321 results on '"Roach PJ"'
Search Results
2. Quantative presurgical lung function estimation with SPECT/CT
- Author
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Timmins, S, Bailey, EA, Willowson, KP, Roach, PJ, Harris, BE, and Bailey, DL
- Published
- 2009
3. RESULTS OF AN AUSTRALIAN AND NEW ZEALAND AUDIT OF LEFT VENTRICULAR EJECTION FRACTION USING A VALIDATED DATASET: 208
- Author
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Bailey, EA, Bailey, DL, and Roach, PJ
- Published
- 2010
4. A Prevalent Variant inPPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice
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Savage, DB, Zhai, L, Ravikumar, B, Choi, CS, Snaar, JE, McGuire, AC, Wou, SE, Medina-Gomez, G, Kim, S, Bock, CB, Segvich, DM, Solanky, B, Deelchand, D, Vidal-Puig, A, Wareham, NJ, Shulman, GI, Karpe, F, Taylor, R, Pederson, BA, Roach, PJ, O'Rahilly, S, and DePaoli-Roach, AA
- Subjects
Male ,lcsh:Medicine ,medicine.disease_cause ,Biochemistry ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Endocrinology ,Gene Frequency ,Phosphoprotein Phosphatases ,Frameshift Mutation ,0303 health sciences ,Mutation ,education.field_of_study ,Glycogen ,Glycogen Phosphorylase ,Diabetes ,General Medicine ,Middle Aged ,16. Peace & justice ,Postprandial Period ,Diabetes and Endocrinology ,medicine.anatomical_structure ,Glycogen Synthase ,Codon, Nonsense ,Female ,Perspectives ,Adult ,medicine.medical_specialty ,Population ,Molecular Sequence Data ,030209 endocrinology & metabolism ,Mice, Transgenic ,Biology ,White People ,Frameshift mutation ,Glycogen debranching enzyme ,03 medical and health sciences ,Glycogen phosphorylase ,Structure-Activity Relationship ,Internal medicine ,medicine ,Animals ,Humans ,education ,Glycogen synthase ,Muscle, Skeletal ,030304 developmental biology ,lcsh:R ,Skeletal muscle ,United Kingdom ,chemistry ,Diabetes Mellitus, Type 2 ,biology.protein - Abstract
Background: Stored glycogen is an important source of energy for skeletal muscle. Human genetic disorders primarily affecting skeletal muscle glycogen turnover are well-recognised, but rare. We previously reported that a frameshift/premature stop mutation in PPP1R3A, the gene encoding RGL, a key regulator of muscle glycogen metabolism, was present in 1.36% of participants from a population of white individuals in the UK. However, the functional implications of the mutation were not known. The objective of this study was to characterise the molecular and physiological consequences of this genetic variant. Methods and Findings: In this study we found a similar prevalence of the variant in an independent UK white population of 744 participants (1.46%) and, using in vivo 13C magnetic resonance spectroscopy studies, demonstrate that human carriers (n= 6) of the variant have low basal (65% lower, p = 0.002) and postprandial muscle glycogen levels. Mice engineered to express the equivalent mutation had similarly decreased muscle glycogen levels (40% lower in heterozygous knock-in mice, p < 0.05). In muscle tissue from these mice, failure of the truncated mutant to bind glycogen and colocalize with glycogen synthase (GS) decreased GS and increased glycogen phosphorylase activity states, which account for the decreased glycogen content. Conclusions: Thus, PPP1R3A C1984DAG (stop codon 668) is, to our knowledge, the first prevalent mutation described that directly impairs glycogen synthesis and decreases glycogen levels in human skeletal muscle. The fact that it is present in ∼1 in 70 UK whites increases the potential biomedical relevance of these observations. © 2008 Savage et al.
- Published
- 2016
5. A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice (vol 5, pg e27, 2008)
- Author
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Savage, DB, Zhai, L, Ravikumar, B, Choi, CS, Snaar, JE, McGuire, AC, Wou, S-E, Medina-Gomez, G, Kim, S, Bock, CB, Segvich, DM, Solanky, B, Deelchand, D, Vidal-Puig, A, Wareham, NJ, Shulman, GI, Karpe, F, Taylor, R, Pederson, BA, Roach, PJ, O'Rahilly, S, and DePaoli-Roach, AA
- Published
- 2016
6. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy
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Klionsky, Dj, Abdelmohsen, K, Abe, A, Abedin, Mj, Abeliovich, H, Acevedo Arozena, A, Adachi, H, Adams, Cm, Adams, Pd, Adeli, K, Adhihetty, Pj, Adler, Sg, Agam, G, Agarwal, R, Aghi, Mk, Agnello, M, Agostinis, P, Aguilar, Pv, Aguirre-Ghiso, J, Airoldi, Em, Ait-Si-Ali, S, Akematsu, T, Akporiaye, Et, Al-Rubeai, M, Albaiceta, Gm, Albanese, C, Albani, D, Albert, Ml, Aldudo, J, Algül, H, Alirezaei, M, Alloza, I, Almasan, A, Almonte-Beceril, M, Alnemri, Es, Alonso, C, Altan-Bonnet, N, Altieri, Dc, Alvarez, S, Alvarez-Erviti, L, Alves, S, Amadoro, G, Amano, A, Amantini, C, Ambrosio, S, Amelio, I, Amer, Ao, Amessou, M, Amon, A, An, Z, Anania, Fa, Andersen, Su, Andley, Up, Andreadi, Ck, Andrieu-Abadie, N, Anel, A, Ann, Dk, Anoopkumar-Dukie, S, Antonioli, M, Aoki, H, Apostolova, N, Aquila, S, Aquilano, K, Araki, K, Arama, E, Aranda, A, Araya, J, Arcaro, A, Arias, E, Arimoto, H, Ariosa, Ar, Armstrong, Jl, Arnould, T, Arsov, I, Asanuma, K, Askanas, V, Asselin, E, Atarashi, R, Atherton, Ss, Atkin, Jd, Attardi, Ld, Auberger, P, Auburger, G, Aurelian, L, Autelli, R, Avagliano, L, Avantaggiati, Ml, Avrahami, L, Awale, S, Azad, N, Bachetti, Tiziana, Backer, Jm, Bae, Dh, Bae, Js, Bae, On, Bae, Sh, Baehrecke, Eh, Baek, Sh, Baghdiguian, S, Bagniewska-Zadworna, A, Bai, H, Bai, J, Bai, Xy, Bailly, Y, Balaji, Kn, Balduini, W, Ballabio, A, Balzan, R, Banerjee, R, Bánhegyi, G, Bao, H, Barbeau, B, Barrachina, Md, Barreiro, E, Bartel, B, Bartolomé, A, Bassham, Dc, Bassi, Mt, Bast RC Jr, Basu, A, Batista, Mt, Batoko, H, Battino, M, Bauckman, K, Baumgarner, Bl, Bayer, Ku, Beale, R, Beaulieu, Jf, Beck GR Jr, Becker, C, Beckham, Jd, Bédard, Pa, Bednarski, Pj, Begley, Tj, Behl, C, Behrends, C, Behrens, Gm, Behrns, Ke, Bejarano, E, Belaid, A, Belleudi, F, Bénard, G, Berchem, G, Bergamaschi, D, Bergami, M, Berkhout, B, Berliocchi, L, Bernard, A, Bernard, M, Bernassola, F, Bertolotti, A, Bess, As, Besteiro, S, Bettuzzi, S, Bhalla, S, Bhattacharyya, S, Bhutia, Sk, Biagosch, C, Bianchi, Mw, Biard-Piechaczyk, M, Billes, V, Bincoletto, C, Bingol, B, Bird, Sw, Bitoun, M, Bjedov, I, Blackstone, C, Blanc, L, Blanco, Ga, Blomhoff, Hk, Boada-Romero, E, Böckler, S, Boes, M, Boesze-Battaglia, K, Boise, Lh, Bolino, A, Boman, A, Bonaldo, P, Bordi, M, Bosch, J, Botana, Lm, Botti, J, Bou, G, Bouché, M, Bouchecareilh, M, Boucher, Mj, Boulton, Me, Bouret, Sg, Boya, P, Boyer-Guittaut, M, Bozhkov, Pv, Brady, N, Braga, Vm, Brancolini, C, Braus, Gh, Bravo-San Pedro JM, Brennan, La, Bresnick, Eh, Brest, P, Bridges, D, Bringer, Ma, Brini, M, Brito, Gc, Brodin, B, Brookes, Ps, Brown, Ej, Brown, K, Broxmeyer, He, Bruhat, A, Brum, Pc, Brumell, Jh, Brunetti-Pierri, N, Bryson-Richardson, Rj, Buch, S, Buchan, Am, Budak, H, Bulavin, Dv, Bultman, Sj, Bultynck, G, Bumbasirevic, V, Burelle, Y, Burke, Re, Burmeister, M, Bütikofer, P, Caberlotto, L, Cadwell, K, Cahova, M, Cai, D, Cai, J, Cai, Q, Calatayud, S, Camougrand, N, Campanella, M, Campbell, Gr, Campbell, M, Campello, S, Candau, R, Caniggia, I, Cantoni, L, Cao, L, Caplan, Ab, Caraglia, M, Cardinali, C, Cardoso, Sm, Carew, Js, Carleton, La, Carlin, Cr, Carloni, S, Carlsson, Sr, Carmona-Gutierrez, D, Carneiro, La, Carnevali, O, Carra, S, Carrier, A, Carroll, B, Casas, C, Casas, J, Cassinelli, G, Castets, P, Castro-Obregon, S, Cavallini, G, Ceccherini, I, Cecconi, F, Cederbaum, Ai, Ceña, V, Cenci, S, Cerella, C, Cervia, D, Cetrullo, S, Chaachouay, H, Chae, Hj, Chagin, As, Chai, Cy, Chakrabarti, G, Chamilos, G, Chan, Ey, Chan, Mt, Chandra, D, Chandra, P, Chang, Cp, Chang, Rc, Chang, Ty, Chatham, Jc, Chatterjee, S, Chauhan, S, Che, Y, Cheetham, Me, Cheluvappa, R, Chen, Cj, Chen, G, Chen, Gc, Chen, H, Chen, Jw, Chen, Jk, Chen, M, Chen, P, Chen, Q, Chen, Sd, Chen, S, Chen, Ss, Chen, W, Chen, Wj, Chen, Wq, Chen, X, Chen, Yh, Chen, Yg, Chen, Y, Chen, Yj, Chen, Yq, Chen, Z, Cheng, A, Cheng, Ch, Cheng, H, Cheong, H, Cherry, S, Chesney, J, Cheung, Ch, Chevet, E, Chi, Hc, Chi, Sg, Chiacchiera, F, Chiang, Hl, Chiarelli, R, Chiariello, M, Chieppa, M, Chin, Ls, Chiong, M, Chiu, Gn, Cho, Dh, Cho, Sg, Cho, Wc, Cho, Yy, Cho, Ys, Choi, Am, Choi, Ej, Choi, Ek, Choi, J, Choi, Me, Choi, Si, Chou, Tf, Chouaib, S, Choubey, D, Choubey, V, Chow, Kc, Chowdhury, K, Chu, Ct, Chuang, Th, Chun, T, Chung, H, Chung, T, Chung, Yl, Chwae, Yj, Cianfanelli, V, Ciarcia, R, Ciechomska, Ia, Ciriolo, Mr, Cirone, M, Claerhout, S, Clague, Mj, Clària, J, Clarke, Pg, Clarke, R, Clementi, E, Cleyrat, C, Cnop, M, Coccia, Em, Cocco, T, Codogno, P, Coers, J, Cohen, Ee, Colecchia, D, Coletto, L, Coll, Ns, Colucci-Guyon, E, Comincini, S, Condello, M, Cook, Kl, Coombs, Gh, Cooper, Cd, Cooper, Jm, Coppens, I, Corasaniti, Mt, Corazzari, M, Corbalan, R, Corcelle-Termeau, E, Cordero, Md, Corral-Ramos, C, Corti, O, Cossarizza, A, Costelli, P, Costes, S, Cotman, Sl, Coto-Montes, A, Cottet, S, Couve, E, Covey, Lr, Cowart, La, Cox, Js, Coxon, Fp, Coyne, Cb, Cragg, Ms, Craven, Rj, Crepaldi, T, Crespo, Jl, Criollo, A, Crippa, V, Cruz, Mt, Cuervo, Am, Cuezva, Jm, Cui, T, Cutillas, Pr, Czaja, Mj, Czyzyk-Krzeska, Mf, Dagda, Rk, Dahmen, U, Dai, C, Dai, W, Dai, Y, Dalby, Kn, Dalla Valle, L, Dalmasso, G, D'Amelio, M, Damme, M, Darfeuille-Michaud, A, Dargemont, C, Darley-Usmar, Vm, Dasarathy, S, Dasgupta, B, Dash, S, Dass, Cr, Davey, Hm, Davids, Lm, Dávila, D, Davis, Rj, Dawson, Tm, Dawson, Vl, Daza, P, de Belleroche, J, de Figueiredo, P, de Figueiredo RC, de la Fuente, J, De Martino, L, De Matteis, A, De Meyer GR, De Milito, A, De Santi, M, de Souza, W, De Tata, V, De Zio, D, Debnath, J, Dechant, R, Decuypere, Jp, Deegan, S, Dehay, B, Del Bello, B, Del Re DP, Delage-Mourroux, R, Delbridge, Lm, Deldicque, L, Delorme-Axford, E, Deng, Y, Dengjel, J, Denizot, M, Dent, P, Der, Cj, Deretic, V, Derrien, B, Deutsch, E, Devarenne, Tp, Devenish, Rj, Di Bartolomeo, S, Di Daniele, N, Di Domenico, F, Di Nardo, A, Di Paola, S, Di Pietro, A, Di Renzo, L, Diantonio, A, Díaz-Araya, G, Díaz-Laviada, I, Diaz-Meco, Mt, Diaz-Nido, J, Dickey, Ca, Dickson, Rc, Diederich, M, Digard, P, Dikic, I, Dinesh-Kumar, Sp, Ding, C, Ding, Wx, Ding, Z, Dini, L, Distler, Jh, Diwan, A, Djavaheri-Mergny, M, Dmytruk, K, Dobson, Rc, Doetsch, V, Dokladny, K, Dokudovskaya, S, Donadelli, M, Dong, Xc, Dong, X, Dong, Z, Donohue TM Jr, Doran, Ks, D'Orazi, G, Dorn GW 2nd, Dosenko, V, Dridi, S, Drucker, L, Du, J, Du, Ll, Du, L, du Toit, A, Dua, P, Duan, L, Duann, P, Dubey, Vk, Duchen, Mr, Duchosal, Ma, Duez, H, Dugail, I, Dumit, Vi, Duncan, Mc, Dunlop, Ea, Dunn WA Jr, Dupont, N, Dupuis, L, Durán, Rv, Durcan, Tm, Duvezin-Caubet, S, Duvvuri, U, Eapen, V, Ebrahimi-Fakhari, D, Echard, A, Eckhart, L, Edelstein, Cl, Edinger, Al, Eichinger, L, Eisenberg, T, Eisenberg-Lerner, A, Eissa, Nt, El-Deiry, Ws, El-Khoury, V, Elazar, Z, Eldar-Finkelman, H, Elliott, Cj, Emanuele, E, Emmenegger, U, Engedal, N, Engelbrecht, Am, Engelender, S, Enserink, Jm, Erdmann, R, Erenpreisa, J, Eri, R, Eriksen, Jl, Erman, A, Escalante, R, Eskelinen, El, Espert, L, Esteban-Martínez, L, Evans, Tj, Fabri, M, Fabrias, G, Fabrizi, C, Facchiano, A, Færgeman, Nj, Faggioni, A, Fairlie, Wd, Fan, C, Fan, D, Fan, J, Fang, S, Fanto, M, Fanzani, A, Farkas, T, Faure, M, Favier, Fb, Fearnhead, H, Federici, M, Fei, E, Felizardo, Tc, Feng, H, Feng, Y, Ferguson, Ta, Fernández, Áf, Fernandez-Barrena, Mg, Fernandez-Checa, Jc, Fernández-López, A, Fernandez-Zapico, Me, Feron, O, Ferraro, E, Ferreira-Halder, Cv, Fesus, L, Feuer, R, Fiesel, Fc, Filippi-Chiela, Ec, Filomeni, G, Fimia, Gm, Fingert, Jh, Finkbeiner, S, Finkel, T, Fiorito, F, Fisher, Pb, Flajolet, M, Flamigni, F, Florey, O, Florio, S, Floto, Ra, Folini, M, Follo, C, Fon, Ea, Fornai, F, Fortunato, F, Fraldi, A, Franco, R, Francois, A, François, A, Frankel, Lb, Fraser, Id, Frey, N, Freyssenet, Dg, Frezza, C, Friedman, Sl, Frigo, De, Fu, D, Fuentes, Jm, Fueyo, J, Fujitani, Y, Fujiwara, Y, Fujiya, M, Fukuda, M, Fulda, S, Fusco, C, Gabryel, B, Gaestel, M, Gailly, P, Gajewska, M, Galadari, S, Galili, G, Galindo, I, Galindo, Mf, Galliciotti, G, Galluzzi, 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J, Zeng, M, Zeng, Q, Zervos, As, Zhang, Dd, Zhang, F, Zhang, G, Zhang, Gc, Zhang, H, Zhang, J, Zhang, Jp, Zhang, L, Zhang, My, Zhang, X, Zhang, Xd, Zhang, Y, Zhao, M, Zhao, Wl, Zhao, X, Zhao, Yg, Zhao, Y, Zhao, Yx, Zhao, Z, Zhao, Zj, Zheng, D, Zheng, Xl, Zheng, X, Zhivotovsky, B, Zhong, Q, Zhou, Gz, Zhou, G, Zhou, H, Zhou, Sf, Zhou, Xj, Zhu, H, Zhu, Wg, Zhu, W, Zhu, Xf, Zhu, Y, Zhuang, Sm, Zhuang, X, Ziparo, E, Zois, Ce, Zoladek, T, Zong, Wx, Zorzano, A, and Zughaier, Sm
- Published
- 2016
7. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
- Author
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Klionsky, Dj, Abdelmohsen, K, Abe, A, Abedin, Mj, Abeliovich, H, Acevedo Arozena, A, Adachi, H, Adams, Cm, Adams, Pd, Adeli, K, Adhihetty, Pj, Adler, Sg, Agam, G, Agarwal, R, Aghi, Mk, Agnello, M, Agostinis, P, Aguilar, Pv, Aguirre-Ghiso, J, Airoldi, Em, Ait-Si-Ali, S, Akematsu, T, Akporiaye, Et, Al-Rubeai, M, Albaiceta, Gm, Albanese, C, Albani, D, Albert, Ml, Aldudo, J, Algül, H, Alirezaei, M, Alloza, I, Almasan, A, Almonte-Beceril, M, Alnemri, E, Alonso, C, Altan-Bonnet, N, Altieri, Dc, Alvarez, S, Alvarez-Erviti, L, Alves, S, Amadoro, G, Amano, A, Amantini, C, Ambrosio, S, Amelio, I, Amer, Ao, Amessou, M, Amon, A, An, Z, Anania, Fa, Andersen, Su, Andley, Up, Andreadi, Ck, Andrieu-Abadie, N, Anel, A, Ann, Dk, Anoopkumar-Dukie, S, Antonioli, M, Aoki, H, Apostolova, N, Aquila, S, Aquilano, K, Araki, K, Arama, E, Aranda, A, Araya, J, Arcaro, A, Arias, E, Arimoto, H, Ariosa, Ar, Armstrong, Jl, Arnould, T, Arsov, I, Asanuma, K, Askanas, V, Asselin, E, Atarashi, R, Atherton, S, Atkin, Jd, Attardi, Ld, Auberger, P, Auburger, G, Aurelian, L, Autelli, R, Avagliano, L, Avantaggiati, Ml, Avrahami, L, Awale, S, Azad, N, Bachetti, T, Backer, Jm, Bae, Dh, Bae, J, Bae, On, Bae, Sh, Baehrecke, Eh, Baek, Sh, Baghdiguian, S, Bagniewska-Zadworna, A, Bai, H, Bai, J, Bai, Xy, Bailly, Y, Balaji, Kn, Balduini, W, Ballabio, A, Balzan, R, Banerjee, R, Bánhegyi, G, Bao, H, Barbeau, B, Barrachina, Md, Barreiro, E, Bartel, B, Bartolomé, A, Bassham, Dc, Bassi, Mt, Bast RC, Jr, Basu, A, Batista, Mt, Batoko, H, Battino, M, Bauckman, K, Baumgarner, Bl, Bayer, Ku, Beale, R, Beaulieu, Jf, Beck GR, Jr, Becker, C, Beckham, Jd, Bédard, Pa, Bednarski, Pj, Begley, Tj, Behl, C, Behrends, C, Behrens, Gm, Behrns, Ke, Bejarano, E, Belaid, A, Belleudi, F, Bénard, G, Berchem, G, Bergamaschi, D, Bergami, M, Berkhout, B, Berliocchi, L, Bernard, A, Bernard, M, Bernassola, F, Bertolotti, A, Bess, A, Besteiro, S, Bettuzzi, S, Bhalla, S, Bhattacharyya, S, Bhutia, Sk, Biagosch, C, Bianchi, Mw, Biard-Piechaczyk, M, Billes, V, Bincoletto, C, Bingol, B, Bird, Sw, Bitoun, M, Bjedov, I, Blackstone, C, Blanc, L, Blanco, Ga, Blomhoff, Hk, Boada-Romero, E, Böckler, S, Boes, M, Boesze-Battaglia, K, Boise, Lh, Bolino, A, Boman, A, Bonaldo, P, Bordi, M, Bosch, J, Botana, Lm, Botti, J, Bou, G, Bouché, M, Bouchecareilh, M, Boucher, Mj, Boulton, Me, Bouret, Sg, Boya, P, Boyer-Guittaut, M, Bozhkov, Pv, Brady, N, Braga, Vm, Brancolini, C, Braus, Gh, Bravo-San Pedro, Jm, Brennan, La, Bresnick, Eh, Brest, P, Bridges, D, Bringer, Ma, Brini, M, Brito, Gc, Brodin, B, Brookes, P, Brown, Ej, Brown, K, Broxmeyer, He, Bruhat, A, Brum, Pc, Brumell, Jh, Brunetti-Pierri, N, Bryson-Richardson, Rj, Buch, S, Buchan, Am, Budak, H, Bulavin, Dv, Bultman, Sj, Bultynck, G, Bumbasirevic, V, Burelle, Y, Burke, Re, Burmeister, M, Bütikofer, P, Caberlotto, L, Cadwell, K, Cahova, M, Cai, D, Cai, J, Cai, Q, Calatayud, S, Camougrand, N, Campanella, M, Campbell, Gr, Campbell, M, Campello, S, Candau, R, Caniggia, I, Cantoni, L, Cao, L, Caplan, Ab, Caraglia, M, Cardinali, C, Cardoso, Sm, Carew, J, Carleton, La, Carlin, Cr, Carloni, S, Carlsson, Sr, Carmona-Gutierrez, D, Carneiro, La, Carnevali, O, Carra, S, Carrier, A, Carroll, B, Casas, C, Casas, J, Cassinelli, G, Castets, P, Castro-Obregon, S, Cavallini, G, Ceccherini, I, Cecconi, F, Cederbaum, Ai, Ceña, V, Cenci, S, Cerella, C, Cervia, D, Cetrullo, S, Chaachouay, H, Chae, Hj, Chagin, A, Chai, Cy, Chakrabarti, G, Chamilos, G, Chan, Ey, Chan, Mt, Chandra, D, Chandra, P, Chang, Cp, Chang, Rc, Chang, Ty, Chatham, Jc, Chatterjee, S, Chauhan, S, Che, Y, Cheetham, Me, Cheluvappa, R, Chen, Cj, Chen, G, Chen, Gc, Chen, H, Chen, Jw, Chen, Jk, Chen, M, Chen, P, Chen, Q, Chen, Sd, Chen, S, Chen, W, Chen, Wj, Chen, Wq, Chen, X, Chen, Yh, Chen, Yg, Chen, Y, Chen, Yj, Chen, Yq, Chen, Z, Cheng, A, Cheng, Ch, Cheng, H, Cheong, H, Cherry, S, Chesney, J, Cheung, Ch, Chevet, E, Chi, Hc, Chi, Sg, Chiacchiera, F, Chiang, Hl, Chiarelli, R, Chiariello, M, Chieppa, M, Chin, L, Chiong, M, Chiu, Gn, Cho, Dh, Cho, Sg, Cho, Wc, Cho, Yy, Cho, Y, Choi, Am, Choi, Ej, Choi, Ek, Choi, J, Choi, Me, Choi, Si, Chou, Tf, Chouaib, S, Choubey, D, Choubey, V, Chow, Kc, Chowdhury, K, Chu, Ct, Chuang, Th, Chun, T, Chung, H, Chung, T, Chung, Yl, Chwae, Yj, Cianfanelli, V, Ciarcia, R, Ciechomska, Ia, Ciriolo, Mr, Cirone, M, Claerhout, S, Clague, Mj, Clària, J, Clarke, Pg, Clarke, R, Clementi, E, Cleyrat, C, Cnop, M, Coccia, Em, Cocco, T, Codogno, P, Coers, J, Cohen, Ee, Colecchia, D, Coletto, L, Coll, N, Colucci-Guyon, E, Comincini, S, Condello, M, Cook, Kl, Coombs, Gh, Cooper, Cd, Cooper, Jm, Coppens, I, Corasaniti, Mt, Corazzari, M, Corbalan, R, Corcelle-Termeau, E, Cordero, Md, Corral-Ramos, C, Corti, O, Cossarizza, A, Costelli, P, Costes, S, Cotman, Sl, Coto-Montes, A, Cottet, S, Couve, E, Covey, Lr, Cowart, La, Cox, J, Coxon, Fp, Coyne, Cb, Cragg, M, Craven, Rj, Crepaldi, T, Crespo, Jl, Criollo, A, Crippa, V, Cruz, Mt, Cuervo, Am, Cuezva, Jm, Cui, T, Cutillas, Pr, Czaja, Mj, Czyzyk-Krzeska, Mf, Dagda, Rk, Dahmen, U, Dai, C, Dai, W, Dai, Y, Dalby, Kn, Dalla Valle, L, Dalmasso, G, D'Amelio, M, Damme, M, Darfeuille-Michaud, A, Dargemont, C, Darley-Usmar, Vm, Dasarathy, S, Dasgupta, B, Dash, S, Dass, Cr, Davey, Hm, Davids, Lm, Dávila, D, Davis, Rj, Dawson, Tm, Dawson, Vl, Daza, P, de Belleroche, J, de Figueiredo, P, de Figueiredo, Rc, de la Fuente, J, De Martino, L, De Matteis, A, De Meyer, Gr, De Milito, A, De Santi, M, de Souza, W, De Tata, V, De Zio, D, Debnath, J, Dechant, R, Decuypere, Jp, Deegan, S, Dehay, B, Del Bello, B, Del Re, Dp, Delage-Mourroux, R, Delbridge, Lm, Deldicque, L, Delorme-Axford, E, Deng, Y, Dengjel, J, Denizot, M, Dent, P, Der, Cj, Deretic, V, Derrien, B, Deutsch, E, Devarenne, Tp, Devenish, Rj, Di Bartolomeo, S, Di Daniele, N, Di Domenico, F, Di Nardo, A, Di Paola, S, Di Pietro, A, Di Renzo, L, Diantonio, A, Díaz-Araya, G, Díaz-Laviada, I, Diaz-Meco, Mt, Diaz-Nido, J, Dickey, Ca, Dickson, Rc, Diederich, M, Digard, P, Dikic, I, Dinesh-Kumar, Sp, Ding, C, Ding, Wx, Ding, Z, Dini, L, Distler, Jh, Diwan, A, Djavaheri-Mergny, M, Dmytruk, K, Dobson, Rc, Doetsch, V, Dokladny, K, Dokudovskaya, S, Donadelli, M, Dong, Xc, Dong, X, Dong, Z, Donohue TM, Jr, Doran, K, D'Orazi, G, Dorn GW, 2nd, Dosenko, V, Dridi, S, Drucker, L, Du, J, Du, Ll, Du, L, du Toit, A, Dua, P, Duan, L, Duann, P, Dubey, Vk, Duchen, Mr, Duchosal, Ma, Duez, H, Dugail, I, Dumit, Vi, Duncan, Mc, Dunlop, Ea, Dunn