary, Kompa, A., additional, Hartman, J., additional, Eichinger, F., additional, Godfrey, B., additional, Tanner, E., additional, Ju, W., additional, Edgely, A., additional, Langham, R., additional, Mariani, L., additional, Kretzler, M., additional, and Kelly, D., additional
- Published
- 2023
- Full Text
- View/download PDF
6. WCN23-0682 LNcRNAs IN LN (LUPUS NEPHRITIS)
- Author
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EICHINGER, F., primary, Berthier, C.C., additional, McCown, P.J., additional, Fermin, D., additional, and Kretzler, M., additional
- Published
- 2023
- Full Text
- View/download PDF
7. The synorogenic pegmatitic quartz veins of the Guacha Corral Shear zone (Sierra de Comechingones, Argentina): A textural, chemical, isotopic, cathodoluminescence and fluid inclusion study
- Author
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Morteani, G., Eichinger, F., Tarantola, A., Müller, A., Götze, J., and Sfragulla, J.A.
- Published
- 2016
- Full Text
- View/download PDF
8. Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial
- Author
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Florescu, S, Stanciu, D, Zaharia, M, Kosa, A, Codreanu, D, Kidwai, A, Masood, S, Kaye, C, Coutts, A, MacKay, L, Summers, C, Polgarova, P, Farahi, N, Fox, E, McWilliam, S, Hawcutt, D, Rad, L, O’Malley, L, Whitbread, J, Jones, D, Dore, R, Saunderson, P, Kelsall, O, Cowley, N, Wild, L, Thrush, J, Wood, H, Austin, K, Bélteczki, J, Magyar, I, Fazekas, Á, Kovács, S, Szőke, V, Donnelly, A, Kelly, M, Smyth, N, O’Kane, S, McClintock, D, Warnock, M, Campbell, R, McCallion, E, Azaiz, A, Charron, C, Godement, M, Geri, G, Vieillard-Baron, A, Johnson, P, McKenna, S, Hanley, J, Currie, A, Allen, B, McGoldrick, C, McMaster, M, Mani, A, Mathew, M, Kandeepan, R, Vignesh, C, TV, B, Ramakrishnan, N, James, A, Elvira, E, Jayakumar, D, Pratheema, R, Babu, S, Ebenezer, R, Krishnaoorthy, S, Ranganathan, L, Ganesan, M, Shree, M, Guilder, E, Butler, M, Cowdrey, K-A, Robertson, M, Ali, F, McMahon, E, Duffy, E, Chen, Y, Simmonds, C, McConnochie, R, O’Connor, C, El-Khawas, K, Richardson, A, Hill, D, Commons, R, Abdelkharim, H, Saxena, M, Muteithia, M, Dobell-Brown, K, Jha, R, Kalogirou, M, Ellis, C, Krishnamurthy, V, O’Connor, A, Thurairatnam, S, Mukherjee, D, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Maloney, G, Kittridge, L, Solesbury, A, Ramos, A, Collins, D, Brickell, K, Reid, L, Smyth, M, Breen, P, Spain, S, Curley, G, McEvoy, N, Geoghegan, P, Clarke, J, Silversides, J, McGuigan, P, Ward, K, O’Neill, A, Finn, S, Wright, C, Green, J, Collins, É, Knott, C, Smith, J, Boschert, C, Slieker, K, Ewalds, E, Sanders, A, Wittenberg, W, Geurts, H, Poojara, L, Sara, T, Nand, K, Reeve, B, Dechert, W, Phillips, B, Oritz-Ruiz de Gordoa, L, Affleck, J, Shaikh, A, Murray, A, Ramanan, M, Frakking, T, Pinnell, J, Robinson, M, Gledhill, L, Wood, T, Sanghavi, R, Bhonagiri, D, Ford, M, Parikh, HG, Avard, B, Nourse, M, McDonald, B, Edmunds, N, Hoiting, O, Peters, M, Rengers, E, Evers, M, Prinssen, A, Morgan, M, Cole, J, Hill, H, Davies, M, Williams, A, Thomas, E, Davies, R, Wise, M, Grimm, P, Soukup, J, Wetzold, R, Löbel, M, Starke, L, Lellouche, F, Lizotte, P, Declerq, P, Antoine, M, Stephanie, G, Jean-Pierre, E, François, B, Marion, B, Philippe, R, Pourcine, F, Monchi, M, Luis, D, Mercier, R, Sagnier, A, Verrier, N, Caplin, C, Richecoeu, J, Combaux, D, Siami, S, Aparicio, C, Vautier, S, Jeblaoui, A, Lemaire-Brunel, D, D'Aragon, F, Carbonneau, E, Leblond, J, Plantefeve, G, Leparco, C, Contou, D, Fartoukh, M, Courtin, L, Labbe, V, Voiriot, G, Salhi, S, Chassé, M, Carrier, F, Boumahni, D, Benettaib, F, Ghamraoui, A, Sement, A, Gachet, A, Hanisch, A, Haffiane, A, Boivin, A-H, Barreau, A, Guerineau, E, Poupblanc, S, Egreteau, P, Lefevre, M, Bocher, S, Le Loup, G, Le Guen, L, Carn, V, Bertel, M, Antcliffe, D, Templeton, M, Rojo, R, Coghlan, P, Smee, J, Barker, G, Finn, A, Kreb, G, Hoff, U, Hinrichs, C, Nee, J, Mackay, E, Cort, J, Whileman, A, Spencer, T, Spittle, N, Beavis, S, Padmakumar, A, Dale, K, Hawes, J, Moakes, E, Gascoyne, R, Pritchard, K, Stevenson, L, Cooke, J, Nemeth-Roszpopa, K, Gauli, B, Bastola, S, Muller, G, Nay, M-A, Kamel, T, Benzekri, D, Jacquier, S, Runge, I, Mathonnet, A, Barbier, F, Bretagnol, A, Carter, J, Van Der Heyden, K, Mehrtens, J, Morris, A, Morgan, S, Burke, T, Mercier, E, Chartier, D, Salmon, C, Dequin, P-F, Garot, D, Bellemare, D, Cloutier, È, Daher, R, Costerousse, O, Boulanger, M-C, Couillard-Chénard, É, Lauzier, F, Francoeur, C, Francois, B, Gay, A, Anne-Laure, F, Ramali, M, HC, O, Ghosh, A, Osagie, R, Arachchige, M, Hartley, M, Cheung, W, Wong, H, Seigne, P, Eustace, J, O'Callaghan, A-M, O'Brien, F, Bamford, P, Reid, A, Cawley, K, Faulkner, M, Pickering, C, Raj, A, Tsinaslanidis, G, Khade, R, Agha, G, Sekiwala, R, Smith, T, Brewer, C, Gregory, J, Limb, J, Cowton, A, O’Brien, J, Postlethwaite, K, Malakouti, S, Music, E, Ricketts, D, King, A, Clermont, G, Bart, R, Mayr, F, Schoenling, A, Andreae, M, Shetty, V, Brant, E, Malley, B, Donadee, C, Sackrowitz, R, Weissman, A, Yealy, D, Barton, D, Talia, N, Nikitas, N, Wells, C, Lankester, L, McMillan, H, Van den Oever, H, Kruisdijk-Gerritsen, A, Haidar, G, Bain, W, Barbash, I, Fitzpatrick, M, Franz, C, Kitsios, G, Moghbeli, K, Rosborough, B, Shah, F, Suber, T, Pulletz, M, Williams, P, Birch, J, Wiseman, S, Horton, S, Alegria, A, Turki, S, Elsefi, T, Crisp, N, Allen, L, Truman, N, Smith, M, Chukkambotla, S, Goddard, W, Duberley, S, Khan, M, Kazi, A, Simpson, J, Duke, G, Chan, P, Carter, B, Hunter, S, Voigt, I, Schueler, R, Blank, E, Hüning, V, Steffen, M, Goralski, P, Litton, E, Regli, A, Pellicano, S, Palermo, A, Eroglu, E, Bihari, S, Laver, RD, Jin, X, Brown, J, McIntyre, J, French, C, Bates, S, Towns, M, Yang, Y, McGain, F, McCullagh, I, Cairns, T, Hanson, H, Patel, B, Clement, I, Evetts, G, Touma, O, Holland, S, Hodge, C, Taylor, H, Alderman, M, Barnes, N, Da Rocha, J, Smith, C, Brooks, N, Weerasinghe, T, Sinclair, J-A, Abusamra, Y, Doherty, R, Cudlipp, J, Singh, R, Yu, H, Daebis, A, Ng, C, Kendrick, S, Saran, A, Makky, A, Greener, D, Rowe-Leete, L, Edwards, A, Bland, Y, Dolman, R, Foster, T, Laffey, J, McNicholas, B, Scully, M, Casey, S, Kernan, M, Brennan, A, Rangan, R, Tully, R, Corbett, S, McCarthy, A, Duffy, O, Burke, D, Linnett, V, Sanderson, A, Ritzema, J, Wild, H, Lucas, R, Marriott, Y, Andric, Z, Cviljevic, S, Br, R, Zapalac, M, Mirković, G, Khare, D, Pinder, M, Gopinath, A, Kannan, T, Dean, S, Vanmali, P, Depuydt, P, De Waele, J, De Bus, L, Fierens, J, Bracke, S, Vermassen, J, Vermeiren, D, Pugh, R, Lean, R, Qiu, X, Scanlan, J, Evans, A, Davies, G, Lewis, J, Plesnikova, Y, Khoud, A, Coetzee, S, Puxty, K, Cathcart, S, Rimmer, D, Bagot, C, Scott, K, Martin, L, Yusuff, H, Isgro, G, Brightling, C, Bourne, M, Craner, M, Boyles, R, Alexander, B, Roberts, T, Nelli, A, Rosenstein-Sisson, R, Speyer, R, Pech, Y, McCullough, J, Tallott, M, Vazquez-Grande, G, Marten, N, Liu, T, Siddiqui, A, Khanal, S, Amatya, S, Szakmany, T, Cherian, S, Williams, G, James, C, Waters, A, Prout, R, Stedman, R, Davies, L, Pegler, S, Kyeremeh, L, Moorhouse, L, Arbane, G, Marotti, M, Bociek, A, Campos, S, Van Nieuwkoop, K, Ottens, T, Visser, Y, Van den Berg, L, Van der