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iScience. 2021:24(7).DOI: 10.1016/j.isci.2021.102797

Effects of early-life penicillin exposure on the gut microbiome and frontal cortex and amygdala gene expression

Volkova, Angelina; Ruggles, Kelly; Schulfer, Anjelique; Gao, Zhan; Ginsberg, Stephen D; Blaser, Martin J
We have established experimental systems to assess the effects of early-life exposures to antibiotics on the intestinal microbiota and gene expression in the brain. This model system is highly relevant to human exposure and may be developed into a preclinical model of neurodevelopmental disorders in which the gut-brain axis is perturbed, leading to organizational effects that permanently alter the structure and function of the brain. Exposing newborn mice to low-dose penicillin led to substantial changes in intestinal microbiota population structure and composition. Transcriptomic alterations implicate pathways perturbed in neurodevelopmental and neuropsychiatric disorders. There also were substantial effects on frontal cortex and amygdala gene expression by bioinformatic interrogation, affecting multiple pathways underlying neurodevelopment. Informatic analyses established linkages between specific intestinal microbial populations and the early-life expression of particular affected genes. These studies provide translational models to explore intestinal microbiome roles in the normal and abnormal maturation of the vulnerable central nervous system.
PMCID:8324854
PMID: 34355145
ISSN: 2589-0042
CID: 4966052
Journal of clinical medicine. 2021:10(13).DOI: 10.3390/jcm10132994

Adiponectin Modulation by Genotype and Maternal Choline Supplementation in a Mouse Model of Down Syndrome and Alzheimer's Disease

Alldred, Melissa J; Lee, Sang Han; Ginsberg, Stephen D
Down syndrome (DS) is a genetic disorder caused by the triplication of human chromosome 21, which results in neurological and physiological pathologies. These deficits increase during aging and are exacerbated by cognitive decline and increase of Alzheimer's disease (AD) neuropathology. A nontoxic, noninvasive treatment, maternal choline supplementation (MCS) attenuates cognitive decline in mouse models of DS and AD. To evaluate potential underlying mechanisms, laser capture microdissection of individual neuronal populations of MCS offspring was performed, followed by RNA sequencing and bioinformatic inquiry. Results at ~6 months of age (MO) revealed DS mice (the well-established Ts65Dn model) have significant dysregulation of select genes within the Type 2 Diabetes Mellitus (T2DM) signaling pathway relative to normal disomic (2N) littermates. Accordingly, we interrogated key T2DM protein hormones by ELISA assay in addition to gene and encoded protein levels in the brain. We found dysregulation of adiponectin (APN) protein levels in the frontal cortex of ~6 MO trisomic mice, which was attenuated by MCS. APN receptors also displayed expression level changes in response to MCS. APN is a potential biomarker for AD pathology and may be relevant in DS. We posit that changes in APN signaling may be an early marker of cognitive decline and neurodegeneration.
PMCID:8267749
PMID: 34279477
ISSN: 2077-0383
CID: 4947912
Neuropsychopharmacology reports. 2021:41(2):255-259.DOI: 10.1002/npr2.12174

Accelerated long-term forgetting is a BACE1 inhibitor-reversible incipient cognitive phenotype in Alzheimer's disease model mice

Ohno, Masuo
AIM/OBJECTIVE:After the continued failure of β-secretase (BACE1) inhibitor clinical trials in prodromal as well as mild-to-moderate Alzheimer's disease (AD), they are shifting to further earlier or asymptomatic stages. The aim of this study is to explore a cognitive paradigm that allows us to more sensitively detect beneficial effects of BACE1 inhibitors in presymptomatic AD. METHODS:GRL-8234 (33.4 mg/kg, ip), a small-molecule BACE1 inhibitor, was administered once daily for 28 days to the 5XAFD transgenic mouse model of AD. The contextual fear conditioning was used to evaluate the effects of GRL-8234 on memory deficits in 5XFAD mice at different ages. RESULTS:Chronic administration of GRL-8234 to 5XFAD mice rescued their contextual memory deficits, when tested 1 day after training at 6-8 months but not at 12 months of age. Importantly, 4-month-old 5XFAD mice retain the ability to form contextual memory equivalent to wild-type controls, demonstrating that the standard method of 1-day memory assessment is not suitable for evaluating BACE1 inhibitor efficacy in ameliorating cognitive declines during earlier disease stages. Despite normal contextual memory formation, young 5XFAD mice showed faster forgetting when a longer delay (28 days) intervened between training and memory testing. Notably, GRL-8234 administered to 4-month-old 5XFAD mice during the 28-day delay reversed accelerated long-term forgetting almost completely back to wild-type control levels. CONCLUSION/CONCLUSIONS:The results provide experimental evidence that accelerated long-term forgetting represents more sensitive memory testing that can help evaluate BACE1 inhibitor therapy in presymptomatic AD populations.
PMID: 33749160
ISSN: 2574-173x
CID: 4822282
Nature reviews. Disease primers. 2021:7(1).DOI: 10.1038/s41572-021-00269-y

Alzheimer disease

Knopman, David S; Amieva, Helene; Petersen, Ronald C; Chételat, Gäel; Holtzman, David M; Hyman, Bradley T; Nixon, Ralph A; Jones, David T
Alzheimer disease (AD) is biologically defined by the presence of β-amyloid-containing plaques and tau-containing neurofibrillary tangles. AD is a genetic and sporadic neurodegenerative disease that causes an amnestic cognitive impairment in its prototypical presentation and non-amnestic cognitive impairment in its less common variants. AD is a common cause of cognitive impairment acquired in midlife and late-life but its clinical impact is modified by other neurodegenerative and cerebrovascular conditions. This Primer conceives of AD biology as the brain disorder that results from a complex interplay of loss of synaptic homeostasis and dysfunction in the highly interrelated endosomal/lysosomal clearance pathways in which the precursors, aggregated species and post-translationally modified products of Aβ and tau play important roles. Therapeutic endeavours are still struggling to find targets within this framework that substantially change the clinical course in persons with AD.
PMID: 33986301
ISSN: 2056-676x
CID: 4889382
Hippocampus. 2021:31(5):522-539.DOI: 10.1002/hipo.23314

Dorsal and ventral mossy cells differ in their axonal projections throughout the dentate gyrus of the mouse hippocampus

Botterill, Justin J; Gerencer, Kathleen J; Vinod, K Yaragudri; Alcantara-Gonzalez, David; Scharfman, Helen E
Glutamatergic hilar mossy cells (MCs) have axons that terminate both near and far from their cell body but stay within the DG, making synapses primarily in the molecular layer. The long-range axons are considered the primary projection, and extend throughout the DG ipsilateral to the soma, and project to the contralateral DG. The specificity of MC axons for the inner molecular layer (IML) has been considered to be a key characteristic of the DG. In the present study, we made the surprising finding that dorsal MC axons are an exception to this rule. We used two mouse lines that allow for Cre-dependent viral labeling of MCs and their axons: dopamine receptor D2 (Drd2-Cre) and calcitonin receptor-like receptor (Crlr-Cre). A single viral injection into the dorsal DG to label dorsal MCs resulted in labeling of MC axons in both the IML and middle molecular layer (MML). Interestingly, this broad termination of dorsal MC axons occurred throughout the septotemporal DG. In contrast, long-range axons of ventral MCs terminated in the IML, consistent with the literature. Taken together, these results suggest that dorsal and ventral MCs differ significantly in their axonal projections. Since MC projections in the ML are thought to terminate primarily on GCs, the results suggest a dorsal-ventral difference in MC activation of GCs. The surprising difference in dorsal and ventral MC projections should therefore be considered when evaluating dorsal-ventral differences in DG function.
PMID: 33600026
ISSN: 1098-1063
CID: 4787032
Cell reports. 2021:35(4).DOI: 10.1016/j.celrep.2021.109034