WA, Jr, Dupont, N, Dupuis, L, Durán, Rv, Durcan, Tm, Duvezin-Caubet, S, Duvvuri, U, Eapen, V, Ebrahimi-Fakhari, D, Echard, A, Eckhart, L, Edelstein, Cl, Edinger, Al, Eichinger, L, Eisenberg, T, Eisenberg-Lerner, A, Eissa, Nt, El-Deiry, W, El-Khoury, V, Elazar, Z, Eldar-Finkelman, H, Elliott, Cj, Emanuele, E, Emmenegger, U, Engedal, N, Engelbrecht, Am, Engelender, S, Enserink, Jm, Erdmann, R, Erenpreisa, J, Eri, R, Eriksen, Jl, Erman, A, Escalante, R, Eskelinen, El, Espert, L, Esteban-Martínez, L, Evans, Tj, Fabri, M, Fabrias, G, Fabrizi, C, Facchiano, A, Færgeman, Nj, Faggioni, A, Fairlie, Wd, Fan, C, Fan, D, Fan, J, Fang, S, Fanto, M, Fanzani, A, Farkas, T, Faure, M, Favier, Fb, Fearnhead, H, Federici, M, Fei, E, Felizardo, Tc, Feng, H, Feng, Y, Ferguson, Ta, Fernández, Áf, Fernandez-Barrena, Mg, Fernandez-Checa, Jc, Fernández-López, A, Fernandez-Zapico, Me, Feron, O, Ferraro, E, Ferreira-Halder, Cv, Fesus, L, Feuer, R, Fiesel, Fc, Filippi-Chiela, Ec, Filomeni, G, Fimia, Gm, Fingert, Jh, Finkbeiner, S, Finkel, T, Fiorito, F, Fisher, Pb, Flajolet, M, Flamigni, F, Florey, O, Florio, S, Floto, Ra, Folini, M, Follo, C, Fon, Ea, Fornai, F, Fortunato, F, Fraldi, A, Franco, R, Francois, A, François, A, Frankel, Lb, Fraser, Id, Frey, N, Freyssenet, Dg, Frezza, C, Friedman, Sl, Frigo, De, Fu, D, Fuentes, Jm, Fueyo, J, Fujitani, Y, Fujiwara, Y, Fujiya, M, Fukuda, M, Fulda, S, Fusco, C, Gabryel, B, Gaestel, M, Gailly, P, Gajewska, M, Galadari, S, Galili, G, Galindo, I, Galindo, Mf, Galliciotti, G, Galluzzi, L, Galy, V, Gammoh, N, Gandy, S, Ganesan, Ak, Ganesan, S, Ganley, Ig, Gannagé, M, Gao, Fb, Gao, F, Gao, Jx, García Nannig, L, García Véscovi, E, Garcia-Macía, M, Garcia-Ruiz, C, Garg, Ad, Garg, Pk, Gargini, R, Gassen, Nc, Gatica, D, Gatti, E, Gavard, J, Gavathiotis, E, Ge, L, Ge, P, Ge, S, Gean, Pw, Gelmetti, V, Genazzani, Aa, Geng, J, Genschik, P, Gerner, L, Gestwicki, Je, Gewirtz, Da, Ghavami, S, Ghigo, E, Ghosh, D, Giammarioli, Am, Giampieri, F, Giampietri, C, Giatromanolaki, A, Gibbings, Dj, Gibellini, L, Gibson, Sb, Ginet, V, Giordano, Alessandro, Giorgini, F, Giovannetti, E, Girardin, Se, Gispert, S, Giuliano, S, Gladson, Cl, Glavic, A, Gleave, M, Godefroy, N, Gogal RM, Jr, Gokulan, K, Goldman, Gh, Goletti, D, Goligorsky, M, Gomes, Av, Gomes, Lc, Gomez, H, Gomez-Manzano, C, Gómez-Sánchez, R, Gonçalves, Da, Goncu, E, Gong, Q, Gongora, C, Gonzalez, Cb, Gonzalez-Alegre, P, Gonzalez-Cabo, P, González-Polo, Ra, Goping, I, Gorbea, C, Gorbunov, Nv, Goring, Dr, Gorman, Am, Gorski, Sm, Goruppi, S, Goto-Yamada, S, Gotor, C, Gottlieb, Ra, Gozes, I, Gozuacik, D, Graba, Y, Graef, M, Granato, Ge, Grant, Gd, Grant, S, Gravina, Gl, Green, Dr, Greenhough, A, Greenwood, Mt, Grimaldi, B, Gros, F, Grose, C, Groulx, Jf, Gruber, F, Grumati, P, Grune, T, Guan, Jl, Guan, Kl, Guerra, B, Guillen, C, Gulshan, K, Gunst, J, Guo, C, Guo, L, Guo, M, Guo, W, Guo, Xg, Gust, Aa, Gustafsson, Åb, Gutierrez, E, Gutierrez, Mg, Gwak, H, Haas, A, Haber, Je, Hadano, S, Hagedorn, M, Hahn, Dr, Halayko, Aj, Hamacher-Brady, A, Hamada, K, Hamai, A, Hamann, A, Hamasaki, M, Hamer, I, Hamid, Q, Hammond, Em, Han, F, Han, W, Handa, Jt, Hanover, Ja, Hansen, M, Harada, M, Harhaji-Trajkovic, L, Harper, Jw, Harrath, Ah, Harris, Al, Harris, J, Hasler, U, Hasselblatt, P, Hasui, K, Hawley, Rg, Hawley, T, He, C, He, Cy, He, F, He, G, He, Rr, He, Xh, He, Yw, He, Yy, Heath, Jk, Hébert, Mj, Heinzen, Ra, Helgason, Gv, Hensel, M, Henske, Ep, Her, C, Herman, Pk, Hernández, A, Hernandez, C, Hernández-Tiedra, S, Hetz, C, Hiesinger, Pr, Higaki, K, Hilfiker, S, Hill, Bg, Hill, Ja, Hill, Wd, Hino, K, Hofius, D, Hofman, P, Höglinger, Gu, Höhfeld, J, Holz, Mk, Hong, Y, Hood, Da, Hoozemans, Jj, Hoppe, T, Hsu, C, Hsu, Cy, Hsu, Lc, Hu, D, Hu, G, Hu, Hm, H, Hu, Hu, Mc, Hu, Yc, Hu, Zw, Hua, F, Hua, Y, Huang, C, Huang, Hl, Huang, Kh, Huang, Ky, Huang, S, Huang, Wp, Huang, Yr, Huang, Y, Huber, Tb, Huebbe, P, Huh, Wk, Hulmi, Jj, Hur, Gm, Hurley, Jh, Husak, Z, Hussain, Sn, Hussain, S, Hwang, Jj, Hwang, S, Hwang, Ti, Ichihara, A, Imai, Y, Imbriano, C, Inomata, M, Into, T, Iovane, V, Iovanna, Jl, Iozzo, Rv, Ip, Ny, Irazoqui, Je, Iribarren, P, Isaka, Y, Isakovic, Aj, Ischiropoulos, H, Isenberg, J, Ishaq, M, Ishida, H, Ishii, I, Ishmael, Je, Isidoro, C, Isobe, K, Isono, E, Issazadeh-Navikas, S, Itahana, K, Itakura, E, Ivanov, Ai, Iyer, Ak, Izquierdo, Jm, Izumi, Y, Izzo, V, Jäättelä, M, Jaber, N, Jackson, Dj, Jackson, Wt, Jacob, Tg, Jacques, T, Jagannath, C, Jain, A, Jana, Nr, Jang, Bk, Jani, A, Janji, B, Jannig, Pr, Jansson, Pj, Jean, S, Jendrach, M, Jeon, Jh, Jessen, N, Jeung, Eb, Jia, K, Jia, L, Jiang, H, Jiang, L, Jiang, T, Jiang, X, Jiang, Y, Jiménez, A, Jin, C, Jin, H, Jin, L, Jin, M, Jin, S, Jinwal, Uk, Jo, Ek, Johansen, T, Johnson, De, Johnson, Gv, Johnson, Jd, Jonasch, E, Jones, C, Joosten, La, Jordan, J, Joseph, Am, Joseph, B, Joubert, Am, Ju, D, J, Ju, Juan, Hf, Juenemann, K, Juhász, G, Jung, H, Jung, Ju, Jung, Yk, Jungbluth, H, Justice, Mj, Jutten, B, Kaakoush, No, Kaarniranta, K, Kaasik, A, Kabuta, T, Kaeffer, B, Kågedal, K, Kahana, A, Kajimura, S, Kakhlon, O, Kalia, M, Kalvakolanu, Dv, Kamada, Y, Kambas, K, Kaminskyy, Vo, Kampinga, Hh, Kandouz, M, Kang, C, Kang, R, Kang, Tc, Kanki, T, Kanneganti, Td, Kanno, H, Kanthasamy, Ag, Kantorow, M, Kaparakis-Liaskos, M, Kapuy, O, Karantza, V, Karim, Mr, Karmakar, P, Kaser, A, Kaushik, S, Kawula, T, Kaynar, Am, Ke, Py, Ke, Zj, Kehrl, Jh, Keller, Ke, Kemper, Jk, Kenworthy, Ak, Kepp, O, Kern, A, Kesari, S, Kessel, D, Ketteler, R, Kettelhut Ido, C, Khambu, B, Khan, Mm, Khandelwal, Vk, Khare, S, Kiang, Jg, Kiger, Aa, Kihara, A, Kim, Al, Kim, Ch, Kim, Dr, Kim, Dh, Kim, Ek, Kim, Hy, Kim, Hr, Kim, J, Kim, Jh, Kim, Jc, Kim, Kw, Kim, Md, Kim, Mm, Kim, Pk, Kim, Sw, Kim, Sy, Kim, Y, Kimchi, A, Kimmelman, Ac, Kimura, T, King, J, Kirkegaard, K, Kirkin, V, Kirshenbaum, La, Kishi, S, Kitajima, Y, Kitamoto, K, Kitaoka, Y, Kitazato, K, Kley, Ra, Klimecki, Wt, Klinkenberg, M, Klucken, J, Knævelsrud, H, Knecht, E, Knuppertz, L, Ko, Jl, Kobayashi, S, Koch, Jc, Koechlin-Ramonatxo, C, Koenig, U, Koh, Yh, Köhler, K, Kohlwein, Sd, Koike, M, Komatsu, M, Kominami, E, Kong, D, Kong, Hj, Konstantakou, Eg, Kopp, Bt, Korcsmaros, T, Korhonen, L, Korolchuk, Vi, Koshkina, Nv, Kou, Y, Koukourakis, Mi, Koumenis, C, Kovács, Al, Kovács, T, Kovacs, Wj, Koya, D, Kraft, C, Krainc, D, Kramer, H, Kravic-Stevovic, T, Krek, W, Kretz-Remy, C, Krick, R, Krishnamurthy, M, Kriston-Vizi, J, Kroemer, G, Kruer, Mc, Kruger, R, Ktistakis, Nt, Kuchitsu, K, Kuhn, C, Kumar, Ap, Kumar, A, Kumar, D, Kumar, R, Kumar, S, Kundu, M, Kung, Hj, Kuno, A, Kuo, Sh, Kuret, J, Kurz, T, Kwok, T, Kwon, Tk, Kwon, Yt, Kyrmizi, I, La Spada, Ar, Lafont, F, Lahm, T, Lakkaraju, A, Lam, T, Lamark, T, Lancel, S, Landowski, Th, Lane, Dj, Lane, Jd, Lanzi, C, Lapaquette, P, Lapierre, Lr, Laporte, J, Laukkarinen, J, Laurie, Gw, Lavandero, S, Lavie, L, Lavoie, Mj, Law, By, Law, Hk, Law, Kb, Layfield, R, Lazo, Pa, Le Cam, L, Le Roch, Kg, Le Stunff, H, Leardkamolkarn, V, Lecuit, M, Lee, Bh, Lee, Ch, Lee, Ef, Lee, Gm, Lee, Hj, Lee, H, Lee, Jk, Lee, J, Lee, Jh, Lee, M, Lee, Pj, Lee, Sw, Lee, Sj, Lee, Sy, Lee, Sh, Lee, S, Lee, Yr, Lee, Yj, Lee, Yh, Leeuwenburgh, C, Lefort, S, Legouis, R, Lei, J, Lei, Qy, Leib, Da, Leibowitz, G, Lekli, I, Lemaire, Sd, Lemasters, Jj, Lemberg, Mk, Lemoine, A, Leng, S, Lenz, G, Lenzi, P, Lerman, Lo, Lettieri Barbato, D, Leu, Ji, Leung, Hy, Levine, B, Lewis, Pa, Lezoualc'H, F, Li, C, Li, F, Li, Fj, Li, J, Li, K, L, Li, Li, M, Li, Q, Li, R, Li, S, Li, W, Li, X, Li, Y, Lian, J, Liang, C, Liang, Q, Liao, Y, Liberal, J, Liberski, Pp, Lie, P, Lieberman, Ap, Lim, Hj, Lim, Kl, Lim, K, Lima, Rt, Lin, C, Lin, Cf, Lin, F, Lin, Fc, Lin, K, Lin, Kh, Lin, Ph, Lin, T, Lin, Ww, Lin, Y, Linden, R, Lindholm, D, Lindqvist, Lm, Lingor, P, Linkermann, A, Liotta, La, Lipinski, Mm, Lira, Va, Lisanti, Mp, Liton, Pb, Liu, B, Liu, C, Liu, Cf, Liu, F, Liu, Hj, Liu, J, Liu, Jj, Liu, Jl, Liu, K, Liu, L, Liu, Q, Liu, Ry, Liu, S, Liu, W, Liu, Xd, Liu, X, Liu, Xh, Liu, Y, Liu, Z, Liuzzi, Jp, Lizard, G, Ljujic, M, Lodhi, Ij, Logue, Se, Lokeshwar, Bl, Long, Yc, Lonial, S, Loos, B, López-Otín, C, López-Vicario, C, Lorente, M, Lorenzi, Pl, Lõrincz, P, Los, M, Lotze, Mt, Lovat, Pe, Lu, B, Lu, J, Lu, Q, Lu, Sm, Lu, S, Lu, Y, Luciano, F, Luckhart, S, Lucocq, Jm, Ludovico, P, Lugea, A, Lukacs, Nw, Lum, Jj, Lund, Ah, Luo, H, Luo, J, Luo, S, Luparello, C, Lyons, T, Ma, J, Ma, Y, Ma, Z, Machado, J, Machado-Santelli, Gm, Macian, F, Macintosh, Gc, Mackeigan, Jp, Macleod, Kf, Macmicking, Jd, MacMillan-Crow, 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Z, Palladino, F, Pallauf, K, Pallet, N, Palmieri, M, Paludan, Sr, Palumbo, C, Palumbo, S, Pampliega, O, Pan, H, Pan, W, Panaretakis, T, Pandey, A, Pantazopoulou, A, Papackova, Z, Papademetrio, Dl, Papassideri, I, Papini, A, Parajuli, N, Pardo, J, Parekh, Vv, Parenti, G, Park, Ji, Park, J, Park, Ok, Parker, R, Parlato, R, Parys, Jb, Parzych, Kr, Pasquet, Jm, Pasquier, B, Pasumarthi, Kb, Patschan, D, Patterson, C, Pattingre, S, Pattison, S, Pause, A, Pavenstädt, H, Pavone, F, Pedrozo, Z, Peña, Fj, Peñalva, Ma, Pende, M, Peng, J, Penna, F, Penninger, Jm, Pensalfini, A, Pepe, S, Pereira, Gj, Pereira, Pc, Pérez-de la Cruz, V, Pérez-Pérez, Me, Pérez-Rodríguez, D, Pérez-Sala, D, Perier, C, Perl, A, Perlmutter, Dh, Perrotta, I, Pervaiz, S, Pesonen, M, Pessin, Je, Peters, Gj, Petersen, M, Petrache, I, Petrof, Bj, Petrovski, G, Phang, Jm, Piacentini, M, Pierdominici, M, Pierre, P, Pierrefite-Carle, V, Pietrocola, F, Pimentel-Muiños, Fx, Pinar, M, Pineda, B, Pinkas-Kramarski, R, Pinti, M, Pinton, 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Rizzi, F, Rizzo, E, Roach, Pj, Robbins, J, Roberge, M, Roca, G, Roccheri, Mc, Rocha, S, Rodrigues, Cm, Rodríguez, Ci, de Cordoba, Sr, Rodriguez-Muela, N, Roelofs, J, Rogov, Vv, Rohn, Tt, Rohrer, B, Romanelli, D, Romani, L, Romano, P, Roncero, Mi, Rosa, Jl, Rosello, A, Rosen, Kv, Rosenstiel, P, Rost-Roszkowska, M, Roth, Ka, Roué, G, Rouis, M, Rouschop, Km, Ruan, Dt, Ruano, D, Rubinsztein, Dc, Rucker EB, 3rd, Rudich, A, Rudolf, E, Rudolf, R, Ruegg, Ma, Ruiz-Roldan, C, Ruparelia, Aa, Rusmini, P, Russ, Dw, Russo, Gl, Russo, G, Russo, R, Rusten, Te, Ryabovol, V, Ryan, Km, Ryter, Sw, Sabatini, Dm, Sacher, M, Sachse, C, Sack, Mn, Sadoshima, J, Saftig, P, Sagi-Eisenberg, R, Sahni, S, Saikumar, P, Saito, T, Saitoh, T, Sakakura, K, Sakoh-Nakatogawa, M, Sakuraba, Y, Salazar-Roa, M, Salomoni, P, Saluja, Ak, Salvaterra, Pm, Salvioli, R, Samali, A, Sanchez, Am, Sánchez-Alcázar, Ja, Sanchez-Prieto, R, Sandri, M, Sanjuan, Ma, Santaguida, S, Santambrogio, L, Santoni, G, Dos Santos, Cn, Saran, S, Sardiello, M, Sargent, G, Sarkar, P, Sarkar, S, Sarrias, Mr, Sarwal, Mm, Sasakawa, C, Sasaki, M, Sass, M, Sato, K, Sato, M, Satriano, J, Savaraj, N, Saveljeva, S, Schaefer, L, Schaible, Ue, Scharl, M, Schatzl, Hm, Schekman, R, Scheper, W, Schiavi, A, Schipper, Hm, Schmeisser, H, Schmidt, J, Schmitz, I, Schneider, Be, Schneider, Em, Schneider, Jl, Schon, Ea, Schönenberger, Mj, Schönthal, Ah, Schorderet, Df, Schröder, B, Schuck, S, Schulze, Rj, Schwarten, M, Schwarz, Tl, Sciarretta, S, Scotto, K, Scovassi, Ai, Screaton, Ra, Screen, M, Seca, H, Sedej, S, Segatori, L, Segev, N, Seglen, Po, Seguí-Simarro, Jm, Segura-Aguilar, J, Seki, E, Sell, C, Seiliez, I, Semenkovich, Cf, Semenza, Gl, Sen, U, Serra, Al, Serrano-Puebla, A, Sesaki, H, Setoguchi, T, Settembre, C, Shacka, Jj, Shajahan-Haq, An, Shapiro, Im, Sharma, S, She, H, Shen, Ck, Shen, Cc, Shen, Hm, Shen, S, Shen, W, Sheng, R, Sheng, X, Sheng, Zh, Shepherd, Tg, Shi, J, Shi, Q, Shi, Y, Shibutani, S, Shibuya, K, Shidoji, Y, Shieh, Jj, Shih, Cm, Shimada, Y, Shimizu, S, Shin, Dw, Shinohara, Ml, Shintani, M, Shintani, T, Shioi, T, Shirabe, K, Shiri-Sverdlov, R, Shirihai, O, Shore, Gc, Shu, Cw, Shukla, D, Sibirny, Aa, Sica, V, Sigurdson, Cj, Sigurdsson, Em, Sijwali, P, Sikorska, B, Silveira, Wa, Silvente-Poirot, S, Silverman, Ga, Simak, J, Simmet, T, Simon, Ak, Simon, Hu, Simone, C, Simons, M, Simonsen, A, Singh, R, Singh, Sv, Singh, Sk, Sinha, D, Sinha, S, Sinicrope, Fa, Sirko, A, Sirohi, K, Sishi, Bj, Sittler, A, Siu, Pm, Sivridis, E, Skwarska, A, Slack, R, Slaninová, I, Slavov, N, Smaili, S, Smalley, K, Smith, Dr, Soenen, Sj, Soleimanpour, Sa, Solhaug, A, Somasundaram, K, Son, Jh, Sonawane, A, Song, C, Song, F, Song, Hk, Song, Jx, Song, W, Soo, Ky, Sood, Ak, Soong, Tw, Soontornniyomkij, V, Sorice, M, Sotgia, F, Soto-Pantoja, Dr, Sotthibundhu, A, Sousa, Mj, Spaink, Hp, Span, Pn, Spang, A, Sparks, Jd, Speck, Pg, Spector, Sa, Spies, Cd, Springer, W, Clair, D, Stacchiotti, A, Staels, B, Stang, Mt, Starczynowski, Dt, Starokadomskyy, P, Steegborn, C, Steele, Jw, Stefanis, L, Steffan, J, Stellrecht, Cm, Stenmark, H, Stepkowski, Tm, Stern, St, Stevens, C, Stockwell, Br, Stoka, V, Storchova, Z, Stork, B, Stratoulias, V, Stravopodis, Dj, Strnad, P, Strohecker, Am, Ström, Al, Stromhaug, P, Stulik, J, Su, Yx, Su, Z, Subauste, C, Subramaniam, S, Sue, Cm, Suh, Sw, Sui, X, Sukseree, S, Sulzer, D, Sun, Fl, Sun, J, Sun, Sy, Sun, Y, Sundaramoorthy, V, Sung, J, Suzuki, H, Suzuki, K, Suzuki, N, Suzuki, T, Suzuki, Yj, Swanson, M, Swanton, C, Swärd, K, Swarup, G, Sweeney, St, Sylvester, Pw, Szatmari, Z, Szegezdi, E, Szlosarek, Pw, Taegtmeyer, H, Tafani, M, Taillebourg, E, Tait, Sw, Takacs-Vellai, K, Takahashi, Y, Takáts, S, Takemura, G, Takigawa, N, Talbot, Nj, Tamagno, E, Tamburini, J, Tan, Cp, Tan, L, Tan, Ml, Tan, M, Tan, Yj, Tanaka, K, Tanaka, M, Tang, D, Tang, G, Tanida, I, Tanji, K, Tannous, Ba, Tapia, Ja, Tasset-Cuevas, I, Tatar, M, Tavassoly, I, Tavernarakis, N, Taylor, A, Taylor, G, Taylor, Ga, Taylor, Jp, Taylor, Mj, Tchetina, Ev, Tee, Ar, Teixeira-Clerc, F, Telang, S, Tencomnao, T, Teng, Bb, Teng, Rj, Terro, F, Tettamanti, G, Theiss, Al, Theron, Ae, Thomas, Kj, Thomé, Mp, Thomes, Pg, Thorburn, A, Thorner, J, Thum, T, Thumm, M, Thurston, Tl, Tian, L, Till, A, Ting, Jp, Titorenko, Vi, Toker, L, Toldo, S, Tooze, Sa, Topisirovic, I, Torgersen, Ml, Torosantucci, L, Torriglia, A, Torrisi, Mr, Tournier, C, Towns, R, Trajkovic, V, Travassos, Lh, Triola, G, Tripathi, Dn, Trisciuoglio, D, Troncoso, R, Trougakos, Ip, Truttmann, Ac, Tsai, Kj, Tschan, Mp, Tseng, Yh, Tsukuba, T, Tsung, A, Tsvetkov, A, Tu, S, Tuan, Hy, Tucci, M, Tumbarello, Da, Turk, B, Turk, V, Turner, Rf, Tveita, Aa, Tyagi, Sc, Ubukata, M, Uchiyama, Y, Udelnow, A, Ueno, T, Umekawa, M, Umemiya-Shirafuji, R, Underwood, Br, Ungermann, C, Ureshino, Rp, Ushioda, R, Uversky, Vn, Uzcátegui, Nl, Vaccari, T, Vaccaro, Mi, Váchová, L, Vakifahmetoglu-Norberg, H, Valdor, R, Valente, Em, Vallette, F, Valverde, Am, Van den Berghe, G, Van Den Bosch, L, van den Brink, Gr, van der Goot, Fg, van der Klei, Ij, van der Laan, Lj, van Doorn, Wg, van Egmond, M, van Golen, Kl, Van Kaer, L, van Lookeren Campagne, M, Vandenabeele, P, Vandenberghe, W, Vanhorebeek, I, Varela-Nieto, I, Vasconcelos, Mh, Vasko, R, Vavvas, Dg, Vega-Naredo, I, Velasco, G, Velentzas, Ad, Velentzas, Pd, Vellai, T, Vellenga, E, Vendelbo, Mh, Venkatachalam, K, Ventura, N, Ventura, S, Veras, P, Verdier, M, Vertessy, Bg, Viale, A, Vidal, M, Vieira, Hl, Vierstra, Rd, Vigneswaran, N, Vij, N, Vila, M, Villar, M, Villar, Vh, Villarroya, J, Vindis, C, Viola, G, Viscomi, Maria Teresa, Vitale, G, Vogl, Dt, Voitsekhovskaja, Ov, von Haefen, C, von Schwarzenberg, K, Voth, De, Vouret-Craviari, V, Vuori, K, Vyas, Jm, Waeber, C, Walker, Cl, Walker, Mj, Walter, J, Wan, L, Wan, X, Wang, B, Wang, C, Wang, Cy, Wang, D, Wang, F, Wang, G, Wang, Hj, Wang, H, Wang, Hg, Wang, Hd, Wang, J, Wang, M, Wang, Mq, Wang, Py, Wang, P, Wang, Rc, Wang, S, Wang, Tf, Wang, X, Wang, Xj, Wang, Xw, Wang, Y, Wang, Yj, Wang, Yt, Wang, Zn, Wappner, P, Ward, C, Ward, Dm, Warnes, G, Watada, H, Watanabe, Y, Watase, K, Weaver, Te, Weekes, Cd, Wei, J, Weide, T, Weihl, Cc, Weindl, G, Weis, Sn, Wen, L, Wen, X, Wen, Y, Westermann, B, Weyand, Cm, White, Ar, White, E, Whitton, Jl, Whitworth, Aj, Wiels, J, Wild, F, Wildenberg, Me, Wileman, T, Wilkinson, D, Wilkinson, S, Willbold, D, Williams, C, Williams, K, Williamson, Pr, Winklhofer, Kf, Witkin, S, Wohlgemuth, Se, Wollert, T, Wolvetang, Ej, Wong, E, Wong, Gw, Wong, Rw, Wong, Vk, Woodcock, Ea, Wright, Kl, Wu, C, Wu, D, Wu, G, Wu, J, Wu, M, Wu, S, Wu, Wk, Wu, Y, Wu, Z, Xavier, Cp, Xavier, Rj, Xia, Gx, Xia, T, Xia, W, Xia, Y, Xiao, H, Xiao, J, Xiao, S, Xiao, W, Xie, Cm, Xie, Z, Xilouri, M, Xiong, Y, Xu, C, Xu, F, Xu, H, Xu, J, Xu, L, X, Xu, Xu, Y, Xu, Zx, Xu, Z, Xue, Y, Yamada, T, Yamamoto, A, Yamanaka, K, Yamashina, S, Yamashiro, S, Yan, B, Yan, X, Yan, Z, Yanagi, Y, Yang, D, Yang, Jm, Yang, L, Yang, M, Yang, Pm, Yang, P, Yang, Q, Yang, W, Yang, Wy, Yang, X, Yang, Y, Yang, Z, Yao, Mc, Yao, Pj, Yao, X, Yao, Z, Yasui, L, Ye, M, Yedvobnick, B, Yeganeh, B, Yeh, E, Yeyati, Pl, Yi, F, Yi, L, Yin, Xm, Yip, Ck, Yoo, Ym, Yoo, Yh, Yoon, Sy, Yoshida, K, Yoshimori, T, Young, Kh, Yu, H, Yu, Jj, Yu, Jt, Yu, J, Yu, L, Yu, Wh, Yu, Xf, Yu, Z, Yuan, J, Yuan, Zm, Yue, By, Yue, J, Yue, Z, Zacks, Dn, Zacksenhaus, E, Zaffaroni, N, Zaglia, T, Zakeri, Z, Zecchini, V, Zeng, J, Zeng, M, Zeng, Q, Zervos, A, Zhang, Dd, Zhang, F, Zhang, G, Zhang, Gc, Zhang, H, Zhang, J, Zhang, Jp, Zhang, L, Zhang, My, Zhang, X, Zhang, Xd, Zhang, Y, Zhao, M, Zhao, Wl, Zhao, X, Zhao, Yg, Zhao, Y, Zhao, Yx, Zhao, Z, Zhao, Zj, Zheng, D, Zheng, Xl, Zheng, X, Zhivotovsky, B, Zhong, Q, Zhou, Gz, Zhou, G, Zhou, H, Zhou, Sf, Zhou, Xj, Zhu, H, Zhu, Wg, Zhu, W, Zhu, Xf, Zhu, Y, Zhuang, Sm, Zhuang, X, Ziparo, E, Zois, Ce, Zoladek, T, Zong, Wx, Zorzano, A, Zughaier, Sm., Giordano A (ORCID:0000-0002-6978-0880), and Viscomi MT (ORCID:0000-0002-9096-4967)
- Abstract
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we prese
- Published
- 2016
8. Bowel Visualization on Bone Scan Because of Protein Losing Enteropathy
- Author
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D Itrato, Salvador Treves, and Roach Pj
- Subjects
medicine.medical_specialty ,Pathology ,Adolescent ,Colon ,Protein-Losing Enteropathies ,chemistry.chemical_element ,Technetium Tc 99m Medronate ,Technetium ,Scintigraphy ,Bone and Bones ,Intestinal malabsorption ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Radionuclide Imaging ,medicine.diagnostic_test ,business.industry ,digestive, oral, and skin physiology ,Protein losing enteropathy ,General Medicine ,medicine.disease ,chemistry ,Bone scintigraphy ,Female ,Radiology ,business - Abstract
A case of visualization of the large bowel on a Tc-99m MDP bone scan is presented. A 14-year-old girl had transit of radiotracer through the intestinal lumen in two studies performed 3 weeks apart. This was almost certainly caused by a severe protein losing enteropathy. Mechanisms and other causes of bowel visualization on bone scintigraphy are discussed
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- 1994
9. Osteoid osteoma: comparative utility of high-resolution planar and pinhole magnification scintigraphy
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Leonard P. Connolly, Salvador Treves, David Zurakowski, and Roach Pj
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musculoskeletal diseases ,Osteoid osteoma ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Appendicular skeleton ,Osteoma, Osteoid ,High resolution ,Magnification ,Bone Neoplasms ,urologic and male genital diseases ,Scintigraphy ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Child ,Tomography, Emission-Computed, Single-Photon ,medicine.diagnostic_test ,Osteoid ,business.industry ,Ultrasound ,musculoskeletal system ,medicine.disease ,body regions ,medicine.anatomical_structure ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Pinhole (optics) ,Female ,Radiology ,business ,Nuclear medicine - Abstract
A characteristic scintigraphic pattern of focally intense skeletal tracer uptake surrounded by less prominently increased uptake has been described for osteoid osteomas. Demonstration of this finding is useful in the evaluation of patients with suspected osteomas. Pinhole magnification scintigraphy was significantly more effective than high-resolution planar scintigraphy at revealing this pattern in 19 osteoid osteomas of the appendicular skeleton. A similar advantage was not observed for vertebral osteoid osteomas. The absence of the characteristic pattern aided in differentiating other pathology from osteoid osteomas in seven patients. The authors recommend that skeletal scintigraphy of patients with suspected osteoid osteomas include pinhole magnification imaging.
