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Olfactory sniffing signals consciousness in unresponsive patients with brain injuries 期刊论文
NATURE, 2020
作者:  Hellmuth, Susanne;  Gomez-H, Laura;  Pendas, Alberto M.;  Stemmann, Olaf
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

After severe brain injury, it can be difficult to determine the state of consciousness of a patient, to determine whether the patient is unresponsive or perhaps minimally conscious(1), and to predict whether they will recover. These diagnoses and prognoses are crucial, as they determine therapeutic strategies such as pain management, and can underlie end-of-life decisions(2,3). Nevertheless, there is an error rate of up to 40% in determining the state of consciousness in patients with brain injuries(4,5). Olfaction relies on brain structures that are involved in the basic mechanisms of arousal(6), and we therefore hypothesized that it may serve as a biomarker for consciousness(7). Here we use a non-verbal non-task-dependent measure known as the sniff response(8-11) to determine consciousness in patients with brain injuries. By measuring odorant-dependent sniffing, we gain a sensitive measure of olfactory function(10-15). We measured the sniff response repeatedly over time in patients with severe brain injuries and found that sniff responses significantly discriminated between unresponsive and minimally conscious states at the group level. Notably, at the single-patient level, if an unresponsive patient had a sniff response, this assured future regaining of consciousness. In addition, olfactory sniff responses were associated with long-term survival rates. These results highlight the importance of olfaction in human brain function, and provide an accessible tool that signals consciousness and recovery in patients with brain injuries.


Odorant-dependent sniff responses predicted the long-term survival rates of patients with severe brain injury, and discriminated between individuals who were unresponsive and in minimally conscious states.


  
Pharmacologic fibroblast reprogramming into photoreceptors restores vision 期刊论文
NATURE, 2020, 581 (7806) : 83-+
作者:  Jiang, Mingkai;  Medlyn, Belinda E.;  Drake, John E.;  Duursma, Remko A.;  Anderson, Ian C.;  Barton, Craig V. M.;  Boer, Matthias M.;  Carrillo, Yolima;  Castaneda-Gomez, Laura;  Collins, Luke;  Crous, Kristine Y.;  De Kauwe, Martin G.;  dos Santos, Bruna M.;  Emmerson, Kathryn M.;  Facey, Sarah L.;  Gherlenda, Andrew N.;  Gimeno, Teresa E.;  Hasegawa, Shun;  Johnson, Scott N.;  Kannaste, Astrid;  Macdonald, Catriona A.;  Mahmud, Kashif;  Moore, Ben D.;  Nazaries, Loic;  Neilson, Elizabeth H. J.;  Nielsen, Uffe N.;  Niinemets, Ulo;  Noh, Nam Jin;  Ochoa-Hueso, Raul;  Pathare, Varsha S.;  Pendall, Elise;  Pihlblad, Johanna;  Pineiro, Juan;  Powell, Jeff R.;  Power, Sally A.;  Reich, Peter B.;  Renchon, Alexandre A.;  Riegler, Markus;  Rinnan, Riikka;  Rymer, Paul D.;  Salomon, Roberto L.;  Singh, Brajesh K.;  Smith, Benjamin;  Tjoelker, Mark G.;  Walker, Jennifer K. M.;  Wujeska-Klause, Agnieszka;  Yang, Jinyan;  Zaehle, Soenke;  Ellsworth, David S.
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Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision(1,2). Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss  however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells. The transplantation of these chemically induced photoreceptor-like cells (CiPCs) into the subretinal space of rod degeneration mice (homozygous for rd1, also known as Pde6b) leads to partial restoration of the pupil reflex and visual function. We show that mitonuclear communication is a key determining factor for the reprogramming of fibroblasts into CiPCs. Specifically, treatment with these five compounds leads to the translocation of AXIN2 to the mitochondria, which results in the production of reactive oxygen species, the activation of NF-kappa B and the upregulation of Ascl1. We anticipate that CiPCs could have therapeutic potential for restoring vision.