Post-Golgi carriers, not lysosomes, confer lysosomal properties to pre-degradative organelles in normal and dystrophic axons

Lie, Pearl P Y; Yang, Dun-Sheng; Stavrides, Philip; Goulbourne, Chris N; Zheng, Ping; Mohan, Panaiyur S; Cataldo, Anne M; Nixon, Ralph A
Lysosomal trafficking and maturation in neurons remain poorly understood and are unstudied in vivo despite high disease relevance. We generated neuron-specific transgenic mice to track vesicular CTSD acquisition, acidification, and traffic within the autophagic-lysosomal pathway in vivo, revealing that mature lysosomes are restricted from axons. Moreover, TGN-derived transport carriers (TCs), not lysosomes, supply lysosomal components to axonal organelles. Ultrastructurally distinctive TCs containing TGN and lysosomal markers enter axons, engaging autophagic vacuoles and late endosomes. This process is markedly upregulated in dystrophic axons of Alzheimer models. In cultured neurons, most axonal LAMP1 vesicles are weakly acidic TCs that shuttle lysosomal components bidirectionally, conferring limited degradative capability to retrograde organelles before they mature fully to lysosomes within perikarya. The minor LAMP1 subpopulation attaining robust acidification are retrograde Rab7+ endosomes/amphisomes, not lysosomes. Restricted lysosome entry into axons explains the unique lysosome distribution in neurons and their vulnerability toward neuritic dystrophy in disease.
PMID: 33910020
ISSN: 2211-1247
CID: 4853382
Nature communications. 2021:12(1).DOI: 10.1038/s41467-021-22003-8

Cerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1

Zhang, Yalan; Varela, Luis; Szigeti-Buck, Klara; Williams, Adam; Stoiljkovic, Milan; Šestan-Peša, Matija; Henao-Mejia, Jorge; D'Acunzo, Pasquale; Levy, Efrat; Flavell, Richard A; Horvath, Tamas L; Kaczmarek, Leonard K
Mutations in KCNC3, which encodes the Kv3.3 potassium channel, cause degeneration of the cerebellum, but exactly how the activity of an ion channel is linked to the survival of cerebellar neurons is not understood. Here, we report that Kv3.3 channels bind and stimulate Tank Binding Kinase 1 (TBK1), an enzyme that controls trafficking of membrane proteins into multivesicular bodies, and that this stimulation is greatly increased by a disease-causing Kv3.3 mutation. TBK1 activity is required for the binding of Kv3.3 to its auxiliary subunit Hax-1, which prevents channel inactivation with depolarization. Hax-1 is also an anti-apoptotic protein required for survival of cerebellar neurons. Overactivation of TBK1 by the mutant channel leads to the loss of Hax-1 by its accumulation in multivesicular bodies and lysosomes, and also stimulates exosome release from neurons. This process is coupled to activation of caspases and increased cell death. Our studies indicate that Kv3.3 channels are directly coupled to TBK1-dependent biochemical pathways that determine the trafficking of cellular constituents and neuronal survival.
PMID: 33741962
ISSN: 2041-1723
CID: 4836162
Journal of neuroscience. 2021:41(11):2475-2495.DOI: 10.1523/JNEUROSCI.1724-20.2021

Bidirectional regulation of cognitive and anxiety-like behaviors by dentate gyrus mossy cells in male and female mice

Botterill, Justin J; Vinod, K Yaragudri; Gerencer, Kathleen J; Teixeira, Cátia M; LaFrancois, John J; Scharfman, Helen E
The dentate gyrus (DG) of the hippocampus is important for cognition and behavior. However, the circuits underlying these functions are unclear. DG mossy cells (MCs) are potentially important because of their excitatory synapses on the primary cell type, granule cells (GCs). However, MCs also activate GABAergic neurons which inhibit GCs. We used viral delivery of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in mice to implement a gain- and loss of function study of MCs in diverse behaviors. Using this approach, manipulations of MCs could bidirectionally regulate behavior. The results suggest that inhibiting MCs can reduce anxiety-like behavior and improve cognitive performance. However, not all cognitive or anxiety-related behaviors were influenced, suggesting specific roles of MCs in some but not all types of cognition and anxiety. Notably, several behaviors showed sex-specific effects, with females often showing more pronounced effects than the males. We also used the immediate early gene c-Fos to address whether DREADDs bidirectionally regulated MC or GC activity. We confirmed excitatory DREADDs increased MC c-Fos. However, there was no change in GC c-Fos, consistent with MC activation leading to GABAergic inhibition of GCs. In contrast, inhibitory DREADDs led to a large increase in GC c-Fos, consistent with a reduction in MC excitation of GABAergic neurons, and reduced inhibition of GCs. Taken together, these results suggest that MCs regulate anxiety and cognition in specific ways. We also raise the possibility that cognitive performance may be improved by reducing anxiety.SIGNIFICANCE STATEMENT: The dentate gyrus (DG) has many important cognitive roles as well as being associated with affective behavior. This study addressed how a glutamatergic DG cell type called mossy cells (MCs) contributes to diverse behaviors, which is timely because it is known that MCs regulate the activity of the primary DG cell type, granule cells (GCs), but how MC activity influences behavior is unclear. We show, surprisingly, that activating MCs can lead to adverse behavioral outcomes, and inhibiting MCs have an opposite effect. Importantly, the results appeared to be task-dependent and showed that testing both sexes was important. Additional experiments indicated what MC and GC circuitry was involved. Taken together, the results suggest how MCs influence behaviors that involve the DG.
PMID: 33472828
ISSN: 1529-2401
CID: 4760652
Autophagy. 2021:1-382.DOI: 10.1080/15548627.2020.1797280