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- 1996
10. The value of bronchodilator administration in asthmatic patients before lung imaging
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Salvador Treves and Roach Pj
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Male ,Pulmonary Circulation ,Adolescent ,medicine.drug_class ,Atelectasis ,Bronchi ,Chest pain ,Ventilation/perfusion ratio ,Bronchospasm ,Bronchodilator ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Radionuclide Imaging ,Lung ,Technetium Tc 99m Aggregated Albumin ,medicine.diagnostic_test ,business.industry ,General Medicine ,respiratory system ,medicine.disease ,Asthma ,respiratory tract diseases ,Pulmonary embolism ,Bronchodilator Agents ,Anesthesia ,Breathing ,medicine.symptom ,business ,Chest radiograph ,Xenon Radioisotopes - Abstract
A 17-year-old boy with chest pain and severe bronchospasm underwent lung imaging to exclude pulmonary embolism. This showed widespread nonsegmental defects in both the ventilation and perfusion scans. A repeat study performed immediately after nebulized bronchodilator administration was normal apart from changes consistent with left lower lobe pneumonia and atelectasis which had subsequently evolved on the chest radiograph. Bronchodilator administration is valuable in improving the accuracy of lung scanning in asthmatic patients by reducing the perfusion and ventilation abnormalities caused by hypoxia-induced vasoconstriction.
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- 1995
11. Arm splints seen on bone scan in a volleyball player
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Roach Pj, Watson As, and Cooper Ra
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musculoskeletal diseases ,Adult ,Periosteum ,Arm Injuries ,Stress fractures ,Shin splints ,business.industry ,General Medicine ,Anatomy ,Technetium Tc 99m Medronate ,medicine.disease ,body regions ,Bone scanning ,Splints ,medicine.anatomical_structure ,Athletic Injuries ,medicine ,Upper limb ,Humans ,Radiology, Nuclear Medicine and imaging ,Humerus ,Female ,Elbow extension ,business ,Radionuclide Imaging - Abstract
Periosteal bone reaction manifested by shin splints and stress fractures on Tc-99m MDP bone scanning have been widely described in athletes. In this case, an elite volleyball player, whose primary role is blocking and spiking (forced elbow extension), demonstrates increased linear periosteal uptake of isotope along the medial aspect of the right humerus-so called «arm splints»
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- 1993
12. Sympathetic Denervation Due to Neuroblastoma
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Roach Pj and Salvador Treves
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Pathology ,medicine.medical_specialty ,Technetium Tc 99m Medronate ,Scintigraphy ,Mediastinal Neoplasms ,Bone and Bones ,Sympathetic Denervation ,Neuroblastoma ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radionuclide Imaging ,Denervation ,Leg ,Thoracic Nerves ,medicine.diagnostic_test ,business.industry ,Infant ,Soft tissue ,General Medicine ,Anatomy ,medicine.disease ,Mediastinal Neuroblastoma ,body regions ,Female ,business ,Complication ,Infiltration (medical) - Abstract
A case of sympathetic denervation due to infiltration of the thoracic sympathetic chain by a posterior mediastinal neuroblastoma is presented. A Tc-99m MDP bone scan in a 15-month-old girl showed increased activity in the bones and soft tissues of the left lower limb. Other causes of asymmetrical uptake of bone-seeking radiotracers in the lower limbs are discussed
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- 1994
13. Portal vein glucose entry triggers a coordinated cellular response that potentiates hepatic glucose uptake and storage in normal but not high-fat/high-fructose-fed dogs.
- Author
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Coate KC, Kraft G, Irimia JM, Smith MS, Farmer B, Neal DW, Roach PJ, Shiota M, Cherrington AD, Coate, Katie C, Kraft, Guillaume, Irimia, Jose M, Smith, Marta S, Farmer, Ben, Neal, Doss W, Roach, Peter J, Shiota, Masakazu, and Cherrington, Alan D
- Abstract
The cellular events mediating the pleiotropic actions of portal vein glucose (PoG) delivery on hepatic glucose disposition have not been clearly defined. Likewise, the molecular defects associated with postprandial hyperglycemia and impaired hepatic glucose uptake (HGU) following consumption of a high-fat, high-fructose diet (HFFD) are unknown. Our goal was to identify hepatocellular changes elicited by hyperinsulinemia, hyperglycemia, and PoG signaling in normal chow-fed (CTR) and HFFD-fed dogs. In CTR dogs, we demonstrated that PoG infusion in the presence of hyperinsulinemia and hyperglycemia triggered an increase in the activity of hepatic glucokinase (GK) and glycogen synthase (GS), which occurred in association with further augmentation in HGU and glycogen synthesis (GSYN) in vivo. In contrast, 4 weeks of HFFD feeding markedly reduced GK protein content and impaired the activation of GS in association with diminished HGU and GSYN in vivo. Furthermore, the enzymatic changes associated with PoG sensing in chow-fed animals were abolished in HFFD-fed animals, consistent with loss of the stimulatory effects of PoG delivery. These data reveal new insight into the molecular physiology of the portal glucose signaling mechanism under normal conditions and to the pathophysiology of aberrant postprandial hepatic glucose disposition evident under a diet-induced glucose-intolerant condition. [ABSTRACT FROM AUTHOR]
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- 2013
- Full Text
- View/download PDF
14. A cyclic guanosine monophosphate-dependent pathway can regulate net hepatic glucose uptake in vivo.
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An Z, Winnick JJ, Moore MC, Farmer B, Smith M, Irimia JM, Roach PJ, Cherrington AD, An, Zhibo, Winnick, Jason J, Moore, Mary C, Farmer, Ben, Smith, Marta, Irimia, Jose M, Roach, Peter J, and Cherrington, Alan D
- Abstract
We previously showed that hepatic nitric oxide regulates net hepatic glucose uptake (NHGU), an effect that can be eliminated by inhibiting hepatic soluble guanylate cyclase (sGC), suggesting that the sGC pathway is involved in the regulation of NHGU. The aim of the current study was to determine whether hepatic cyclic guanosine monophosphate (cGMP) reduces NHGU. Studies were performed on conscious dogs with transhepatic catheters. A hyperglycemic-hyperinsulinemic clamp was established in the presence of portal vein glucose infusion. 8-Br-cGMP (50 µg/kg/min) was delivered intraportally, and either the glucose load to the liver (CGMP/GLC; n = 5) or the glucose concentration entering the liver (CGMP/GCC; n = 5) was clamped at 2× basal. In the control group, saline was given intraportally (SAL; n = 10), and the hepatic glucose concentration and load were doubled. 8-Br-cGMP increased portal blood flow, necessitating the two approaches to glucose clamping in the cGMP groups. NHGU (mg/kg/min) was 5.8 ± 0.5, 2.7 ± 0.5, and 4.8 ± 0.3, whereas the fractional extraction of glucose was 11.0 ± 1, 5.5 ± 1, and 8.5 ± 1% during the last hour of the study in SAL, CGMP/GLC, and CGMP/GCC, respectively. The reduction of NHGU in response to 8-Br-cGMP was associated with increased AMP-activated protein kinase phosphorylation. These data indicate that changes in liver cGMP can regulate NHGU under postprandial conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2012
15. Acute pulmonary embolism.
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Roach PJ, Bajc M, Roach, Paul J, and Bajc, Marika
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- 2010
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16. Liver and muscle isozymes of glycogen synthase
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Roach, Pj, De Paoli Roach AA, Ahmad, Z, Camici, Marcella, Ciudad, C, Gfell, L, Lee, F. T., and Wang, Y.
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- 1985
17. Why SPECT for V/Q lung scanning?
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Bailey DL, Roach PJ, Bailey, Dale L, and Roach, Paul J
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- 2010
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18. Pulmonary emboli imaging with (99m)Tc-labelled anti-D-dimer (DI-80B3) Fab' followed by SPECT.
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Morris TA, Gerometta M, Smart RC, Eisenberg P, Roach PJ, Tsui WW, Better N, Taubman KL, Unger SA, Macfarlane D, Morris, Timothy A, Gerometta, Michael, Smart, Richard C, Eisenberg, Paul, Roach, Paul J, Tsui, Wendy W, Better, Nathan, Taubman, Kim L, Unger, Steven A, and Macfarlane, David
- Abstract
Objectives: Pre-clinical experiments demonstrated that intravenous (99m)Tc labelled DI-DD-3B6/22-80B3 humanised anti-fibrin-D-dimer Fab' fragments ((99m)Tc-DI-80B3) allowed scintigraphic imaging of acute pulmonary emboli (PE). The aims of this clinical study were to determine the safety of (99m)Tc-DI-80B3 in patients with PE and evaluate the resulting scintigraphic images for the localisation of acute PE.Materials/patients and Methods: (99m)Tc-DI-80B3 (0.5mg, 710-850MBq) was administered intravenously to subjects (n=14) with segmental or larger PE on recent contrast-enhanced helical CT scans. Thoracic SPECT scans were acquired 15 minutes, 2 hours and 4 hours afterwards. Subjects were followed for 90 days subsequently.Results: There were no serious adverse events or antibody responses associated with (99m)Tc-DI-80B3 administration. Focal accumulations of (99m)Tc-DI-80B3 on the SPECT images of the thorax acquired at four hours corresponded to pulmonary emboli detected by CT. Two independent "blinded" SPECT readers identified 79% and 71% (respectively) of the right lung and 79% and 64% (respectively) of the left lung in which CT scans disclosed PE.Conclusions: (99m)Tc-DI-80B3 is well-tolerated in patients with acute PE and does not induce an immune response. (99m)Tc-DI-80B3 may offer a novel approach to imaging PE in a clinically acceptable timeframe without exposure to potentially nephrotoxic radiographic contrast agents. [ABSTRACT FROM AUTHOR]- Published
- 2011
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19. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
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Daniel J. Klionsky, Kotb Abdelmohsen, Akihisa Abe, Md Joynal Abedin, Hagai Abeliovich, Abraham Acevedo Arozena, Hiroaki Adachi, Christopher M. Adams, Peter D. Adams, Khosrow Adeli, Peter J. Adhihetty, Sharon G. Adler, Galila Agam, Rajesh Agarwal, Manish K. Aghi, Maria Agnello, Patrizia Agostinis, Patricia V. Aguilar, Julio Aguirre Ghiso, Edoardo M. Airoldi, Slimane Ait Si Ali, Takahiko Akematsu, Emmanuel T. Akporiaye, Mohamed Al Rubeai, Guillermo M. Albaiceta, Chris Albanese, Diego Albani, Matthew L. Albert, Jesus Aldudo, Hana Algül, Mehrdad Alirezaei, Iraide Alloza, Alexandru Almasan, Maylin Almonte Beceril, Emad S. Alnemri, Covadonga Alonso, Nihal Altan Bonnet, Dario C. Altieri, Silvia Alvarez, Lydia Alvarez Erviti, Sandro Alves, Giuseppina Amadoro, Atsuo Amano, Consuelo Amantini, Santiago Ambrosio, Ivano Amelio, Amal O. Amer, Mohamed Amessou, Angelika Amon, Zhenyi An, Frank A. Anania, Stig U. Andersen, Usha P. Andley, Catherine K. Andreadi, Nathalie Andrieu Abadie, Alberto Anel, David K. Ann, Shailendra Anoopkumar Dukie, Manuela Antonioli, Hiroshi Aoki, Nadezda Apostolova, Saveria Aquila, Katia Aquilano, Koichi Araki, Eli Arama, Agustin Aranda, Jun Araya, Alexandre Arcaro, Esperanza Arias, Hirokazu Arimoto, Aileen R. Ariosa, Jane L. Armstrong, Thierry Arnould, Ivica Arsov, Katsuhiko Asanuma, Valerie Askanas, Eric Asselin, Ryuichiro Atarashi, Sally S. Atherton, Julie D. Atkin, Laura D. Attardi, Patrick Auberger, Georg Auburger, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Maria Laura Avantaggiati, Limor Avrahami, Suresh Awale, Neelam Azad, Tiziana Bachetti, Jonathan M. Backer, Dong Hun Bae, Jae sung Bae, Ok Nam Bae, Soo Han Bae, Eric H. Baehrecke, Seung Hoon Baek, Stephen Baghdiguian, Agnieszka Bagniewska Zadworna, Hua Bai, Jie Bai, Xue Yuan Bai, Yannick Bailly, Kithiganahalli Narayanaswamy Balaji, Walter Balduini, Andrea Ballabio, Rena Balzan, Rajkumar Banerjee, Gábor Bánhegyi, Haijun Bao, Benoit Barbeau, Maria D. Barrachina, Esther Barreiro, Bonnie Bartel, Alberto Bartolomé, Diane C. Bassham, Maria Teresa Bassi, Robert C. Bast Jr, Alakananda Basu, Maria Teresa Batista, Henri Batoko, Maurizio Battino, Kyle Bauckman, Bradley L. Baumgarner, K. Ulrich Bayer, Rupert Beale, Jean François Beaulieu, George R. Beck Jr, Christoph Becker, J. David Beckham, Pierre André Bédard, Patrick J. Bednarski, Thomas J. Begley, Christian Behl, Christian Behrends, Georg MN Behrens, Kevin E. Behrns, Eloy Bejarano, Amine Belaid, Francesca Belleudi, Giovanni Bénard, Guy Berchem, Daniele Bergamaschi, Matteo Bergami, Ben Berkhout, Laura Berliocchi, Amélie Bernard, Monique Bernard, Francesca Bernassola, Anne Bertolotti, Amanda S. Bess, Sébastien Besteiro, Saverio Bettuzzi, Savita Bhalla, Shalmoli Bhattacharyya, Sujit K. Bhutia, Caroline Biagosch, Michele Wolfe Bianchi, Martine Biard Piechaczyk, Viktor Billes, Claudia Bincoletto, Baris Bingol, Sara W. Bird, Marc Bitoun, Ivana Bjedov, Craig Blackstone, Lionel Blanc, Guillermo A. Blanco, Heidi Kiil Blomhoff, Emilio Boada Romero, Stefan Böckler, Marianne Boes, Kathleen Boesze Battaglia, Lawrence H. Boise, Alessandra Bolino, Andrea Boman, Paolo Bonaldo, Matteo Bordi, Jürgen Bosch, Luis M. Botana, Joelle Botti, German Bou, Marina Bouché, Marion Bouchecareilh, Marie Josée Boucher, Michael E. Boulton, Sebastien G. Bouret, Patricia Boya, Michaël Boyer Guittaut, Peter V. Bozhkov, Nathan Brady, Vania MM Braga, Claudio Brancolini, Gerhard H. Braus, José M. Bravo San Pedro, Lisa A. Brennan, Emery H. Bresnick, Patrick Brest, Dave Bridges, MarieAgnès Bringer, Marisa Brini, Glauber C. Brito, Bertha Brodin, Paul S. Brookes, Eric J. Brown, Karen Brown, Hal E. Broxmeyer, Alain Bruhat, Patricia Chakur Brum, John H. Brumell, Nicola Brunetti Pierri, Robert J. Bryson Richardson, Shilpa Buch, Alastair M. Buchan, Hikmet Budak, Dmitry V. Bulavin, Scott J. Bultman, Geert Bultynck, Vladimir Bumbasirevic, Yan Burelle, Robert E. Burke, Margit Burmeister, Peter Bütikofer, Laura Caberlotto, Ken Cadwell, Monika Cahova, Dongsheng Cai, Jingjing Cai, Qian Cai, Sara Calatayud, Nadine Camougrand, Michelangelo Campanella, Grant R. Campbell, Matthew Campbell, Silvia Campello, Robin Candau, Isabella Caniggia, Lavinia Cantoni, Lizhi Cao, Allan B. Caplan, Michele Caraglia, Claudio Cardinali, Sandra Morais Cardoso, Jennifer S. Carew, Laura A. Carleton, Cathleen R. Carlin, Silvia Carloni, Sven R. Carlsson, Didac Carmona Gutierrez, Leticia AM Carneiro, Oliana Carnevali, Serena Carra, Alice Carrier, Bernadette Carroll, Caty Casas, Josefina Casas, Giuliana Cassinelli, Perrine Castets, Susana Castro Obregon, Gabriella Cavallini, Isabella Ceccherini, Francesco Cecconi, Arthur I. Cederbaum, Valentín Ceña, Simone Cenci, Claudia Cerella, Davide Cervia, CETRULLO, SILVIA, Hassan Chaachouay, Han Jung Chae, Andrei S. Chagin, Chee Yin Chai, Gopal Chakrabarti, Georgios Chamilos, Edmond YW Chan, Matthew TV Chan, Dhyan Chandra, Pallavi Chandra, Chih Peng Chang, Raymond Chuen Chung Chang, Ta Yuan Chang, John C. Chatham, Saurabh Chatterjee, Santosh Chauhan, Yongsheng Che, Michael E. Cheetham, Rajkumar Cheluvappa, Chun Jung Chen, Gang Chen, Guang Chao Chen, Guoqiang Chen, Hongzhuan Chen, Jeff W. Chen, Jian Kang Chen, Min Chen, Mingzhou Chen, Peiwen Chen, Qi Chen, Quan Chen, Shang Der Chen, Si Chen, Steve S. L. Chen, Wei Chen, Wei Jung Chen, Wen Qiang Chen, Wenli Chen, Xiangmei Chen, Yau Hung Chen, Ye Guang Chen, Yin Chen, Yingyu Chen, Yongshun Chen, Yu Jen Chen, Yue Qin Chen, Yujie Chen, Zhen Chen, Zhong Chen, Alan Cheng, Christopher HK Cheng, Hua Cheng, Heesun Cheong, Sara Cherry, Jason Chesney, Chun Hei Antonio Cheung, Eric Chevet, Hsiang Cheng Chi, Sung Gil Chi, Fulvio Chiacchiera, Hui Ling Chiang, Roberto Chiarelli, Mario Chiariello, Marcello Chieppa, Lih Shen Chin, Mario Chiong, Gigi NC Chiu, Dong Hyung Cho, Ssang Goo Cho, William C. Cho, Yong Yeon Cho, Young Seok Cho, Augustine MK Choi, Eui Ju Choi, Eun Kyoung Choi, Jayoung Choi, Mary E. Choi, Seung Il Choi, Tsui Fen Chou, Salem Chouaib, Divaker Choubey, Vinay Choubey, Kuan Chih Chow, Kamal Chowdhury, Charleen T. Chu, Tsung Hsien Chuang, Taehoon Chun, Hyewon Chung, Taijoon Chung, Yuen Li Chung, Yong Joon Chwae, Valentina Cianfanelli, Roberto Ciarcia, Iwona A. Ciechomska, Maria Rosa Ciriolo, Mara Cirone, Sofie Claerhout, Michael J. Clague, Joan Clària, Peter GH Clarke, Robert Clarke, Emilio Clementi, Cédric Cleyrat, Miriam Cnop, Eliana M. Coccia, Tiziana Cocco, Patrice Codogno, Jörn Coers, Ezra EW Cohen, David Colecchia, Luisa Coletto, Núria S. Coll, Emma Colucci Guyon, Sergio Comincini, Maria Condello, Katherine L. Cook, Graham H. Coombs, Cynthia D. Cooper, J. Mark Cooper, Isabelle Coppens, Maria Tiziana Corasaniti, Marco Corazzari, Ramon Corbalan, Elisabeth Corcelle Termeau, Mario D. Cordero, Cristina Corral Ramos, Olga Corti, Andrea Cossarizza, Paola Costelli, Safia Costes, Susan L. Cotman, Ana Coto Montes, Sandra Cottet, Eduardo Couve, Lori R. Covey, L. Ashley Cowart, Jeffery S. Cox, Fraser P. Coxon, Carolyn B. Coyne, Mark S. Cragg, Rolf J. Craven, Tiziana Crepaldi, Jose L. Crespo, Alfredo Criollo, Valeria Crippa, Maria Teresa Cruz, Ana Maria Cuervo, Jose M. Cuezva, Taixing Cui, Pedro R. Cutillas, Mark J. Czaja, Maria F. Czyzyk Krzeska, Ruben K. Dagda, Uta Dahmen, Chunsun Dai, Wenjie Dai, Yun Dai, Kevin N. Dalby, Luisa Dalla Valle, Guillaume Dalmasso, Marcello D'Amelio, Markus Damme, Arlette Darfeuille Michaud, Catherine Dargemont, Victor M. Darley Usmar, Srinivasan Dasarathy, Biplab Dasgupta, Srikanta Dash, Crispin R. Dass, Hazel Marie Davey, Lester M. Davids, David Dávila, Roger J. Davis, Ted M. Dawson, Valina L. Dawson, Paula Daza, Jackie de Belleroche, Paul de Figueiredo, Regina Celia Bressan Queiroz de Figueiredo, José de la Fuente, Luisa De Martino, Antonella De Matteis, Guido RY De Meyer, Angelo De Milito, Mauro De Santi, Wanderley de Souza, Vincenzo De Tata, Daniela De Zio, Jayanta Debnath, Reinhard Dechant, Jean Paul Decuypere, Shane Deegan, Benjamin Dehay, Barbara Del Bello, Dominic P. Del Re, Régis Delage Mourroux, Lea MD Delbridge, Louise Deldicque, Elizabeth Delorme Axford, Yizhen Deng, Joern Dengjel, Melanie Denizot, Paul Dent, Channing J. Der, Vojo Deretic, Benoît Derrien, Eric Deutsch, Timothy P. Devarenne, Rodney J. Devenish, Sabrina Di Bartolomeo, Nicola Di Daniele, Fabio Di Domenico, Alessia Di Nardo, Simone Di Paola, Antonio Di Pietro, Livia Di Renzo, Aaron DiAntonio, Guillermo Díaz Araya, Ines Díaz Laviada, Maria T. Diaz Meco, Javier Diaz Nido, Chad A. Dickey, Robert C. Dickson, Marc Diederich, Paul Digard, Ivan Dikic, Savithrama P. Dinesh Kumar, Chan Ding, Wen Xing Ding, Zufeng Ding, Luciana Dini, Jörg HW Distler, Abhinav Diwan, Mojgan Djavaheri Mergny, Kostyantyn Dmytruk, Renwick CJ Dobson, Volker Doetsch, Karol Dokladny, Svetlana Dokudovskaya, Massimo Donadelli, X. Charlie Dong, Xiaonan Dong, Zheng Dong, Terrence M. Donohue Jr, Kelly S. Doran, Gabriella D'Orazi, Gerald W. Dorn II, Victor Dosenko, Sami Dridi, Liat Drucker, Jie Du, Li Lin Du, Lihuan Du, André du Toit, Priyamvada Dua, Lei Duan, Pu Duann, Vikash Kumar Dubey, Michael R. Duchen, Michel A. Duchosal, Helene Duez, Isabelle Dugail, Verónica I. Dumit, Mara C. Duncan, Elaine A. Dunlop, William A. Dunn Jr, Nicolas Dupont, Luc Dupuis, Raúl V. Durán, Thomas M. Durcan, Stéphane Duvezin Caubet, Umamaheswar Duvvuri, Vinay Eapen, Darius Ebrahimi Fakhari, Arnaud Echard, Leopold Eckhart, Charles L. Edelstein, Aimee L. Edinger, Ludwig Eichinger, Tobias Eisenberg, Avital Eisenberg Lerner, N. Tony Eissa, Wafik S. El Deiry, Victoria El Khoury, Zvulun Elazar, Hagit Eldar Finkelman, Chris JH Elliott, Enzo Emanuele, Urban Emmenegger, Nikolai Engedal, Anna Mart Engelbrecht, Simone Engelender, Jorrit M. Enserink, Ralf Erdmann, Jekaterina Erenpreisa, Rajaraman Eri, Jason L. Eriksen, Andreja Erman, Ricardo Escalante, Eeva Liisa Eskelinen, Lucile Espert, Lorena Esteban Martínez, Thomas J. Evans, Mario Fabri, Gemma Fabrias, Cinzia Fabrizi, Antonio Facchiano, Nils J. Færgeman, Alberto Faggioni, W. Douglas Fairlie, Chunhai Fan, Daping Fan, Jie Fan, Shengyun Fang, Manolis Fanto, Alessandro Fanzani, Thomas Farkas, Mathias Faure, Francois B. Favier, Howard Fearnhead, Massimo Federici, Erkang Fei, Tania C. Felizardo, Hua Feng, Yibin Feng, Yuchen Feng, Thomas A. Ferguson, Álvaro F. Fernández, Maite G. Fernandez Barrena, Jose C. Fernandez Checa, Arsenio Fernández López, Martin E. Fernandez Zapico, Olivier Feron, Elisabetta Ferraro, Carmen Veríssima Ferreira Halder, Laszlo Fesus, Ralph Feuer, Fabienne C. Fiesel, Eduardo C. Filippi Chiela, Giuseppe Filomeni, Gian Maria Fimia, John H. Fingert, Steven Finkbeiner, Toren Finkel, Filomena Fiorito, Paul B. Fisher, Marc Flajolet, FLAMIGNI, FLAVIO, Oliver Florey, Salvatore Florio, R. Andres Floto, Marco Folini, Carlo Follo, Edward A. Fon, Francesco Fornai, Franco Fortunato, Alessandro Fraldi, Rodrigo Franco, Arnaud Francois, Aurélie François, Lisa B. Frankel, Iain DC Fraser, Norbert Frey, Damien G. Freyssenet, Christian Frezza, Scott L. Friedman, Daniel E. Frigo, Dongxu Fu, José M. Fuentes, Juan Fueyo, Yoshio Fujitani, Yuuki Fujiwara, Mikihiro Fujiya, Mitsunori Fukuda, Simone Fulda, Carmela Fusco, Bozena Gabryel, Matthias Gaestel, Philippe Gailly, Malgorzata Gajewska, Sehamuddin Galadari, Gad Galili, Inmaculada Galindo, Maria F. Galindo, Giovanna Galliciotti, Lorenzo Galluzzi, Luca Galluzzi, Vincent Galy, Noor Gammoh, Sam Gandy, Anand K. Ganesan, Swamynathan Ganesan, Ian G. Ganley, Monique Gannagé, Fen Biao Gao, Feng Gao, Jian Xin Gao, Lorena García Nannig, Eleonora García Véscovi, Marina Garcia Macía, Carmen Garcia Ruiz, Abhishek D. Garg, Pramod Kumar Garg, Ricardo Gargini, Nils Christian Gassen, Damián Gatica, Evelina Gatti, Julie Gavard, Evripidis