Kraan-Donker, A, Brett, S, Arias, S, Hall, R, Paneru, H, Koirala, S, Paudel, P, Wilson, M, Vaara, S, Pettilä, L, Heinonen, J, Pettilä, V, Jain, S, Gupta, A, Holbrook, C, Antoine, P, Meziani, F, Allam, H, Cattelan, J, Clere-Jehl, R, Helms, J, Kummerlen, C, Merdji, H, Monnier, A, Rahmani, H, Studer, A, Schneider, F, Castelain, V, Morel, G, L’Hotellier, S, Ochin, E, Vanjak, C, Rouge, P, Bendjemar, L, Albert, M, Serri, K, Cavayas, A, Duplaix, M, Williams, V, Catorze, NJTADS, Pereira, TNAL, Ferreira, RMC, Bastos, JMPS, Batista, TMO, Badie, J, Berdaguer, F, Malfroy, S, Mezher, C, Bourgoin, C, Moneger, G, Bouvier, E, Muñoz-Bermúdez, R, Marin-Corral, J, Degracia, A, Gómez, F, López, M, Aceto, R, Aghemo, A, Badalamenti, S, Brunetta, E, Cecconi, M, Ciccarelli, M, Constantini, E, Greco, M, Folci, M, Selmi, C, Voza, A, Henning, J, Bonner, S, Hugill, K, Cirstea, E, Wilkinson, D, Jones, J, Altomy, M, Karlikowski, M, Sutherland, H, Wilhelmsen, E, Woods, J, North, J, Pletz, M, Hagel, S, Ankert, J, Kolanos, S, Bloos, F, Simons, K, Van Zuylen, T, Bouman, A, Kumar, N, Panwar, R, Poulter, A-L, Sunkara, K, Szigligeti, G, Leszkoven, J, Rochwerg, B, Karachi, T, Oczkowski, S, Centofanti, J, Millen, T, Sundaran, D, Hollos, L, Turns, M, Walsh, J, Al Qasim, E, Alswaidan, L, Hegazy, M, Arishi, H, Al Amri, A, AlQahtani, S, Naidu, B, Tlayjeh, H, Hussain, S, Al Enezi, F, Abdukahil, SA, Hopkins, P, Noble, H, O’Reilly, K, Mehta, R, Wong, O, Makanju, E, Rao, D, Sikondari, N, Saha, S, Corcoran, E, Pappa, E, Cockrell, M, Donegan, C, Balaie, M, Nickoleit-Bitzenberger, D, Schaaf, B, Meermeier, W, Prebeg, K, Azzaui, H, Hower, M, Brieger, K-G, Elender, C, Sabelhaus, T, Riepe, A, Akamp, C, Kremling, J, Klein, D, Landsiedel-Mechenbier, E, Laha, S, Verlander, M, Jha, A, Megarbane, B, Voicu, S, Deye, N, Malissin, I, Sutterlin, L, Mrad, A, Lehalleur, A, Naim, G, Nguyen, P, Ekhérian, J-M, Boué, Y, Sidéris, G, Vodovar, D, Guérin, E, Grant, C, Brain, M, Mineall, S, Paramasivam, E, Wilby, E, Ogg, B, Howcroft, C, Aspinwall, A, Charlton, S, Gould, R, Mistry, D, Awan, S, Bedford, C, Carr-Wilkinson, J, Hall, A, Gardiner-Hill, C, Maloney, C, Brunskill, N, Watchorn, O, Hardy, C, Qureshi, H, Flint, N, Nicholson, S, Southin, S, Ghattaoraya, A, Harding, D, O’Halloran, S, Collins, A, Smith, E, Trues, E, Borgatta, B, Turner-Bone, I, Reddy, A, Wilding, L, Wilson, C, Surti, Z, Aneman, A, Miller, J, White, H, Estensen, K, Morrison, L, Sutton, J, Cooper, M, Warnapura, L, Agno, R, Sathianathan, P, Shaw, D, Ijaz, N, Spong, A, Sabaretnam, S, Burns, D, Lang, E, Tate, M, Fischer, R, Biradar, V, Soar, N, Golden, D, Davey, M, Seaman, R, Osborne, A, Bannard-Smith, J, Clark, R, Birchall, K, Henry, J, Pomeroy, F, Quayle, R, Wylie, K, Sukuraman, A, John, M, Sibin, S, Leditschke, A, Finnis, M, Jongebloed, K, Khwaja, K, Campisi, J, Van Vonderen, M, Pietersma, M, Vrolijk, L, Kampschreur, L, Van Gulik, L, Makowski, A, Misztal, B, Haider, S, Liao, A, Squires, R, Oborska, A, Kayani, A, Kalchko-Veyssal, S, Prabakaran, R, Hadebe, B, KalchkoVeyssal, S, Williams, T, Song, R, Morpeth, S, Lai, V, Habraken, H, Stewart, R, Mwaura, E, Mew, L, Wren, L, Willams, F, Sutherland, S-B, Rebello, R, Shehabi, Y, Al-Bassam, W, Hulley, A, Kadam, U, Sathianathan, K, Innes, R, Doble, P, Graham, L, Shovelton, C, Dean, T, Salahuddin, N, Aryal, D, Koirala, K, Rai, N, Luitel, S, Seppelt, I, Whitehead, C, Lowrey, J, Gresham, R, Masters, K, Hamlyn, V, Hawkins, N, Roynon-Reed, A, Cutler, S, Lewis, S, Lazaro, J, Newman, T, Aravindan, L, Asghar, A, Bartholomew, J, Bayne, M, Beddows, S, Birch, C, Brend, M, Byrne, R, Campbell, D, Campbell, H, Chambers, E, Clinton, A, Collins, J, Crawshaw, S, Dawson, LA, Donaldson, K, Drake, C, Dyas, S, Ellis, Y, Gilmour, K, Goodwin, J, Halden, S, Hall, AS, Hanson, J, Harper, H, Harrison, S, Hayes, A, Hodgson, H, Hurford, S-A, Jackson, S, Levett, C, Lock, S, Lockett, T, Logan, M, Lomme, K, Luo, J, Marsh, E, Mguni, N, Monaghan, H, Murphy, S, Muzengi, N, Naz, M, O'Kell, E, Oliver, A, O'Reilly, J, Pearson, K, Porter, D, Potter, A, Rook, C, Rounds, C, Sheffield, J, Shirley, K, Siewersk, C, Skinner, T, Speight, H, Sutu, M, Unsworth, A, Van’t Hoff, W, Walker, S, Williams, H, Williamson, D, Williamson, JD, Duan, E, Tsang, J, Patterson, L, Austin, P, Chapman, S, Cabrelli, L, Fletcher, S, Nortje, J, Fottrell-Gould, D, Randell, G, Stammers, K, Healey, G, Pinto, M, Borrill, Z, Duncan, T, Ustianowski, A, Uriel, A, Eltayeb, A, Alfonso, J, Hey, S, Shaw, J, Fox, C, Lindergard, G, Charles, B, Blackledge, B, Connolly, K, Harris, J, Cuesta, J, Xavier, K, Purohit, D, Elhassan, M, Haldeos, A, Vincent, R, Abdelrazik, M, Jenkins, S, Ganesan, A, Kumar, R, Carter, D, Bakthavatsalam, D, Frater, A, Saleem, M, Everitt, R, Hacking, D, Zaman, M, Elmahi, E, Jones, A, Hall, K, Phillips, M, Terrill, L, Mills, G, Raithatha, A, Bauchmuller, K, Ryalls, K, Harrington, K, Bowler, H, Sall, J, Bourne, R, Gross, J, Massey, N, Adebambo, O, Long, M, Tony, K, Juffermans, N, Koopmans, M, Dujardin, R, Alderink, B, Rowland, M, Hutton, P, Bashyal, A, Davidson, N, Hird, C, Chhablani, M, Phalod, G, Kirkby, A, Archer, S, Netherton, K, Reschreiter, H, Camsooksai, J, Patch, S, Humphrey, C, Flynn, G, Harrington, C, Kruger, P, Walsham, J, Meyer, J, Harward, M, Jones, C, Sathe, S, Roche, L, Davies, E, Skinner, D, Gaylard, J, Newman, J, Pogson, D, Rose, S, Daly, Z, Brimfield, L, Nown, A, Parekh, D, Bergin, C, Bates, M, McGhee, C, Lynch, D, Bhandal, K, Tsakiridou, K, Bamford, A, Cooper, L, Whitehouse, T, Veenith, T, Forster, E, O'Connell, M, Sim, M, Hay, S, Henderson, S, Nygren, M, Valentine, E, Katary, A, Bell, G, Wilcox, L, Mataliotakis, M, Smith, P, Ali, M, Isguzar, A, Phull, M-K, Zaidi, A, Pogreban, T, Rosaroso, L, Harvey, D, Lowe, B, Meredith, M, Ryan, L, Schouten, J, Pickkers, P, Roovers, N, Klop-Riehl, M, Van der Eng, H, Sloots-Cuppen, S, Preijers, L, Van Oosten, N, Moine, P, Heming, N, Maxime, V, Bossard, I, Nicholier, T, Clair, B, Orlikowski, D, Bounab, R, Abdeladim, L, Baker, S, Duroux, M, Ratcliffe, M, Sy, E, Mailman, J, Lee, S, Gupta, C, Kassir, S, López, R, Rodríguez-Gómez, J, Cárcel, S, Carmona, R, De la Fuente, C, Rodriguez, M, Jan Hassing, R, Greven, F, Huijbens, D, Roebers, L, Verheij, H, Miles, H, Attokaran, A, Buehner, U, Williams, E, Chapman, M, O’Connor, S, Glasby, K, Rivett, J, Brown, N, Kutsogiannis, D, Thompson, P, Rooney, K, Rodden, N, Thomson, N, McGlynn, D, Abel, L, Gemmell, L, Sundaram, R, Hornsby, J, Walden, A, Keating, L, Frise, M, Rai, S, Bartley, S, Schuster-Bruce, M, Pitts, S, Miln, R, Purandare, L, Vamplew, L, Dempster, D, Gummadi, M, Dormand, N, Wang, S, Spivey, M, Bean, S, Burt, K, Moore, L, Hammonds, F, Richards, C, Campbell, L, Smyth, K, Day, C, Zitter, L, Benyon, S, Singh, J, Lynch, C, Mikusek, J, Deacon, B, Turner, K, Baker, E, Hickey, J, Champanerkar, S, Aitken, L, LewisProsser, L, Ahmad, N, Wiles, M, Willson, J, Grecu, I, Martin, J, Wrey Brown, C, Arias, A-M, Bevan, E, Westlake, S, Craven, T, Hope, D, Singleton, J, Clark, S, McCulloch, C, Biddie, S, Welters, I, Hamilton, D, Williams, K, Waugh, V, Mulla, S, Waite, A, Roman, J, Martinez, M, Johnston, B, Puthucheary, Z, Martin, T, Santos, F, Uddin, R, Fernandez, M, Seidu, F, Somerville, A, Pakats, M-L, Begum, S, Shahid, T, Presneill, J, Barge, D, Byrne, K, Janin, P, Yarad, E, Bass, F, Hammond, N, Vuylsteke, A, Chan, C, Victor, S, Waterson, S, McNamara, R, Boardman, M, Gattas, D, Buhr, H, Coles, J, Matsa, R, Gellamucho, M, Creagh-Brown, B, Marriot, C, Salberg, A, Zouita, L, Stone, S, Michalak, N, Donlon, S, Mtuwa, S, Mayangao, I, Verula, J, Burda, D, Harris, C, Jones, E, Bradley, P, Tarr, E, Harden, L, Piercy, C, Nolan, J, Kerslake, I, Cook, T, Simpson, T, Dalton, J, Demetriou, C, Mitchard, S, Ramos, L, White, K, Johnson, T, Headdon, W, Spencer, S, White, A, Howie, L, Reay, M, Watts, A, Traverse, E, Jennings, S, Anumakonda, V, Tuckwell, C, Harrow, K, Matthews, J, McGarry, K, Moore, V, Smith, L, Summerfield, A, Dark, P, Harvey, A, Doonan, R, McMorrow, L, Knowles, K, Pendlebury, J, Perez, J, Marsden, T, Taylor, M, Michael, A, Collis, M, Claxton, A, Habeichi, W, Horner, D, Slaughter, M, Thomas, V, Proudfoot, N, Keatley, C, Donnison, P, Casey, R, Irving, B, Matimba-Mupaya, W, Reed, C, Anthony, A, Trim, F, Cambalova, L, Robertson, D, Wilson, A, Hulme, J, Kannan, S, Kinney, F, Senya, H, Ratnam, V, Gill, M, Kirk, J, Shelton, S, Schweikert, S, Wibrow, B, Anstey, M, Rauniyar, R, Khoso, N, Asif, N, Taqdees, H, Frey, C, Scano, R, McKee, M, Murphy, P, Thomas, M, Worner, R, Faulkner, B, Gendall, E, Hayes, K, Blakemore, H, Borislavova, B, Deshpande, K, Van