A set of five small molecules can induce the transformation of fibroblasts into rod photoreceptor-like cells, which can partially restore pupil reflex and visual function when transplanted into a rod degeneration mouse model.


  
Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity 期刊论文
NATURE COMMUNICATIONS, 2017, 8
作者:  Joshi, Peter K.;  Pirastu, Nicola;  Kentistou, Katherine A.;  Fischer, Krista;  Hofer, Edith;  Schraut, Katharina E.;  Clark, David W.;  Nutile, Teresa;  Barnes, Catriona L. K.;  Timmers, Paul R. H. J.;  Shen, Xia;  Gandin, Ilaria;  McDaid, Aaron F.;  Hansen, Thomas Folkmann;  Gordon, Scott D.;  Giulianini, Franco;  Boutin, Thibaud S.;  Abdellaoui, Abdel;  Zhao, Wei;  Medina-Gomez, Carolina;  Bartz, Traci M.;  Trompet, Stella;  Lange, Leslie A.;  Raffield, Laura;  van der Spek, Ashley;  Galesloot, Tessel E.;  Proitsi, Petroula;  Yanek, Lisa R.;  Bielak, Lawrence F.;  Payton, Antony;  Murgia, Federico;  Concas, Maria Pina;  Biino, Ginevra;  Tajuddin, Salman M.;  Seppala, Ilkka;  Amin, Najaf;  Boerwinkle, Eric;  Borglum, Anders D.;  Campbell, Archie;  Demerath, Ellen W.;  Demuth, Ilja;  Faul, Jessica D.;  Ford, Ian;  Gialluisi, Alessandro;  Gogele, Martin;  Graff, MariaElisa;  Hingorani, Aroon;  Hottenga, Jouke-Jan;  Hougaard, David M.;  Hurme, Mikko A.;  Ikram, M. Arfan;  Jylha, Marja;  Kuh, Diana;  Ligthart, Lannie;  Lill, Christina M.;  Lindenberger, Ulman;  Lumley, Thomas;  Magi, Reedik;  Marques-Vidal, Pedro;  Medland, Sarah E.;  Milani, Lili;  Nagy, Reka;  Ollier, William E. R.;  Peyser, Patricia A.;  Pramstaller, Peter P.;  Ridker, Paul M.;  Rivadeneira, Fernando;  Ruggiero, Daniela;  Saba, Yasaman;  Schmidt, Reinhold;  Schmidt, Helena;  Slagboom, P. Eline;  Smith, Blair H.;  Smith, Jennifer A.;  Sotoodehnia, Nona;  Steinhagen-Thiessen, Elisabeth;  van Rooij, Frank J. A.;  Verbeek, Andre L.;  Vermeulen, Sita H.;  Vollenweider, Peter;  Wang, Yunpeng;  Werge, Thomas;  Whitfield, John B.;  Zonderman, Alan B.;  Lehtimaki, Terho;  Evans, Michele K.;  Pirastu, Mario;  Fuchsberger, Christian;  Bertram, Lars;  Pendleton, Neil;  Kardia, Sharon L. R.;  Ciullo, Marina;  Becker, Diane M.;  Wong, Andrew;  Psaty, Bruce M.;  van Duijn, Cornelia M.;  Wilson, James G.;  Jukema, J. Wouter;  Kiemeney, Lambertus;  Uitterlinden, Andre G.;  Franceschini, Nora;  North, Kari E.;  Weir, David R.;  Metspalu, Andres;  Boomsma, Dorret I.;  Hayward, Caroline;  Chasman, Daniel;  Martin, Nicholas G.;  Sattar, Naveed;  Campbell, Harry;  Esko, Tonu;  Kutalik, Zoltan;  Wilson, James F.
收藏  |  浏览/下载:39/0  |  提交时间:2019/11/27