Gavathiotis, Liang Ge, Pengfei Ge, Shengfang Ge, Po Wu Gean, Vania Gelmetti, Armando A. Genazzani, Jiefei Geng, Pascal Genschik, Lisa Gerner, Jason E. Gestwicki, David A. Gewirtz, Saeid Ghavami, Eric Ghigo, Debabrata Ghosh, Anna Maria Giammarioli, Francesca Giampieri, Claudia Giampietri, Alexandra Giatromanolaki, Derrick J. Gibbings, Lara Gibellini, Spencer B. Gibson, Vanessa Ginet, Antonio Giordano, Flaviano Giorgini, Elisa Giovannetti, Stephen E. Girardin, Suzana Gispert, Sandy Giuliano, Candece L. Gladson, Alvaro Glavic, Martin Gleave, Nelly Godefroy, Robert M. Gogal Jr, Kuppan Gokulan, Gustavo H. Goldman, Delia Goletti, Michael S. Goligorsky, Aldrin V. Gomes, Ligia C. Gomes, Hernando Gomez, Candelaria Gomez Manzano, Rubén Gómez Sánchez, Dawit AP Gonçalves, Ebru Goncu, Qingqiu Gong, Céline Gongora, Carlos B. Gonzalez, Pedro Gonzalez Alegre, Pilar Gonzalez Cabo, Rosa Ana González Polo, Ing Swie Goping, Carlos Gorbea, Nikolai V. Gorbunov, Daphne R. Goring, Adrienne M. Gorman, Sharon M. Gorski, Sandro Goruppi, Shino Goto Yamada, Cecilia Gotor, Roberta A. Gottlieb, Illana Gozes, Devrim Gozuacik, Yacine Graba, Martin Graef, Giovanna E. Granato, Gary Dean Grant, Steven Grant, Giovanni Luca Gravina, Douglas R. Green, Alexander Greenhough, Michael T. Greenwood, Benedetto Grimaldi, Frédéric Gros, Charles Grose, Jean Francois Groulx, Florian Gruber, Paolo Grumati, Tilman Grune, Jun Lin Guan, Kun Liang Guan, Barbara Guerra, Carlos Guillen, Kailash Gulshan, Jan Gunst, Chuanyong Guo, Lei Guo, Ming Guo, Wenjie Guo, Xu Guang Guo, Andrea A. Gust, Åsa B. Gustafsson, Elaine Gutierrez, Maximiliano G. Gutierrez, Ho Shin Gwak, Albert Haas, James E. Haber, Shinji Hadano, Monica Hagedorn, David R. Hahn, Andrew J. Halayko, Anne Hamacher Brady, Kozo Hamada, Ahmed Hamai, Andrea Hamann, Maho Hamasaki, Isabelle Hamer, Qutayba Hamid, Ester M. Hammond, Feng Han, Weidong Han, James T. Handa, John A. Hanover, Malene Hansen, Masaru Harada, Ljubica Harhaji Trajkovic, J. Wade Harper, Abdel Halim Harrath, Adrian L. Harris, James Harris, Udo Hasler, Peter Hasselblatt, Kazuhisa Hasui, Robert G. Hawley, Teresa S. Hawley, Congcong He, Cynthia Y. He, Fengtian He, Gu He, Rong Rong He, Xian Hui He, You Wen He, Yu Ying He, Joan K. Heath, Marie Josée Hébert, Robert A. Heinzen, Gudmundur Vignir Helgason, Michael Hensel, Elizabeth P. Henske, Chengtao Her, Paul K. Herman, Agustín Hernández, Carlos Hernandez, Sonia Hernández Tiedra, Claudio Hetz, P. Robin Hiesinger, Katsumi Higaki, Sabine Hilfiker, Bradford G. Hill, Joseph A. Hill, William D. Hill, Keisuke Hino, Daniel Hofius, Paul Hofman, Günter U. Höglinger, Jörg Höhfeld, Marina K. Holz, Yonggeun Hong, David A. Hood, Jeroen JM Hoozemans, Thorsten Hoppe, Chin Hsu, Chin Yuan Hsu, Li Chung Hsu, Dong Hu, Guochang Hu, Hong Ming Hu, Hongbo Hu, Ming Chang Hu, Yu Chen Hu, Zhuo Wei Hu, Fang Hua, Ya Hua, Canhua Huang, Huey Lan Huang, Kuo How Huang, Kuo Yang Huang, Shile Huang, Shiqian Huang, Wei Pang Huang, Yi Ran Huang, Yong Huang, Yunfei Huang, Tobias B. Huber, Patricia Huebbe, Won Ki Huh, Juha J. Hulmi, Gang Min Hur, James H. Hurley, Zvenyslava Husak, Sabah NA Hussain, Salik Hussain, Jung Jin Hwang, Seungmin Hwang, Thomas IS Hwang, Atsuhiro Ichihara, Yuzuru Imai, Carol Imbriano, Megumi Inomata, Takeshi Into, Valentina Iovane, Juan L. Iovanna, Renato V. Iozzo, Nancy Y. Ip, Javier E. Irazoqui, Pablo Iribarren, Yoshitaka Isaka, Aleksandra J. Isakovic, Harry Ischiropoulos, Jeffrey S. Isenberg, Mohammad Ishaq, Hiroyuki Ishida, Isao Ishii, Jane E. Ishmael, Ciro Isidoro, Ken ichi Isobe, Erika Isono, Shohreh Issazadeh Navikas, Koji Itahana, Eisuke Itakura, Andrei I. Ivanov, Anand Krishnan V. Iyer, José M. Izquierdo, Yotaro Izumi, Valentina Izzo, Marja Jäättelä, Nadia Jaber, Daniel John Jackson, William T. Jackson, Tony George Jacob, Thomas S. Jacques, Chinnaswamy Jagannath, Ashish Jain, Nihar Ranjan Jana, Byoung Kuk Jang, Alkesh Jani, Bassam Janji, Paulo Roberto Jannig, Patric J. Jansson, Steve Jean, Marina Jendrach, Ju Hong Jeon, Niels Jessen, Eui Bae Jeung, Kailiang Jia, Lijun Jia, Hong Jiang, Hongchi Jiang, Liwen Jiang, Teng Jiang, Xiaoyan Jiang, Xuejun Jiang, Ying Jiang, Yongjun Jiang, Alberto Jiménez, Cheng Jin, Hongchuan Jin, Lei Jin, Meiyan Jin, Shengkan Jin, Umesh Kumar Jinwal, Eun Kyeong Jo, Terje Johansen, Daniel E. Johnson, Gail VW Johnson, James D. Johnson, Eric Jonasch, Chris Jones, Leo AB Joosten, Joaquin Jordan, Anna Maria Joseph, Bertrand Joseph, Annie M. Joubert, Dianwen Ju, Jingfang Ju, Hsueh Fen Juan, Katrin Juenemann, Gábor Juhász, Hye Seung Jung, Jae U. Jung, Yong Keun Jung, Heinz Jungbluth, Matthew J. Justice, Barry Jutten, Nadeem O. Kaakoush, Kai Kaarniranta, Allen Kaasik, Tomohiro Kabuta, Bertrand Kaeffer, Katarina Kågedal, Alon Kahana, Shingo Kajimura, Or Kakhlon, Manjula Kalia, Dhan V. Kalvakolanu, Yoshiaki Kamada, Konstantinos Kambas, Vitaliy O. Kaminskyy, Harm H. Kampinga, Mustapha Kandouz, Chanhee Kang, Rui Kang, Tae Cheon Kang, Tomotake Kanki, Thirumala Devi Kanneganti, Haruo Kanno, Anumantha G. Kanthasamy, Marc Kantorow, Maria Kaparakis Liaskos, Orsolya Kapuy, Vassiliki Karantza, Md Razaul Karim, Parimal Karmakar, Arthur Kaser, Susmita Kaushik, Thomas Kawula, A. Murat Kaynar, Po Yuan Ke, Zun Ji Ke, John H. Kehrl, Kate E. Keller, Jongsook Kim Kemper, Anne K. Kenworthy, Oliver Kepp, Andreas Kern, Santosh Kesari, David Kessel, Robin Ketteler, Isis do Carmo Kettelhut, Bilon Khambu, Muzamil Majid Khan, Vinoth KM Khandelwal, Sangeeta Khare, Juliann G. Kiang, Amy A. Kiger, Akio Kihara, Arianna L. Kim, Cheol Hyeon Kim, Deok Ryong Kim, Do Hyung Kim, Eung Kweon Kim, Hye Young Kim, Hyung Ryong Kim, Jae Sung Kim, Jeong Hun Kim, Jin Cheon Kim, Jin Hyoung Kim, Kwang Woon Kim, Michael D. Kim, Moon Moo Kim, Peter K. Kim, Seong Who Kim, Soo Youl Kim, Yong Sun Kim, Yonghyun Kim, Adi Kimchi, Alec C. Kimmelman, Tomonori Kimura, Jason S. King, Karla Kirkegaard, Vladimir Kirkin, Lorrie A. Kirshenbaum, Shuji Kishi, Yasuo Kitajima, Katsuhiko Kitamoto, Yasushi Kitaoka, Kaio Kitazato, Rudolf A. Kley, Walter T. Klimecki, Michael Klinkenberg, Jochen Klucken, Helene Knævelsrud, Erwin Knecht, Laura Knuppertz, Jiunn Liang Ko, Satoru Kobayashi, Jan C. Koch, Christelle Koechlin Ramonatxo, Ulrich Koenig, Young Ho Koh, Katja Köhler, Sepp D. Kohlwein, Masato Koike, Masaaki Komatsu, Eiki Kominami, Dexin Kong, Hee Jeong Kong, Eumorphia G. Konstantakou, Benjamin T. Kopp, Tamas Korcsmaros, Laura Korhonen, Viktor I. Korolchuk, Nadya V. Koshkina, Yanjun Kou, Michael I. Koukourakis, Constantinos Koumenis, Attila L. Kovács, Tibor Kovács, Werner J. Kovacs, Daisuke Koya, Claudine Kraft, Dimitri Krainc, Helmut Kramer, Tamara Kravic Stevovic, Wilhelm Krek, Carole Kretz Remy, Roswitha Krick, Malathi Krishnamurthy, Janos Kriston Vizi, Guido Kroemer, Michael C. Kruer, Rejko Kruger, Nicholas T. Ktistakis, Kazuyuki Kuchitsu, Christian Kuhn, Addanki Pratap Kumar, Anuj Kumar, Ashok Kumar, Deepak Kumar, Dhiraj Kumar, Rakesh Kumar, Sharad Kumar, Mondira Kundu, Hsing Jien Kung, Atsushi Kuno, Sheng Han Kuo, Jeff Kuret, Tino Kurz, Terry Kwok, Taeg Kyu Kwon, Yong Tae Kwon, Irene Kyrmizi, Albert R. La Spada, Frank Lafont, Tim Lahm, Aparna Lakkaraju, Truong Lam, Trond Lamark, Steve Lancel, Terry H. Landowski, Darius JR Lane, Jon D. Lane, Cinzia Lanzi, Pierre Lapaquette, Louis R. Lapierre, Jocelyn Laporte, Johanna Laukkarinen, Gordon W. Laurie, Sergio Lavandero, Lena Lavie, Matthew J. LaVoie, Betty Yuen Kwan Law, Helen Ka wai Law, Kelsey B. Law, Robert Layfield, Pedro A. Lazo, Laurent Le Cam, Karine G. Le Roch, Hervé Le Stunff, Vijittra Leardkamolkarn, Marc Lecuit, Byung Hoon Lee, Che Hsin Lee, Erinna F. Lee, Gyun Min Lee, He Jin Lee, Hsinyu Lee, Jae Keun Lee, Jongdae Lee, Juhyun Lee, Jun Hee Lee, Michael Lee, Myung Shik Lee, Patty J. Lee, Sam W. Lee, Seung Jae Lee, Shiow Ju Lee, Stella Y. Lee, Sug Hyung Lee, Sung Sik Lee, Sung Joon Lee, Sunhee Lee, Ying Ray Lee, Yong J. Lee, Young H. Lee, Christiaan Leeuwenburgh, Sylvain Lefort, Renaud Legouis, Jinzhi Lei, Qun Ying Lei, David A. Leib, Gil Leibowitz, Istvan Lekli, Stéphane D. Lemaire, John J. Lemasters, Marius K. Lemberg, Antoinette Lemoine, Shuilong Leng, Guido Lenz, Paola Lenzi, Lilach O. Lerman, Daniele Lettieri Barbato, Julia I. Ju Leu, Hing Y. Leung, Beth Levine, Patrick A. Lewis, Frank Lezoualc'h, Chi Li, Faqiang Li, Feng Jun Li, Jun Li, Ke Li, Lian Li, Min Li, Qiang Li, Rui Li, Sheng Li, Wei Li, Xiaotao Li, Yumin Li, Jiqin Lian, Chengyu Liang, Qiangrong Liang, Yulin Liao, Joana Liberal, Pawel P. Liberski, Pearl Lie, Andrew P. Lieberman, Hyunjung Jade Lim, Kah Leong Lim, Kyu Lim, Raquel T. Lima, Chang Shen Lin, Chiou Feng Lin, Fang Lin, Fangming Lin, Fu Cheng Lin, Kui Lin, Kwang Huei Lin, Pei Hui Lin, Tianwei Lin, Wan Wan Lin, Yee Shin Lin, Yong Lin, Rafael Linden, Dan Lindholm, Lisa M. Lindqvist, Paul Lingor, Andreas Linkermann, Lance A. Liotta, Marta M. Lipinski, Vitor A. Lira, Michael P. Lisanti, Paloma B. Liton, Bo Liu, Chong Liu, Chun Feng Liu, Fei Liu, Hung Jen Liu, Jianxun Liu, Jing Jing Liu, Jing Lan Liu, Ke Liu, Leyuan Liu, Liang Liu, Quentin Liu, Rong Yu Liu, Shiming Liu, Shuwen Liu, Wei Liu, Xian De Liu, Xiangguo Liu, Xiao Hong Liu, Xinfeng Liu, Xu Liu, Xueqin Liu, Yang Liu, Yule Liu, Zexian Liu, Zhe Liu, Juan P. Liuzzi, Gérard Lizard, Mila Ljujic, Irfan J. Lodhi, Susan E. Logue, Bal L. Lokeshwar, Yun Chau Long, Sagar Lonial, Benjamin Loos, Carlos López Otín, Cristina López Vicario, Mar Lorente, Philip L. Lorenzi, Péter Lõrincz, Marek Los, Michael T. Lotze, Penny E. Lovat, Binfeng Lu, Bo Lu, Jiahong Lu, Qing Lu, She Min Lu, Shuyan Lu, Yingying Lu, Frédéric Luciano, Shirley Luckhart, John Milton Lucocq, Paula Ludovico, Aurelia Lugea, Nicholas W. Lukacs, Julian J. Lum, Anders H. Lund, Honglin Luo, Jia Luo, Shouqing Luo, Claudio Luparello, Timothy Lyons, Jianjie Ma, Yi Ma, Yong Ma, Zhenyi Ma, Juliano Machado, Glaucia M. Machado Santelli, Fernando Macian, Gustavo C. MacIntosh, Jeffrey P. MacKeigan, Kay F. Macleod, John D. MacMicking, Lee Ann MacMillan Crow, Frank Madeo, Muniswamy Madesh, Julio Madrigal Matute, Akiko Maeda, Tatsuya Maeda, Gustavo Maegawa, Emilia Maellaro, Hannelore Maes, Marta Magariños, Kenneth Maiese, Tapas K. Maiti, Luigi Maiuri, Maria Chiara Maiuri, Carl G. Maki, Roland Malli, Walter Malorni, Alina Maloyan, Fathia Mami Chouaib, Na Man, Joseph D. Mancias, Eva Maria Mandelkow, Michael A. Mandell, Angelo A. Manfredi, Serge N. Manié, Claudia Manzoni, Kai Mao, Zixu Mao, Zong Wan Mao, Philippe Marambaud, Anna Maria Marconi, Zvonimir Marelja, Gabriella Marfe, Marta Margeta, Eva Margittai, Muriel Mari, Francesca V. Mariani, Concepcio Marin, Sara Marinelli, Guillermo Mariño, Ivanka Markovic, Rebecca Marquez, MARTELLI, ALBERTO MARIA, Sascha Martens, Katie R. Martin, Seamus J. Martin, Shaun Martin, Miguel A. Martin Acebes, Paloma Martín Sanz, Camille Martinand Mari, Wim Martinet, Jennifer Martinez, Nuria Martinez Lopez, Ubaldo Martinez Outschoorn, Moisés Martínez Velázquez, Marta Martinez Vicente, Waleska Kerllen Martins, Hirosato Mashima, James A. Mastrianni, Giuseppe Matarese, Paola Matarrese, Roberto Mateo, Satoaki Matoba, Naomichi Matsumoto, Takehiko Matsushita, Akira Matsuura, Takeshi Matsuzawa, Mark P. Mattson, Soledad Matus, Norma Maugeri, Caroline Mauvezin, Andreas Mayer, Dusica Maysinger, Guillermo D. Mazzolini, Mary Kate McBrayer, Kimberly McCall, Craig McCormick, Gerald M. McInerney, Skye C. McIver, Sharon McKenna, John J. McMahon, Iain A. McNeish, Fatima Mechta Grigoriou, Jan Paul Medema, Diego L. Medina, Klara Megyeri, Maryam Mehrpour, Jawahar L. Mehta, Yide Mei, Ute Christiane Meier, Alfred J. Meijer, Alicia Meléndez, Gerry Melino, Sonia Melino, Edesio Jose Tenorio de Melo, Maria A. Mena, Marc D. Meneghini, Javier A. Menendez, Regina Menezes, Liesu Meng, Ling hua Meng, Songshu Meng, Rossella Menghini, A. Sue Menko, Rubem FS Menna Barreto, Manoj B. Menon, Marco A. Meraz Ríos, Giuseppe Merla, Luciano Merlini, Angelica M. Merlot, Andreas Meryk, Stefania Meschini, Joel N. Meyer, Man tian Mi, Chao Yu Miao, Lucia Micale, Simon Michaeli, Carine Michiels, FRANCO MIGLIACCIO, ANNA RITA, Anastasia Susie Mihailidou, Dalibor Mijaljica, Katsuhiko Mikoshiba, Enrico Milan, Leonor Miller Fleming, Gordon B. Mills, Ian G. Mills, Georgia Minakaki, Berge A. Minassian, Xiu Fen Ming, Farida Minibayeva, Elena A. Minina, Justine D. Mintern, Saverio Minucci, Antonio Miranda Vizuete, Claire H. Mitchell, Shigeki Miyamoto, Keisuke Miyazawa, Noboru Mizushima, Katarzyna Mnich, Baharia Mograbi, Simin Mohseni, Luis Ferreira Moita, Marco Molinari, Maurizio Molinari, Andreas Buch Møller, Bertrand Mollereau, Faustino Mollinedo, Marco Mongillo, Martha M. Monick, Serena Montagnaro, Craig Montell, Darren J. Moore, Michael N. Moore, Rodrigo Mora Rodriguez, Paula I. Moreira, Etienne Morel, Maria Beatrice Morelli, Sandra Moreno, Michael J. Morgan, Arnaud Moris, Yuji Moriyasu, Janna L. Morrison, Lynda A. Morrison, Eugenia Morselli, Jorge Moscat, Pope L. Moseley, Serge Mostowy, Elisa Motori, Denis Mottet, Jeremy C. Mottram, Charbel E. H. Moussa, Vassiliki E. Mpakou, Hasan Mukhtar, Jean M. Mulcahy Levy, Sylviane Muller, Raquel Muñoz Moreno, Cristina Muñoz Pinedo, Christian Münz, Maureen E. Murphy, James T. Murray, Aditya Murthy, Indira U. Mysorekar, Ivan R. Nabi, Massimo Nabissi, Gustavo A. Nader, Yukitoshi Nagahara, Yoshitaka Nagai, Kazuhiro Nagata, Anika Nagelkerke, Péter Nagy, Samisubbu R. Naidu, Sreejayan Nair, Hiroyasu Nakano, Hitoshi Nakatogawa, Meera Nanjundan, Gennaro Napolitano, Naweed I. Naqvi, Roberta Nardacci, Derek P. Narendra, Masashi Narita, Anna Chiara Nascimbeni, Ramesh Natarajan, Luiz C. Navegantes, Steffan T. Nawrocki, Taras Y. Nazarko, Volodymyr Y. Nazarko, Thomas Neill, Luca M. Neri, Mihai G. Netea, Romana T. Netea Maier, Bruno M. Neves, Paul A. Ney, Ioannis P. Nezis, Hang TT Nguyen, Huu Phuc Nguyen, Anne Sophie Nicot, Hilde Nilsen, Per Nilsson, Mikio Nishimura, Ichizo Nishino, Mireia Niso Santano, Hua Niu, Ralph A. Nixon, Vincent CO Njar, Takeshi Noda, Angelika A. Noegel, Elsie Magdalena Nolte, Erik Norberg, Koenraad K. Norga, Sakineh Kazemi Noureini, Shoji Notomi, Lucia Notterpek, Karin Nowikovsky, Nobuyuki Nukina, Thorsten Nürnberger, Valerie B. O'Donnell, Tracey O'Donovan, Peter J. O'Dwyer, Ina Oehme, Clara L. Oeste, Michinaga Ogawa, Besim Ogretmen, Yuji Ogura, Young J. Oh, Masaki Ohmuraya, Takayuki Ohshima, Rani Ojha, Koji Okamoto, Toshiro Okazaki, F. Javier Oliver, Karin Ollinger, Stefan Olsson, Daniel P. Orban, Paulina Ordonez, Idil Orhon, Laszlo Orosz, Eyleen J. O'Rourke, Helena Orozco, Angel L. Ortega, Elena Ortona, Laura D. Osellame, Junko Oshima, Shigeru Oshima, Heinz D. Osiewacz, Takanobu Otomo, Kinya Otsu, Jing hsiung James Ou, Tiago F. Outeiro, Dong yun Ouyang, Hongjiao Ouyang, Michael Overholtzer, Michelle A. Ozbun, P. Hande Ozdinler, Bulent Ozpolat, Consiglia Pacelli, Paolo Paganetti, Guylène Page, Gilles Pages, Ugo Pagnini, Beata Pajak, Stephen C. Pak, Karolina Pakos Zebrucka, Nazzy Pakpour, Zdena Palková, Francesca Palladino, Kathrin Pallauf, Nicolas Pallet, Marta Palmieri, Søren R. Paludan, Camilla Palumbo, Silvia Palumbo, Olatz Pampliega, Hongming Pan, Wei Pan, Theocharis Panaretakis, Aseem Pandey, Areti Pantazopoulou, Zuzana Papackova, Daniela L. Papademetrio, Issidora Papassideri, Alessio Papini, Nirmala Parajuli, Julian Pardo, Vrajesh V. Parekh, Giancarlo Parenti, Jong In Park, Junsoo Park, Ohkmae K. Park, Roy Parker, Rosanna Parlato, Jan B. Parys, Katherine R. Parzych, Jean Max Pasquet, Benoit Pasquier, Kishore BS Pasumarthi, Daniel Patschan, Cam Patterson, Sophie Pattingre, Scott Pattison, Arnim Pause, Hermann Pavenstädt, Flaminia Pavone, Zully Pedrozo, Fernando J. Peña, Miguel A. Peñalva, Mario Pende, Jianxin Peng, Fabio Penna, Josef M. Penninger, Anna Pensalfini, Salvatore Pepe, Gustavo JS Pereira, Paulo C. Pereira, Verónica Pérez de la Cruz, María Esther Pérez Pérez, Diego Pérez Rodríguez, Dolores Pérez Sala, Celine Perier, Andras Perl, David H. Perlmutter, Ida Perrotta, Shazib Pervaiz, Maija Pesonen, Jeffrey E. Pessin, Godefridus J. Peters, Morten Petersen, Irina Petrache, Basil J. Petrof, Goran Petrovski, James M. Phang, Mauro Piacentini, Marina Pierdominici, Philippe Pierre, Valérie Pierrefite Carle, Federico Pietrocola, Felipe X. Pimentel Muiños, Mario Pinar, Benjamin Pineda, Ronit Pinkas Kramarski, Marcello Pinti, Paolo Pinton, Bilal Piperdi, James M. Piret, Leonidas C. Platanias, Harald W. Platta, Edward D. Plowey, Stefanie Pöggeler, Marc Poirot, Peter Polčic, Angelo Poletti, Audrey H. Poon, Hana Popelka, Blagovesta Popova, Izabela Poprawa, Shibu M. Poulose, Joanna Poulton, Scott K. Powers, Ted Powers, Mercedes Pozuelo Rubio, Krisna Prak, Reinhild Prange, Mark Prescott, Muriel Priault, Sharon Prince, Richard L. Proia, Tassula Proikas Cezanne, Holger Prokisch, Vasilis J. Promponas, Karin Przyklenk, Rosa Puertollano, Subbiah Pugazhenthi, Luigi Puglielli, Aurora Pujol, Julien Puyal, Dohun Pyeon, Xin Qi, Wen bin Qian, Zheng Hong Qin, Yu Qiu, Ziwei Qu, Joe Quadrilatero, Frederick Quinn, Nina Raben, Hannah Rabinowich, Flavia Radogna, Michael J. Ragusa, Mohamed Rahmani, Komal Raina, Sasanka Ramanadham, Rajagopal Ramesh, Abdelhaq Rami, Sarron Randall Demllo, Felix Randow, Hai Rao, V. Ashutosh Rao, Blake B. Rasmussen, Tobias M. Rasse, Edward A. Ratovitski, Pierre Emmanuel Rautou, Swapan K. Ray, Babak Razani, Bruce H. Reed, Fulvio Reggiori, Markus Rehm, Andreas S. Reichert, Theo Rein, David J. Reiner, Eric Reits, Jun Ren, Xingcong Ren, Maurizio Renna, Jane EB Reusch, Jose L. Revuelta, Leticia Reyes, Alireza R. Rezaie, Robert I. Richards, Des R. Richardson, Clémence Richetta, Michael A. Riehle, Bertrand H. Rihn, Yasuko Rikihisa, Brigit E. Riley, Gerald Rimbach, Maria Rita Rippo, Konstantinos Ritis, Federica Rizzi, Elizete Rizzo, Peter J. Roach, Jeffrey Robbins, Michel Roberge, Gabriela Roca, Maria Carmela Roccheri, Sonia Rocha, Cecilia MP Rodrigues, Clara I. Rodríguez, Santiago Rodriguez de Cordoba, Natalia Rodriguez Muela, Jeroen Roelofs, Vladimir V. Rogov, Troy T. Rohn, Bärbel Rohrer, Davide Romanelli, Luigina Romani, Patricia Silvia Romano, M. Isabel G. Roncero, Jose Luis Rosa, Alicia Rosello, Kirill V. Rosen, Philip Rosenstiel, Magdalena Rost Roszkowska, Kevin A. Roth, Gael Roué, Mustapha Rouis, Kasper M. Rouschop, Daniel T. Ruan, Diego Ruano, David C. Rubinsztein, Edmund B. Rucker III, Assaf Rudich, Emil Rudolf, Ruediger Rudolf, Markus A. Ruegg, Carmen Ruiz Roldan, Avnika Ashok Ruparelia, Paola Rusmini, David W. Russ, Gian Luigi Russo, Giuseppe Russo, Rossella Russo, Tor Erik Rusten, Victoria Ryabovol, Kevin M. Ryan, Stefan W. Ryter, David M. Sabatini, Michael Sacher, Carsten Sachse, Michael N. Sack, Junichi Sadoshima, Paul Saftig, Ronit Sagi Eisenberg, Sumit Sahni, Pothana Saikumar, Tsunenori Saito, Tatsuya Saitoh, Koichi Sakakura, Machiko Sakoh Nakatogawa, Yasuhito Sakuraba, María Salazar Roa, Paolo Salomoni, Ashok K. Saluja, Paul M. Salvaterra, Rosa Salvioli, Afshin Samali, Anthony MJ Sanchez, José A. Sánchez Alcázar, Ricardo Sanchez Prieto, Marco Sandri, Miguel A. Sanjuan, Stefano Santaguida, Laura Santambrogio, Giorgio Santoni, Claudia Nunes dos Santos, Shweta Saran, Marco Sardiello, Graeme Sargent, Pallabi Sarkar, Sovan Sarkar, Maria Rosa Sarrias, Minnie M. Sarwal, Chihiro Sasakawa, Motoko Sasaki, Miklos Sass, Ken Sato, Miyuki Sato, Joseph Satriano, Niramol Savaraj, Svetlana Saveljeva, Liliana Schaefer, Ulrich E. Schaible, Michael Scharl, Hermann M. Schatzl, Randy Schekman, Wiep Scheper, Alfonso Schiavi, Hyman M. Schipper, Hana Schmeisser, Jens Schmidt, Ingo Schmitz, Bianca E. Schneider, E. Marion Schneider, Jaime L. Schneider, Eric A. Schon, Miriam J. Schönenberger, Axel H. Schönthal, Daniel F. Schorderet, Bernd Schröder, Sebastian Schuck, Ryan J. Schulze, Melanie Schwarten, Thomas L. Schwarz, Sebastiano Sciarretta, Kathleen Scotto, A. Ivana Scovassi, Robert A. Screaton, Mark Screen, Hugo Seca, Simon Sedej, Laura Segatori, Nava Segev, Per O. Seglen, Jose M. Seguí Simarro, Juan Segura Aguilar, Ekihiro Seki, Iban Seiliez, Christian Sell, Clay F. Semenkovich, Gregg L. Semenza, Utpal Sen, Andreas L. Serra, Ana Serrano Puebla, Hiromi Sesaki, Takao Setoguchi, Carmine Settembre, John J. Shacka, Ayesha N. Shajahan Haq, Irving M. Shapiro, Shweta Sharma, Hua She, C. K. James Shen, Chiung Chyi Shen, Han Ming Shen, Sanbing Shen, Weili Shen, Rui Sheng, Xianyong Sheng, Zu Hang Sheng, Trevor G. Shepherd, Junyan Shi, Qiang Shi, Qinghua Shi, Yuguang Shi, Shusaku Shibutani, Kenichi Shibuya, Yoshihiro Shidoji, Jeng Jer Shieh, Chwen Ming Shih, Yohta Shimada, Shigeomi Shimizu, Dong Wook Shin, Mari L. Shinohara, Michiko Shintani, Takahiro Shintani, Tetsuo Shioi, Ken Shirabe, Ronit Shiri Sverdlov, Orian Shirihai, Gordon C. Shore, Chih Wen Shu, Deepak Shukla, Andriy A. Sibirny, Valentina Sica, Christina J. Sigurdson, Einar M. Sigurdsson, Puran Singh Sijwali, Beata Sikorska, Wilian A. Silveira, Sandrine Silvente Poirot, Gary A. 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Szlosarek, Heinrich Taegtmeyer, Marco Tafani, Emmanuel Taillebourg, Stephen WG Tait, Krisztina Takacs Vellai, Yoshinori Takahashi, Szabolcs Takáts, Genzou Takemura, Nagio Takigawa, Nicholas J. Talbot, Elena Tamagno, Jerome Tamburini, Cai Ping Tan, Lan Tan, Mei Lan Tan, Ming Tan, Yee Joo Tan, Keiji Tanaka, Masaki Tanaka, Daolin Tang, Dingzhong Tang, Guomei Tang, Isei Tanida, Kunikazu Tanji, Bakhos A. Tannous, Jose A. Tapia, Inmaculada Tasset Cuevas, Marc Tatar, Iman Tavassoly, Nektarios Tavernarakis, Allen Taylor, Graham S. Taylor, Gregory A. Taylor, J. Paul Taylor, Mark J. Taylor, Elena V. Tchetina, Andrew R. Tee, Fatima Teixeira Clerc, Sucheta Telang, Tewin Tencomnao, Ba Bie Teng, Ru Jeng Teng, Faraj Terro, Gianluca Tettamanti, Arianne L. Theiss, Anne E. Theron, Kelly Jean Thomas, Marcos P. Thomé, Paul G. Thomes, Andrew Thorburn, Jeremy Thorner, Thomas Thum, Michael Thumm, Teresa LM Thurston, Ling Tian, Andreas Till, Jenny Pan yun Ting, Vladimir I. 