Haren, F, Konecny, P, Inskip, D, Tung, R, Hayes, L, Murphy, L, Neill, A, Reidy, B, O’Dwyer, M, Ryan, D, Ainscough, K, Hamilton-Davies, C, Mfuko, C, Abbass, H, Mandadapu, V, Leaver, S, Patel, K, Farnell-Ward, S, Saluzzio, R, Rawlins, S, Sicat, C, De Keulenaer, B, Ferrier, J, Fysh, E, Davda, A, Mevavala, B, Cook, D, Clarke, F, Banach, D, Fernández de Pinedo Artaraz, Z, Cabreros, L, Latham, V, Kruisselbrink, R, Brochard, L, Burns, K, Sandhu, G, Khalid, I, White, I, Croft, M, Holland, N, Pereira, R, Nair, P, Buscher, H, Reynolds, C, Newman, S, Santamaria, J, Barbazza, L, Homes, J, Smith, R, Zaki, A, Johnson, D, Garrard, H, Juhaz, V, Brown, L, Pemberton, A, Roy, A, Rostron, A, Woods, L, Cornell, S, Fowler, R, Adhikari, N, Kamra, M, Marinoff, N, Garrett, P, Murray, L, Brailsford, J, Fennessy, G, Mulder, J, Morgan, R, Pillai, S, Harford, R, Ivatt, H, Evans, D, Richards, S, Roberts, E, Bowen, J, Ainsworth, J, Kuitunen, A, Karlsson, S, Vahtera, A, Kiiski, H, Ristimäki, S, Albrett, J, Jackson, C, Kirkham, S, Tamme, K, Reinhard, V, Ellervee, A, Põldots, L, Rennit, P, Svitškar, N, Browne, T, Grimwade, K, Goodson, J, Keet, O, Callender, O, Udy, A, McCracken, P, Young, M, Board, J, Martin, E, Kasipandian, V, Patel, A, Allibone, S, Mary-Genetu, R, English, S, Watpool, I, Porteous, R, Miezitis, S, McIntyre, L, Brady, K, Vale, C, Shekar, K, Lavana, J, Parmar, D, Peake, S, Kurenda, C, Hormis, A, Walker, R, Collier, D, Kimpton, S, Oakley, S, Bhagani, S, De Neef, M, Garcia, S, Maharajh, A, Nandani, A, Dobson, J, Fernando, G, Eastgate, C, Gomez, K, Abdi, Z, Tatham, K, Jhanji, S, Black, E, Dela Rosa, A, Howle, R, Baikady, R, Drummond, A, Dearden, J, Philbin, J, Munt, S, Gopal, S, Pooni, J-S, Ganguly, S, Smallwood, A, Metherell, S, Naeem, A, Fagan, L, Ryan, E, Mariappa, V, Foulds, A, Revill, A, Bhattarai, B, De Jonge, E, Wigbers, J, Del Prado, M, Cremer, O, Mulier, J, Peters, A, Romberg, B, Schutgens, R, Troeman, D, Van Opdorp, M, Besten, H, Brakké, K, Barber, R, Hilldrith, A, Kluge, S, Nierhaus, A, Jarczak, D, Roedl, K, Kochanek, M, Rueß-Paterno, G, Mc-Kenzie, J, Eichenauer, D, Shimabukuro-Vornhagen, A, Wilcox, E, Del Sorbo, L, Abdelhady, H, Romagnuolo, T, Simpson, S, Maiden, M, Horton, M, Trickey, J, Krajinovic, V, Kutleša, M, Kotarski, V, Brohi, F, Jagannathan, V, Clark, M, Purvis, S, Wetherill, B, Brajković, A, Babel, J, Sever, H, Dragija, L, Kušan, I, Dushianthan, A, Cusack, R, De Courcy-Golder, K, Salmon, K, Burnish, R, Smith, S, Ruiz, W, Duke, Z, Johns, M, Male, M, Gladas, K, Virdee, S, Swabe, J, Tomlinson, H, Rohde, G, Grünewaldt, A, Bojunga, J, Petros, S, Kunz, K, Schütze, B, Weismann, D, Frey, A, Drayss, M, Goebeler, ME, Flor, T, Fragner, G, Wahl, N, Totzke, J, Sayehli, C, Hakak, S, Altaf, W, O'Sullivan, M, Murphy, A, Walsh, L, Rega La Valle, A, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Wyatt, R, Morgan, K, Varghese, S, Willis, J, Stratton, E, Kyle, L, Putensen, D, Drury, K, Skorko, A, Bremmer, P, Ward, G, Bassford, C, Sligl, W, Baig, N, Rewa, O, Bagshaw, S, Basile, K, Stavor, D, Burbee, D, McNamara, A, Wunderley, R, Bensen, N, Adams, P, Vita, T, Buhay, M, Scholl, D, Gilliam, M, Winters, J, Doherty, K, Berryman, E, Ghaffari, M, Marroquin, O, Quinn, K, Garrard, W, Kalchthaler, K, Beard, G, Skrtich, A, Bagavathy, K, Drapola, D, Bryan-Morris, K, Arnold, J, Reynolds, B, Hussain, M, Dunsavage, J, Saiyed, S, Hernandez, E, Goldman, J, Brown, C, Comp, S, Raczek, J, Morris, J, Vargas Jr., J, Weiss, D, Hensley, J, Kochert, E, Wnuk, C, Nemeth, C, Mowery, B, Hutchinson, C, Winters, L, McAdams, D, Walker, G, Minnier, T, Wisniewski, M, Mayak, K, McCreary, E, Bariola, R, Viehman, A, Daley, J, Lopus, A, Schmidhofer, M, Ambrosino, R, Keen, S, Toffalo, S, Stambaugh, M, Trimmer, K, Perri, R, Casali, S, Medva, R, Massar, B, Beyerl, A, Burkey, J, Keeler, S, Lowery, M, Oncea, L, Daugherty, J, Sevilla, C, Woelke, A, Dice, J, Weber, L, Roth, J, Ferringer, C, Beer, D, Fesz, J, Carpio, L, Colin, G, Zinzoni, V, Maquigneau, N, Henri-Lagarrigue, M, Pouplet, C, Reill, L, Distler, M, Maselli, A, Martynoga, R, Trask, K, Butler, A, Attwood, B, Parsons, P, Campbell, B, Smith, A, Page, V, Zhao, X, Oza, D, Abrahamson, G, Sheath, B, Young, P, Young, C, Lesona, E, Navarra, L, Cruz, R, Delaney, K, Aguilar-Dano, A, Gojanovic, M, Rhodes, J, Anderson, T, Morris, S, Nayyar, V, Bowen, D, Kong, J, Joy, J, Fuchs, R, Lambert, B, Tai, C, Thomas, A, Keen, A, Tierney, C, Omer, N, Bacon, G, Tridente, A, Shuker, K, Anders, J, Greer, S, Scott, P, Millington, A, Buchanan, P, Binnie, A, Powell, E, McMillan, A, Luk, T, Aref, N, Denmade, C, Sadera, G, Jacob, R, Hughes, D, Sterba, M, Geng, W, Digby, S, Southern, D, Reddy, H, Hulse, S, Campbell, A, Garton, M, Watkins, C, Smuts, S, Quinn, A, Simpson, B, McMillan, C, Finch, C, Hill, C, Cooper, J, Budd, J, Small, C, O’Leary, R, Collins, E, Holland, A, Alexander, P, Felton, T, Ferguson, S, Sellers, K, Ward, L, Yates, D, Birkinshaw, I, Kell, K, Scott, Z, Pearson, H, Hashmi, M, Hassan, N, Panjwani, A, Umrani, Z, Shaikh, M, Ain, Q, Kanwal, D, Van Bree, S, Bouw-Ruiter, M, Osinga, M, Van Zanten, A, McEldrew, R, Rashan, S, Singh, V, Azergui, N, Bari, S, Beltran, M, Brugman, C, Groeneveld, E, Jafarzadeh, M, Keijzer-Timmers, N, Kester, E, Koelink, M, Kwakkenbos-Craanen, M, Okundaye, C, Parker, L, Peters, S, Post, S, Rietveld, I, Scheepstra-Beukers, I, Schreuder, G, Smit, A, Brillinger, N, Markgraf, R, Eichinger, F, Doran, P, Anjum, A, Best-Lane, J, Barton, F, Miller, L, Richards-Belle, A, Saull, M, Sprinckmoller, S, Wiley, D, Darnell, R, Au, C, Lindstrum, K, Cheng, A, Forbes, A, Heritier, S, Trapani, T, Cuthbertson, B, Manoharan, V, Dondrop, A, Tolppa, T, Ehrmann, S, Hullegie, S, Povoa, P, Beasley, R, Daneman, N, McGloughlin, S, Paterson, D, Venkatesh, B, De Jong, M, Uyeki, T, Baillie, K, Netea, M, Orr, K, Patanwala, A, Tong, S, Cooper, N, Galea, J, Leavis, H, Ogungbenro, K, Patawala, A, Rademaker, E, Youngstein, T, Carrier, M, Fergusson, D, Hunt, B, Kumar, A, Laffan, M, Lother, S, Middeldorp, S, Stanworth, S, De Man, A, Masse, M-H, Abraham, J, Arnold, D, Begin, P, Charlewood, R, Chasse, M, Coyne, M, Daly, J, Gosbell, I, Harvala-Simmonds, H, MacLennan, S, McDyer, J, Menon, D, Pridee, N, Roberts, D, Thomas, H, Tinmouth, A, Triulzi, D, Walsh, T, Wood, E, Calfee, C, O’Kane, C, Shyamsundar, M, Sinha, P, Thompson, T, Young, I, Burrell, A, Ferguson, N, Hodgson, C, Orford, N, Phua, J, Baron, R, Epelman, S, Frankfurter, C, Gommans, F, Kim, E, Leaf, D, Vaduganathan, M, Van Kimmenade, R, Sanil, A, Van Beurden, M, Effelaar, E, Schotsman, J, Boyd, C, Harland, C, Shearer, A, Wren, J, Attanayaka, U, Darshana, S, Ishani, P, Udayanga, I, Higgins, AM, Berry, LR, Lorenzi, E, Murthy, S, McQuilten, Z, Mouncey, PR, Al-Beidh, F, Annane, D, Arabi, YM, Beane, A, Van Bentum-Puijk, W, Bhimani, Z, Bonten, MJM, Bradbury, CA, Brunkhorst, FM, Buzgau, A, Buxton, M, Charles, WN, Cove, M, Detry, MA, Estcourt, LJ, Fagbodun, EO, Fitzgerald, M, Girard, TD, Goligher, EC, Goossens, H, Haniffa, R, Hills, T, Horvat, CM, Huang, DT, Ichihara, N, Lamontagne, F, Marshall, JC, McAuley, DF, McGlothlin, A, McGuinness, SP, McVerry, BJ, Neal, MD, Nichol, AD, Parke, RL, Parker, JC, Parry-Billings, K, Peters, SEC, Reyes, LF, Rowan, KM, Saito, H, Santos, MS, Saunders, CT, Serpa-Neto, A, Seymour, CW, Shankar-Hari, M, Stronach, LM, Turgeon, AF, Turner, AM, Van