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Klionsky, Daniel J; Abdel-Aziz, Amal Kamal; Abdelfatah, Sara; Abdellatif, Mahmoud; Abdoli, Asghar; Abel, Steffen; Abeliovich, Hagai; Abildgaard, Marie H; Abudu, Yakubu Princely; Acevedo-Arozena, Abraham; Adamopoulos, Iannis E; Adeli, Khosrow; Adolph, Timon E; Adornetto, Annagrazia; Aflaki, Elma; Agam, Galila; Agarwal, Anupam; Aggarwal, Bharat B; Agnello, Maria; Agostinis, Patrizia; Agrewala, Javed N; Agrotis, Alexander; Aguilar, Patricia V; Ahmad, S Tariq; Ahmed, Zubair M; Ahumada-Castro, Ulises; Aits, Sonja; Aizawa, Shu; Akkoc, Yunus; Akoumianaki, Tonia; Akpinar, Hafize Aysin; Al-Abd, Ahmed M; Al-Akra, Lina; Al-Gharaibeh, Abeer; Alaoui-Jamali, Moulay A; Alberti, Simon; Alcocer-Gómez, Elísabet; Alessandri, Cristiano; Ali, Muhammad; Alim Al-Bari, M Abdul; Aliwaini, Saeb; Alizadeh, Javad; Almacellas, Eugènia; Almasan, Alexandru; Alonso, Alicia; Alonso, Guillermo D; Altan-Bonnet, Nihal; Altieri, Dario C; Álvarez, Élida M C; Alves, Sara; Alves da Costa, Cristine; Alzaharna, Mazen M; Amadio, Marialaura; Amantini, Consuelo; Amaral, Cristina; Ambrosio, Susanna; Amer, Amal O; Ammanathan, Veena; An, Zhenyi; Andersen, Stig U; Andrabi, Shaida A; Andrade-Silva, Magaiver; Andres, Allen M; Angelini, Sabrina; Ann, David; Anozie, Uche C; Ansari, Mohammad Y; Antas, Pedro; Antebi, Adam; Antón, Zuriñe; Anwar, Tahira; Apetoh, Lionel; Apostolova, Nadezda; Araki, Toshiyuki; Araki, Yasuhiro; Arasaki, Kohei; Araújo, Wagner L; Araya, Jun; Arden, Catherine; Arévalo, Maria-Angeles; Arguelles, Sandro; Arias, Esperanza; Arikkath, Jyothi; Arimoto, Hirokazu; Ariosa, Aileen R; Armstrong-James, Darius; Arnauné-Pelloquin, Laetitia; Aroca, Angeles; Arroyo, Daniela S; Arsov, Ivica; Artero, Rubén; Asaro, Dalia Maria Lucia; Aschner, Michael; Ashrafizadeh, Milad; Ashur-Fabian, Osnat; Atanasov, Atanas G; Au, Alicia K; Auberger, Patrick; Auner, Holger W; Aurelian, Laure; Autelli, Riccardo; Avagliano, Laura; Ávalos, Yenniffer; Aveic, Sanja; Aveleira, Célia Alexandra; Avin-Wittenberg, Tamar; Aydin, Yucel; Ayton, Scott; Ayyadevara, Srinivas; Azzopardi, Maria; Baba, Misuzu; Backer, Jonathan M; Backues, Steven K; Bae, Dong-Hun; Bae, Ok-Nam; Bae, Soo Han; Baehrecke, Eric H; Baek, Ahruem; Baek, Seung-Hoon; Baek, Sung Hee; Bagetta, Giacinto; Bagniewska-Zadworna, Agnieszka; Bai, Hua; Bai, Jie; Bai, Xiyuan; Bai, Yidong; Bairagi, Nandadulal; Baksi, Shounak; Balbi, Teresa; Baldari, Cosima T; Balduini, Walter; Ballabio, Andrea; Ballester, Maria; Balazadeh, Salma; Balzan, Rena; Bandopadhyay, Rina; Banerjee, Sreeparna; Banerjee, Sulagna; Bánréti, Ágnes; Bao, Yan; Baptista, Mauricio S; Baracca, Alessandra; Barbati, Cristiana; Bargiela, Ariadna; Barilà, Daniela; Barlow, Peter G; Barmada, Sami J; Barreiro, Esther; Barreto, George E; Bartek, Jiri; Bartel, Bonnie; Bartolome, Alberto; Barve, Gaurav R; Basagoudanavar, Suresh H; Bassham, Diane C; Bast, Robert C; Basu, Alakananda; Batoko, Henri; Batten, Isabella; Baulieu, Etienne E; Baumgarner, Bradley L; Bayry, Jagadeesh; Beale, Rupert; Beau, Isabelle; Beaumatin, Florian; Bechara, Luiz R G; Beck, George R; Beers, Michael F; Begun, Jakob; Behrends, Christian; Behrens, Georg M N; Bei, Roberto; Bejarano, Eloy; Bel, Shai; Behl, Christian; Belaid, Amine; Belgareh-Touzé, Naïma; Bellarosa, Cristina; Belleudi, Francesca; Belló Pérez, Melissa; Bello-Morales, Raquel; Beltran, Jackeline Soares de Oliveira; Beltran, Sebastián; Benbrook, Doris Mangiaracina; Bendorius, Mykolas; Benitez, Bruno A; Benito-Cuesta, Irene; Bensalem, Julien; Berchtold, Martin W; Berezowska, Sabina; Bergamaschi, Daniele; Bergami, Matteo; Bergmann, Andreas; Berliocchi, Laura; Berlioz-Torrent, Clarisse; Bernard, Amélie; Berthoux, Lionel; Besirli, Cagri G; Besteiro, Sebastien; Betin, Virginie M; Beyaert, Rudi; Bezbradica, Jelena S; Bhaskar, Kiran; Bhatia-Kissova, Ingrid; Bhattacharya, Resham; Bhattacharya, Sujoy; Bhattacharyya, Shalmoli; Bhuiyan, Md Shenuarin; Bhutia, Sujit Kumar; Bi, Lanrong; Bi, Xiaolin; Biden, Trevor J; Bijian, Krikor; Billes, Viktor A; Binart, Nadine; Bincoletto, Claudia; Birgisdottir, Asa B; Bjorkoy, Geir; Blanco, Gonzalo; Blas-Garcia, Ana; Blasiak, Janusz; Blomgran, Robert; Blomgren, Klas; Blum, Janice S; Boada-Romero, Emilio; Boban, Mirta; Boesze-Battaglia, Kathleen; Boeuf, Philippe; Boland, Barry; Bomont, Pascale; Bonaldo, Paolo; Bonam, Srinivasa Reddy; Bonfili, Laura; Bonifacino, Juan S; Boone, Brian A; Bootman, Martin D; Bordi, Matteo; Borner, Christoph; Bornhauser, Beat C; Borthakur, Gautam; Bosch, Jürgen; Bose, Santanu; Botana, Luis M; Botas, Juan; Boulanger, Chantal M; Boulton, Michael E; Bourdenx, Mathieu; Bourgeois, Benjamin; Bourke, Nollaig M; Bousquet, Guilhem; Boya, Patricia; Bozhkov, Peter V; Bozi, Luiz H M; Bozkurt, Tolga O; Brackney, Doug E; Brandts, Christian H; Braun, Ralf J; Braus, Gerhard H; Bravo-Sagua, Roberto; Bravo-San Pedro, José M; Brest, Patrick; Bringer, Marie-Agnès; Briones-Herrera, Alfredo; Broaddus, V Courtney; Brodersen, Peter; Brodsky, Jeffrey L; Brody, Steven L; Bronson, Paola G; Bronstein, Jeff M; Brown, Carolyn N; Brown, Rhoderick E; Brum, Patricia C; Brumell, John H; Brunetti-Pierri, Nicola; Bruno, Daniele; Bryson-Richardson, Robert J; Bucci, Cecilia; Buchrieser, Carmen; Bueno, Marta; Buitrago-Molina, Laura Elisa; Buraschi, Simone; Buch, Shilpa; Buchan, J Ross; Buckingham, Erin M; Budak, Hikmet; Budini, Mauricio; Bultynck, Geert; Burada, Florin; Burgoyne, Joseph R; Burón, M Isabel; Bustos, Victor; Büttner, Sabrina; Butturini, Elena; Byrd, Aaron; Cabas, Isabel; Cabrera-Benitez, Sandra; Cadwell, Ken; Cai, Jingjing; Cai, Lu; Cai, Qian; Cairó, Montserrat; Calbet, Jose A; Caldwell, Guy A; Caldwell, Kim A; Call, Jarrod A; Calvani, Riccardo; Calvo, Ana C; Calvo-Rubio Barrera, Miguel; Camara, Niels Os; Camonis, Jacques H; Camougrand, Nadine; Campanella, Michelangelo; Campbell, Edward M; Campbell-Valois, François-Xavier; Campello, Silvia; Campesi, Ilaria; Campos, Juliane