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Valverde, Greet Van den Berghe, Ludo Van Den Bosch, Gijs R. van den Brink, F. Gisou van der Goot, Ida J. van der Klei, Luc JW van der Laan, Wouter G. van Doorn, Marjolein van Egmond, Kenneth L. van Golen, Luc Van Kaer, Menno van Lookeren Campagne, Peter Vandenabeele, Wim Vandenberghe, Ilse Vanhorebeek, Isabel Varela Nieto, M. Helena Vasconcelos, Radovan Vasko, Demetrios G. Vavvas, Ignacio Vega Naredo, Guillermo Velasco, Athanassios D. Velentzas, Panagiotis D. Velentzas, Tibor Vellai, Edo Vellenga, Mikkel Holm Vendelbo, Kartik Venkatachalam, Natascia Ventura, Salvador Ventura, Patrícia ST Veras, Mireille Verdier, Beata G. Vertessy, Andrea Viale, Michel Vidal, Helena LA Vieira, Richard D. Vierstra, Nadarajah Vigneswaran, Neeraj Vij, Miquel Vila, Margarita Villar, Victor H. Villar, Joan Villarroya, Cécile Vindis, Giampietro Viola, Maria Teresa Viscomi, Giovanni Vitale, Dan T. Vogl, Olga V. Voitsekhovskaja, Clarissa von Haefen, Karin von Schwarzenberg, Daniel E. Voth, Valérie Vouret Craviari, Kristina Vuori, Jatin M. Vyas, Christian Waeber, Cheryl Lyn Walker, Mark J. Walker, Jochen Walter, Lei Wan, Xiangbo Wan, Bo Wang, Caihong Wang, Chao Yung Wang, Chengshu Wang, Chenran Wang, Chuangui Wang, Dong Wang, Fen Wang, Fuxin Wang, Guanghui Wang, Hai jie Wang, Haichao Wang, Hong Gang Wang, Hongmin Wang, Horng Dar Wang, Jing Wang, Junjun Wang, Mei Wang, Mei Qing Wang, Pei Yu Wang, Peng Wang, Richard C. Wang, Shuo Wang, Ting Fang Wang, Xian Wang, Xiao jia Wang, Xiao Wei Wang, Xin Wang, Xuejun Wang, Yan Wang, Yanming Wang, Ying Wang, Ying Jan Wang, Yipeng Wang, Yu Wang, Yu Tian Wang, Yuqing Wang, Zhi Nong Wang, Pablo Wappner, Carl Ward, Diane McVey Ward, Gary Warnes, Hirotaka Watada, Yoshihisa Watanabe, Kei Watase, Timothy E. Full Terms, Conditions of access, use can be found at h.t.t.p.:././.w.w.w. t.a.n.d.f.o.n.l.i.n.e. com/action/journalInformation?journalCode=kaup20 Download by: [Alma Mater Studiorum Università di Bologna] Date: 23 September 2016, At: 06:43 Weaver, Colin D. Weekes, Jiwu Wei, Thomas Weide, Conrad C. Weihl, Günther Weindl, Simone Nardin Weis, Longping Wen, Xin Wen, Yunfei Wen, Benedikt Westermann, Cornelia M. Weyand, Anthony R. White, Eileen White, J. Lindsay Whitton, Alexander J. Whitworth, Joëlle Wiels, Franziska Wild, Manon E. Wildenberg, Tom Wileman, Deepti Srinivas Wilkinson, Simon Wilkinson, Dieter Willbold, Chris Williams, Katherine Williams, Peter R. Williamson, Konstanze F. Winklhofer, Steven S. Witkin, Stephanie E. Wohlgemuth, Thomas Wollert, Ernst J. Wolvetang, Esther Wong, G. William Wong, Richard W. Wong, Vincent Kam Wai Wong, Elizabeth A. Woodcock, Karen L. Wright, Chunlai Wu, Defeng Wu, Gen Sheng Wu, Jian Wu, Junfang Wu, Mian Wu, Min Wu, Shengzhou Wu, William KK Wu, Yaohua Wu, Zhenlong Wu, Cristina PR Xavier, Ramnik J. Xavier, Gui Xian Xia, Tian Xia, Weiliang Xia, Yong Xia, Hengyi Xiao, Jian Xiao, Shi Xiao, Wuhan Xiao, Chuan Ming Xie, Zhiping Xie, Zhonglin Xie, Maria Xilouri, Yuyan Xiong, Chuanshan Xu, Congfeng Xu, Feng Xu, Haoxing Xu, Hongwei Xu, Jian Xu, Jianzhen Xu, Jinxian Xu, Liang Xu, Xiaolei Xu, Yangqing Xu, Ye Xu, Zhi Xiang Xu, Ziheng Xu, Yu Xue, Takahiro Yamada, Ai Yamamoto, Koji Yamanaka, Shunhei Yamashina, Shigeko Yamashiro, Bing Yan, Bo Yan, Xianghua Yan, Zhen Yan, Yasuo Yanagi, Dun Sheng Yang, Jin Ming Yang, Liu Yang, Minghua Yang, Pei Ming Yang, Peixin Yang, Qian Yang, Wannian Yang, Wei Yuan Yang, Xuesong Yang, Yi Yang, Ying Yang, Zhifen Yang, Zhihong Yang, Meng Chao Yao, Pamela J. Yao, Xiaofeng Yao, Zhenyu Yao, Zhiyuan Yao, Linda S. Yasui, Mingxiang Ye, Barry Yedvobnick, Behzad Yeganeh, Elizabeth S. Yeh, Patricia L. Yeyati, Fan Yi, Long Yi, Xiao Ming Yin, Calvin K. Yip, Yeong Min Yoo, Young Hyun Yoo, Seung Yong Yoon, Ken Ichi Yoshida, Tamotsu Yoshimori, Ken H. Young, Huixin Yu, Jane J. Yu, Jin Tai Yu, Jun Yu, Li Yu, W. Haung Yu, Xiao Fang Yu, Zhengping Yu, Junying Yuan, Zhi Min Yuan, Beatrice YJT Yue, Jianbo Yue, Zhenyu Yue, David N. Zacks, Eldad Zacksenhaus, Nadia Zaffaroni, Tania Zaglia, Zahra Zakeri, Vincent Zecchini, Jinsheng Zeng, Min Zeng, Qi Zeng, Antonis S. Zervos, Donna D. Zhang, Fan Zhang, Guo Zhang, Guo Chang Zhang, Hao Zhang, Hong Zhang, Hongbing Zhang, Jian Zhang, Jiangwei Zhang, Jianhua Zhang, Jing pu Zhang, Li Zhang, Lin Zhang, Long Zhang, Ming Yong Zhang, Xiangnan Zhang, Xu Dong Zhang, Yan Zhang, Yang Zhang, Yanjin Zhang, Yingmei Zhang, Yunjiao Zhang, Mei Zhao, Wei Li Zhao, Xiaonan Zhao, Yan G. Zhao, Ying Zhao, Yongchao Zhao, Yu xia Zhao, Zhendong Zhao, Zhizhuang J. Zhao, Dexian Zheng, Xi Long Zheng, Xiaoxiang Zheng, Boris Zhivotovsky, Qing Zhong, Guang Zhou Zhou, Guofei Zhou, Huiping Zhou, Shu Feng Zhou, Xu jie Zhou, Hongxin Zhu, Hua Zhu, Wei Guo Zhu, Wenhua Zhu, Xiao Feng Zhu, Yuhua Zhu, Shi Mei Zhuang, Xiaohong Zhuang, Elio Ziparo, Christos E. Zois, Teresa Zoladek, Wei Xing Zong, Antonio Zorzano, Susu M. Zughaier, Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Tokyo Medical University, The Hebrew University of Jerusalem (HUJ), Mammalian Genetics Unit, Medical Research Council Harwell, University of Occupational and Environmental Health School of Medicine, Partenaires INRAE, University of Toronto, Ben-Gurion University of the Negev (BGU), University of Colorado [Boulder], Cell Death Research & Therapy (CDRT) Lab, Université Catholique de Louvain = Catholic University of Louvain (UCL), University of Vienna [Vienna], Conway Institute of Biomolecular and Biomedical Research and School of Chemical and Bioprocess Engineering, University College Dublin [Dublin] (UCD), Georgetown University, Candiolo Cancer Institute (IRCCS), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Ikerbasque - Basque Foundation for Science, Cleveland Clinic, Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University), Universidad de Buenos Aires (UBA), Department of Clinical Neurosciences, University College of London [London] (UCL)-Institute of Neurology, Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Consiglio Nazionale delle Ricerche (CNR), Osaka University, Department of Experimental Medicine and Public Health, University of Camerino, University of Barcelona, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Physics, Technical University of Denmark [Lyngby] (DTU), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pharmaco-Biology, Università della Calabria [Arcavacata di Rende] (Unical), Fondation Universitaire Notre Dame de la Paix (FUNDP), Facultés Universitaires Notre Dame de la Paix (FUNDP), USC Neuromuscular Center, Department of Neurology, University of Southern California (USC), Physiopathologie de la survie et de la mort cellulaire et infection virale, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Giannina Gaslini Institute, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Inner Mongolia Agricultural University (IMAU), Politecnico di Milano [Milan] (POLIMI), Department of Civil, Geological, and Mining Engineering, École Polytechnique de Montréal (EPM)-NSERC Industrial Chair on Drinking Water, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Molecular Medicine, Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Experimental Virology - Department of Medical Microbiology [Amsterdam, The Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Infection and Immunity Amsterdam - CINIMA [Amsterdam, The Netherlands], Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Department of Internal Medicine, Hospital Universitario Infanta Sofía, Celullar and Molecular Medicine, Infection bactérienne, inflammation, et carcinogenèse digestive, University of Edinburgh, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Faculty of Engineering and Natural Sciences, Sabanci University [Istanbul], University of Science and Technology Beijing [Beijing] (USTB), Centre for Computational and Systems Biology (COSBI), Sun Yat-Sen University [Guangzhou] (SYSU), Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), CAS Institute of Oceanology (IOCAS), Chinese Academy of Sciences [Beijing] (CAS), Polytechnic University of Marche, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cell Biology, Physiology and Immunology, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Pisa - Università di Pisa, Dulbecco Telethon Institute/Department of Biology, Fondation de Recherche Cancer et Sang - Hôpital Kirchberg, China University of Petroleum, Unilever R&D, University of Queensland [Brisbane], University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Laboratoire de Génie des Procédés et Matériaux - EA 4038 (LGPM), CentraleSupélec, Institute for Advanced Study [Tsinghua], Tsinghua University [Beijing] (THU), Nanayang Technological University (NTU), Nanayang Technological University, Institute of Microelectronics [Beijing] (IMETU), Laboratoire de photonique et de nanostructures (LPN), Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Northwestern Polytechnical University [Xi'an] (NPU), University of Pennsylvania [Philadelphia], City University of Hong Kong (CityU), Department of Mathematics [Berkeley], University of California [Berkeley], University of California-University of California, ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang University, University of Cincinnati (UC), Réponses immunes : régulation et développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), The University of New Mexico [Albuquerque], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Department of Experimental Medicine and Oncology, University of Turin, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), CNV, University of Valparaiso, Université Paris 1 Panthéon-Sorbonne - UFR d'Arts plastiques et sciences de l'art (UP1 UFR04), Université Paris 1 Panthéon-Sorbonne (UP1), Department of General, Visceral and Vascular Surgery [Jena], Friedrich-Schiller-Universität Jena, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau International des Instituts Pasteur (RIIP), Macrophages et Développement de l’Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), This work was supported in part by the National Institutes of Health, including Public Health Service grant GM053396 to D.J.K. Due to space and other limitations, it is not possible to include all other sources of financial support., In a rapidly expanding and highly dynamic field such as autophagy, it is possible that some authors who should have been included on this article have been missed. D.J.K. extends his apologies to researchers in the field of autophagy who, due to oversight or any other reason, could not be included on this article. I also note that two of our colleagues on this manuscript have passed away: Arlette Darfeuille-Michaud and Wouter van Doorn., Life Sciences Institute [Ann Arbor, MI, USA], Laboratoire de Biogenèse Membranaire, CNRS UMR 5200, Université de Bordeaux, INRA Bordeaux Aquitaine, Villenave d'Ornon, France., Amelio, Ivano [0000-0002-9126-5391], Beale, Rupert [0000-0002-6705-8560], Floto, Andres [0000-0002-2188-5659], Frezza, Christian [0000-0002-3293-7397], Ktistakis, Nicholas [0000-0001-9397-2914], Melino, Gerry [0000-0001-9428-5972], Narita, Masashi [0000-0001-7764-577X], Rubinsztein, David [0000-0001-5002-5263], Underwood, Benjamin [0000-0003-3427-9487], Whitworth, Alex [0000-0002-1154-6629], Apollo - University of Cambridge Repository, Université Catholique de Louvain, Facultés Universitaires Notre-Dame de la Paix, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Department of Clinical and Molecular Medicine, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' [Rome], Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Sun Yat-Sen University (SYSU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), University of Minnesota [Twin Cities], Tsinghua University [Beijing], Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Panthéon-Sorbonne - UFR d'Arts plastiques et sciences de l'art (UP1 UFR04), Université Panthéon-Sorbonne (UP1), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Necker - Enfants Malades [AP-HP], Trafic membranaire et Division cellulaire, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Klionsky, D., Abdelmohsen, K., Abe, A., Abedin, M., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C., Adams, P., Adeli, K., Adhihetty, P., Adler, S., Agam, G., Agarwal, R., Aghi, M., Agnello, M., Agostinis, P., Aguilar, P., Aguirre-Ghiso, J., Airoldi, E., Ait-Si-Ali, S., Akematsu, T., Akporiaye, E., Al-Rubeai, M., Albaiceta, G., Albanese, C., Albani, D., Albert, M., Aldudo, J., Algül, H., Alirezaei, M., Alloza, I., Almasan, A., Almonte-Beceril, M., Alnemri, E., Alonso, C., Altan-Bonnet, N., Altieri, D., Alvarez, S., Alvarez-Erviti, L., Alves, S., Amadoro, G., Amano, A., Amantini, C., Ambrosio, S., Amelio, I., Amer, A., Amessou, M., Amon, A., An, Z., Anania, F., Andersen, S., Andley, U., Andreadi, C., Andrieu-Abadie, N., Anel, A., Ann, D., Anoopkumar-Dukie, S., Antonioli, M., Aoki, H., Apostolova, N., Aquila, S., Aquilano, K., Araki, K., Arama, E., Aranda, A., Araya, J., Arcaro, A., Arias, E., Arimoto, H., Ariosa, A., Armstrong, J., Arnould, T., Arsov, I., Asanuma, K., Askanas, V., Asselin, E., Atarashi, R., Atherton, S., Atkin, J., Attardi, L., Auberger, P., Auburger, G., Aurelian, L., Autelli, R., Avagliano, L., Avantaggiati, M., Avrahami, L., Awale, S., Azad, N., Bachetti, T., Backer, J., Bae, D., Bae, J., Bae, O., Bae, S., Baehrecke, E., Baek, S., Baghdiguian, S., Bagniewska-Zadworna, A., Bai, H., Bai, J., Bai, X., Bailly, Y., Balaji, K., Balduini, W., Ballabio, A., Balzan, R., Banerjee, R., Bánhegyi, G., Bao, H., Barbeau, B., Barrachina, M., Barreiro, E., Bartel, B., Bartolomé, A., Bassham, D., Bassi, M., Bast, R., Basu, A., Batista, M., Batoko, H., Battino, M., Bauckman, K., Baumgarner, B., Bayer, K., Beale, R., Beaulieu, J., Beck, G., Becker, C., Beckham, J., Bédard, P., Bednarski, P., Begley, T., Behl, C., Behrends, C., Behrens, G., Behrns, K., Bejarano, E., Belaid, A., Belleudi, F., Bénard, G., Berchem, G., Bergamaschi, D., Bergami, M., Berkhout, B., Berliocchi, L., Bernard, A., Bernard, M., Bernassola, F., Bertolotti, A., Bess, A., Besteiro, S., Bettuzzi, S., Bhalla, S., Bhattacharyya, S., Bhutia, S., Biagosch, C., Bianchi, M., Biard-Piechaczyk, M., Billes, V., Bincoletto, C., Bingol, B., Bird, S., Bitoun, M., Bjedov, I., Blackstone, C., Blanc, L., Blanco, G., Blomhoff, H., Boada-Romero, E., Böckler, S., Boes, M., Boesze-Battaglia, K., Boise, L., Bolino, A., Boman, A., Bonaldo, P., Bordi, M., Bosch, J., Botana, L., Botti, J., Bou, G., Bouché, M., Bouchecareilh, M., Boucher, M., Boulton, M., Bouret, S., Boya, P., Boyer-Guittaut, M., Bozhkov, P., Brady, N., Braga, V., Brancolini, C., Braus, G., Bravo-San Pedro, J., Brennan, L., Bresnick, E., Brest, P., Bridges, D., Bringer, M., Brini, M., 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Charlie, Dong, Xiaonan, Dong, Zheng, Donohue, Terrence M, Doran, Kelly S, D'Orazi, Gabriella, Dorn, Gerald W, Dosenko, Victor, Dridi, Sami, Drucker, Liat, Du, Jie, Du, Li Lin, Du, Lihuan, du Toit, André, Dua, Priyamvada, Duan, Lei, Duann, Pu, Dubey, Vikash Kumar, Duchen, Michael R, Duchosal, Michel A, Duez, Helene, Dugail, Isabelle, Dumit, Verónica I, Duncan, Mara C, Dunlop, Elaine A, Dunn, William A, Dupont, Nicola, Dupuis, Luc, Durán, Raúl V, Durcan, Thomas M, Duvezin Caubet, Stéphane, Duvvuri, Umamaheswar, Eapen, Vinay, Ebrahimi Fakhari, Dariu, Echard, Arnaud, Eckhart, Leopold, Edelstein, Charles L, Edinger, Aimee L, Eichinger, Ludwig, Eisenberg, Tobia, Eisenberg Lerner, Avital, Eissa, N. Tony, El Deiry, Wafik S, El Khoury, Victoria, Elazar, Zvulun, Eldar Finkelman, Hagit, Elliott, Chris Jh, Emanuele, Enzo, Emmenegger, Urban, Engedal, Nikolai, Engelbrecht, Anna Mart, Engelender, Simone, Enserink, Jorrit M, Erdmann, Ralf, Erenpreisa, Jekaterina, Eri, Rajaraman, Eriksen, Jason L, Erman, Andreja, Escalante, Ricardo, Eskelinen, Eeva Liisa, Espert, Lucile, Esteban Martínez, Lorena, Evans, Thomas J, Fabri, Mario, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Færgeman, Nils J, Faggioni, Alberto, Fairlie, W. Dougla, Fan, Chunhai, Fan, Daping, Fan, Jie, Fang, Shengyun, Fanto, Manoli, Fanzani, Alessandro, Farkas, Thoma, Faure, Mathia, Favier, Francois B, Fearnhead, Howard, Federici, Massimo, Fei, Erkang, Felizardo, Tania C, Feng, Hua, Feng, Yibin, Feng, Yuchen, Ferguson, Thomas A, Fernández, Álvaro F, Fernandez Barrena, Maite G, Fernandez Checa, Jose C, Fernández López, Arsenio, Fernandez Zapico, Martin E, Feron, Olivier, Ferraro, Elisabetta, Ferreira Halder, Carmen Veríssima, Fesus, Laszlo, Feuer, Ralph, Fiesel, Fabienne C, Filippi Chiela, Eduardo C, Filomeni, Giuseppe, Fimia, Gian Maria, Fingert, John H, Finkbeiner, Steven, Finkel, Toren, Fiorito, Filomena, Fisher, Paul B, Flajolet, Marc, Flamigni, Flavio, Florey, Oliver, Florio, Salvatore, Floto, R. 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Shieh, Jj, Shih, Cm, Shimada, Y, Shimizu, S, Shin, Dw, Shinohara, Ml, Shintani, M, Shintani, T, Shioi, T, Shirabe, K, Shiri Sverdlov, R, Shirihai, O, Shore, Gc, Shu, Cw, Shukla, D, Sibirny, Aa, Sica, V, Sigurdson, Cj, Sigurdsson, Em, Sijwali, P, Sikorska, B, Silveira, Wa, Silvente Poirot, S, Silverman, Ga, Simak, J, Simmet, T, Simon, Ak, Simon, Hu, Simone, C, Simons, M, Simonsen, A, Singh, R, Singh, Sv, Singh, Sk, Sinha, D, Sinha, S, Sinicrope, Fa, Sirko, A, Sirohi, K, Sishi, Bj, Sittler, A, Siu, Pm, Sivridis, E, Skwarska, A, Slack, R, Slaninová, I, Slavov, N, Smaili, S, Smalley, K, Smith, Dr, Soenen, Sj, Soleimanpour, Sa, Solhaug, A, Somasundaram, K, Son, Jh, Sonawane, A, Song, C, Song, F, Song, Hk, Song, Jx, Song, W, Soo, Ky, Sood, Ak, Soong, Tw, Soontornniyomkij, V, Sorice, M, Sotgia, F, Soto Pantoja, Dr, Sotthibundhu, A, Sousa, Mj, Spaink, Hp, Span, Pn, Spang, A, Sparks, Jd, Speck, Pg, Spector, Sa, Spies, Cd, Springer, W, Clair, D, Stacchiotti, A, Staels, B, Stang, Mt, 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Taylor, Ga, Taylor, Jp, Taylor, Mj, Tchetina, Ev, Tee, Ar, Teixeira Clerc, F, Telang, S, Tencomnao, T, Teng, Bb, Teng, Rj, Terro, F, Tettamanti, G, Theiss, Al, Theron, Ae, Thomas, Kj, Thomé, Mp, Thomes, Pg, Thorburn, A, Thorner, J, Thum, T, Thumm, M, Thurston, Tl, Tian, L, Till, A, Ting, Jp, Titorenko, Vi, Toker, L, Toldo, S, Tooze, Sa, Topisirovic, I, Torgersen, Ml, Torosantucci, L, Torriglia, A, Torrisi, Mr, Tournier, C, Towns, R, Trajkovic, V, Travassos, Lh, Triola, G, Tripathi, Dn, Trisciuoglio, D, Troncoso, R, Trougakos, Ip, Truttmann, Ac, Tsai, Kj, Tschan, Mp, Tseng, Yh, Tsukuba, T, Tsung, A, Tsvetkov, A, Tu, S, Tuan, Hy, Tucci, M, Tumbarello, Da, Turk, B, Turk, V, Turner, Rf, Tveita, Aa, Tyagi, Sc, Ubukata, M, Uchiyama, Y, Udelnow, A, Ueno, T, Umekawa, M, Umemiya Shirafuji, R, Underwood, Br, Ungermann, C, Ureshino, Rp, Ushioda, R, Uversky, Vn, Uzcátegui, Nl, Vaccari, T, Vaccaro, Mi, Váchová, L, Vakifahmetoglu Norberg, H, Valdor, R, Valente, Em, Vallette, F, Valverde, Am, Van den Berghe, G, Van Den Bosch, L, van den Brink, Gr, van der Goot, Fg, van der Klei, Ij, van der Laan, Lj, van Doorn, Wg, van Egmond, M, van Golen, Kl, Van Kaer, L, van Lookeren Campagne, M, Vandenabeele, P, Vandenberghe, W, Vanhorebeek, I, Varela Nieto, I, Vasconcelos, Mh, Vasko, R, Vavvas, Dg, Vega Naredo, I, Velasco, G, Velentzas, Ad, Velentzas, Pd, Vellai, T, Vellenga, E, Vendelbo, Mh, Venkatachalam, K, Ventura, N, Ventura, S, Veras, P, Verdier, M, Vertessy, Bg, Viale, A, Vidal, M, Vieira, H, Vierstra, Rd, Vigneswaran, N, Vij, N, Vila, M, Villar, M, Villar, Vh, Villarroya, J, Vindis, C, Viola, G, Viscomi, Mt, Vitale, G, Vogl, Dt, Voitsekhovskaja, Ov, von Haefen, C, von Schwarzenberg, K, Voth, De, Vouret Craviari, V, Vuori, K, Vyas, Jm, Waeber, C, Walker, Cl, Walker, Mj, Walter, J, Wan, L, Wan, X, Wang, B, Wang, C, Wang, Cy, Wang, D, Wang, F, Wang, G, Wang, Hj, Wang, H, Wang, Hg, Wang, Hd, Wang, J, Wang, M, Wang, Mq, Wang, Py, Wang, P, Wang, Rc, Wang, S, Wang, Tf, Wang, X, Wang, Xj, Wang, Xw, Wang, Y, Wang, Yj, Wang, Yt, Wang, Zn, Wappner, P, Ward, C, Ward, Dm, Warnes, G, Watada, H, Watanabe, Y, Watase, K, Weaver, Te, Weekes, Cd, Wei, J, Weide, T, Weihl, Cc, Weindl, G, Weis, Sn, Wen, L, Wen, X, Wen, Y, Westermann, B, Weyand, Cm, White, Ar, White, E, Whitton, Jl, Whitworth, Aj, Wiels, J, Wild, F, Wildenberg, Me, Wileman, T, Wilkinson, D, Wilkinson, S, Willbold, D, Williams, C, Williams, K, Williamson, Pr, Winklhofer, Kf, Witkin, S, Wohlgemuth, Se, Wollert, T, Wolvetang, Ej, Wong, E, Wong, Gw, Wong, Rw, Wong, Vk, Woodcock, Ea, Wright, Kl, Wu, C, Wu, D, Wu, G, Wu, J, Wu, M, Wu, S, Wu, Wk, Wu, Y, Wu, Z, Xavier, Cp, Xavier, Rj, Xia, Gx, Xia, T, Xia, W, Xia, Y, Xiao, H, Xiao, J, Xiao, S, Xiao, W, Xie, Cm, Xie, Z, Xilouri, M, Xiong, Y, Xu, C, Xu, F, Xu, H, Xu, J, Xu, L, Xu, X, Xu, Y, Xu, Zx, Xu, Z, Xue, Y, Yamada, T, Yamamoto, A, Yamanaka, K, Yamashina, S, Yamashiro, S, Yan, B, Yan, X, Yan, Z, Yanagi, Y, Yang, D, Yang, Jm, Yang, L, Yang, M, Yang, Pm, Yang, P, Yang, Q, Yang, W, Yang, Wy, Yang, X, Yang, Y, Yang, Z, Yao, Mc, Yao, Pj, Yao, X, Yao, Z, Yasui, L, Ye, M, Yedvobnick, B, Yeganeh, B, Yeh, E, Yeyati, Pl, Yi, F, Yi, L, Yin, Xm, Yip, Ck, Yoo, Ym, Yoo, Yh, Yoon, Sy, Yoshida, Ki, Yoshimori, T, Young, Kh, Yu, H, Yu, Jj, Yu, Jt, Yu, J, Yu, L, Yu, Wh, Yu, Xf, Yu, Z, Yuan, J, Yuan, Zm, Yue, By, Yue, J, Yue, Z, Zacks, Dn, Zacksenhaus, E, Zaffaroni, N, Zaglia, T, Zakeri, Z, Zecchini, V, Zeng, J, Zeng, M, Zeng, Q, Zervos, A, Zhang, Dd, Zhang, F, Zhang, G, Zhang, Gc, Zhang, H, Zhang, J, Zhang, Jp, Zhang, L, Zhang, My, Zhang, X, Zhang, Xd, Zhang, Y, Zhao, M, Zhao, Wl, Zhao, X, Zhao, Yg, Zhao, Y, Zhao, Yx, Zhao, Z, Zhao, Zj, Zheng, D, Zheng, Xl, Zheng, X, Zhivotovsky, B, Zhong, Q, Zhou, Gz, Zhou, G, Zhou, H, Zhou, Sf, Zhou, Xj, Zhu, H, Zhu, Wg, Zhu, W, Zhu, Xf, Zhu, Y, Zhuang, Sm, Zhuang, X, Ziparo, E, Zois, Ce, Zoladek, T, Zong, Wx, Zorzano, A, Zughaier, Sm, AII - Amsterdam institute for Infection and Immunity, Medical Microbiology and Infection Prevention, Other departments, CCA -Cancer Center Amsterdam, Center of Experimental and Molecular Medicine, Radiotherapy, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Medical Biochemistry, ANS - Cellular & Molecular Mechanisms, Cell Biology and Histology, Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Daniel J Klionsky, Kotb Abdelmohsen, Akihisa Abe, Md Joynal Abedin, Hagai Abeliovich, Abraham Acevedo Arozena, Hiroaki Adachi, Christopher M Adam, Peter D Adam, Khosrow Adeli, Peter J