de Veerdonk, FL, Zarychanski, R, Green, C, Lewis, RJ, Angus, DC, McArthur, CJ, Berry, S, Derde, LPG, Gordon, AC, Webb, SA, Lawler, PR, Comm REMAP-CAP Investigators, Apollo - University of Cambridge Repository, Intensive Care Medicine, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pittsburgh Foundation, PF, Amgen, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, Translational Breast Cancer Research Consortium, TBCRC, Canadian Institutes of Health Research, IRSC: 158584, Heart and Stroke Foundation of Canada, HSF, National Institute for Health and Care Research, NIHR, European Commission, EC, National Health and Medical Research Council, NHMRC: 1101719, APP194811, CS-2016-16-011, GNT2008447, RP-2015-06-18, Office of Health and Medical Research, OHMR, Health Research Council of New Zealand, HRC: 16/631, Eisai, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Université Pierre et Marie Curie, UPMC, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support : The Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) consortium by the European Union, FP7-HEALTH-2013-INNOVATION-1 (#602525), the Rapid European COVID-19 Emergency Research response (RECOVER) consortium by the European Union’s Horizon 2020 research and innovation programme (#101003589), the Australian National Health and Medical Research Council (#APP1101719), the Australian Medical Research Future Fund (#APP2002132), the Health Research Council of New Zealand (#16/631), the Canadian Institutes of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant (#158584) and the Canadian Institute of Health Research COVID-19 Rapid Research Funding (#447335), the UK National Institute for Health Research (NIHR) and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (CTN 2014-012), the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (PHRC-20-0147), the Wellcome Trust Innovations Project (215522), the Minderoo Foundation, the EU Programme Emergency Support Instrument, the NHS Blood and Transplant Research and Development Programme, the Translational Breast Cancer Research Consortium, the NSW Office of Health and Medical Research, Amgen, Eisai, and the Pittsburgh Foundation. Dr Higgins is funded by an NHMRC Emerging Leadership Fellowship (GNT2008447). Dr McQuilten is funded by an NHMRC Emerging Leadership Fellowship (APP194811). Dr Gordon is funded by an NIHR Research Professorship (RP-2015-06-18) and Dr Shankar-Hari by an NIHR Clinician Scientist Fellowship (CS-2016-16-011). Dr Turgeon is the Chairholder of the Canada Research Chair in Critical Care Neurology and Trauma. Dr Lawler is supported by a career award from the Heart and Stroke Foundation of Canada., and European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014)
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Adult ,Male ,corticosteroid ,[SDV]Life Sciences [q-bio] ,Critical Illness ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,antiplatelet ,Lopinavir ,Adaptive platform trial randomized controlled trial intensive care, pneumonia COVID-19 antiplatelet immunoglobulin antiviral corticosteroid immune modulation anticoagulation ,All institutes and research themes of the Radboud University Medical Center ,Adrenal Cortex Hormones ,Humans ,anticoagulation ,intensive care, pneumonia ,COVID-19 Serotherapy ,Original Investigation ,Medicine(all) ,immune modulation ,Ritonavir ,SARS-CoV-2 ,COVID-19 ,Anticoagulants ,Bayes Theorem ,General Medicine ,Middle Aged ,antiviral ,Receptors, Interleukin-6 ,Adaptive platform trial ,randomized controlled trial ,Female ,Human medicine ,immunoglobulin ,Follow-Up Studies ,Hydroxychloroquine - Abstract
ImportanceThe longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.ObjectiveTo determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.Design, Setting, and ParticipantsPrespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.InterventionsPatients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).Main Outcomes and MeasuresThe main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.ResultsAmong 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.Conclusions and RelevanceAmong critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
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- 2023
9. T-Box Genes in Drosophila Limb Development
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Pflugfelder, G.O., primary, Eichinger, F., additional, and Shen, J., additional
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- 2017
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10. Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney
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Eales, JM, Jiang, X, Xu, X, Saluja, S, Akbarov, A, Cano-Gamez, E, McNulty, MT, Finan, C, Guo, H, Wystrychowski, W, Szulinska, M, Thomas, HB, Pramanik, S, Chopade, S, Prestes, PR, Wise, I, Evangelou, E, Salehi, M, Shakanti, Y, Ekholm, M, Denniff, M, Nazgiewicz, A, Eichinger, F, Godfrey, B, Antczak, A, Glyda, M, Krol, R, Eyre, S, Brown, J, Berzuini, C, Bowes, J, Caulfield, M, Zukowska-Szczechowska, E, Zywiec, J, Bogdanski, P, Kretzler, M, Woolf, AS, Talavera, D, Keavney, B, Maffia, P, Guzik, TJ, O'Keefe, RT, Trynka, G, Samani, NJ, Hingorani, A, Sampson, MG, Morris, AP, Charchar, FJ, Tomaszewski, M, Eales, JM, Jiang, X, Xu, X, Saluja, S, Akbarov, A, Cano-Gamez, E, McNulty, MT, Finan, C, Guo, H, Wystrychowski, W, Szulinska, M, Thomas, HB, Pramanik, S, Chopade, S, Prestes, PR, Wise, I, Evangelou, E, Salehi, M, Shakanti, Y, Ekholm, M, Denniff, M, Nazgiewicz, A, Eichinger, F, Godfrey, B, Antczak, A, Glyda, M, Krol, R, Eyre, S, Brown, J, Berzuini, C, Bowes, J, Caulfield, M, Zukowska-Szczechowska, E, Zywiec, J, Bogdanski, P, Kretzler, M, Woolf, AS, Talavera, D, Keavney, B, Maffia, P, Guzik, TJ, O'Keefe, RT, Trynka, G, Samani, NJ, Hingorani, A, Sampson, MG, Morris, AP, Charchar, FJ, and Tomaszewski, M
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The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.
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- 2021
11. POS-372 A PRECISION MEDICINE APPROACH IDENTIFIES NONINVASIVE BIOMARKERS ASSOCIATED WITH INTRARENAL PATHWAY ACTIVATION IN PATIENTS WITH PROTEINURIC RENAL DISEASES
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Eddy PhD, S., primary, Mariani, L., additional, Alakwaa, F., additional, McCown, P.J., additional, Ju, W., additional, Harder, J., additional, Reich, H., additional, Eichinger, F., additional, Godfrey, B., additional, Boima, V., additional, Ademola, A., additional, Hodgin, J., additional, Ojo, A.O., additional, and Kretzler, M., additional
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- 2021
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12. POS-360 MULTISCALAR DATA INTEGRATION LINKS GLOMERULAR ANGIOPOIETIN SIGNALING PATHWAY ACTIVATION WITH PROGRESSION OF DIABETIC KIDNEY DISEASE
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LIU, J., primary, Nair, V., additional, Menon, R., additional, Eichinger, F., additional, Kretzler, M., additional, and Ju, W., additional
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- 2021
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13. Profiles of chloride in matrix porewater as natural tracer for matrix diffusion in crystalline rocks
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Eichinger, F., Gimmi, T., Möri, A., and Rüedi, J.