C; Camuzard, Olivier; Cancino, Jorge; Candido de Almeida, Danilo; Canesi, Laura; Caniggia, Isabella; Canonico, Barbara; Cantí, Carles; Cao, Bin; Caraglia, Michele; Caramés, Beatriz; Carchman, Evie H; Cardenal-Muñoz, Elena; Cardenas, Cesar; Cardenas, Luis; Cardoso, Sandra M; Carew, Jennifer S; Carle, Georges F; Carleton, Gillian; Carloni, Silvia; Carmona-Gutierrez, Didac; Carneiro, Leticia A; Carnevali, Oliana; Carosi, Julian M; Carra, Serena; Carrier, Alice; Carrier, Lucie; Carroll, Bernadette; Carter, A Brent; Carvalho, Andreia Neves; Casanova, Magali; Casas, Caty; Casas, Josefina; Cassioli, Chiara; Castillo, Eliseo F; Castillo, Karen; Castillo-Lluva, Sonia; Castoldi, Francesca; Castori, Marco; Castro, Ariel F; Castro-Caldas, Margarida; Castro-Hernandez, Javier; Castro-Obregon, Susana; Catz, Sergio D; Cavadas, Claudia; Cavaliere, Federica; Cavallini, Gabriella; Cavinato, Maria; Cayuela, Maria L; Cebollada Rica, Paula; Cecarini, Valentina; Cecconi, Francesco; Cechowska-Pasko, Marzanna; Cenci, Simone; Ceperuelo-Mallafré, Victòria; Cerqueira, João J; Cerutti, Janete M; Cervia, Davide; Cetintas, Vildan Bozok; Cetrullo, Silvia; Chae, Han-Jung; Chagin, Andrei S; Chai, Chee-Yin; Chakrabarti, Gopal; Chakrabarti, Oishee; Chakraborty, Tapas; Chakraborty, Trinad; Chami, Mounia; Chamilos, Georgios; Chan, David W; Chan, Edmond Y W; Chan, Edward D; Chan, H Y Edwin; Chan, Helen H; Chan, Hung; Chan, Matthew T V; Chan, Yau Sang; Chandra, Partha K; Chang, Chih-Peng; Chang, Chunmei; Chang, Hao-Chun; Chang, Kai; Chao, Jie; Chapman, Tracey; Charlet-Berguerand, Nicolas; Chatterjee, Samrat; Chaube, Shail K; Chaudhary, Anu; Chauhan, Santosh; Chaum, Edward; Checler, Frédéric; Cheetham, Michael E; Chen, Chang-Shi; Chen, Guang-Chao; Chen, Jian-Fu; Chen, Liam L; Chen, Leilei; Chen, Lin; Chen, Mingliang; Chen, Mu-Kuan; Chen, Ning; Chen, Quan; Chen, Ruey-Hwa; Chen, Shi; Chen, Wei; Chen, Weiqiang; Chen, Xin-Ming; Chen, Xiong-Wen; Chen, Xu; Chen, Yan; Chen, Ye-Guang; Chen, Yingyu; Chen, Yongqiang; Chen, Yu-Jen; Chen, Yue-Qin; Chen, Zhefan Stephen; Chen, Zhi; Chen, Zhi-Hua; Chen, Zhijian J; Chen, Zhixiang; Cheng, Hanhua; Cheng, Jun; Cheng, Shi-Yuan; Cheng, Wei; Cheng, Xiaodong; Cheng, Xiu-Tang; Cheng, Yiyun; Cheng, Zhiyong; Chen, Zhong; Cheong, Heesun; Cheong, Jit Kong; Chernyak, Boris V; Cherry, Sara; Cheung, Chi Fai Randy; Cheung, Chun Hei Antonio; Cheung, King-Ho; Chevet, Eric; Chi, Richard J; Chiang, Alan Kwok Shing; Chiaradonna, Ferdinando; Chiarelli, Roberto; Chiariello, Mario; Chica, Nathalia; Chiocca, Susanna; Chiong, Mario; Chiou, Shih-Hwa; Chiramel, Abhilash I; Chiurchiù, Valerio; Cho, Dong-Hyung; Choe, Seong-Kyu; Choi, Augustine M K; Choi, Mary E; Choudhury, Kamalika Roy; Chow, Norman S; Chu, Charleen T; Chua, Jason P; Chua, John Jia En; Chung, Hyewon; Chung, Kin Pan; Chung, Seockhoon; Chung, So-Hyang; Chung, Yuen-Li; Cianfanelli, Valentina; Ciechomska, Iwona A; Cifuentes, Mariana; Cinque, Laura; Cirak, Sebahattin; Cirone, Mara; Clague, Michael J; Clarke, Robert; Clementi, Emilio; Coccia, Eliana M; Codogno, Patrice; Cohen, Ehud; Cohen, Mickael M; Colasanti, Tania; Colasuonno, Fiorella; Colbert, Robert A; Colell, Anna; ÄŒolić, Miodrag; Coll, Nuria S; Collins, Mark O; Colombo, María I; Colón-Ramos, Daniel A; Combaret, Lydie; Comincini, Sergio; Cominetti, Márcia R; Consiglio, Antonella; Conte, Andrea; Conti, Fabrizio; Contu, Viorica Raluca; Cookson, Mark R; Coombs, Kevin M; Coppens, Isabelle; Corasaniti, Maria Tiziana; Corkery, Dale P; Cordes, Nils; Cortese, Katia; Costa, Maria do Carmo; Costantino, Sarah; Costelli, Paola; Coto-Montes, Ana; Crack, Peter J; Crespo, Jose L; Criollo, Alfredo; Crippa, Valeria; Cristofani, Riccardo; Csizmadia, Tamas; Cuadrado, Antonio; Cui, Bing; Cui, Jun; Cui, Yixian; Cui, Yong; Culetto, Emmanuel; Cumino, Andrea C; Cybulsky, Andrey V; Czaja, Mark J; Czuczwar, Stanislaw J; D'Adamo, Stefania; D'Amelio, Marcello; D'Arcangelo, Daniela; D'Lugos, Andrew C; D'Orazi, Gabriella; da Silva, James A; Dafsari, Hormos Salimi; Dagda, Ruben K; Dagdas, Yasin; Daglia, Maria; Dai, Xiaoxia; Dai, Yun; Dai, Yuyuan; Dal Col, Jessica; Dalhaimer, Paul; Dalla Valle, Luisa; Dallenga, Tobias; Dalmasso, Guillaume; Damme, Markus; Dando, Ilaria; Dantuma, Nico P; Darling, April L; Das, Hiranmoy; Dasarathy, Srinivasan; Dasari, Santosh K; Dash, Srikanta; Daumke, Oliver; Dauphinee, Adrian N; Davies, Jeffrey S; Dávila, Valeria A; Davis, Roger J; Davis, Tanja; Dayalan Naidu, Sharadha; De Amicis, Francesca; De Bosscher, Karolien; De Felice, Francesca; De Franceschi, Lucia; De Leonibus, Chiara; de Mattos Barbosa, Mayara G; De Meyer, Guido R Y; De Milito, Angelo; De Nunzio, Cosimo; De Palma, Clara; De Santi, Mauro; De Virgilio, Claudio; De Zio, Daniela; Debnath, Jayanta; DeBosch, Brian J; Decuypere, Jean-Paul; Deehan, Mark A; Deflorian, Gianluca; DeGregori, James; Dehay, Benjamin; Del Rio, Gabriel; Delaney, Joe R; Delbridge, Lea M D; Delorme-Axford, Elizabeth; Delpino, M Victoria; Demarchi, Francesca; Dembitz, Vilma; Demers, Nicholas D; Deng, Hongbin; Deng, Zhiqiang; Dengjel, Joern; Dent, Paul; Denton, Donna; DePamphilis, Melvin L; Der, Channing J; Deretic, Vojo; Descoteaux, Albert; Devis, Laura; Devkota, Sushil; Devuyst, Olivier; Dewson, Grant; Dharmasivam, Mahendiran; Dhiman, Rohan; di Bernardo, Diego; Di Cristina, Manlio; Di Domenico, Fabio; Di Fazio, Pietro; Di Fonzo, Alessio; Di Guardo, Giovanni; Di Guglielmo, Gianni M; Di Leo, Luca; Di Malta, Chiara; Di Nardo, Alessia; Di Rienzo, Martina; Di Sano, Federica; Diallinas, George; Diao, Jiajie; Diaz-Araya, Guillermo; Díaz-Laviada, Inés; Dickinson, Jared M; Diederich, Marc; Dieudé, Mélanie; Dikic, Ivan; Ding, Shiping; Ding, Wen-Xing; Dini, Luciana; Dinić, Jelena; Dinic, Miroslav; Dinkova-Kostova, Albena T; Dionne, Marc S; Distler, Jörg H W; Diwan, Abhinav; Dixon, Ian M C; Djavaheri-Mergny, Mojgan; Dobrinski, Ina; Dobrovinskaya, Oxana; Dobrowolski, Radek; Dobson, Renwick