Adhihetty, Sharon G Adler, Galila Agam, Rajesh Agarwal, Manish K Aghi, Maria Agnello, Patrizia Agostini, Patricia V Aguilar, Julio Aguirre-Ghiso, Edoardo M Airoldi, Slimane Ait-Si-Ali, Takahiko Akematsu, Emmanuel T Akporiaye, Mohamed Al-Rubeai, Guillermo M Albaiceta, Chris Albanese, Diego Albani, Matthew L Albert, Jesus Aldudo, Hana Algül, Mehrdad Alirezaei, Iraide Alloza, Alexandru Almasan, Maylin Almonte-Beceril, Emad S Alnemri, Covadonga Alonso, Nihal Altan-Bonnet, Dario C Altieri, Silvia Alvarez, Lydia Alvarez- Erviti, Sandro Alve, Giuseppina Amadoro, Atsuo Amano, Consuelo Amantini, Santiago Ambrosio, Ivano Amelio, Amal O Amer, Mohamed Amessou, Angelika Amon, Zhenyi An, Frank A Anania, Stig U Andersen, Usha P Andley, Catherine K Andreadi, Nathalie Andrieu- Abadie, Alberto Anel, David K Ann, Shailendra Anoopkumar-Dukie, Manuela Antonioli, Hiroshi Aoki, Nadezda Apostolova, Saveria Aquila, Katia Aquilano, Koichi Araki, Eli Arama, Agustin Aranda, Jun Araya, Alexandre Arcaro, Esperanza Aria, Hirokazu Arimoto, Aileen R Ariosa, Jane L Armstrong, Thierry Arnould, Ivica Arsov, Katsuhiko Asanuma, Valerie Askana, Eric Asselin, Ryuichiro Atarashi, Sally S Atherton, Julie D Atkin, Laura D Attardi, Patrick Auberger, Georg Auburger, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Maria Laura Avantaggiati, Limor Avrahami, Suresh Awale, Neelam Azad, Tiziana Bachetti, Jonathan M Backer, Dong- Hun Bae, Jae-sung Bae, Ok-Nam Bae, Soo Han Bae, Eric H Baehrecke, Seung-Hoon Baek, Stephen Baghdiguian, Agnieszka Bagniewska-Zadworna, Hua Bai, Jie Bai, Xue-Yuan Bai, Yannick Bailly, Kithiganahalli Narayanaswamy Balaji, Walter Balduini, Andrea Ballabio, Rena Balzan, Rajkumar Banerjee, Gábor Bánhegyi, Haijun Bao, Benoit Barbeau, Maria D Barrachina, Esther Barreiro, Bonnie Bartel, Alberto Bartolomé, Diane C Bassham, Maria Teresa Bassi, Robert C Bast Jr, Alakananda Basu, Maria Teresa Batista, Henri Batoko, Maurizio Battino, Kyle Bauckman, Bradley L Baumgarner, K Ulrich Bayer, Rupert Beale, Jean-François Beaulieu, George R. Beck Jr, Christoph Becker, J David Beckham, Pierre-André Bédard, Patrick J Bednarski, Thomas J Begley, Christian Behl, Christian Behrend, Georg MN Behren, Kevin E Behrn, Eloy Bejarano, Amine Belaid, Francesca Belleudi, Giovanni Bénard, Guy Berchem, Daniele Bergamaschi, Matteo Bergami, Ben Berkhout, Laura Berliocchi, Amélie Bernard, Monique Bernard, Francesca Bernassola, Anne Bertolotti, Amanda S Be, Sébastien Besteiro, Saverio Bettuzzi, Savita Bhalla, Shalmoli Bhattacharyya, Sujit K Bhutia, Caroline Biagosch, Michele Wolfe Bianchi, Martine Biard-Piechaczyk, Viktor Bille, Claudia Bincoletto, Baris Bingol, Sara W Bird, Marc Bitoun, Ivana Bjedov, Craig Blackstone, Lionel Blanc, Guillermo A Blanco, Heidi Kiil Blomhoff, Emilio Boada-Romero, Stefan Böckler, Marianne Boe, Kathleen Boesze-Battaglia, Lawrence H Boise, Alessandra Bolino, Andrea Boman, Paolo Bonaldo, Matteo Bordi, Jürgen Bosch, Luis M Botana, Joelle Botti, German Bou, Marina Bouché, Marion Bouchecareilh, Marie- Josée Boucher, Michael E Boulton, Sebastien G Bouret, Patricia Boya, Michaël Boyer-Guittaut, Peter V Bozhkov, Nathan Brady, Vania MM Braga, Claudio Brancolini, Gerhard H Brau, José M Bravo-San Pedro, Lisa A Brennan, Emery H Bresnick, Patrick Brest, Dave Bridge, MarieAgnès Bringer, Marisa Brini, Glauber C Brito, Bertha Brodin, Paul S Brooke, Eric J Brown, Karen Brown, Hal E Broxmeyer, Alain Bruhat, Patricia Chakur Brum, John H Brumell, Nicola Brunetti-Pierri, Robert J Bryson-Richardson, Shilpa Buch, Alastair M Buchan, Hikmet Budak, Dmitry V Bulavin, Scott J Bultman, Geert Bultynck, Vladimir Bumbasirevic, Yan Burelle, Robert E Burke, Margit Burmeister, Peter Bütikofer, Laura Caberlotto, Ken Cadwell, Monika Cahova, Dongsheng Cai, Jingjing Cai, Qian Cai, Sara Calatayud, Nadine Camougrand, Michelangelo Campanella, Grant R Campbell, Matthew Campbell, Silvia Campello, Robin Candau, Isabella Caniggia, Lavinia Cantoni, Lizhi Cao, Allan B Caplan, Michele Caraglia, Claudio Cardinali, Sandra Morais Cardoso, Jennifer S Carew, Laura A Carleton, Cathleen R Carlin, Silvia Carloni, Sven R Carlsson, Didac Carmona-Gutierrez, Leticia AM Carneiro, Oliana Carnevali, Serena Carra, Alice Carrier, Bernadette Carroll, Caty Casa, Josefina Casa, Giuliana Cassinelli, Perrine Castet, Susana Castro-Obregon, Gabriella Cavallini, Isabella Ceccherini, Francesco Cecconi, Arthur I Cederbaum, Valentín Ceña, Simone Cenci, Claudia Cerella, Davide Cervia, Silvia Cetrullo, Hassan Chaachouay, Han-Jung Chae, Andrei S Chagin, Chee-Yin Chai, Gopal Chakrabarti, Georgios Chamilo, Edmond YW Chan, Matthew TV Chan, Dhyan Chandra, Pallavi Chandra, Chih-Peng Chang, Raymond Chuen-Chung Chang, Ta Yuan Chang, John C Chatham, Saurabh Chatterjee, Santosh Chauhan, Yongsheng Che, Michael E Cheetham, Rajkumar Cheluvappa, Chun-Jung Chen, Gang Chen, Guang-Chao Chen, Guoqiang Chen, Hongzhuan Chen, Jeff W Chen, Jian-Kang Chen, Min Chen, Mingzhou Chen, Peiwen Chen, Qi Chen, Quan Chen, Shang- Der Chen, Si Chen, Steve S-L Chen, Wei Chen, 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Vincent CO Njar, Takeshi Noda, Angelika A Noegel, Elsie Magdalena Nolte, Erik Norberg, Koenraad K Norga, Sakineh Kazemi Noureini, Shoji Notomi, Lucia Notterpek, Karin Nowikovsky, Nobuyuki Nukina, Thorsten Nürnberger, Valerie B O'Donnell, Tracey O'Donovan, Peter J O'Dwyer, Ina Oehme, Clara L Oeste, Michinaga Ogawa, Besim Ogretmen, Yuji Ogura, Young J Oh, Masaki Ohmuraya, Takayuki Ohshima, Rani Ojha, Koji Okamoto, Toshiro Okazaki, F Javier Oliver, Karin Ollinger, Stefan Olsson, Daniel P Orban, Paulina Ordonez, Idil Orhon, Laszlo Orosz, Eyleen J O'Rourke, Helena Orozco, Angel L Ortega, Elena Ortona, Laura D Osellame, Junko Oshima, Shigeru Oshima, Heinz D Osiewacz, Takanobu Otomo, Kinya Otsu, Jing-hsiung James Ou, Tiago F Outeiro, Dong-yun Ouyang, Hongjiao Ouyang, Michael Overholtzer, Michelle A Ozbun, P Hande Ozdinler, Bulent Ozpolat, Consiglia Pacelli, Paolo Paganetti, Guylène Page, Gilles Page, Ugo Pagnini, Beata Pajak, Stephen C Pak, Karolina Pakos-Zebrucka, Nazzy Pakpour, Zdena Palková, Francesca Palladino, Kathrin Pallauf, Nicolas Pallet, Marta Palmieri, Søren R Paludan, Camilla Palumbo, Silvia Palumbo, Olatz Pampliega, Hongming Pan, Wei Pan, Theocharis Panaretaki, Aseem Pandey, Areti Pantazopoulou, Zuzana Papackova, Daniela L Papademetrio, Issidora Papassideri, Alessio Papini, Nirmala Parajuli, Julian Pardo, Vrajesh V Parekh, Giancarlo Parenti, Jong-In Park, Junsoo Park, Ohkmae K Park, Roy Parker, Rosanna Parlato, Jan B Pary, Katherine R Parzych, Jean-Max Pasquet, Benoit Pasquier, Kishore BS Pasumarthi, Daniel Patschan, Cam Patterson, Sophie Pattingre, Scott Pattison, Arnim Pause, Hermann Pavenstädt, Flaminia Pavone, Zully Pedrozo, Fernando J Peña, Miguel A Peñalva, Mario Pende, Jianxin Peng, Fabio Penna, Josef M Penninger, Anna Pensalfini, Salvatore Pepe, Gustavo JS Pereira, Paulo C Pereira, Verónica Pérez-de la Cruz, María Esther Pérez-Pérez, Diego Pérez-Rodríguez, Dolores Pérez-Sala, Celine Perier, Andras Perl, David H Perlmutter, Ida Perrotta, Shazib Pervaiz, Maija Pesonen, Jeffrey E Pessin, Godefridus J Peter, Morten Petersen, Irina Petrache, Basil J Petrof, Goran Petrovski, James M Phang, Mauro Piacentini, Marina Pierdominici, Philippe Pierre, Valérie Pierrefite-Carle, Federico Pietrocola, Felipe X Pimentel-Muiño, Mario Pinar, Benjamin Pineda, Ronit Pinkas-Kramarski, Marcello Pinti, Paolo Pinton, Bilal Piperdi, James M Piret, Leonidas C Platania, Harald W Platta, Edward D Plowey, Stefanie Pöggeler, Marc Poirot, Peter Polčic, Angelo Poletti, Audrey H Poon, Hana Popelka, Blagovesta Popova, Izabela Poprawa, Shibu M Poulose, Joanna Poulton, Scott K Power, Ted Power, Mercedes Pozuelo- Rubio, Krisna Prak, Reinhild Prange, Mark Prescott, Muriel Priault, Sharon Prince, Richard L Proia, Tassula Proikas-Cezanne, Holger Prokisch, Vasilis J Prompona, Karin Przyklenk, Rosa Puertollano, Subbiah Pugazhenthi, Luigi Puglielli, Aurora Pujol, Julien Puyal, Dohun Pyeon, Xin Qi, Wen-bin Qian, Zheng-Hong Qin, Yu Qiu, Ziwei Qu, Joe Quadrilatero, Frederick Quinn, Nina Raben, Hannah Rabinowich, Flavia Radogna, Michael J Ragusa, Mohamed Rahmani, Komal Raina, Sasanka Ramanadham, Rajagopal Ramesh, Abdelhaq Rami, Sarron Randall- Demllo, Felix Randow, Hai Rao, V Ashutosh Rao, Blake B Rasmussen, Tobias M Rasse, Edward A Ratovitski, Pierre-Emmanuel Rautou, Swapan K Ray, Babak Razani, Bruce H Reed, Fulvio Reggiori, Markus Rehm, Andreas S Reichert, Theo Rein, David J Reiner, Eric Reit, Jun Ren, Xingcong Ren, Maurizio Renna, Jane EB Reusch, Jose L Revuelta, Leticia Reye, Alireza R Rezaie, Robert I Richard, Des R Richardson, Clémence Richetta, Michael A Riehle, Bertrand H Rihn, Yasuko Rikihisa, Brigit E Riley, Gerald Rimbach, Maria Rita Rippo, Konstantinos Riti, Federica Rizzi, Elizete Rizzo, Peter J Roach, Jeffrey Robbin, Michel Roberge, Gabriela Roca, Maria Carmela Roccheri, Sonia Rocha, Cecilia MP Rodrigue, Clara I Rodríguez, Santiago Rodriguez de Cordoba, Natalia Rodriguez-Muela, Jeroen Roelof, Vladimir V Rogov, Troy T Rohn, Bärbel Rohrer, Davide Romanelli, Luigina Romani, Patricia Silvia Romano, M Isabel G Roncero, Jose Luis Rosa, Alicia Rosello, Kirill V Rosen, Philip Rosenstiel, Magdalena Rost-Roszkowska, Kevin A Roth, Gael Roué, Mustapha Roui, Kasper M Rouschop, Daniel T Ruan, Diego Ruano, David C Rubinsztein, Edmund B Rucker III, Assaf Rudich, Emil Rudolf, Ruediger Rudolf, Markus A Ruegg, Carmen Ruiz-Roldan, Avnika Ashok Ruparelia, Paola Rusmini, David W Ru, Gian Luigi Russo, Giuseppe Russo, Rossella Russo, Tor Erik Rusten, Victoria Ryabovol, Kevin M Ryan, Stefan W Ryter, David M Sabatini, Michael Sacher, Carsten Sachse, Michael N Sack, Junichi Sadoshima, Paul Saftig, Ronit Sagi-Eisenberg, Sumit Sahni, Pothana Saikumar, Tsunenori Saito, Tatsuya Saitoh, Koichi Sakakura, Machiko Sakoh-Nakatogawa, Yasuhito Sakuraba, María Salazar-Roa, Paolo Salomoni, Ashok K Saluja, Paul M Salvaterra, Rosa Salvioli, Afshin Samali, Anthony MJ Sanchez, José A Sánchez-Alcázar, Ricardo Sanchez-Prieto, Marco Sandri, Miguel A Sanjuan, Stefano Santaguida, Laura Santambrogio, Giorgio Santoni, Claudia Nunes dos Santo, Shweta Saran, Marco Sardiello, Graeme Sargent, Pallabi Sarkar, Sovan Sarkar, Maria Rosa Sarria, Minnie M Sarwal, Chihiro Sasakawa, Motoko Sasaki, Miklos Sa, Ken Sato, Miyuki Sato, Joseph Satriano, Niramol Savaraj, Svetlana Saveljeva, Liliana Schaefer, Ulrich E Schaible, Michael Scharl, Hermann M Schatzl, Randy Schekman, Wiep Scheper, Alfonso Schiavi, Hyman M Schipper, Hana Schmeisser, Jens Schmidt, Ingo Schmitz, Bianca E Schneider, E Marion Schneider, Jaime L Schneider, Eric A Schon, Miriam J Schönenberger, Axel H Schönthal, Daniel F Schorderet, Bernd Schröder, Sebastian Schuck, Ryan J Schulze, Melanie Schwarten, Thomas L Schwarz, Sebastiano Sciarretta, Kathleen Scotto, A Ivana Scovassi, Robert A Screaton, Mark Screen, Hugo Seca, Simon Sedej, Laura Segatori, Nava Segev, Per O Seglen, Jose M Seguí- Simarro, Juan Segura-Aguilar, Ekihiro Seki, Iban Seiliez, Christian Sell, Clay F Semenkovich, Gregg L Semenza, Utpal Sen, Andreas L Serra, Ana Serrano-Puebla, Hiromi Sesaki, Takao Setoguchi, Carmine Settembre, John J Shacka, Ayesha N Shajahan-Haq, Irving M Shapiro, Shweta Sharma, Hua She, C-K James Shen, Chiung-Chyi Shen, Han-Ming Shen, Sanbing Shen, Weili Shen, Rui Sheng, Xianyong Sheng, Zu-Hang Sheng, Trevor G Shepherd, Junyan Shi, Qiang Shi, Qinghua Shi, Yuguang Shi, Shusaku Shibutani, Kenichi Shibuya, Yoshihiro Shidoji, Jeng- Jer Shieh, Chwen-Ming Shih, Yohta Shimada, Shigeomi Shimizu, Dong Wook Shin, Mari L Shinohara, Michiko Shintani, Takahiro Shintani, Tetsuo Shioi, Ken Shirabe, Ronit Shiri-Sverdlov, Orian Shirihai, Gordon C Shore, Chih-Wen Shu, Deepak Shukla, Andriy A Sibirny, Valentina Sica, Christina J Sigurdson, Einar M Sigurdsson, Puran Singh Sijwali, Beata Sikorska, Wilian A Silveira, Sandrine Silvente-Poirot, Gary A Silverman, Jan Simak, Thomas Simmet, Anna Katharina Simon, Hans-Uwe Simon, Cristiano Simone, Matias Simon, Anne Simonsen, Rajat Singh, Shivendra V Singh, Shrawan K Singh, Debasish Sinha, Sangita Sinha, Frank A Sinicrope, Agnieszka Sirko, Kapil Sirohi, Balindiwe JN Sishi, Annie Sittler, Parco M Siu, Efthimios Sivridi, Anna Skwarska, Ruth Slack, Iva Slaninová, Nikolai Slavov, Soraya S Smaili, Keiran SM Smalley, Duncan R Smith, Stefaan J Soenen, Scott A Soleimanpour, Anita Solhaug, Kumaravel Somasundaram, Jin H Son, Avinash Sonawane, Chunjuan Song, Fuyong Song, Hyun Kyu Song, Ju-Xian Song, Wei Song, Kai Y Soo, Anil K Sood, Tuck Wah Soong, Virawudh Soontornniyomkij, Maurizio Sorice, Federica Sotgia, David R Soto-Pantoja, Areechun Sotthibundhu, Maria João Sousa, Herman P Spaink, Paul N Span, Anne Spang, Janet D Spark, Peter G Speck, Stephen A Spector, Claudia D Spie, Wolfdieter Springer, Daret St Clair, Alessandra Stacchiotti, Bart Stael, Michael T Stang, Daniel T Starczynowski, Petro Starokadomskyy, Clemens Steegborn, John W Steele, Leonidas Stefani, Joan Steffan, Christine M Stellrecht, Harald Stenmark, Tomasz M Stepkowski, Stęphan T Stern, Craig Steven, Brent R Stockwell, Veronika Stoka, Zuzana Storchova, Björn Stork, Vassilis Stratoulia, Dimitrios J Stravopodi, Pavel Strnad, Anne Marie Strohecker, Anna- Lena Ström, Per Stromhaug, Jiri Stulik, Yu-Xiong Su, Zhaoliang Su, Carlos S Subauste, Srinivasa Subramaniam, Carolyn M Sue, Sang Won Suh, Xinbing Sui, Supawadee Sukseree, David Sulzer, Fang-Lin Sun, Jiaren Sun, Jun Sun, Shi-Yong Sun, Yang Sun, Yi Sun, Yingjie Sun, Vinod Sundaramoorthy, Joseph Sung, Hidekazu Suzuki, Kuninori Suzuki, Naoki Suzuki, Tadashi Suzuki, Yuichiro J Suzuki, Michele S Swanson, Charles Swanton, Karl Swärd, Ghanshyam Swarup, Sean T Sweeney, Paul W Sylvester, Zsuzsanna Szatmari, Eva Szegezdi, Peter W Szlosarek, Heinrich Taegtmeyer, Marco Tafani, Emmanuel Taillebourg, Stephen WG Tait, Krisztina Takacs-Vellai, Yoshinori Takahashi, Szabolcs Takát, Genzou Takemura, Nagio Takigawa, Nicholas J Talbot, Elena Tamagno, Jerome Tamburini, Cai-Ping Tan, Lan Tan, Mei Lan Tan, Ming Tan, Yee-Joo Tan, Keiji Tanaka, Masaki Tanaka, Daolin Tang, Dingzhong Tang, Guomei Tang, Isei Tanida, Kunikazu Tanji, Bakhos A Tannou, Jose A Tapia, Inmaculada Tasset-Cueva, Marc Tatar, Iman Tavassoly, Nektarios Tavernaraki, Allen Taylor, Graham S Taylor, Gregory A Taylor, J Paul Taylor, Mark J Taylor, Elena V Tchetina, Andrew R Tee, Fatima Teixeira-Clerc, Sucheta Telang, Tewin Tencomnao, Ba-Bie Teng, Ru-Jeng Teng, Faraj Terro, Gianluca Tettamanti, Arianne L Thei, Anne E Theron, Kelly Jean Thoma, Marcos P Thomé, Paul G Thome, Andrew Thorburn, Jeremy Thorner, Thomas Thum, Michael Thumm, Teresa LM Thurston, Ling Tian, Andreas Till, Jenny Pan-yun Ting, Vladimir I Titorenko, Lilach Toker, Stefano Toldo, Sharon A Tooze, Ivan Topisirovic, Maria Lyngaas Torgersen, Liliana Torosantucci, Alicia Torriglia, Maria Rosaria Torrisi, Cathy Tournier, Roberto Town, Vladimir Trajkovic, Leonardo H Travasso, Gemma Triola, Durga Nand Tripathi, Daniela Trisciuoglio, Rodrigo Troncoso, Ioannis P Trougako, Anita C Truttmann, Kuen-Jer Tsai, Mario P Tschan, Yi-Hsin Tseng, Takayuki Tsukuba, Allan Tsung, Andrey S Tsvetkov, Shuiping Tu, Hsing-Yu Tuan, Marco Tucci, David A Tumbarello, Boris Turk, Vito Turk, Robin FB Turner, Anders A Tveita, Suresh C Tyagi, Makoto Ubukata, Yasuo Uchiyama, Andrej Udelnow, Takashi Ueno, Midori Umekawa, Rika Umemiya-Shirafuji, Benjamin R Underwood, Christian Ungermann, Rodrigo P. Ureshino, Ryo Ushioda, Vladimir N Uversky, Néstor L Uzcátegui, Thomas Vaccari, Maria I Vaccaro, Libuše Váchová, Helin Vakifahmetoglu-Norberg, Rut Valdor, Enza Maria Valente, Francois Vallette, Angela M Valverde, Greet Van den Berghe, Ludo Van Den Bosch, Gijs R van den Brink, F Gisou van der Goot, Ida J van der Klei, Luc JW van der Laan, Wouter G van Doorn, Marjolein van Egmond, Kenneth L van Golen, Luc Van Kaer, Menno van Lookeren Campagne, Peter Vandenabeele, Wim Vandenberghe, Ilse Vanhorebeek, Isabel Varela-Nieto, M Helena Vasconcelo, Radovan Vasko, Demetrios G Vavva, Ignacio Vega- Naredo, Guillermo Velasco, Athanassios D Velentza, Panagiotis D Velentza, Tibor Vellai, Edo Vellenga, Mikkel Holm Vendelbo, Kartik Venkatachalam, Natascia Ventura, Salvador Ventura, Patrícia ST Vera, Mireille Verdier, Beata G Vertessy, Andrea Viale, Michel Vidal, Helena LA Vieira, Richard D Vierstra, Nadarajah Vigneswaran, Neeraj Vij, Miquel Vila, Margarita Villar, Victor H Villar, Joan Villarroya, Cécile Vindi, Giampietro Viola, Maria Teresa Viscomi, Giovanni Vitale, Dan T Vogl, Olga V Voitsekhovskaja, Clarissa von Haefen, Karin von Schwarzenberg, Daniel E Voth, Valérie Vouret-Craviari, Kristina Vuori, Jatin M Vya, Christian Waeber, Cheryl Lyn Walker, Mark J Walker, Jochen Walter, Lei Wan, Xiangbo Wan, Bo Wang, Caihong Wang, Chao-Yung Wang, Chengshu Wang, Chenran Wang, Chuangui Wang, Dong Wang, Fen Wang, Fuxin Wang, Guanghui Wang, Hai-jie Wang, Haichao Wang, Hong-Gang Wang, Hongmin Wang, Horng-Dar Wang, Jing Wang, Junjun Wang, Mei Wang, Mei-Qing Wang, Pei-Yu Wang, Peng Wang, Richard C Wang, Shuo Wang, Ting-Fang Wang, Xian Wang, Xiao-jia Wang, Xiao-Wei Wang, Xin Wang, Xuejun Wang, Yan Wang, Yanming Wang, Ying Wang, Ying-Jan Wang, Yipeng Wang, Yu Wang, Yu Tian Wang, Yuqing Wang, Zhi-Nong Wang, Pablo Wappner, Carl Ward, Diane McVey Ward, Gary Warne, Hirotaka Watada, Yoshihisa Watanabe, Kei Watase, Timothy E Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=kaup20 Download by: [Alma Mater Studiorum - Università di Bologna] Date: 23 September 2016, At: 06:43 Weaver, Colin D Weeke, Jiwu Wei, Thomas Weide, Conrad C Weihl, Günther Weindl, Simone Nardin Wei, Longping Wen, Xin Wen, Yunfei Wen, Benedikt Westermann, Cornelia M Weyand, Anthony R White, Eileen White, J Lindsay Whitton, Alexander J Whitworth, Joëlle Wiel, Franziska Wild, Manon E Wildenberg, Tom Wileman, Deepti Srinivas Wilkinson, Simon Wilkinson, Dieter Willbold, Chris William, Katherine William, Peter R Williamson, Konstanze F Winklhofer, Steven S Witkin, Stephanie E Wohlgemuth, Thomas Wollert, Ernst J Wolvetang, Esther Wong, G William Wong, Richard W Wong, Vincent Kam Wai Wong, Elizabeth A Woodcock, Karen L Wright, Chunlai Wu, Defeng Wu, Gen Sheng Wu, Jian Wu, Junfang Wu, Mian Wu, Min Wu, Shengzhou Wu, William KK Wu, Yaohua Wu, Zhenlong Wu, Cristina PR Xavier, Ramnik J Xavier, Gui-Xian Xia, Tian Xia, Weiliang Xia, Yong Xia, Hengyi Xiao, Jian Xiao, Shi Xiao, Wuhan Xiao, Chuan-Ming Xie, Zhiping Xie, Zhonglin Xie, Maria Xilouri, Yuyan Xiong, Chuanshan Xu, Congfeng Xu, Feng Xu, Haoxing Xu, Hongwei Xu, Jian Xu, Jianzhen Xu, Jinxian Xu, Liang Xu, Xiaolei Xu, Yangqing Xu, Ye Xu, Zhi-Xiang Xu, Ziheng Xu, Yu Xue, Takahiro Yamada, Ai Yamamoto, Koji Yamanaka, Shunhei Yamashina, Shigeko Yamashiro, Bing Yan, Bo Yan, Xianghua Yan, Zhen Yan, Yasuo Yanagi, Dun-Sheng Yang, Jin-Ming Yang, Liu Yang, Minghua Yang, Pei-Ming Yang, Peixin Yang, Qian Yang, Wannian Yang, Wei Yuan Yang, Xuesong Yang, Yi Yang, Ying Yang, Zhifen Yang, Zhihong Yang, Meng-Chao Yao, Pamela J Yao, Xiaofeng Yao, Zhenyu Yao, Zhiyuan Yao, Linda S Yasui, Mingxiang Ye, Barry Yedvobnick, Behzad Yeganeh, Elizabeth S Yeh, Patricia L Yeyati, Fan Yi, Long Yi, Xiao-Ming Yin, Calvin K Yip, Yeong-Min Yoo, Young Hyun Yoo, Seung-Yong Yoon, Ken-Ichi Yoshida, Tamotsu Yoshimori, Ken H Young, Huixin Yu, Jane J Yu, Jin-Tai Yu, Jun Yu, Li Yu, W Haung Yu, Xiao-Fang Yu, Zhengping Yu, Junying Yuan, Zhi-Min Yuan, Beatrice YJT Yue, Jianbo Yue, Zhenyu Yue, David N Zack, Eldad Zacksenhau, Nadia Zaffaroni, Tania Zaglia, Zahra Zakeri, Vincent Zecchini, Jinsheng Zeng, Min Zeng, Qi Zeng, Antonis S Zervo, Donna D Zhang, Fan Zhang, Guo Zhang, Guo-Chang Zhang, Hao Zhang, Hong Zhang, Hongbing Zhang, Jian Zhang, Jiangwei Zhang, Jianhua Zhang, Jing-pu Zhang, Li Zhang, Lin Zhang, Long Zhang, Ming-Yong Zhang, Xiangnan Zhang, Xu Dong Zhang, Yan Zhang, Yang Zhang, Yanjin Zhang, Yingmei Zhang, Yunjiao Zhang, Mei Zhao, Wei-Li Zhao, Xiaonan Zhao, Yan G Zhao, Ying Zhao, Yongchao Zhao, Yu-xia Zhao, Zhendong Zhao, Zhizhuang J Zhao, Dexian Zheng, Xi-Long Zheng, Xiaoxiang Zheng, Boris Zhivotovsky, Qing Zhong, Guang-Zhou Zhou, Guofei Zhou, Huiping Zhou, Shu-Feng Zhou, Xu-jie Zhou, Hongxin Zhu, Hua Zhu, Wei- Guo Zhu, Wenhua Zhu, Xiao-Feng Zhu, Yuhua Zhu, Shi-Mei Zhuang, Xiaohong Zhuang, Elio Ziparo, Christos E Zoi, Teresa Zoladek, Wei-Xing Zong, and Antonio Zorzano & Susu M Zughaier
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[SDV]Life Sciences [q-bio] ,autophagosome ,Review Article ,ddc:616.07 ,stress ,stre ,LC3 ,MESH: Animals ,Settore MED/49 - Scienze Tecniche Dietetiche Applicate ,Settore BIO/06 - Anatomia Comparata E Citologia ,chaperone-mediated autophagy ,ComputingMilieux_MISCELLANEOUS ,Settore BIO/11 ,Pharmacology. Therapy ,Settore BIO/13 ,standards [Biological Assay] ,autolysosome ,MESH: Autophagy*/physiology ,lysosome ,methods [Biological Assay] ,Biological Assay ,Settore BIO/17 - ISTOLOGIA ,Erratum ,Human ,Biochemistry & Molecular Biology ,Settore BIO/06 ,physiology [Autophagy] ,Chaperonemediated autophagy ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,NO ,autophagy, guidelines, molecular biology, ultrastructure ,flux ,macroautophagy ,phagophore ,vacuole ,MESH: Biological Assay/methods ,MESH: Computer Simulation ,ddc:570 ,Autolysosome, Autophagosome, Chaperonemediated autophagy, Flux, LC3, Lysosome, Macroautophagy, Phagophore, Stress, Vacuole ,Autophagy ,Animals ,Humans ,Computer Simulation ,Settore BIO/10 ,ddc:612 ,Biology ,MESH: Humans ,Animal ,0601 Biochemistry And Cell Biology ,MESH: Biological Assay/standards ,Human medicine - Abstract
Seuls les 100 premiers auteurs dont les auteurs INRA ont été entrés dans la notice. La liste complète des auteurs et de leurs affiliations est accessible sur la publication.; International audience; In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
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- 2016
20. Metabolic Tumor Volume on 18-Fluorodeoxyglucose Positron Emission Tomography as a Prognostic Marker of Survival in Patients With Locally Advanced or Metastatic Neuroendocrine Neoplasms Treated With 177Lutetium-DOTA-Octreotate Peptide Receptor Radionuclide Therapy.