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550 Earth sciences & geology - Abstract
Matrix porewater from low permeable Grimsel granodiorite was successfully characterised using indirect methods applied to originally saturated core samples. Core samples were taken from a 17 m long borehole originating from a tunnel of the Grimsel Test Site into the crystalline bedrock intersecting a tectonic shear zone with a water-conducting fracture. Matrix porewater chloride profiles on the meter scale were determined on both sides of the water-conducting fracture. To evaluate transport processes within the bedrock formation, a series of diffusive model calculations were performed, which to fit the porewater data. Boundary and initial conditions were varied according to the geological conditions, whereas other required parameters such as the connected porosity and pore diffusion coefficients were determined by laboratory experiments on the cores and extrapo- lated to in situ conditions. The main conclusions can be summarized as follows: (1) Chloride porewater profiles at the meter scale can be simulated using diffusive transport models. This provides evidence that diffusive exchange with active fractures occurs over a range of a few meters in the low-permeable crystalline bedrock; (2) the best fit of the diffusion profile was achieved by a model approach, which takes asymmetric initial Cl-concentrations into account. This indicates that prior to the activation of the present water-conducting fracture, the porewater system in the bedrock was already active showing a concentration gradient in chloride; (3) the water-conducting fracture was activated at least between 850 and 1700 years before present, with a best-fit 1200 years before present; and (4) the hydraulic were affected by the construction of the rock laboratory 20 years ago, resulting in a rapid dilution of the fracture groundwater by advection.
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- 2020
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14. Molecular Characterization of Dissolved Organic Matter in Deep Geothermal Fluids
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Leins, A., primary, Vieth-Hillebrand, A., additional, Regenspurg, S., additional, Eichinger, F., additional, and Pötz, S., additional
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- 2021
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15. Profiles of chloride in matrix porewater as natural tracer for matrix diffusion in crystalline rocks
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Eichinger, F., primary, Gimmi, T., additional, Möri, A., additional, and Rüedi, J., additional
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- 2020
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16. Biomedical Serious Game System for Lower Limb Motor Rehabilitation of Hemiparetic Stroke Patients
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Noveletto, F., primary, Soares, A. V., additional, Eichinger, F. L. F., additional, Domenech, S. C., additional, Hounsell, M. da S., additional, and Filho, P. Bertemes, additional
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- 2020
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17. Diabetic nephropathy: TO01 GENOME-WIDE TRANSCRIPTOMIC ANALYSIS IDENTIFIES GENE EXPRESSION SIGNATURE OF NF-κB PATHWAY ACTIVATION IN PROGRESSIVE HUMAN DIABETIC NEPHROPATHY
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Yasuda, Y., Schmid, H., Boucherot, A., Eichinger, F., Brunner, B., Sadlier, D.M., Henger, A., Nitsche, A., Bleich, M., Cohen, C. D., Doran, P., Brady, H. R., Groene, H. J., Schloendorff, D., Nelson, P. J., and Kretzler, M.
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- 2005
18. Verbundvorhaben: PERFORM – Improving Geothermal System Performance
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Regenspurg, S., Zotzmann, J., Feldbusch, E., Eichinger, F., and Milsch, H.
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- 2018
19. MON-332 ADVANCING SYSTEMS-BIOLOGY FOCUSED, GLOMERULAR DISEASE RESEARCH THROUGH PUBLIC-PRIVATE PARTNERSHIPS
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Ascani, H., primary, Tomilo, M., additional, Nair, V., additional, Eichinger, F., additional, Eddy, S., additional, Ju, W., additional, Hodgin, J., additional, Steck, R., additional, Grega, D., additional, and Kretzler, M., additional
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- 2019
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20. Isotopenanalysen zur Klärung von Wasserschäden
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Wiesmaier, S., Eichinger, F., Voropaev, A., and Rocholl, A.
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- 2017
21. Biomedical Serious Game System for Balance Rehabilitation of Hemiparetic Stroke Patients
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Noveletto, F., primary, Soares, A. V., additional, Mello, B. A., additional, Sevegnani, C. N., additional, Eichinger, F. L. F., additional, Hounsell, M. Da S., additional, and Bertemes-Filho, P., additional
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- 2018
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22. Reconstruction of in-situ porosity and porewater compositions of low-permeability crystalline rocks: Magnitude of artefacts induced by drilling and sample recovery
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Meier, D.B., primary, Waber, H.N., additional, Gimmi, T., additional, Eichinger, F., additional, and Diamond, L.W., additional
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- 2015
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23. Squeezing of Porewater from Core Samples of DGR Boreholes: Feasibility Study
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Mazurek, M., Oyama, T., Eichinger, F., and De Haller, Antoine
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Ontario ,Physical properties ,Hydrochemistry ,Salina F Unit ,Squeezing ,SEM ,Queenston Formation ,Blue Mountain Formation ,DGR boreholes ,Georgian Bay Formation ,Mineralogy ,Pore water - Abstract
Three archived core samples from boreholes DGR-4, DGR-5 and DGR-6 from the Salina F Unit, Queenston Formation and the Georgian Bay Formation were subjected to squeezing tests at pressures of up to 500 MPa. Two samples did not yield any water, while a total of 0.88 g pore water was obtained from a clay-rich sample from the Blue Mountain Formation (water content = 2.8 wt.%, porosity = 8 %). This water mass was sufficient for a full chemical and water-isotope analysis – the first direct determination of porewater composition in rocks from the DGR boreholes. The results are generally in reasonable agreement with those of independent methods, or the observed differences can be explained. Ancillary investigations included the determination of water content, densities and mineralogy, aqueous extraction of squeezed cores, and SEM investigations to characterise the microtexture of unsqueezed and squeezed rock materials. It is concluded that squeezing is a promising method of porewater extraction and characterisation and is recommended as a complementary method for future studies. Selection criteria for potentially squeezable samples include high clay-mineral content (correlating to high water content) and low carbonate content (low stiffness, limited cementation). Potential artefacts of the method, such as ion filtration or pressure solution, should be explored and quantified in future efforts.
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- 2013
24. Genexpressionsanalysen von FSGS- und MCD-Nierenbiopsien identifizieren eine klinische Subgruppe mit spezifischem TNF-alpha-mRNA-Profil
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Martini, S., primary, Nair, V., additional, Eichinger, F., additional, Reich, H., additional, Lindenmeyer, M., additional, Kretzler, M., additional, and (NEPTUNE), Nephrotic Syndrome Study Network, additional
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- 2015
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25. A molecular signature of proteinuria in glomerulonephritis
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Reich, H N, Tritchler, D, Cattran, D C, Herzenberg, A M, Eichinger, F, Boucherot, A, Henger, A, Berthier, C C, Nair, V, Cohen, C D, Scholey, J W, Kretzler, M, and University of Zurich
- Subjects
1000 Multidisciplinary ,1300 General Biochemistry, Genetics and Molecular Biology ,570 Life sciences ,biology ,610 Medicine & health ,10035 Clinic for Nephrology ,1100 General Agricultural and Biological Sciences ,10052 Institute of Physiology - Published
- 2010
26. Renal gene and protein expression signatures for prediction of kidney disease progression
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Ju, W, Eichinger, F, Bitzer, M, Oh, J, McWeeney, S, Berthier, C C, Shedden, K, Cohen, C D, and University of Zurich
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2734 Pathology and Forensic Medicine ,570 Life sciences ,biology ,610 Medicine & health ,10035 Clinic for Nephrology ,10052 Institute of Physiology - Published
- 2009
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27. Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset
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Lindenmeyer, M T, Eichinger, F, Sen, K, Anders, Hans-Joachim, Edenhofer, I, Mattinzoli, D, Kretzler, M, Rastaldi, M P, Cohen, C D, Lindenmeyer, M T, Eichinger, F, Sen, K, Anders, Hans-Joachim, Edenhofer, I, Mattinzoli, D, Kretzler, M, Rastaldi, M P, and Cohen, C D
- Abstract
Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-enriched gene expression dataset (REGGED) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with 'a priori' known prominent glomerular expression served for validation and were all found in the novel dataset (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression of several novel glomerulus-enriched genes in REGGED was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli of healthy human adult kidneys including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. In diabetic nephropathy, a prevalent glomerulopathy, differential regulation of glomerular ROBO2 mRNA was found.In summary, novel transcripts with predominant expression in the human glomerulus could be identified using a comparative strategy on microdissected nephrons. A systematic analysis of this glomerulus-specific gene expression dataset allows the detection of target molecules and biological processes involved in glomerular biology and renal disease.
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- 2010
28. Improved elucidation of biological processes linked to diabetic nephropathy by single probe-based microarray data analysis
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Cohen, C D, Lindenmeyer, M T, Eichinger, F, Hahn, A, Seifert, M, Moll, A G, Schmid, H, Kiss, E, Gröne, E, Gröne, H J, Kretzler, M, Werner, T, Nelson, P J, Cohen, C D, Lindenmeyer, M T, Eichinger, F, Hahn, A, Seifert, M, Moll, A G, Schmid, H, Kiss, E, Gröne, E, Gröne, H J, Kretzler, M, Werner, T, and Nelson, P J
- Abstract
Background: Diabetic nephropathy (DN) is a complex and chronic metabolic disease that evolves into a progressive fibrosing renal disorder. Effective transcriptomic profiling of slowly evolving disease processes such as DN can be problematic. The changes that occur are often subtle and can escape detection by conventional oligonucleotide DNA array analyses. Methodology/Principal Findings: We examined microdissected human renal tissue with or without DN using Affymetrix oligonucleotide microarrays (HG-U133A) by standard Robust Multi-array Analysis (RMA). Subsequent gene ontology analysis by Database for Annotation, Visualization and Integrated Discovery (DAVID) showed limited detection of biological processes previously identified as central mechanisms in the development of DN (e.g. inflammation and angiogenesis). This apparent lack of sensitivity may be associated with the gene-oriented averaging of oligonucleotide probe signals, as this includes signals from cross-hybridizing probes and gene annotation that is based on out of date genomic data. We then examined the same CEL file data using a different methodology to determine how well it could correlate transcriptomic data with observed biology. ChipInspector (CI) is based on single probe analysis and de novo gene annotation that bypasses probe set definitions. Both methods, RMA and CI, used at default settings yielded comparable numbers of differentially regulated genes. However, when verified by RT-PCR, the single probe based analysis demonstrated reduced background noise with enhanced sensitivity and fewer false positives. Conclusions/Significance: Using a single probe based analysis approach with de novo gene annotation allowed an improved representation of the biological processes linked to the development and progression of DN. The improved analysis was exemplified by the detection of Wnt signaling pathway activation in DN, a process not previously reported to be involved in this disease.
- Published
- 2008
29. New Environmental Analytical Techniques to Monitor Carbon Sequestration
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Kuells, CH., primary, Eichinger, F., additional, Fader, H.J., additional, Leistert, H., additional, and Lorenz and E. Szakacs, G., additional
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- 2011
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30. Matrix Pore Water in Crystalline Rocks
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Eichinger, F., primary and Waber and J.A.T. Smellie, H.N., additional
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- 2011
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31. Energy Savings at Deutsche Telekom - Two Case Studies.
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Eichinger, F.