C J; Đokić, Jelena; Dokmeci Emre, Serap; Donadelli, Massimo; Dong, Bo; Dong, Xiaonan; Dong, Zhiwu; Dorn Ii, Gerald W; Dotsch, Volker; Dou, Huan; Dou, Juan; Dowaidar, Moataz; Dridi, Sami; Drucker, Liat; Du, Ailian; Du, Caigan; Du, Guangwei; Du, Hai-Ning; Du, Li-Lin; du Toit, André; Duan, Shao-Bin; Duan, Xiaoqiong; Duarte, Sónia P; Dubrovska, Anna; Dunlop, Elaine A; Dupont, Nicolas; Durán, Raúl V; Dwarakanath, Bilikere S; Dyshlovoy, Sergey A; Ebrahimi-Fakhari, Darius; Eckhart, Leopold; Edelstein, Charles L; Efferth, Thomas; Eftekharpour, Eftekhar; Eichinger, Ludwig; Eid, Nabil; Eisenberg, Tobias; Eissa, N Tony; Eissa, Sanaa; Ejarque, Miriam; El Andaloussi, Abdeljabar; El-Hage, Nazira; El-Naggar, Shahenda; Eleuteri, Anna Maria; El-Shafey, Eman S; Elgendy, Mohamed; Eliopoulos, Aristides G; Elizalde, María M; Elks, Philip M; Elsasser, Hans-Peter; Elsherbiny, Eslam S; Emerling, Brooke M; Emre, N C Tolga; Eng, Christina H; Engedal, Nikolai; Engelbrecht, Anna-Mart; Engelsen, Agnete S T; Enserink, Jorrit M; Escalante, Ricardo; Esclatine, Audrey; Escobar-Henriques, Mafalda; Eskelinen, Eeva-Liisa; Espert, Lucile; Eusebio, Makandjou-Ola; Fabrias, Gemma; Fabrizi, Cinzia; Facchiano, Antonio; Facchiano, Francesco; Fadeel, Bengt; Fader, Claudio; Faesen, Alex C; Fairlie, W Douglas; Falcó, Alberto; Falkenburger, Bjorn H; Fan, Daping; Fan, Jie; Fan, Yanbo; Fang, Evandro F; Fang, Yanshan; Fang, Yognqi; Fanto, Manolis; Farfel-Becker, Tamar; Faure, Mathias; Fazeli, Gholamreza; Fedele, Anthony O; Feldman, Arthur M; Feng, Du; Feng, Jiachun; Feng, Lifeng; Feng, Yibin; Feng, Yuchen; Feng, Wei; Fenz Araujo, Thais; Ferguson, Thomas A; Fernández, Álvaro F; Fernandez-Checa, Jose C; Fernández-Veledo, Sonia; Fernie, Alisdair R; Ferrante, Anthony W; Ferraresi, Alessandra; Ferrari, Merari F; Ferreira, Julio C B; Ferro-Novick, Susan; Figueras, Antonio; Filadi, Riccardo; Filigheddu, Nicoletta; Filippi-Chiela, Eduardo; Filomeni, Giuseppe; Fimia, Gian Maria; Fineschi, Vittorio; Finetti, Francesca; Finkbeiner, Steven; Fisher, Edward A; Fisher, Paul B; Flamigni, Flavio; Fliesler, Steven J; Flo, Trude H; Florance, Ida; Florey, Oliver; Florio, Tullio; Fodor, Erika; Follo, Carlo; Fon, Edward A; Forlino, Antonella; Fornai, Francesco; Fortini, Paola; Fracassi, Anna; Fraldi, Alessandro; Franco, Brunella; Franco, Rodrigo; Franconi, Flavia; Frankel, Lisa B; Friedman, Scott L; Fröhlich, Leopold F; Frühbeck, Gema; Fuentes, Jose M; Fujiki, Yukio; Fujita, Naonobu; Fujiwara, Yuuki; Fukuda, Mitsunori; Fulda, Simone; Furic, Luc; Furuya, Norihiko; Fusco, Carmela; Gack, Michaela U; Gaffke, Lidia; Galadari, Sehamuddin; Galasso, Alessia; Galindo, Maria F; Gallolu Kankanamalage, Sachith; Galluzzi, Lorenzo; Galy, Vincent; Gammoh, Noor; Gan, Boyi; Ganley, Ian G; Gao, Feng; Gao, Hui; Gao, Minghui; Gao, Ping; Gao, Shou-Jiang; Gao, Wentao; Gao, Xiaobo; Garcera, Ana; Garcia, Maria Noé; Garcia, Verónica E; García-Del Portillo, Francisco; Garcia-Escudero, Vega; Garcia-Garcia, Aracely; Garcia-Macia, Marina; García-Moreno, Diana; Garcia-Ruiz, Carmen; García-Sanz, Patricia; Garg, Abhishek D; Gargini, Ricardo; Garofalo, Tina; Garry, Robert F; Gassen, Nils C; Gatica, Damian; Ge, Liang; Ge, Wanzhong; Geiss-Friedlander, Ruth; Gelfi, Cecilia; Genschik, Pascal; Gentle, Ian E; Gerbino, Valeria; Gerhardt, Christoph; Germain, Kyla; Germain, Marc; Gewirtz, David A; Ghasemipour Afshar, Elham; Ghavami, Saeid; Ghigo, Alessandra; Ghosh, Manosij; Giamas, Georgios; Giampietri, Claudia; Giatromanolaki, Alexandra; Gibson, Gary E; Gibson, Spencer B; Ginet, Vanessa; Giniger, Edward; Giorgi, Carlotta; Girao, Henrique; Girardin, Stephen E; Giridharan, Mridhula; Giuliano, Sandy; Giulivi, Cecilia; Giuriato, Sylvie; Giustiniani, Julien; Gluschko, Alexander; Goder, Veit; Goginashvili, Alexander; Golab, Jakub; Goldstone, David C; Golebiewska, Anna; Gomes, Luciana R; Gomez, Rodrigo; Gómez-Sánchez, Rubén; Gomez-Puerto, Maria Catalina; Gomez-Sintes, Raquel; Gong, Qingqiu; Goni, Felix M; González-Gallego, Javier; Gonzalez-Hernandez, Tomas; Gonzalez-Polo, Rosa A; Gonzalez-Reyes, Jose A; González-Rodríguez, Patricia; Goping, Ing Swie; Gorbatyuk, Marina S; Gorbunov, Nikolai V; Görgülü, Kıvanç; Gorojod, Roxana M; Gorski, Sharon M; Goruppi, Sandro; Gotor, Cecilia; Gottlieb, Roberta A; Gozes, Illana; Gozuacik, Devrim; Graef, Martin; Gräler, Markus H; Granatiero, Veronica; Grasso, Daniel; Gray, Joshua P; Green, Douglas R; Greenhough, Alexander; Gregory, Stephen L; Griffin, Edward F; Grinstaff, Mark W; Gros, Frederic; Grose, Charles; Gross, Angelina S; Gruber, Florian; Grumati, Paolo; Grune, Tilman; Gu, Xueyan; Guan, Jun-Lin; Guardia, Carlos M; Guda, Kishore; Guerra, Flora; Guerri, Consuelo; Guha, Prasun; Guillén, Carlos; Gujar, Shashi; Gukovskaya, Anna; Gukovsky, Ilya; Gunst, Jan; Günther, Andreas; Guntur, Anyonya R; Guo, Chuanyong; Guo, Chun; Guo, Hongqing; Guo, Lian-Wang; Guo, Ming; Gupta, Pawan; Gupta, Shashi Kumar; Gupta, Swapnil; Gupta, Veer Bala; Gupta, Vivek; Gustafsson, Asa B; Gutterman, David D; H B, Ranjitha; Haapasalo, Annakaisa; Haber, James E; Hać, Aleksandra; Hadano, Shinji; Hafrén, Anders J; Haidar, Mansour; Hall, Belinda S; Halldén, Gunnel; Hamacher-Brady, Anne; Hamann, Andrea; Hamasaki, Maho; Han, Weidong; Hansen, Malene; Hanson, Phyllis I; Hao, Zijian; Harada, Masaru; Harhaji-Trajkovic, Ljubica; Hariharan, Nirmala; Haroon, Nigil; Harris, James; Hasegawa, Takafumi; Hasima Nagoor, Noor; Haspel, Jeffrey A; Haucke, Volker; Hawkins, Wayne D; Hay, Bruce A; Haynes, Cole M; Hayrabedyan, Soren B; Hays, Thomas S; He, Congcong; He, Qin; He, Rong-Rong; He, You-Wen; He, Yu-Ying; Heakal, Yasser; Heberle, Alexander M; Hejtmancik, J Fielding; Helgason, Gudmundur Vignir; Henkel, Vanessa; Herb, Marc; Hergovich, Alexander; Herman-Antosiewicz, Anna; Hernández, Agustín; Hernandez, Carlos; Hernandez-Diaz, Sergio; Hernandez-Gea, Virginia; Herpin, Amaury; Herreros, Judit; Hervás, Javier