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De Silva MK, Chan DLH, Bernard EJ, Conner AJ, Mascall SL, Bailey DL, Roach PJ, Clarke SJ, Diakos CI, Pavlakis N, and Schembri G
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- Humans, Male, Middle Aged, Female, Retrospective Studies, Aged, Prognosis, Adult, Receptors, Peptide metabolism, Glycolysis, Aged, 80 and over, Pancreatic Neoplasms pathology, Pancreatic Neoplasms radiotherapy, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms mortality, Progression-Free Survival, Treatment Outcome, Neuroendocrine Tumors pathology, Neuroendocrine Tumors radiotherapy, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors metabolism, Neuroendocrine Tumors mortality, Fluorodeoxyglucose F18, Octreotide analogs & derivatives, Octreotide therapeutic use, Radiopharmaceuticals, Positron-Emission Tomography methods, Tumor Burden, Organometallic Compounds therapeutic use
- Abstract
Objective: We investigated metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on pre-treatment FDG-PET as prognostic markers for survival in patients with metastatic neuroendocrine neoplasms (NENs) receiving peptide receptor radionuclide therapy (PRRT)., Methods: A retrospective review of patients with metastatic NENs receiving PRRT was undertaken. Pre-treatment FDG-PET images were analyzed and variables collected included MTV and TLG (dichotomized by median into high vs low). Main Outcomes were overall survival (OS) and progression-free survival (PFS) by MTV and TLG (high vs low)., Results: One hundred five patients were included. Median age was 64 years (50% male). Main primary NEN sites were small bowel (43.8%) and pancreas (40.0%). Median MTV was 3.8 mL and median TLG was 19.9. Dichotomization formed identical cohorts regardless of whether MTV or TLG were used. Median OS was 72 months; OS did not differ based on MTV/TLG high versus low (47.4 months vs not reached; hazard ratio, 0.43; 95% confidence interval [CI], 0.18-1.04; P = 0.0594). Median PFS was 30.4 months; PFS differed based on MTV/TLG high versus low (21.6 months vs 45.7 months; hazard ratio, 0.35; 95% CI, 0.19-0.64; P = 0.007)., Conclusions: Low MTV/TLG on pre-treatment FDG-PET was associated with longer PFS in metastatic NEN patients receiving PRRT., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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21. Impaired malin expression and interaction with partner proteins in Lafora disease.
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Skurat AV, Segvich DM, Contreras CJ, Hu YC, Hurley TD, DePaoli-Roach AA, and Roach PJ
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- Animals, Mice, Humans, Dual-Specificity Phosphatases metabolism, Dual-Specificity Phosphatases genetics, Disease Models, Animal, Glycogen metabolism, Glycogen genetics, Lafora Disease metabolism, Lafora Disease genetics, Lafora Disease pathology, Ubiquitin-Protein Ligases metabolism, Ubiquitin-Protein Ligases genetics, Protein Tyrosine Phosphatases, Non-Receptor metabolism, Protein Tyrosine Phosphatases, Non-Receptor genetics
- Abstract
Lafora disease (LD) is an autosomal recessive myoclonus epilepsy with onset in the teenage years leading to death within a decade of onset. LD is characterized by the overaccumulation of hyperphosphorylated, poorly branched, insoluble, glycogen-like polymers called Lafora bodies. The disease is caused by mutations in either EPM2A, encoding laforin, a dual specificity phosphatase that dephosphorylates glycogen, or EMP2B, encoding malin, an E3-ubiquitin ligase. While glycogen is a widely accepted laforin substrate, substrates for malin have been difficult to identify partly due to the lack of malin antibodies able to detect malin in vivo. Here we describe a mouse model in which the malin gene is modified at the C-terminus to contain the c-myc tag sequence, making an expression of malin-myc readily detectable. Mass spectrometry analyses of immunoprecipitates using c-myc tag antibodies demonstrate that malin interacts with laforin and several glycogen-metabolizing enzymes. To investigate the role of laforin in these interactions we analyzed two additional mouse models: malin-myc/laforin knockout and malin-myc/LaforinCS, where laforin was either absent or the catalytic Cys was genomically mutated to Ser, respectively. The interaction of malin with partner proteins requires laforin but is not dependent on its catalytic activity or the presence of glycogen. Overall, the results demonstrate that laforin and malin form a complex in vivo, which stabilizes malin and enhances interaction with partner proteins to facilitate normal glycogen metabolism. They also provide insights into the development of LD and the rescue of the disease by the catalytically inactive phosphatase., Competing Interests: Conflict of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T. D. H., A. A. D.-R., and P. J. R. were consultants for Maze Therapeutics. T. D. H. is also a consultant for SAJE Pharma. The other authors declare that they have no competing interest. None of the work in this article was supported by these entities., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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- View/download PDF
22. Letter to the Editor: FDG Liver Biodistribution.
- Author
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Bailey DL, Schembri GP, Willowson KP, and Roach PJ
- Subjects
- Humans, Tissue Distribution, Positron-Emission Tomography, Liver diagnostic imaging, Fluorodeoxyglucose F18, Radiopharmaceuticals
- Published
- 2024
- Full Text
- View/download PDF
23. Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog.
- Author
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Coate KC, Ramnanan CJ, Smith M, Winnick JJ, Kraft G, Irimia-Dominguez J, Farmer B, Donahue EP, Roach PJ, Cherrington AD, and Edgerton DS
- Subjects
- Humans, Dogs, Animals, Transcriptome, Glucose metabolism, Liver metabolism, Gluconeogenesis genetics, Blood Glucose metabolism, Glucagon metabolism, Insulin metabolism
- Abstract
Glucagon rapidly and profoundly stimulates hepatic glucose production (HGP), but for reasons that are unclear, this effect normally wanes after a few hours, despite sustained plasma glucagon levels. This study characterized the time course of glucagon-mediated molecular events and their relevance to metabolic flux in the livers of conscious dogs. Glucagon was either infused into the hepato-portal vein at a sixfold basal rate in the presence of somatostatin and basal insulin, or it was maintained at a basal level in control studies. In one control group, glucose remained at basal, whereas in the other, glucose was infused to match the hyperglycemia that occurred in the hyperglucagonemic group. Elevated glucagon caused a rapid (30 min) and largely sustained increase in hepatic cAMP over 4 h, a continued elevation in glucose-6-phosphate (G6P), and activation and deactivation of glycogen phosphorylase and synthase activities, respectively. Net hepatic glycogenolysis increased rapidly, peaking at 15 min due to activation of the cAMP/PKA pathway, then slowly returned to baseline over the next 3 h in line with allosteric inhibition by glucose and G6P. Glucagon's stimulatory effect on HGP was sustained relative to the hyperglycemic control group due to continued PKA activation. Hepatic gluconeogenic flux did not increase due to the lack of glucagon's effect on substrate supply to the liver. Global gene expression profiling highlighted glucagon-regulated activation of genes involved in cellular respiration, metabolic processes, and signaling, as well as downregulation of genes involved in extracellular matrix assembly and development. NEW & NOTEWORTHY Glucagon rapidly stimulates hepatic glucose production, but these effects are transient. This study links the molecular and metabolic flux changes that occur in the liver over time in response to a rise in glucagon, demonstrating the strength of the dog as a translational model to couple findings in small animals and humans. In addition, this study clarifies why the rapid effects of glucagon on liver glycogen metabolism are not sustained.
- Published
- 2024
- Full Text
- View/download PDF
24. Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders.
- Author
-
Ullman JC, Mellem KT, Xi Y, Ramanan V, Merritt H, Choy R, Gujral T, Young LEA, Blake K, Tep S, Homburger JR, O'Regan A, Ganesh S, Wong P, Satterfield TF, Lin B, Situ E, Yu C, Espanol B, Sarwaikar R, Fastman N, Tzitzilonis C, Lee P, Reiton D, Morton V, Santiago P, Won W, Powers H, Cummings BB, Hoek M, Graham RR, Chandriani SJ, Bainer R, DePaoli-Roach AA, Roach PJ, Hurley TD, Sun RC, Gentry MS, Sinz C, Dick RA, Noonberg SB, Beattie DT, Morgans DJ Jr, and Green EM
- Subjects
- Mice, Animals, Glycogen Synthase metabolism, Glycogen Synthase pharmacology, Mice, Knockout, Glycogen metabolism, Muscle, Skeletal metabolism, Enzyme Replacement Therapy methods, Glycogen Storage Disease Type II drug therapy
- Abstract
Glycogen synthase 1 (GYS1), the rate-limiting enzyme in muscle glycogen synthesis, plays a central role in energy homeostasis and has been proposed as a therapeutic target in multiple glycogen storage diseases. Despite decades of investigation, there are no known potent, selective small-molecule inhibitors of this enzyme. Here, we report the preclinical characterization of MZ-101, a small molecule that potently inhibits GYS1 in vitro and in vivo without inhibiting GYS2, a related isoform essential for synthesizing liver glycogen. Chronic treatment with MZ-101 depleted muscle glycogen and was well tolerated in mice. Pompe disease, a glycogen storage disease caused by mutations in acid α glucosidase (GAA), results in pathological accumulation of glycogen and consequent autophagolysosomal abnormalities, metabolic dysregulation, and muscle atrophy. Enzyme replacement therapy (ERT) with recombinant GAA is the only approved treatment for Pompe disease, but it requires frequent infusions, and efficacy is limited by suboptimal skeletal muscle distribution. In a mouse model of Pompe disease, chronic oral administration of MZ-101 alone reduced glycogen buildup in skeletal muscle with comparable efficacy to ERT. In addition, treatment with MZ-101 in combination with ERT had an additive effect and could normalize muscle glycogen concentrations. Biochemical, metabolomic, and transcriptomic analyses of muscle tissue demonstrated that lowering of glycogen concentrations with MZ-101, alone or in combination with ERT, corrected the cellular pathology in this mouse model. These data suggest that substrate reduction therapy with GYS1 inhibition may be a promising therapeutic approach for Pompe disease and other glycogen storage diseases.
- Published
- 2024
- Full Text
- View/download PDF
25. Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog.
- Author
-
Coate KC, Ramnanan CJ, Smith M, Winnick JJ, Kraft G, Irimia JM, Farmer B, Donahue P, Roach PJ, Cherrington AD, and Edgerton DS
- Abstract
Glucagon rapidly and profoundly simulates hepatic glucose production (HGP), but for reasons which are unclear, this effect normally wanes after a few hours, despite sustained plasma glucagon levels. This study characterized the time course and relevance (to metabolic flux) of glucagon mediated molecular events in the livers of conscious dogs. Glucagon was either infused into the hepato-portal vein at a 6-fold basal rate in the presence of somatostatin and basal insulin, or it was maintained at a basal level in control studies. In one control group glucose remained at basal while in the other glucose was infused to match the hyperglycemia that occurred in the hyperglucagonemic group. Elevated glucagon caused a rapid (30 min) but only partially sustained increase in hepatic cAMP over 4h, a continued elevation in G6P, and activation and deactivation of glycogen phosphorylase and synthase activities, respectively. Net hepatic glycogenolysis and HGP increased rapidly, peaking at 30 min, then returned to baseline over the next 3h (although glucagons stimulatory effect on HGP was sustained relative to the hyperglycemic control group). Hepatic gluconeogenic flux did not increase due to lack of glucagon effect on substrate supply to the liver. Global gene expression profiling highlighted glucagon-regulated activation of genes involved in cellular respiration, metabolic processes, and signaling, and downregulation of genes involved in extracellular matrix assembly and development.
- Published
- 2023
- Full Text
- View/download PDF
26. Single-centre experience with peptide receptor radionuclide therapy for neuroendocrine tumours (NETs): results using a theranostic molecular imaging-guided approach.
- Author
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Gordon S, Chan DLH, Bernard EJ, Eslick ME, Willowson KP, Roach PJ, Engel AF, Maher R, Clarke SJ, Agarwal V, Yasmin L, De Silva M, Mascall S, Conner A, Nevell D, Pavlakis N, and Bailey DL
- Subjects
- Male, Female, Humans, Adult, Middle Aged, Aged, Aged, 80 and over, Precision Medicine, Octreotide therapeutic use, Molecular Imaging, Receptors, Peptide, Radioisotopes, Neuroendocrine Tumors pathology
- Abstract
Aim: To summarise our centre's experience managing patients with neuroendocrine tumours (NETs) in the first 5 years after the introduction of peptide receptor radionuclide therapy (PRRT) with [
177 Lu]Lu-DOTA-octreotate (LUTATE). The report emphasises aspects of the patient management related to functional imaging and use of radionuclide therapy., Methods: We describe the criteria for treatment with LUTATE at our centre, the methodology for patient selection, and the results of an audit of clinical measures, imaging results and patient-reported outcomes. Subjects are treated initially with four cycles of ~ 8 GBq of LUTATE administered as an outpatient every 8 weeks., Results: In the first 5 years offering LUTATE, we treated 143 individuals with a variety of NETs of which approx. 70% were gastroentero-pancreatic in origin (small bowel: 42%, pancreas: 28%). Males and females were equally represented. Mean age at first treatment with LUTATE was 61 ± 13 years with range 28-87 years. The radiation dose to the organs considered most at risk, the kidneys, averaged 10.6 ± 4.0 Gy in total. Median overall survival (OS) from first receiving LUTATE was 72.5 months with a median progression-free survival (PFS) of 32.3 months. No evidence of renal toxicity was seen. The major long-term complication seen was myelodysplastic syndrome (MDS) with a 5% incidence., Conclusions: LUTATE treatment for NETs is a safe and effective treatment. Our approach relies heavily on functional and morphological imaging informing the multidisciplinary team of NET specialists to guide appropriate therapy, which we suggest has contributed to the favourable outcomes seen., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
27. 64 Cu Treatment Planning and 67 Cu Therapy with Radiolabeled [ 64 Cu/ 67 Cu]MeCOSar-Octreotate in Subjects with Unresectable Multifocal Meningioma: Initial Results for Human Imaging, Safety, Biodistribution, and Radiation Dosimetry.
- Author
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Bailey DL, Willowson KP, Harris M, Biggin C, Aslani A, Lengkeek NA, Stoner J, Eslick ME, Marquis H, Parker M, Roach PJ, and Schembri GP
- Subjects
- Humans, Positron Emission Tomography Computed Tomography methods, Radioisotopes, Radiometry, Radiopharmaceuticals therapeutic use, Tissue Distribution, Meningeal Neoplasms, Meningioma diagnostic imaging, Meningioma radiotherapy
- Abstract
Our aim was to report the use of
64 Cu and67 Cu as a theranostic pair of radionuclides in human subjects. An additional aim was to measure whole-organ dosimetry of64 Cu and67 Cu attached to the somatostatin analog octreotate using the sarcophagine MeCOSar chelator (SARTATE) in subjects with somatostatin receptor-expressing lesions confined to the cranium, thereby permitting normal-organ dosimetry for the remainder of the body. Methods: Pretreatment PET imaging studies were performed up to 24 h after injection of [64 Cu]Cu-SARTATE, and normal-organ dosimetry was estimated using OLINDA/EXM. Subsequently, the trial subjects with multifocal meningiomas were given therapeutic doses of [67 Cu]Cu-SARTATE and imaged over several days using SPECT/CT. Results: Five subjects were initially recruited and imaged using PET/CT before treatment. Three of the subjects were subsequently administered 4 cycles each of [67 Cu]Cu-SARTATE followed by multiple SPECT/CT imaging time points. No serious adverse events were observed, and no adverse events led to withdrawal from the study or discontinuation from treatment. The estimated mean effective dose was 3.95 × 10-2 mSv/MBq for [64 Cu]Cu-SARTATE and 7.62 × 10-2 mSv/MBq for [67 Cu]Cu-SARTATE. The highest estimated organ dose was in spleen, followed by kidneys, liver, adrenals, and small intestine. The matched pairing was shown by PET and SPECT intrasubject imaging to have nearly identical targeting to tumors for guiding therapy, demonstrating a potentially accurate and precise theranostic product. Conclusion:64 Cu and67 Cu show great promise as a theranostic pair of radionuclides. Further clinical studies will be required to examine the therapeutic dose required for [67 Cu]Cu-SARTATE for various indications. In addition, the ability to use predictive64 Cu-based dosimetry for treatment planning with67 Cu should be further explored., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2023
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28. Australasian Consensus Statement on the Identification, Prevention, and Management of Hormonal Crises in Patients with Neuroendocrine Neoplasms Undergoing Peptide Receptor Radionuclide Therapy.
- Author
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Li M, Chan DL, Tapia Rico G, Cehic G, Lawrence B, Wyld D, Pattison DA, Kong G, Hicks R, Michael M, Kiberu AD, Lim J, Clifton-Bligh R, Tsang V, Roach PJ, Leyden J, Diakos CI, Price TJ, and Pavlakis N
- Subjects
- Humans, Australia, Radioisotopes therapeutic use, Receptors, Peptide, Neuroendocrine Tumors drug therapy, Pancreatic Neoplasms drug therapy
- Abstract
Hormonal crises are a rare but increasingly recognized phenomenon following peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine neoplasms (NENs). Due to the paucity of published studies, approaches to the identification, prevention, and management of risk factors are inconsistent between different institutions. This consensus statement aimed to provide guidance for NEN patients undergoing PRRT. Our statement has been created on the basis of clinical demand and concerns regarding the precipitation of hormonal crises. A formal literature review was conducted to identify available studies. A total of 19 Australian and New Zealand experts in the fields of medical oncology, nuclear medicine, anaesthetics, and endocrinology collaborated on this consensus statement. The main focus is on carcinoid crises. Other hormonal crises seen in patients with functional pancreatic NENs are addressed briefly. These recommendations are relevant to PRRT centres internationally and should be tailored to local experience and available resources., (© 2022 S. Karger AG, Basel.)
- Published
- 2023
- Full Text
- View/download PDF
29. Letter to Editor Re: "Combined Quantification of 18F-FDG and 68Ga-DOTATATE PET/CT for Prognosis in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms" (https://doi.org/10.1016/j.acra.2021.10.004).
- Author
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Chan DL, Roach PJ, and Bailey DL
- Subjects
- Fluorodeoxyglucose F18, Humans, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Prognosis, Radionuclide Imaging, Neuroendocrine Tumors diagnostic imaging, Organometallic Compounds
- Published
- 2022
- Full Text
- View/download PDF
30. The structural mechanism of human glycogen synthesis by the GYS1-GYG1 complex.
- Author
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Fastman NM, Liu Y, Ramanan V, Merritt H, Ambing E, DePaoli-Roach AA, Roach PJ, Hurley TD, Mellem KT, Ullman JC, Green E, Morgans D Jr, and Tzitzilonis C
- Subjects
- Glucosyltransferases metabolism, Glycogen metabolism, Humans, Glycogen Synthase metabolism, Glycogenolysis, Glycoproteins metabolism
- Abstract
Glycogen is the primary energy reserve in mammals, and dysregulation of glycogen metabolism can result in glycogen storage diseases (GSDs). In muscle, glycogen synthesis is initiated by the enzymes glycogenin-1 (GYG1), which seeds the molecule by autoglucosylation, and glycogen synthase-1 (GYS1), which extends the glycogen chain. Although both enzymes are required for proper glycogen production, the nature of their interaction has been enigmatic. Here, we present the human GYS1:GYG1 complex in multiple conformations representing different functional states. We observe an asymmetric conformation of GYS1 that exposes an interface for close GYG1 association, and propose this state facilitates handoff of the GYG1-associated glycogen chain to a GYS1 subunit for elongation. Full activation of GYS1 widens the GYG1-binding groove, enabling GYG1 release concomitant with glycogen chain growth. This structural mechanism connecting chain nucleation and extension explains the apparent stepwise nature of glycogen synthesis and suggests distinct states to target for GSD-modifying therapeutics., Competing Interests: Declaration of interests N.M.F., Y.L., H.M., E.A., K.T.M., J.C.U., E.G., D.M., and C.T. are full time employees and stockholders of Maze Therapeutics. V.R., A.D.-R., and T.D.H. are advisors and stockholders of Maze Therapeutics., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
31. Computed tomography (CT)-defined sarcopenia and myosteatosis are prevalent in patients with neuroendocrine neoplasms (NENs) treated with peptide receptor radionuclide therapy (PRRT).
- Author
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Chan DL, Clarke SJ, Engel A, Diakos CI, Pavlakis N, Roach PJ, Bailey DL, Bauer J, and Findlay M
- Subjects
- Adult, Aged, Aged, 80 and over, Humans, Middle Aged, Muscle, Skeletal diagnostic imaging, Muscle, Skeletal pathology, Positron Emission Tomography Computed Tomography, Prognosis, Radioisotopes, Receptors, Peptide, Retrospective Studies, Tomography, X-Ray Computed, Neoplasms, Sarcopenia diagnostic imaging, Sarcopenia epidemiology, Sarcopenia etiology
- Abstract
Background/objectives: Neuroendocrine neoplasms (NEN) may predispose patients to malnutrition. CT-defined sarcopenia and myosteatosis are common in other tumour types and recognized adverse prognostic factors. However, the prevalence and prognostic impact of sarcopenia and myosteatosis remain undetermined in NEN patients to date., Methods: A retrospective study of NEN patients treated with peptide receptor radionuclide therapy (PRRT) at a tertiary institution from 2012 to 2017. Patients with PET/CT imaging at baseline and follow-up were included. The L3 slice of the co-localizing CT was analysed using the Alberta Protocol. Skeletal muscle cross-sectional area and muscle attenuation were measured and compared with pre-defined cut-offs. The primary endpoint was the prevalence of sarcopenia and myosteatosis according to previously published cut-offs., Results: Fourty-nine patients (median age 64 (range 26-80) years) were included. The most common primary sites of tumour were the small bowel (51%) and pancreas (26%). Baseline sarcopenia was prevalent in 67% of patients and myosteatosis in 71%. Forty-five percent of patients gained weight over the course of PRRT. The presence of baseline sarcopenia was not associated with progression-free survival (20.8 mo vs. 20.7 mo, HR 0.86, p = 0.70) nor overall survival. Similarly, baseline myosteatosis (PFS 19.5 mo vs. 20.8 mo, HR 0.77, p = 0.47) was not significantly associated with survival outcomes. The mean (SD) age of those with myosteatosis was 60.8 ± 11.6 years compared to 49.7 ± 12.7 years for those without (p = 0.003)., Conclusions: Body composition analysis is feasible using routinely acquired PET/CT data for patients with NEN. CT-defined sarcopenia and myosteatosis are prevalent in NEN patients, although myosteatosis is more common with increasing age. These findings were not associated with worsened overall or progression-free survival in the current study., (© 2021. Crown.)