- Published
- 2005
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32. A molecular signature of proteinuria in glomerulonephritis
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Reich, H N, Tritchler, D, Cattran, D C, Herzenberg, A M, Eichinger, F, Boucherot, A, Henger, A, Berthier, C C, Nair, V, Cohen, C D, Scholey, J W, and Kretzler, M
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3. Good health
33. Conception des équipements et résultats d’exploitation liés à une consommation élevée de ferrailles dans un convertisseur à soufflage par le fond
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von Bogdandy, L., primary, Eichinger, F., additional, Grossmann, J.R., additional, Schafer, K., additional, and Selenz, H.J., additional
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- 1985
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34. Long-term preservation and enhancement of flow paths in deep geothermal reservoirs.
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Eichinger, F., Bratzdrum, Ch., Merkel, B., Kaulisky, A., Matthes, L., and Gräber, K.
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RESERVOIRS ,GEOTHERMAL resources ,HYDRAULIC structures ,SILICATE minerals ,ELECTRIC power - Abstract
The preservation and enhancement of the transmissivity of water-conducting fractures in the area of the injection of thermal water is one of the main goals within the long-term operation of geothermal power plants. In the Bavarian Molasse basin thermal water is produced for heat and energy generation from the carbonaceous Malm aquifer with temperatures between 65 and 145°C with pumping rates up to 150 1/s. The thermal water, which is cooled down at the surface is pumped back to the carbonaceous reservoir. In spite of the higher carbonate solubility of cooled down water and the solution of carbonaceous host rocks in the close vicinity of the injection well, the transmissivities of waterconducting fractures and pores can be long-term decreased by precipitating e.g. silicate minerals. [ABSTRACT FROM AUTHOR]
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- 2015
35. Network analysis of genes regulated in renal diseases: implications for a molecular-based classification
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Jagadish HV, Saxman Paul, Martini Sebastian, Eichinger Felix, Bhavnani Suresh K, and Kretzler Matthias
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Chronic renal diseases are currently classified based on morphological similarities such as whether they produce predominantly inflammatory or non-inflammatory responses. However, such classifications do not reliably predict the course of the disease and its response to therapy. In contrast, recent studies in diseases such as breast cancer suggest that a classification which includes molecular information could lead to more accurate diagnoses and prediction of treatment response. This article describes how we extracted gene expression profiles from biopsies of patients with chronic renal diseases, and used network visualizations and associated quantitative measures to rapidly analyze similarities and differences between the diseases. Results The analysis revealed three main regularities: (1) Many genes associated with a single disease, and fewer genes associated with many diseases. (2) Unexpected combinations of renal diseases that share relatively large numbers of genes. (3) Uniform concordance in the regulation of all genes in the network. Conclusion The overall results suggest the need to define a molecular-based classification of renal diseases, in addition to hypotheses for the unexpected patterns of shared genes and the uniformity in gene concordance. Furthermore, the results demonstrate the utility of network analyses to rapidly understand complex relationships between diseases and regulated genes.
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- 2009
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36. Discovering hidden relationships between renal diseases and regulated genes through 3D network visualizations
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Bhavnani Suresh K, Ganesan Arunkumaar, Hall Theodore, Maslowski Eric, Eichinger Felix, Martini Sebastian, Saxman Paul, Bellala Gowtham, and Kretzler Matthias
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Medicine ,Biology (General) ,QH301-705.5 ,Science (General) ,Q1-390 - Abstract
Abstract Background In a recent study, two-dimensional (2D) network layouts were used to visualize and quantitatively analyze the relationship between chronic renal diseases and regulated genes. The results revealed complex relationships between disease type, gene specificity, and gene regulation type, which led to important insights about the underlying biological pathways. Here we describe an attempt to extend our understanding of these complex relationships by reanalyzing the data using three-dimensional (3D) network layouts, displayed through 2D and 3D viewing methods. Findings The 3D network layout (displayed through the 3D viewing method) revealed that genes implicated in many diseases (non-specific genes) tended to be predominantly down-regulated, whereas genes regulated in a few diseases (disease-specific genes) tended to be up-regulated. This new global relationship was quantitatively validated through comparison to 1000 random permutations of networks of the same size and distribution. Our new finding appeared to be the result of using specific features of the 3D viewing method to analyze the 3D renal network. Conclusions The global relationship between gene regulation and gene specificity is the first clue from human studies that there exist common mechanisms across several renal diseases, which suggest hypotheses for the underlying mechanisms. Furthermore, the study suggests hypotheses for why the 3D visualization helped to make salient a new regularity that was difficult to detect in 2D. Future research that tests these hypotheses should enable a more systematic understanding of when and how to use 3D network visualizations to reveal complex regularities in biological networks.
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- 2010
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37. Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney
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Ingrid Wise, Bradley Godfrey, Raymond T. O'Keefe, Mikael Ekholm, Wojciech Wystrychowski, Pasquale Maffia, Matthias Kretzler, Sushant Saluja, James Eales, Artur Akbarov, Christopher Finan, Maciej Tomaszewski, Monika Szulińska, Gosia Trynka, Matthew Denniff, Sanjeev Pramanik, Ewa Zukowska-Szczechowska, Bernard Keavney, Andrew P. Morris, Yusif Shakanti, Sandesh Chopade, John Bowes, Eddie Cano-Gamez, Huw B. Thomas, Matthew G. Sampson, Xiaoguang Xu, Evangelos Evangelou, Paweł Bogdański, Priscilla R. Prestes, Stephen Eyre, Xiao Jiang, David Talavera, Fadi J. Charchar, Hui Guo, Andrzej Antczak, Joanna Zywiec, Nilesh J. Samani, Alicja Nazgiewicz, Michelle T. McNulty, Adrian S. Woolf, Robert Król, Tomasz J. Guzik, Jason Brown, Carlo Berzuini, Mahan Salehi, Maciej Glyda, Aroon D. Hingorani, Felix Eichinger, Mark J. Caulfield, Eales, J. M., Jiang, X., Xu, X., Saluja, S., Akbarov, A., Cano-Gamez, E., Mcnulty, M. T., Finan, C., Guo, H., Wystrychowski, W., Szulinska, M., Thomas, H. B., Pramanik, S., Chopade, S., Prestes, P. R., Wise, I., Evangelou, E., Salehi, M., Shakanti, Y., Ekholm, M., Denniff, M., Nazgiewicz, A., Eichinger, F., Godfrey, B., Antczak, A., Glyda, M., Krol, R., Eyre, S., Brown, J., Berzuini, C., Bowes, J., Caulfield, M., Zukowska-Szczechowska, E., Zywiec, J., Bogdanski, P., Kretzler, M., Woolf, A. S., Talavera, D., Keavney, B., Maffia, P., Guzik, T. J., O'Keefe, R. T., Trynka, G., Samani, N. J., Hingorani, A., Sampson, M. G., Morris, A. P., Charchar, F. J., and Tomaszewski, M.
- Subjects
Quantitative Trait Loci ,Genome-wide association study ,Blood Pressure ,Quantitative trait locus ,Biology ,Kidney ,Polymorphism, Single Nucleotide ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Mendelian randomization ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Mendelian Randomization Analysi ,030304 developmental biology ,0303 health sciences ,Genetic Variation ,Mendelian Randomization Analysis ,Epigenome ,Genomics ,DNA Methylation ,Alternative Splicing ,medicine.anatomical_structure ,DNA methylation ,Hypertension ,030217 neurology & neurosurgery ,Human ,Genome-Wide Association Study - Abstract
The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.
- Published
- 2021
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38. Association of Genetically Predicted Skipping of COL4A4 Exon 27 with Hematuria and Albuminuria.
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Lona-Durazo F, Omachi K, Fermin D, Eichinger F, Troost JP, Lin MH, Dinsmore IR, Mirshahi T, Chang AR, Miner JH, Paterson AD, Barua M, and Gagliano Taliun SA
- Published
- 2024
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39. Gene Expression Sets and Renal Profiling from the Renal AL Amyloid Involvement and NEOD00 (RAIN) Trial.
- Author
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Varga C, Eichinger F, Nair V, Naik AS, Nasr SH, Fogo AB, Toskic D, Kretzler M, and Comenzo RL
- Abstract
Introduction: There is an unmet need to understand the mechanisms by which amyloid deposition drives alterations in the kidney. We leveraged renal biopsies from amyloid light-chain (AL) amyloidosis participants of the Renal AL Amyloid Involvement and NEOD00 (RAIN) trial (NCT03168906) to perform transcriptional profiling and to employ a novel histologic scoring tool. Our objective was to utilize a transcriptome-driven approach to identify AL molecular signatures that may be prognostic., Methods: Clinical data were correlated to histologic and molecular findings. A composite scarring injury and amyloid score (AS) were assigned to each biopsy. Glomerular and tubulointerstitial (TI) compartments were microdissected and sequenced separately. Expression data were compared to healthy living donors and focal segmental glomerulosclerosis (FSGS) profiles. Differentially expressed genes were determined., Results: Cluster analysis revealed 2 distinct patient clusters (G1 and G2) based on gene expression. The AS was higher in the TI compartment (6.5 vs. 4.5; P = 0.0290) of G2. Glomeruli showed activation of fibrotic pathways and increased canonical signaling of LPS/IL-1. TNF activation was noted in TI. Enriched ingenuity canonical pathways included "coagulation system," "GADD45 signaling," and "Wnt/Ca+ pathway," among others. For AL versus living donors, ingenuity pathway analysis identified enrichment in PI3K/Akt signaling. Gene regulators of cellular proliferation were enriched in the amyloid group., Conclusion: Despite the small sample size, we identified 2 distinct groups of patients with AL based on molecular signatures. Detailed studies of a larger cohort encompassing omics technologies at a single cell resolution will further help to identify the response of individual kidney cell types to amyloid deposits, potentially leading to the development of novel therapeutic targets., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)
- Published
- 2024
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40. Defining the molecular correlate of arteriolar hyalinosis in kidney disease progression by integration of single cell transcriptomic analysis and pathology scoring.