H; Hesselson, Daniel; Hetz, Claudio; Heussler, Volker T; Higuchi, Yujiro; Hilfiker, Sabine; Hill, Joseph A; Hlavacek, William S; Ho, Emmanuel A; Ho, Idy H T; Ho, Philip Wing-Lok; Ho, Shu-Leong; Ho, Wan Yun; Hobbs, G Aaron; Hochstrasser, Mark; Hoet, Peter H M; Hofius, Daniel; Hofman, Paul; Höhn, Annika; Holmberg, Carina I; Hombrebueno, Jose R; Yi-Ren Hong, Chang-Won Hong; Hooper, Lora V; Hoppe, Thorsten; Horos, Rastislav; Hoshida, Yujin; Hsin, I-Lun; Hsu, Hsin-Yun; Hu, Bing; Hu, Dong; Hu, Li-Fang; Hu, Ming Chang; Hu, Ronggui; Hu, Wei; Hu, Yu-Chen; Hu, Zhuo-Wei; Hua, Fang; Hua, Jinlian; Hua, Yingqi; Huan, Chongmin; Huang, Canhua; Huang, Chuanshu; Huang, Chuanxin; Huang, Chunling; Huang, Haishan; Huang, Kun; Huang, Michael L H; Huang, Rui; Huang, Shan; Huang, Tianzhi; Huang, Xing; Huang, Yuxiang Jack; Huber, Tobias B; Hubert, Virginie; Hubner, Christian A; Hughes, Stephanie M; Hughes, William E; Humbert, Magali; Hummer, Gerhard; Hurley, James H; Hussain, Sabah; Hussain, Salik; Hussey, Patrick J; Hutabarat, Martina; Hwang, Hui-Yun; Hwang, Seungmin; Ieni, Antonio; Ikeda, Fumiyo; Imagawa, Yusuke; Imai, Yuzuru; Imbriano, Carol; Imoto, Masaya; Inman, Denise M; Inoki, Ken; Iovanna, Juan; Iozzo, Renato V; Ippolito, Giuseppe; Irazoqui, Javier E; Iribarren, Pablo; Ishaq, Mohd; Ishikawa, Makoto; Ishimwe, Nestor; Isidoro, Ciro; Ismail, Nahed; Issazadeh-Navikas, Shohreh; Itakura, Eisuke; Ito, Daisuke; Ivankovic, Davor; Ivanova, SaÅ¡ka; Iyer, Anand Krishnan V; Izquierdo, José M; Izumi, Masanori; Jäättelä, Marja; Jabir, Majid Sakhi; Jackson, William T; Jacobo-Herrera, Nadia; Jacomin, Anne-Claire; Jacquin, Elise; Jadiya, Pooja; Jaeschke, Hartmut; Jagannath, Chinnaswamy; Jakobi, Arjen J; Jakobsson, Johan; Janji, Bassam; Jansen-Dürr, Pidder; Jansson, Patric J; Jantsch, Jonathan; Januszewski, SÅ‚awomir; Jassey, Alagie; Jean, Steve; Jeltsch-David, Hélène; Jendelova, Pavla; Jenny, Andreas; Jensen, Thomas E; Jessen, Niels; Jewell, Jenna L; Ji, Jing; Jia, Lijun; Jia, Rui; Jiang, Liwen; Jiang, Qing; Jiang, Richeng; Jiang, Teng; Jiang, Xuejun; Jiang, Yu; Jimenez-Sanchez, Maria; Jin, Eun-Jung; Jin, Fengyan; Jin, Hongchuan; Jin, Li; Jin, Luqi; Jin, Meiyan; Jin, Si; Jo, Eun-Kyeong; Joffre, Carine; Johansen, Terje; Johnson, Gail V W; Johnston, Simon A; Jokitalo, Eija; Jolly, Mohit Kumar; Joosten, Leo A B; Jordan, Joaquin; Joseph, Bertrand; Ju, Dianwen; Ju, Jeong-Sun; Ju, Jingfang; Juárez, Esmeralda; Judith, Delphine; Juhász, Gábor; Jun, Youngsoo; Jung, Chang Hwa; Jung, Sung-Chul; Jung, Yong Keun; Jungbluth, Heinz; Jungverdorben, Johannes; Just, Steffen; Kaarniranta, Kai; Kaasik, Allen; Kabuta, Tomohiro; Kaganovich, Daniel; Kahana, Alon; Kain, Renate; Kajimura, Shinjo; Kalamvoki, Maria; Kalia, Manjula; Kalinowski, Danuta S; Kaludercic, Nina; Kalvari, Ioanna; Kaminska, Joanna; Kaminskyy, Vitaliy O; Kanamori, Hiromitsu; Kanasaki, Keizo; Kang, Chanhee; Kang, Rui; Kang, Sang Sun; Kaniyappan, Senthilvelrajan; Kanki, Tomotake; Kanneganti, Thirumala-Devi; Kanthasamy, Anumantha G; Kanthasamy, Arthi; Kantorow, Marc; Kapuy, Orsolya; Karamouzis, Michalis V; Karim, Md Razaul; Karmakar, Parimal; Katare, Rajesh G; Kato, Masaru; Kaufmann, Stefan H E; Kauppinen, Anu; Kaushal, Gur P; Kaushik, Susmita; Kawasaki, Kiyoshi; Kazan, Kemal; Ke, Po-Yuan; Keating, Damien J; Keber, Ursula; Kehrl, John H; Keller, Kate E; Keller, Christian W; Kemper, Jongsook Kim; Kenific, Candia M; Kepp, Oliver; Kermorgant, Stephanie; Kern, Andreas; Ketteler, Robin; Keulers, Tom G; Khalfin, Boris; Khalil, Hany; Khambu, Bilon; Khan, Shahid Y; Khandelwal, Vinoth Kumar Megraj; Khandia, Rekha; Kho, Widuri; Khobrekar, Noopur V; Khuansuwan, Sataree; Khundadze, Mukhran; Killackey, Samuel A; Kim, Dasol; Kim, Deok Ryong; Kim, Do-Hyung; Kim, Dong-Eun; Kim, Eun Young; Kim, Eun-Kyoung; Kim, Hak-Rim; Kim, Hee-Sik; Kim, Jeong Hun; Kim, Jin Kyung; Kim, Jin-Hoi; Kim, Joungmok; Kim, Ju Hwan; Kim, Keun Il; Kim, Peter K; Kim, Seong-Jun; Kimball, Scot R; Kimchi, Adi; Kimmelman, Alec C; Kimura, Tomonori; King, Matthew A; Kinghorn, Kerri J; Kinsey, Conan G; Kirkin, Vladimir; Kirshenbaum, Lorrie A; Kiselev, Sergey L; Kishi, Shuji; Kitamoto, Katsuhiko; Kitaoka, Yasushi; Kitazato, Kaio; Kitsis, Richard N; Kittler, Josef T; Kjaerulff, Ole; Klein, Peter S; Klopstock, Thomas; Klucken, Jochen; Knævelsrud, Helene; Knorr, Roland L; Ko, Ben C B; Ko, Fred; Ko, Jiunn-Liang; Kobayashi, Hotaka; Kobayashi, Satoru; Koch, Ina; Koch, Jan C; Koenig, Ulrich; Kögel, Donat; Koh, Young Ho; Koike, Masato; Kohlwein, Sepp D; Kocaturk, Nur M; Komatsu, Masaaki; König, Jeannette; Kono, Toru; Kopp, Benjamin T; Korcsmaros, Tamas; Korkmaz, Gözde; Korolchuk, Viktor I; Korsnes, Mónica Suárez; Koskela, Ali; Kota, Janaiah; Kotake, Yaichiro; Kotler, Monica L; Kou, Yanjun; Koukourakis, Michael I; Koustas, Evangelos; Kovacs, Attila L; Kovács, Tibor; Koya, Daisuke; Kozako, Tomohiro; Kraft, Claudine; Krainc, Dimitri; Krämer, Helmut; Krasnodembskaya, Anna D; Kretz-Remy, Carole; Kroemer, Guido; Ktistakis, Nicholas T; Kuchitsu, Kazuyuki; Kuenen, Sabine; Kuerschner, Lars; Kukar, Thomas; Kumar, Ajay; Kumar, Ashok; Kumar, Deepak; Kumar, Dhiraj; Kumar, Sharad; Kume, Shinji; Kumsta, Caroline; Kundu, Chanakya N; Kundu, Mondira; Kunnumakkara, Ajaikumar B; Kurgan, Lukasz; Kutateladze, Tatiana G; Kutlu, Ozlem; Kwak, SeongAe; Kwon, Ho Jeong; Kwon, Taeg Kyu; Kwon, Yong Tae; Kyrmizi, Irene; La Spada, Albert; Labonté, Patrick; Ladoire, Sylvain; Laface, Ilaria; Lafont, Frank; Lagace, Diane C; Lahiri, Vikramjit; Lai, Zhibing; Laird, Angela S; Lakkaraju, Aparna; Lamark, Trond; Lan, Sheng-Hui; Landajuela, Ane; Lane, Darius J R; Lane, Jon D; Lang, Charles H; Lange, Carsten; Langel, Ãœlo; Langer, Rupert; Lapaquette, Pierre; Laporte, Jocelyn; LaRusso, Nicholas F; Lastres-Becker, Isabel; Lau, Wilson Chun Yu; Laurie, Gordon W; Lavandero, Sergio; Law, Betty Yuen Kwan; Law, Helen Ka-Wai; Layfield, Rob; Le, Weidong; Le Stunff, Herve; Leary, Alexandre Y; Lebrun, Jean-Jacques; Leck, Lionel