- Author
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Menon R, Otto EA, Barisoni L, Melo Ferreira R, Limonte CP, Godfrey B, Eichinger F, Nair V, Naik AS, Subramanian L, D'Agati V, Henderson JM, Herlitz L, Kiryluk K, Moledina DG, Moeckel GW, Palevsky PM, Parikh CR, Randhawa P, Rosas SE, Rosenberg AZ, Stillman I, Toto R, Torrealba J, Vazquez MA, Waikar SS, Alpers CE, Nelson RG, Eadon MT, Kretzler M, and Hodgin JB
- Abstract
Arteriolar hyalinosis in kidneys is an independent predictor of cardiovascular disease, the main cause of mortality in chronic kidney disease (CKD). The underlying molecular mechanisms of protein accumulation in the subendothelial space are not well understood. Using single cell transcriptomic data and whole slide images from kidney biopsies of patients with CKD and acute kidney injury in the Kidney Precision Medicine Project, the molecular signals associated with arteriolar hyalinosis were evaluated. Co-expression network analysis of the endothelial genes yielded three gene set modules as significantly associated with arteriolar hyalinosis. Pathway analysis of these modules showed enrichment of transforming growth factor beta / bone morphogenetic protein (TGFβ / BMP) and vascular endothelial growth factor (VEGF) signaling pathways in the endothelial cell signatures. Ligand-receptor analysis identified multiple integrins and cell adhesion receptors as over-expressed in arteriolar hyalinosis, suggesting a potential role of integrin-mediated TGFβ signaling. Further analysis of arteriolar hyalinosis associated endothelial module genes identified focal segmental glomerular sclerosis as an enriched term. On validation in gene expression profiles from the Nephrotic Syndrome Study Network cohort, one of the three modules was significantly associated with the composite endpoint (> 40% reduction in estimated glomerular filtration rate (eGFR) or kidney failure) independent of age, sex, race, and baseline eGFR, suggesting poor prognosis with elevated expression of genes in this module. Thus, integration of structural and single cell molecular features yielded biologically relevant gene sets, signaling pathways and ligand-receptor interactions, underlying arteriolar hyalinosis and putative targets for therapeutic intervention.
- Published
- 2023
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41. An integrated organoid omics map extends modeling potential of kidney disease.
- Author
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Lassé M, El Saghir J, Berthier CC, Eddy S, Fischer M, Laufer SD, Kylies D, Hutzfeldt A, Bonin LL, Dumoulin B, Menon R, Vega-Warner V, Eichinger F, Alakwaa F, Fermin D, Billing AM, Minakawa A, McCown PJ, Rose MP, Godfrey B, Meister E, Wiech T, Noriega M, Chrysopoulou M, Brandts P, Ju W, Reinhard L, Hoxha E, Grahammer F, Lindenmeyer MT, Huber TB, Schlüter H, Thiel S, Mariani LH, Puelles VG, Braun F, Kretzler M, Demir F, Harder JL, and Rinschen MM
- Subjects
- Humans, Proteome metabolism, Kidney, Organoids metabolism, Tumor Necrosis Factor-alpha metabolism, Kidney Diseases genetics, Kidney Diseases metabolism
- Abstract
Kidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins. Single cell transcriptome integration reveals that most proteome changes localize to podocytes, tubular and stromal cells. TNFα treatment of organoids results in 322 differentially expressed proteins, including cytokines and complement components. Transcript expression of these 322 proteins is significantly higher in individuals with poorer clinical outcomes in proteinuric kidney disease. Key TNFα-associated protein (C3 and VCAM1) expression is increased in both human tubular and organoid kidney cell populations, highlighting the potential for organoids to advance biomarker development. By integrating kidney organoid omic layers, incorporating a disease-relevant cytokine stressor and comparing with human data, we provide crucial evidence for the functional relevance of the kidney organoid model to human kidney disease., (© 2023. Springer Nature Limited.)
- Published
- 2023
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42. Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis.
- Author
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Mariani LH, Eddy S, AlAkwaa FM, McCown PJ, Harder JL, Nair V, Eichinger F, Martini S, Ademola AD, Boima V, Reich HN, El Saghir J, Godfrey B, Ju W, Tanner EC, Vega-Warner V, Wys NL, Adler SG, Appel GB, Athavale A, Atkinson MA, Bagnasco SM, Barisoni L, Brown E, Cattran DC, Coppock GM, Dell KM, Derebail VK, Fervenza FC, Fornoni A, Gadegbeku CA, Gibson KL, Greenbaum LA, Hingorani SR, Hladunewich MA, Hodgin JB, Hogan MC, Holzman LB, Jefferson JA, Kaskel FJ, Kopp JB, Lafayette RA, Lemley KV, Lieske JC, Lin JJ, Menon R, Meyers KE, Nachman PH, Nast CC, O'Shaughnessy MM, Otto EA, Reidy KJ, Sambandam KK, Sedor JR, Sethna CB, Singer P, Srivastava T, Tran CL, Tuttle KR, Vento SM, Wang CS, Ojo AO, Adu D, Gipson DS, Trachtman H, and Kretzler M
- Subjects
- Humans, Tissue Inhibitor of Metalloproteinase-1, Tumor Necrosis Factors therapeutic use, Glomerulosclerosis, Focal Segmental pathology, Nephrosis, Lipoid diagnosis, Nephrology, Nephrotic Syndrome diagnosis
- Abstract
The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic profile-based clustering identified three patient subgroups with shared molecular signatures across independent, North American, European, and African cohorts. One subgroup had significantly greater disease progression (Hazard Ratio 5.2) which persisted after adjusting for diagnosis and clinical measures (Hazard Ratio 3.8). Inclusion in this subgroup was retained even when clustering was limited to those with less than 25% interstitial fibrosis. The molecular profile of this subgroup was largely consistent with tumor necrosis factor (TNF) pathway activation. Two TNF pathway urine markers were identified, tissue inhibitor of metalloproteinases-1 (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1), that could be used to predict an individual's TNF pathway activation score. Kidney organoids and single-nucleus RNA-sequencing of participant kidney biopsies, validated TNF-dependent increases in pathway activation score, transcript and protein levels of TIMP-1 and MCP-1, in resident kidney cells. Thus, molecular profiling identified a subgroup of patients with either MCD or FSGS who shared kidney TNF pathway activation and poor outcomes. A clinical trial testing targeted therapies in patients selected using urinary markers of TNF pathway activation is ongoing., (Copyright © 2022 International Society of Nephrology. All rights reserved.)
- Published
- 2023
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43. Viral associations with kidney disease diagnosis and altered kidney metatranscriptome by kidney function.
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Hong C, Eichinger F, Atta MG, Estrella MM, Fine DM, Ross MJ, Wyatt C, Hwang TH, Kretzler M, Sedor JR, O'Toole JF, Miller AW, and Bruggeman LA
- Subjects
- Humans, Gene Expression Profiling, Kidney diagnostic imaging, Transcriptome, Kidney Diseases diagnosis, Kidney Diseases genetics
- Published
- 2023
- Full Text
- View/download PDF
44. Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease.
- Author
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Liu J, Nair V, Zhao YY, Chang DY, Limonte C, Bansal N, Fermin D, Eichinger F, Tanner EC, Bellovich KA, Steigerwalt S, Bhat Z, Hawkins JJ, Subramanian L, Rosas SE, Sedor JR, Vasquez MA, Waikar SS, Bitzer M, Pennathur S, Brosius FC, De Boer I, Chen M, Kretzler M, and Ju W
- Subjects
- Humans, Angiopoietin-1 genetics, Receptor, TIE-2 genetics, Cohort Studies, Endothelial Cells, Angiopoietin-2 genetics, Angiopoietins, Signal Transduction, Biomarkers, Disease Progression, Diabetic Nephropathies genetics, Kidney Failure, Chronic, Diabetes Mellitus
- Abstract
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD). Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of DKD. A three-marker panel was derived from a proteomics analysis of plasma samples by an unbiased machine learning approach from participants (N = 58) in the Clinical Phenotyping and Resource Biobank study. In combination with standard clinical parameters, this panel improved prediction of the composite outcome of ESKD or a 40% decline in glomerular filtration rate. The panel was validated in an independent group (N = 68), who also had kidney transcriptomic profiles. One marker, plasma angiopoietin 2 (ANGPT2), was significantly associated with outcomes in cohorts from the Cardiovascular Health Study (N = 3,183) and the Chinese Cohort Study of Chronic Kidney Disease (N = 210). Glomerular transcriptional angiopoietin/Tie (ANG-TIE) pathway scores, derived from the expression of 154 ANG-TIE signaling mediators, correlated positively with plasma ANGPT2 levels and kidney outcomes. Higher receptor expression in glomeruli and higher ANG-TIE pathway scores in endothelial cells corroborated potential functional effects in the kidney from elevated plasma ANGPT2 levels. Our work suggests that ANGPT2 is a promising prognostic endothelial biomarker with likely functional impact on glomerular pathogenesis in DKD., (© 2022 by the American Diabetes Association.)
- Published
- 2022
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45. Molecular programs associated with glomerular hyperfiltration in early diabetic kidney disease.
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Stefansson VTN, Nair V, Melsom T, Looker HC, Mariani LH, Fermin D, Eichinger F, Menon R, Subramanian L, Ladd P, Harned R, Harder JL, Hodgin JB, Bjornstad P, Nelson PJ, Eriksen BO, Nelson RG, and Kretzler M
- Subjects
- Humans, Kidney Glomerulus pathology, Glomerular Filtration Rate, Glycated Hemoglobin metabolism, Diabetic Nephropathies genetics, Diabetic Nephropathies complications, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 pathology
- Abstract
Hyperfiltration is a state of high glomerular filtration rate (GFR) observed in early diabetes that damages glomeruli, resulting in an iterative process of increasing filtration load on fewer and fewer remaining functional glomeruli. To delineate underlying cellular mechanisms of damage associated with hyperfiltration, transcriptional profiles of kidney biopsies from Pima Indians with type 2 diabetes with or without early-stage diabetic kidney disease were grouped into two hyperfiltration categories based on annual iothalamate GFR measurements. Twenty-six participants with a peak GFR measurement within two years of biopsy were categorized as the hyperfiltration group, and 26 in whom biopsy preceded peak GFR by over two years were considered pre-hyperfiltration. The hyperfiltration group had higher hemoglobin A1c, higher urine albumin-to-creatinine ratio, increased glomerular basement membrane width and lower podocyte density compared to the pre-hyperfiltration group. A glomerular 1240-gene transcriptional signature identified in the hyperfiltration group was enriched for endothelial stress response signaling genes, including endothelin-1, tec-kinase and transforming growth factor-β1 pathways, with the majority of the transcripts mapped to endothelial and inflammatory cell clusters in kidney single cell transcriptional data. Thus, our analysis reveals molecular pathomechanisms associated with hyperfiltration in early diabetic kidney disease involving putative ligand-receptor pairs with downstream intracellular targets linked to cellular crosstalk between endothelial and mesangial cells., (Copyright © 2022 International Society of Nephrology. All rights reserved.)
- Published
- 2022
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46. ADAR regulates APOL1 via A-to-I RNA editing by inhibition of MDA5 activation in a paradoxical biological circuit.
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Riella CV, McNulty M, Ribas GT, Tattersfield CF, Perez-Gill C, Eichinger F, Kelly J, Chun J, Subramanian B, Guizelini D, Alper SL, Pollak MR, Sampson MG, and Friedman DJ
- Subjects
- Humans, Animals, Mice, RNA Editing, Interferon-Induced Helicase, IFIH1 metabolism, RNA, Double-Stranded genetics, 3' Untranslated Regions, Apolipoprotein L1 genetics, Interferon-gamma genetics, Interferon-gamma metabolism, RNA, Messenger metabolism, Inosine genetics, Inosine metabolism, Adenosine metabolism, Adenosine Deaminase genetics, Adenosine Deaminase metabolism, Interferon Type I metabolism
- Abstract
APOL1 risk variants are associated with increased risk of kidney disease in patients of African ancestry, but not all individuals with the APOL1 high-risk genotype develop kidney disease. As APOL1 gene expression correlates closely with the degree of kidney cell injury in both cell and animal models, the mechanisms regulating APOL1 expression may be critical determinants of risk allele penetrance. The APOL1 messenger RNA includes Alu elements at the 3' untranslated region that can form a double-stranded RNA structure (Alu-dsRNA) susceptible to posttranscriptional adenosine deaminase acting on RNA (ADAR)-mediated adenosine-to-inosine (A-to-I) editing, potentially impacting gene expression. We studied the effects of ADAR expression and A-to-I editing on APOL1 levels in podocytes, human kidney tissue, and a transgenic APOL1 mouse model. In interferon-γ (IFN-γ)-stimulated human podocytes, ADAR down-regulates APOL1 by preventing melanoma differentiation-associated protein 5 (MDA5) recognition of dsRNA and the subsequent type I interferon (IFN-I) response. Knockdown experiments showed that recognition of APOL1 messenger RNA itself is an important contributor to the MDA5-driven IFN-I response. Mathematical modeling suggests that the IFN-ADAR-APOL1 network functions as an incoherent feed-forward loop, a biological circuit capable of generating fast, transient responses to stimuli. Glomeruli from human kidney biopsies exhibited widespread editing of APOL1 Alu-dsRNA, while the transgenic mouse model closely replicated the edited sites in humans. APOL1 expression in mice was inversely correlated with Adar1 expression under IFN-γ stimuli, supporting the idea that ADAR regulates APOL1 levels in vivo. ADAR-mediated A-to-I editing is an important regulator of APOL1 expression that could impact both penetrance and severity of APOL1-associated kidney disease.
- Published
- 2022
- Full Text
- View/download PDF
47. A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis.
- Author
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McNulty MT, Fermin D, Eichinger F, Jang D, Kretzler M, Burtt NP, Pollak MR, Flannick J, Weins A, Friedman DJ, and Sampson MG
- Subjects
- HEK293 Cells, Humans, Kidney Glomerulus pathology, Transcriptome, Apolipoprotein L1 genetics, Glomerulosclerosis, Focal Segmental genetics, Glomerulosclerosis, Focal Segmental pathology
- Abstract
Apolipoprotein L1 (APOL1)-associated focal segmental glomerulosclerosis (FSGS) is the dominant form of FSGS in Black individuals. There are no targeted therapies for this condition, in part because the molecular mechanisms underlying APOL1's pathogenic contribution to FSGS are incompletely understood. Studying the transcriptomic landscape of APOL1 FSGS in patient kidneys is an important way to discover genes and molecular behaviors that are unique or most relevant to the human disease. With the hypothesis that the pathology driven by the high-risk APOL1 genotype is reflected in alteration of gene expression across the glomerular transcriptome, we compared expression and co-expression profiles of 15,703 genes in 16 Black patients with FSGS at high-risk vs 14 Black patients with a low-risk APOL1 genotype. Expression data from APOL1-inducible HEK293 cells and normal human glomeruli were used to pursue genes and molecular pathways uncovered in these studies. We discovered increased expression of APOL1 and nine other significant differentially expressed genes in high-risk patients. This included stanniocalcin, which has a role in mitochondrial and calcium-related processes along with differential correlations between high- and low-risk APOL1 and metabolism pathway genes. There were similar correlations with extracellular matrix- and immune-related genes, but significant loss of co-expression of mitochondrial genes in high-risk FSGS, and an NF-κB-down regulating gene, NKIRAS1, as the most significant hub gene with strong differential correlations with NDUF family (mitochondrial respiratory genes) and immune-related (JAK-STAT) genes. Thus, differences in mitochondrial gene regulation appear to underlie many differences observed between high- and low-risk Black patients with FSGS., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
48. Renin-angiotensin system inhibition reverses the altered triacylglycerol metabolic network in diabetic kidney disease.
- Author
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Sas KM, Lin J, Wang CH, Zhang H, Saha J, Rajendiran TM, Soni T, Nair V, Eichinger F, Kretzler M, Brosius FC 3rd, Michailidis G, and Pennathur S
- Subjects
- Animals, Antihypertensive Agents metabolism, Kidney metabolism, Metabolic Networks and Pathways, Mice, Renin-Angiotensin System drug effects, Triglycerides metabolism, Diabetes Mellitus metabolism, Diabetic Nephropathies drug therapy, Diabetic Nephropathies metabolism
- Abstract
Objective: Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). Determining the changes in individual lipids and lipid networks across a spectrum of DKD severity may identify lipids that are pathogenic to DKD progression., Methods: We performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS
-/- mice along with non-diabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS-/- mouse model., Results: Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS-/- mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition., Conclusions: In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network.- Published
- 2021
- Full Text
- View/download PDF
49. Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs.
- Author
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Solagna F, Tezze C, Lindenmeyer MT, Lu S, Wu G, Liu S, Zhao Y, Mitchell R, Meyer C, Omairi S, Kilic T, Paolini A, Ritvos O, Pasternack A, Matsakas A, Kylies D, Wiesch JSZ, Turner JE, Wanner N, Nair V, Eichinger F, Menon R, Martin IV, Klinkhammer BM, Hoxha E, Cohen CD, Tharaux PL, Boor P, Ostendorf T, Kretzler M, Sandri M, Kretz O, Puelles VG, Patel K, and Huber TB
- Subjects
- Activin Receptors, Type II genetics, Activin Receptors, Type II metabolism, Activins genetics, Activins metabolism, Animals, Cachexia etiology, Cachexia genetics, Disease Models, Animal, HEK293 Cells, Humans, Mice, Mice, Knockout, Muscular Atrophy etiology, Muscular Atrophy genetics, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic genetics, Wasting Syndrome etiology, Wasting Syndrome genetics, Cachexia metabolism, Muscle, Skeletal metabolism, Muscular Atrophy metabolism, Renal Insufficiency, Chronic metabolism, Wasting Syndrome metabolism
- Abstract
Skeletal muscle wasting is commonly associated with chronic kidney disease (CKD), resulting in increased morbidity and mortality. However, the link between kidney and muscle function remains poorly understood. Here, we took a complementary interorgan approach to investigate skeletal muscle wasting in CKD. We identified increased production and elevated blood levels of soluble pro-cachectic factors, including activin A, directly linking experimental and human CKD to skeletal muscle wasting programs. Single-cell sequencing data identified the expression of activin A in specific kidney cell populations of fibroblasts and cells of the juxtaglomerular apparatus. We propose that persistent and increased kidney production of pro-cachectic factors, combined with a lack of kidney clearance, facilitates a vicious kidney/muscle signaling cycle, leading to exacerbated blood accumulation and, thereby, skeletal muscle wasting. Systemic pharmacological blockade of activin A using soluble activin receptor type IIB ligand trap as well as muscle-specific adeno-associated virus-mediated downregulation of its receptor ACVR2A/B prevented muscle wasting in different mouse models of experimental CKD, suggesting that activin A is a key factor in CKD-induced cachexia. In summary, we uncovered a crosstalk between kidney and muscle and propose modulation of activin signaling as a potential therapeutic strategy for skeletal muscle wasting in CKD.
- Published
- 2021
- Full Text
- View/download PDF
50. Gene expression profiles of diabetic kidney disease and neuropathy in eNOS knockout mice: Predictors of pathology and RAS blockade effects.
- Author
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Eid SA, Hinder LM, Zhang H, Eksi R, Nair V, Eddy S, Eichinger F, Park M, Saha J, Berthier CC, Jagadish HV, Guan Y, Pennathur S, Hur J, Kretzler M, Feldman EL, and Brosius FC
- Subjects
- Animals, Diabetic Nephropathies etiology, Diabetic Nephropathies metabolism, Diabetic Neuropathies etiology, Diabetic Neuropathies metabolism, Gene Expression Regulation, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Diabetes Mellitus, Experimental complications, Diabetes Mellitus, Type 2 complications, Diabetic Nephropathies pathology, Diabetic Neuropathies pathology, Nitric Oxide Synthase Type III physiology, Transcriptome, ras Proteins antagonists & inhibitors
- Abstract
Diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN) are two common diabetic complications. However, their pathogenesis remains elusive and current therapies are only modestly effective. We evaluated genome-wide expression to identify pathways involved in DKD and DPN progression in db/db eNOS-/- mice receiving renin-angiotensin-aldosterone system (RAS)-blocking drugs to mimic the current standard of care for DKD patients. Diabetes and eNOS deletion worsened DKD, which improved with RAS treatment. Diabetes also induced DPN, which was not affected by eNOS deletion or RAS blockade. Given the multiple factors affecting DKD and the graded differences in disease severity across mouse groups, an automatic data analysis method, SOM, or self-organizing map was used to elucidate glomerular transcriptional changes associated with DKD, whereas pairwise bioinformatic analysis was used for DPN. These analyses revealed that enhanced gene expression in several pro-inflammatory networks and reduced expression of development genes correlated with worsening DKD. Although RAS treatment ameliorated the nephropathy phenotype, it did not alter the more abnormal gene expression changes in kidney. Moreover, RAS exacerbated expression of genes related to inflammation and oxidant generation in peripheral nerves. The graded increase in inflammatory gene expression and decrease in development gene expression with DKD progression underline the potentially important role of these pathways in DKD pathogenesis. Since RAS blockers worsened this gene expression pattern in both DKD and DPN, it may partly explain the inadequate therapeutic efficacy of such blockers., (© 2021 Federation of American Societies for Experimental Biology.)
- Published
- 2021
- Full Text
- View/download PDF
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