Y W; Leduc-Gaudet, Jean-Philippe; Lee, Changwook; Lee, Chung-Pei; Lee, Da-Hye; Lee, Edward B; Lee, Erinna F; Lee, Gyun Min; Lee, He-Jin; Lee, Heung Kyu; Lee, Jae Man; Lee, Jason S; Lee, Jin-A; Lee, Joo-Yong; Lee, Jun Hee; Lee, Michael; Lee, Min Goo; Lee, Min Jae; Lee, Myung-Shik; Lee, Sang Yoon; Lee, Seung-Jae; Lee, Stella Y; Lee, Sung Bae; Lee, Won Hee; Lee, Ying-Ray; Lee, Yong-Ho; Lee, Youngil; Lefebvre, Christophe; Legouis, Renaud; Lei, Yu L; Lei, Yuchen; Leikin, Sergey; Leitinger, Gerd; Lemus, Leticia; Leng, Shuilong; Lenoir, Olivia; Lenz, Guido; Lenz, Heinz Josef; Lenzi, Paola; León, Yolanda; Leopoldino, Andréia M; Leschczyk, Christoph; Leskelä, Stina; Letellier, Elisabeth; Leung, Chi-Ting; Leung, Po Sing; Leventhal, Jeremy S; Levine, Beth; Lewis, Patrick A; Ley, Klaus; Li, Bin; Li, Da-Qiang; Li, Jianming; Li, Jing; Li, Jiong; Li, Ke; Li, Liwu; Li, Mei; Li, Min; Li, Min; Li, Ming; Li, Mingchuan; Li, Pin-Lan; Li, Ming-Qing; Li, Qing; Li, Sheng; Li, Tiangang; Li, Wei; Li, Wenming; Li, Xue; Li, Yi-Ping; Li, Yuan; Li, Zhiqiang; Li, Zhiyong; Li, Zhiyuan; Lian, Jiqin; Liang, Chengyu; Liang, Qiangrong; Liang, Weicheng; Liang, Yongheng; Liang, YongTian; Liao, Guanghong; Liao, Lujian; Liao, Mingzhi; Liao, Yung-Feng; Librizzi, Mariangela; Lie, Pearl P Y; Lilly, Mary A; Lim, Hyunjung J; Lima, Thania R R; Limana, Federica; Lin, Chao; Lin, Chih-Wen; Lin, Dar-Shong; Lin, Fu-Cheng; Lin, Jiandie D; Lin, Kurt M; Lin, Kwang-Huei; Lin, Liang-Tzung; Lin, Pei-Hui; Lin, Qiong; Lin, Shaofeng; Lin, Su-Ju; Lin, Wenyu; Lin, Xueying; Lin, Yao-Xin; Lin, Yee-Shin; Linden, Rafael; Lindner, Paula; Ling, Shuo-Chien; Lingor, Paul; Linnemann, Amelia K; Liou, Yih-Cherng; Lipinski, Marta M; LipovÅ¡ek, SaÅ¡ka; Lira, Vitor A; Lisiak, Natalia; Liton, Paloma B; Liu, Chao; Liu, Ching-Hsuan; Liu, Chun-Feng; Liu, Cui Hua; Liu, Fang; Liu, Hao; Liu, Hsiao-Sheng; Liu, Hua-Feng; Liu, Huifang; Liu, Jia; Liu, Jing; Liu, Julia; Liu, Leyuan; Liu, Longhua; Liu, Meilian; Liu, Qin; Liu, Wei; Liu, Wende; Liu, Xiao-Hong; Liu, Xiaodong; Liu, Xingguo; Liu, Xu; Liu, Xuedong; Liu, Yanfen; Liu, Yang; Liu, Yang; Liu, Yueyang; Liu, Yule; Livingston, J Andrew; Lizard, Gerard; Lizcano, Jose M; Ljubojevic-Holzer, Senka; LLeonart, Matilde E; Llobet-Navàs, David; Llorente, Alicia; Lo, Chih Hung; Lobato-Márquez, Damián; Long, Qi; Long, Yun Chau; Loos, Ben; Loos, Julia A; López, Manuela G; López-Doménech, Guillermo; López-Guerrero, José Antonio; López-Jiménez, Ana T; López-Pérez, Óscar; López-Valero, Israel; Lorenowicz, Magdalena J; Lorente, Mar; Lorincz, Peter; Lossi, Laura; Lotersztajn, Sophie; Lovat, Penny E; Lovell, Jonathan F; Lovy, Alenka; LÅ‘w, Péter; Lu, Guang; Lu, Haocheng; Lu, Jia-Hong; Lu, Jin-Jian; Lu, Mengji; Lu, Shuyan; Luciani, Alessandro; Lucocq, John M; Ludovico, Paula; Luftig, Micah A; Luhr, Morten; Luis-Ravelo, Diego; Lum, Julian J; Luna-Dulcey, Liany; Lund, Anders H; Lund, Viktor K; Lünemann, Jan D; Lüningschrör, Patrick; Luo, Honglin; Luo, Rongcan; Luo, Shouqing; Luo, Zhi; Luparello, Claudio; Lüscher, Bernhard; Luu, Luan; Lyakhovich, Alex; Lyamzaev, Konstantin G; Lystad, Alf HÃ¥kon; Lytvynchuk, Lyubomyr; Ma, Alvin C; Ma, Changle; Ma, Mengxiao; Ma, Ning-Fang; Ma, Quan-Hong; Ma, Xinliang; Ma, Yueyun; Ma, Zhenyi; MacDougald, Ormond A; Macian, Fernando; MacIntosh, Gustavo C; MacKeigan, Jeffrey P; Macleod, Kay F; Maday, Sandra; Madeo, Frank; Madesh, Muniswamy; Madl, Tobias; Madrigal-Matute, Julio; Maeda, Akiko; Maejima, Yasuhiro; Magarinos, Marta; Mahavadi, Poornima; Maiani, Emiliano; Maiese, Kenneth; Maiti, Panchanan; Maiuri, Maria Chiara; Majello, Barbara; Major, Michael B; Makareeva, Elena; Malik, Fayaz; Mallilankaraman, Karthik; Malorni, Walter; Maloyan, Alina; Mammadova, Najiba; Man, Gene Chi Wai; Manai, Federico; Mancias, Joseph D; Mandelkow, Eva-Maria; Mandell, Michael A; Manfredi, Angelo A; Manjili, Masoud H; Manjithaya, Ravi; Manque, Patricio; Manshian, Bella B; Manzano, Raquel; Manzoni, Claudia; Mao, Kai; Marchese, Cinzia; Marchetti, Sandrine; Marconi, Anna Maria; Marcucci, Fabrizio; Mardente, Stefania; Mareninova, Olga A; Margeta, Marta; Mari, Muriel; Marinelli, Sara; Marinelli, Oliviero; Mariño, Guillermo; Mariotto, Sofia; Marshall, Richard S; Marten, Mark R; Martens, Sascha; Martin, Alexandre P J; Martin, Katie R; Martin, Sara; Martin, Shaun; Martín-Segura, Adrián; Martín-Acebes, Miguel A; Martin-Burriel, Inmaculada; Martin-Rincon, Marcos; Martin-Sanz, Paloma; Martina, José A; Martinet, Wim; Martinez, Aitor; Martinez, Ana; Martinez, Jennifer; Martinez Velazquez, Moises; Martinez-Lopez, Nuria; Martinez-Vicente, Marta; Martins, Daniel O; Martins, Joilson O; Martins, Waleska K; Martins-Marques, Tania; Marzetti, Emanuele; Masaldan, Shashank; Masclaux-Daubresse, Celine; Mashek, Douglas G; Massa, Valentina; Massieu, Lourdes; Masson, Glenn R; Masuelli, Laura; Masyuk, Anatoliy I; Masyuk, Tetyana V; Matarrese, Paola; Matheu, Ander; Matoba, Satoaki; Matsuzaki, Sachiko; Mattar, Pamela; Matte, Alessandro; Mattoscio, Domenico; Mauriz, José L; Mauthe, Mario; Mauvezin, Caroline; Maverakis, Emanual; Maycotte, Paola; Mayer, Johanna; Mazzoccoli, Gianluigi; Mazzoni, Cristina; Mazzulli, Joseph R; McCarty, Nami; McDonald, Christine; McGill, Mitchell R; McKenna, Sharon L; McLaughlin, BethAnn; McLoughlin, Fionn; McNiven, Mark A; McWilliams, Thomas G; Mechta-Grigoriou, Fatima; Medeiros, Tania Catarina; Medina, Diego L; Megeney, Lynn A; Megyeri, Klara; Mehrpour, Maryam; Mehta, Jawahar L; Meijer, Alfred J; Meijer, Annemarie H; Mejlvang, Jakob; Meléndez, Alicia; Melk, Annette; Memisoglu, Gonen; Mendes, Alexandrina F; Meng, Delong; Meng, Fei; Meng, Tian; Menna-Barreto, Rubem; Menon, Manoj B; Mercer, Carol; Mercier, Anne E; Mergny, Jean-Louis; 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In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
PMID: 33634751
ISSN: 1554-8635
CID: 4800842
Science advances. 2021:7(7).DOI: 10.1126/sciadv.abe5085

Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome

D'Acunzo, Pasquale; Pérez-González, Rocío; Kim, Yohan; Hargash, Tal; Miller, Chelsea; Alldred, Melissa J; Erdjument-Bromage, Hediye; Penikalapati, Sai C; Pawlik, Monika; Saito, Mitsuo; Saito, Mariko; Ginsberg, Stephen D; Neubert, Thomas A; Goulbourne, Chris N; Levy, Efrat
Mitochondrial dysfunction is an established hallmark of aging and neurodegenerative disorders such as Down syndrome (DS) and Alzheimer's disease (AD). Using a high-resolution density gradient separation of extracellular vesicles (EVs) isolated from murine and human DS and diploid control brains, we identify and characterize a previously unknown population of double-membraned EVs containing multiple mitochondrial proteins distinct from previously described EV subtypes, including microvesicles and exosomes. We term these newly identified mitochondria-derived EVs "mitovesicles." We demonstrate that brain-derived mitovesicles contain a specific subset of mitochondrial constituents and that their levels and cargo are altered during pathophysiological processes where mitochondrial dysfunction occurs, including in DS. The development of a method for the selective isolation of mitovesicles paves the way for the characterization in vivo of biological processes connecting EV biology and mitochondria dynamics and for innovative therapeutic and diagnostic strategies.
PMID: 33579698
ISSN: 2375-2548
CID: 4786222