- Published
- 2022
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- View/download PDF
32. Dual PET Imaging in Bronchial Neuroendocrine Neoplasms: The NETPET Score as a Prognostic Biomarker.
- Author
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Chan DL, Ulaner GA, Pattison D, Wyld D, Ladwa R, Kirchner J, Li BT, Lai WV, Pavlakis N, Roach PJ, and Bailey DL
- Subjects
- Humans, Male, Female, Middle Aged, Retrospective Studies, Prognosis, Aged, Organometallic Compounds, Adult, Biomarkers, Tumor metabolism, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors pathology, Bronchial Neoplasms diagnostic imaging, Fluorodeoxyglucose F18, Positron-Emission Tomography
- Abstract
PET scans using
18 F-FDG and somatostatin receptor imaging agents are both used in imaging of neuroendocrine neoplasms (NENs). We have suggested the "NETPET score," using uptake of both PET tracers, as a prognostic biomarker in NENs. The name NETPET score was suggested previously to capture the score's intent to summarize information from dual PET imaging in neuroendocrine tumors. We previously demonstrated the effectiveness of the NETPET score in gastroenteropancreatic NENs (GEPNENs). Its prognostic relevance in bronchial NENs remains undetermined. Methods: This is a retrospective multicenter study (2011-2018) assessing patients who had advanced bronchial NEN and who underwent both18 F-FDG and68 Ga-DOTATATE PET within 60 d of each other. The NETPET score was assigned by experienced nuclear medicine physicians and compared with other clinical data such as World Health Organization grade. The primary outcome was overall survival; NETPET score and other prognostic variables were analyzed using univariate and multivariate analyses by the Cox proportional-hazards model. Results: Thirty-eight patients were included for review. The NETPET score and histology were significantly correlated with overall survival in univariate analyses ( P = 0.003, P = 0.01). On multivariate analysis, only the NETPET score remained significant ( P = 0.03). The NETPET score was significantly associated with histologic grade ( P = 0.006, χ2 test). Conclusion: The NETPET score is a prognostic biomarker in bronchial NENs as well as GEPNENs. Although it needs to be validated in prospective studies, it holds significant promise as a biomarker for a wide range of NENs., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2021
- Full Text
- View/download PDF
33. Brain glycogen serves as a critical glucosamine cache required for protein glycosylation.
- Author
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Sun RC, Young LEA, Bruntz RC, Markussen KH, Zhou Z, Conroy LR, Hawkinson TR, Clarke HA, Stanback AE, Macedo JKA, Emanuelle S, Brewer MK, Rondon AL, Mestas A, Sanders WC, Mahalingan KK, Tang B, Chikwana VM, Segvich DM, Contreras CJ, Allenger EJ, Brainson CF, Johnson LA, Taylor RE, Armstrong DD, Shaffer R, Waechter CJ, Vander Kooi CW, DePaoli-Roach AA, Roach PJ, Hurley TD, Drake RR, and Gentry MS
- Subjects
- Animals, Cells, Cultured, Disease Models, Animal, Female, Glycogen metabolism, Glycogen Synthase genetics, Glycogen Synthase metabolism, Glycogenolysis genetics, Glycosylation, Lafora Disease genetics, Lafora Disease metabolism, Lafora Disease pathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Brain metabolism, Glucosamine metabolism, Glycogen physiology, Protein Processing, Post-Translational genetics
- Abstract
Glycosylation defects are a hallmark of many nervous system diseases. However, the molecular and metabolic basis for this pathology is not fully understood. In this study, we found that N-linked protein glycosylation in the brain is metabolically channeled to glucosamine metabolism through glycogenolysis. We discovered that glucosamine is an abundant constituent of brain glycogen, which functions as a glucosamine reservoir for multiple glycoconjugates. We demonstrated the enzymatic incorporation of glucosamine into glycogen by glycogen synthase, and the release by glycogen phosphorylase by biochemical and structural methodologies, in primary astrocytes, and in vivo by isotopic tracing and mass spectrometry. Using two mouse models of glycogen storage diseases, we showed that disruption of brain glycogen metabolism causes global decreases in free pools of UDP-N-acetylglucosamine and N-linked protein glycosylation. These findings revealed fundamental biological roles of brain glycogen in protein glycosylation with direct relevance to multiple human diseases of the central nervous system., Competing Interests: Declaration of interests M.S.G. is a consultant for Maze Therapeutics, Enable Therapeutics, Glut1-Deficiency Syndrome Foundation, and Chelsea's Hope. M.S.G., R.C.S., C.W.V.K., and R.C.B. are founders of Atterogen, LLC., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
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34. Safety and tolerability of Miltuximab ® - a first in human study in patients with advanced solid cancers.
- Author
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Sabanathan D, Campbell DH, Velonas VM, Wissmueller S, Mazure H, Trifunovic M, Poursoltan P, Ho Shon K, Mackay TR, Lund ME, Lu Y, Roach PJ, Bailey DL, Walsh BJ, Gillatt D, and Gurney H
- Abstract
Objectives: Miltuximab
® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab® radiolabelled with Gallium-67 ([67 Ga]Ga-DOTA-Miltuximab® ). The primary study endpoint was to establish safety and tolerability of Miltuximab® . Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis., Methods: Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [67 Ga]Ga-DOTA-Miltuximab® . Cohort 1 received [67 Ga]Ga-DOTA-Miltuximab® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab® -DOTA 1 hour prior to [67 Ga]Ga-DOTA-Miltuximab® . Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans., Results: The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [67 Ga]Ga-DOTA-Miltuximab® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab® -DOTA. Dosimetry analysis showed a favorable exposure profile. [67 Ga]Ga-DOTA-Miltuximab® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life., Conclusions: This study is the first in human for Miltuximab® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab® as a theranostic agent in a planned Phase I human trial., (© 2021 mums.ac.ir All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
35. GYS1 or PPP1R3C deficiency rescues murine adult polyglucosan body disease.
- Author
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Chown EE, Wang P, Zhao X, Crowder JJ, Strober JW, Sullivan MA, Xue Y, Bennett CS, Perri AM, Evers BM, Roach PJ, Depaoli-Roach AA, Akman HO, Pederson BA, and Minassian BA
- Subjects
- Animals, Behavior, Animal physiology, Disease Models, Animal, Glycogen Storage Disease physiopathology, Glycogen Storage Disease therapy, Mice, Mice, Knockout, Nervous System Diseases physiopathology, Nervous System Diseases therapy, Glycogen Storage Disease metabolism, Glycogen Synthase deficiency, Intracellular Signaling Peptides and Proteins deficiency, Nervous System Diseases metabolism
- Abstract
Objective: Adult polyglucosan body disease (APBD) is an adult-onset neurological variant of glycogen storage disease type IV. APBD is caused by recessive mutations in the glycogen branching enzyme gene, and the consequent accumulation of poorly branched glycogen aggregates called polyglucosan bodies in the nervous system. There are presently no treatments for APBD. Here, we test whether downregulation of glycogen synthesis is therapeutic in a mouse model of the disease., Methods: We characterized the effects of knocking out two pro-glycogenic proteins in an APBD mouse model. APBD mice were crossed with mice deficient in glycogen synthase (GYS1), or mice deficient in protein phosphatase 1 regulatory subunit 3C (PPP1R3C), a protein involved in the activation of GYS1. Phenotypic and histological parameters were analyzed and glycogen was quantified., Results: APBD mice deficient in GYS1 or PPP1R3C demonstrated improvements in life span, morphology, and behavioral assays of neuromuscular function. Histological analysis revealed a reduction in polyglucosan body accumulation and of astro- and micro-gliosis in the brains of GYS1- and PPP1R3C-deficient APBD mice. Brain glycogen quantification confirmed the reduction in abnormal glycogen accumulation. Analysis of skeletal muscle, heart, and liver found that GYS1 deficiency reduced polyglucosan body accumulation in all three tissues and PPP1R3C knockout reduced skeletal muscle polyglucosan bodies., Interpretation: GYS1 and PPP1R3C are effective therapeutic targets in the APBD mouse model. These findings represent a critical step toward the development of a treatment for APBD and potentially other glycogen storage disease type IV patients., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Published
- 2020
- Full Text
- View/download PDF
36. Routine Early 68Ga-DOTATATE Positron Emission Tomography Has Low Yield After Resection of Appendiceal Neuroendocrine Neoplasms.
- Author
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Chan DL, Hoang J, Roach PJ, Arena J, Bailey DL, Nevell D, Pavlakis N, Engel A, and Bernard EJ
- Subjects
- Adolescent, Adult, Aged, Appendiceal Neoplasms surgery, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Multimodal Imaging methods, Neoplasm Recurrence, Local, Neuroendocrine Tumors surgery, Prognosis, Retrospective Studies, Tomography, X-Ray Computed methods, Young Adult, Appendiceal Neoplasms diagnostic imaging, Neuroendocrine Tumors diagnostic imaging, Organometallic Compounds, Positron-Emission Tomography methods
- Abstract
Objectives: Appendiceal neuroendocrine neoplasms (appNEN) generally carry a low recurrence risk. Ga-DOTATATE positron emission tomography (DOTA PET) is increasingly used as it is more sensitive than cross-sectional imaging. We hypothesize that early DOTA PET is unlikely to detect recurrent disease in patients with low-risk resected appNEN because of the delayed pattern of recurrence., Methods: Retrospective study (dual review) of patients undergoing DOTA PET 0 to 18 months after resected appNEN. The primary outcome was the proportion of scans demonstrating residual disease., Results: Forty-one patients were included (median age, 29 years; 63% female), most with small, low-grade appNEN. No scans (0%) showed residual/distant disease. Eight (20%) of 41 scans showed indeterminate findings requiring follow-up. Five (12%) scans were recommended for follow-up with modalities other than DOTA PET (vertebra, 3; thyroid; bone, 1 each). Three (7%) were recommended for follow-up with DOTA PET (all with indeterminate abdominal uptake). These 3 patients had no recurrent disease on follow-up., Conclusions: The Ga-DOTATATE PET is of no value when performed in the first 18 months after resected appNEN. Although 20% of scans showed indeterminate findings, more than half did not require repeat DOTA PET. Despite advantages over cross-sectional imaging, DOTA PET is not recommended in staging after completely resected appNEN.
- Published
- 2020
- Full Text
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37. Discovery and Development of Small-Molecule Inhibitors of Glycogen Synthase.
- Author
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Tang B, Frasinyuk MS, Chikwana VM, Mahalingan KK, Morgan CA, Segvich DM, Bondarenko SP, Mrug GP, Wyrebek P, Watt DS, DePaoli-Roach AA, Roach PJ, and Hurley TD
- Subjects
- Animals, Caenorhabditis elegans enzymology, Crystallography, X-Ray, Drug Discovery, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors metabolism, Glycogen Synthase chemistry, Glycogen Synthase metabolism, HEK293 Cells, Humans, Imidazoles chemical synthesis, Imidazoles metabolism, Kinetics, Molecular Structure, Protein Binding, Pyrazoles chemical synthesis, Pyrazoles metabolism, Saccharomyces cerevisiae enzymology, Structure-Activity Relationship, Enzyme Inhibitors chemistry, Glycogen Synthase antagonists & inhibitors, Imidazoles chemistry, Pyrazoles chemistry
- Abstract
The overaccumulation of glycogen appears as a hallmark in various glycogen storage diseases (GSDs), including Pompe, Cori, Andersen, and Lafora disease. Accumulating evidence suggests that suppression of glycogen accumulation represents a potential therapeutic approach for treating these GSDs. Using a fluorescence polarization assay designed to screen for inhibitors of the key glycogen synthetic enzyme, glycogen synthase (GS), we identified a substituted imidazole, ( rac )-2-methoxy-4-(1-(2-(1-methylpyrrolidin-2-yl)ethyl)-4-phenyl-1 H -imidazol-5-yl)phenol ( H23 ), as a first-in-class inhibitor for yeast GS 2 (yGsy2p). Data from X-ray crystallography at 2.85 Å, as well as kinetic data, revealed that H23 bound within the uridine diphosphate glucose binding pocket of yGsy2p. The high conservation of residues between human and yeast GS in direct contact with H23 informed the development of around 500 H23 analogs. These analogs produced a structure-activity relationship profile that led to the identification of a substituted pyrazole, 4-(4-(4-hydroxyphenyl)-3-(trifluoromethyl)-1 H -pyrazol-5-yl)pyrogallol, with a 300-fold improved potency against human GS. These substituted pyrazoles possess a promising scaffold for drug development efforts targeting GS activity in GSDs associated with excess glycogen accumulation.
- Published
- 2020
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38. Accurate and sensitive quantitation of glucose and glucose phosphates derived from storage carbohydrates by mass spectrometry.
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Young LEA, Brizzee CO, Macedo JKA, Murphy RD, Contreras CJ, DePaoli-Roach AA, Roach PJ, Gentry MS, and Sun RC
- Abstract
The addition of phosphate groups into glycogen modulates its branching pattern and solubility which all impact its accessibility to glycogen interacting enzymes. As glycogen architecture modulates its metabolism, it is essential to accurately evaluate and quantify its phosphate content. Simultaneous direct quantitation of glucose and its phosphate esters requires an assay with high sensitivity and a robust dynamic range. Herein, we describe a highly-sensitive method for the accurate detection of both glycogen-derived glucose and glucose-phosphate esters utilizing gas-chromatography coupled mass spectrometry. Using this method, we observed higher glycogen levels in the liver compared to skeletal muscle, but skeletal muscle contained many more phosphate esters. Importantly, this method can detect femtomole levels of glucose and glucose phosphate esters within an extremely robust dynamic range with excellent accuracy and reproducibility. The method can also be easily adapted for the quantification of plant starch, amylopectin or other biopolymers., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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39. A Brief History of Lung Ventilation and Perfusion Imaging Over the 50-Year Tenure of the Editors of Seminars in Nuclear Medicine.
- Author
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Bailey DL and Roach PJ
- Subjects
- History, 20th Century, History, 21st Century, Humans, Positron-Emission Tomography, Nuclear Medicine history, Periodicals as Topic, Ventilation-Perfusion Scan history
- Abstract
The ventilation/perfusion lung scan has been in continuous use for approximately half a century, the same lifetime as Seminars in Nuclear Medicine. Remarkably, the founding Editors-in-Chief have continued to guide the journal over this entire period. In this Feschrift issue celebrating their enormous contribution, we review the history of the lung scan, its highs and lows, the transition from planar to SPECT/CT V/Q scans, and the future that is in store in this age of multimodality functional imaging. We concur with the published view of one of the retiring editors (LMF) that V/Q scintigraphy is indeed alive and well and has a definite future in clinical medicine., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
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40. High Metabolic Tumour Volume on 18-Fluorodeoxyglucose Positron Emission Tomography Predicts Poor Survival from Neuroendocrine Neoplasms.
- Author
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Chan DL, Bernard EJ, Schembri G, Roach PJ, Johnson M, Pavlakis N, Clarke S, and Bailey DL
- Subjects
- Adult, Aged, Aged, 80 and over, Feasibility Studies, Female, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Survival Analysis, Fluorodeoxyglucose F18, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors metabolism, Neuroendocrine Tumors mortality, Positron-Emission Tomography methods, Positron-Emission Tomography standards, Radiopharmaceuticals
- Abstract
Introduction: 18-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) avidity in neuroendocrine neoplasms (NENs) has been associated with higher-grade disease. 18F-FDG avidity and high SUVmax have been demonstrated to predict poor outcome. Quantitative metrics of 18F-FDG PET, specifically metabolic tumour volume (MTV) and total lesion glycolysis (TLG), have been shown to be prognostic factors in other malignancies, but these have not been investigated to date in NENs., Methods: Patients with NEN undergoing 18F-FDG at Royal North Shore Hospital from 2012 to 2018 were included. Images were analysed with automated segmentation (SUV cut-off of 4) followed by contour verification by a nuclear medicine physician and manual segmentation where required. Variables collected included patient age, histological grade, MTV, TLG, and SUVmax/SUVmean. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Univariate (UV) and multivariate (MV) analyses were performed for OS and PFS for MTV and TLG separately. For UV analysis, the median MTV and TLG were used to dichotomise the cohort. MTV/TLG for NENs of different histological grade were compared using ANOVA., Results: One hundred and ninety patients were included (median age 63.5, 49% female). Primary site: 42% small bowel, 32% pancreas, 15% other gastrointestinal, 6% lung, 6% other. Grade for gastroenteropancreatic NENs and bronchial NEN: G1/typical carcinoid 37%, G2/atypical carcinoid 40%, G3/large-cell/small-cell neuroendocrine carcinoma 16%, unknown 8%. Median MTV was 4.83 mL (range 0-3,161 mL) and median TLG was 29.22. Patients with high MTV had worse median OS compared to those with low MTV (29.7 months vs. not reached, HR 4.1, 95% CI 2.25-7.49, p < 0.00001). Considered as a continuous variable, MTV predicted for poorer OS on UV (p < 0.00001) and MV (p = 0.003) analyses. Whilst histological grade was significant on both UV and MV, SUVmax was significant on UV (p < 0.00001) but not MV (p = 0.76). Tumours of higher grade had higher MTV (mean MTV - G1: 39.6 mL, G2: 107 mL, G3: 337 mL; p = 0.0001 by ANOVA)., Conclusions: Quantitative analysis of 18F-FDG PET in NEN is feasible. High MTV/TLG are predictors of poor prognosis in NEN. Further analyses are underway to investigate a larger cohort of NEN patients., (© 2019 S. Karger AG, Basel.)
- Published
- 2020
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41. Glycogen Dynamics Drives Lipid Droplet Biogenesis during Brown Adipocyte Differentiation.
- Author
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Mayeuf-Louchart A, Lancel S, Sebti Y, Pourcet B, Loyens A, Delhaye S, Duhem C, Beauchamp J, Ferri L, Thorel Q, Boulinguiez A, Zecchin M, Dubois-Chevalier J, Eeckhoute J, Vaughn LT, Roach PJ, Dani C, Pederson BA, Vincent SD, Staels B, and Duez H
- Subjects
- Adipocytes, Brown ultrastructure, Adipose Tissue, Brown embryology, Adipose Tissue, Brown ultrastructure, Animals, Autophagy drug effects, Autophagy genetics, CCAAT-Enhancer-Binding Proteins genetics, CCAAT-Enhancer-Binding Proteins metabolism, Cells, Cultured, Fatty Acid-Binding Proteins genetics, Fatty Acid-Binding Proteins metabolism, Glycogen ultrastructure, Humans, Lipid Droplets ultrastructure, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, PPAR gamma genetics, PPAR gamma metabolism, RNA, Small Interfering, Transcriptome, Adipocytes, Brown metabolism, Adipogenesis genetics, Adipose Tissue, Brown metabolism, Embryo, Mammalian metabolism, Glycogen metabolism, Lipid Droplets metabolism
- Abstract
Browning induction or transplantation of brown adipose tissue (BAT) or brown/beige adipocytes derived from progenitor or induced pluripotent stem cells (iPSCs) can represent a powerful strategy to treat metabolic diseases. However, our poor understanding of the mechanisms that govern the differentiation and activation of brown adipocytes limits the development of such therapy. Various genetic factors controlling the differentiation of brown adipocytes have been identified, although most studies have been performed using in vitro cultured pre-adipocytes. We investigate here the differentiation of brown adipocytes from adipose progenitors in the mouse embryo. We demonstrate that the formation of multiple lipid droplets (LDs) is initiated within clusters of glycogen, which is degraded through glycophagy to provide the metabolic substrates essential for de novo lipogenesis and LD formation. Therefore, this study uncovers the role of glycogen in the generation of LDs., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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42. Targeting Pathogenic Lafora Bodies in Lafora Disease Using an Antibody-Enzyme Fusion.
- Author
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Brewer MK, Uittenbogaard A, Austin GL, Segvich DM, DePaoli-Roach A, Roach PJ, McCarthy JJ, Simmons ZR, Brandon JA, Zhou Z, Zeller J, Young LEA, Sun RC, Pauly JR, Aziz NM, Hodges BL, McKnight TR, Armstrong DD, and Gentry MS
- Subjects
- Animals, Brain pathology, Disease Models, Animal, HEK293 Cells, Humans, Immunoglobulin G therapeutic use, Mice, Mice, Inbred C57BL, Pancreatic alpha-Amylases therapeutic use, Rats, Recombinant Fusion Proteins therapeutic use, Brain drug effects, Drug Discovery, Inclusion Bodies drug effects, Lafora Disease therapy, Pancreatic alpha-Amylases pharmacology, Recombinant Fusion Proteins pharmacology
- Abstract
Lafora disease (LD) is a fatal childhood epilepsy caused by recessive mutations in either the EPM2A or EPM2B gene. A hallmark of LD is the intracellular accumulation of insoluble polysaccharide deposits known as Lafora bodies (LBs) in the brain and other tissues. In LD mouse models, genetic reduction of glycogen synthesis eliminates LB formation and rescues the neurological phenotype. Therefore, LBs have become a therapeutic target for ameliorating LD. Herein, we demonstrate that human pancreatic α-amylase degrades LBs. We fused this amylase to a cell-penetrating antibody fragment, and this antibody-enzyme fusion (VAL-0417) degrades LBs in vitro and dramatically reduces LB loads in vivo in Epm2a
-/- mice. Using metabolomics and multivariate analysis, we demonstrate that VAL-0417 treatment of Epm2a-/- mice reverses the metabolic phenotype to a wild-type profile. VAL-0417 is a promising drug for the treatment of LD and a putative precision therapy platform for intractable epilepsy., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
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- View/download PDF
43. Letter From the Guest Editors.
- Author
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Bailey DL and Roach PJ
- Subjects
- Humans, Single Photon Emission Computed Tomography Computed Tomography, Ventilation-Perfusion Scan, Pulmonary Embolism diagnostic imaging
- Published
- 2019
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- View/download PDF
44. FET PET in the evaluation of indeterminate brain lesions on MRI: Differentiating glioma from other non-neoplastic causes - A pilot study.
- Author
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Chan DL, Hsiao E, Schembri G, Bailey DL, Roach PJ, Lee A, Jayamanne D, Ghasemzadeh M, Hayes A, Cook R, Parkinson J, Drummond JP, Ibbett I, Wheeler HR, and Back M
- Subjects
- Adult, Aged, Brain Neoplasms pathology, Female, Fluorine Radioisotopes, Glioma pathology, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Pilot Projects, Retrospective Studies, Brain Neoplasms diagnostic imaging, Glioma diagnostic imaging, Positron-Emission Tomography methods
- Abstract
We aimed to determine the utility of FET PET in the management of indeterminate CNS lesions found on MRI. We performed a retrospective analysis of patients with FET PET at a single tertiary institution from 2011 to 2015. FET PET images were processed using usual methods and measurements taken including SUVmax, TBRmax, and analysis of dynamic series where available (Kipeak, Vdpeak, as well as tumor:background ratio for these variables). Correlation studies were performed using ANOVA between cohorts of high-grade histology, low-grade histology, and benign histology/stable on observation. Thirty-five patients were included, of whom 34 were suitable for analysis with median follow-up of 5 months. The positive predictive value of FET PET in this cohort was 83.3%. FET SUVmax differentiated between patients with high-grade (mean SUV 3.38, 95% CI 2.21-4.55), low-grade (1.88, 95% CI 1.33-2.43) and benign/observation (1.42, 95% CI 1.13-1.71) cohorts (p = 0.0003). Similarly, tumour to brain ratio was significant (p < 0.0001). Kipeak distinguished between high grade and observation cohorts (p = 0.036), as did KiTBR (p = 0.025). Vd peak was not significantly different in these two cohorts (p = 0.057) but Vd TBR was (p = 0.041). In conclusion, FET PET demonstrated a high positive predictive value for glioma in patients with indeterminate brain lesions on MRI. The combination of negative FET and negative FDG PET scans may predict an indolent clinical course. Confirmatory trials are needed to establish the potential value of FET PET in guiding surgical management in this cohort., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
45. Utilizing 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) to define suspected nonenhancing tumor for radiation therapy planning of glioblastoma.
- Author
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Hayes AR, Jayamanne D, Hsiao E, Schembri GP, Bailey DL, Roach PJ, Khasraw M, Newey A, Wheeler HR, and Back M
- Subjects
- Adult, Aged, Aged, 80 and over, Brain Neoplasms pathology, Brain Neoplasms radiotherapy, Contrast Media, Female, Gadolinium therapeutic use, Glioblastoma pathology, Glioblastoma radiotherapy, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Radiopharmaceuticals, Tumor Burden, Tyrosine analogs & derivatives, Tyrosine therapeutic use, Brain Neoplasms diagnostic imaging, Glioblastoma diagnostic imaging, Positron-Emission Tomography methods, Radiotherapy Planning, Computer-Assisted methods
- Abstract
Aim: The authors sought to evaluate the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiation therapy planning for patients diagnosed with glioblastoma (GBM) and the presence of suspected nonenhancing tumors compared with standard magnetic resonance imaging (MRI)., Methods and Materials: Patients with GBM and contrast-enhanced MRI scans showing regions suspicious of nonenhancing tumor underwent postoperative FET-PET before commencing radiation therapy. Two clinical target volumes (CTVs) were created using pre- and postoperative MRI: MRI fluid-attenuated inversion recovery (FLAIR) sequences (CTV
FLAIR ) and MRI contrast sequences with an expansion on the surgical cavity (CTVSx ). FET-PET was used to create biological tumor volumes (BTVs) by encompassing FET-avid regions, forming BTVFLAIR and BTVSx . Volumetric analyses were conducted between CTVs and respective BTVs using Wilcoxon signed-rank tests. The volume increase with addition of FET was analyzed with respect to BTVFLAIR and BTVSx . Presence of focal gadolinium contrast enhancement within previously nonenhancing tumor or within the FET-avid region was noted on MRI scans at 1 and 3 months after radiation therapy., Results: Twenty-six patients were identified retrospectively from our database, of whom 24 had demonstrable FET uptake. The median CTVFLAIR , CTVSx , BTVFLAIR , and BTVSx were 57.1 mL (range, 1.1-217.4), 83.6 mL (range, 27.2-275.8), 62.8 mL (range, 1.1-307.3), and 94.7 mL (range, 27.2-285.5), respectively. When FET-PET was used, there was a mean increase in volume of 26.8% from CTVFLAIR to BTVFLAIR and 20.6% from CTVSx to BTVSx . A statistically significant difference was noted on Wilcoxon signed-rank test when assessing volumetric change between CTVFLAIR and BTVFLAIR (P < .0001) and CTVSx and BTVSx (P < .0001). Six of 24 patients (25%) with FET avidity before radiation therapy showed focal gadolinium enhancement within the radiation therapy portal., Conclusions: FET-PET may help improve delineation of GBM in cases with a suspected nonenhancing component. This may result in improved radiation therapy target delineation and reduce the risk of potential geographical miss., Summary: We investigated the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiation therapy planning for patients diagnosed with glioblastoma (GBM) and a suspected nonenhancing tumor compared with standard magnetic resonance imaging. We performed volumetric analyses between clinical target volumes and respective biological target volumes using Wilcoxon signed-rank tests. FET-PET may help improve delineation of GBM in cases with a suspected nonenhancing component and reduce the risk of potential geographical miss., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
46. Lafora disease offers a unique window into neuronal glycogen metabolism.
- Author
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Gentry MS, Guinovart JJ, Minassian BA, Roach PJ, and Serratosa JM
- Subjects
- Animals, Carbohydrate Conformation, Carrier Proteins genetics, Disease Models, Animal, Glycogen biosynthesis, Glycogen chemistry, Glycogen Phosphorylase genetics, Humans, Lafora Disease genetics, Lafora Disease pathology, Lafora Disease therapy, Phosphates metabolism, Phosphorylation, Protein Tyrosine Phosphatases, Non-Receptor genetics, Ubiquitin-Protein Ligases genetics, Glycogen metabolism, Lafora Disease metabolism, Neurons metabolism
- Abstract
Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase., (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2018
- Full Text
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47. The Impact of 68 Ga-PSMA PET/CT on Management Intent in Prostate Cancer: Results of an Australian Prospective Multicenter Study.
- Author
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Roach PJ, Francis R, Emmett L, Hsiao E, Kneebone A, Hruby G, Eade T, Nguyen QA, Thompson BD, Cusick T, McCarthy M, Tang C, Ho B, Stricker PD, and Scott AM
- Subjects
- Aged, Australia, Humans, Male, Neoplasm Metastasis, Prognosis, Prospective Studies, Prostatic Neoplasms pathology, Prostatic Neoplasms therapy, Recurrence, Patient Care Management, Positron Emission Tomography Computed Tomography, Prostatic Neoplasms diagnostic imaging
- Abstract
68 Ga-PSMA PET/CT scanning has been shown to be more sensitive than conventional imaging techniques in patients with prostate cancer. This prospective Australian multicenter study assessed whether68 Ga-PSMA PET/CT imaging affects management intent in patients with primary or recurrent prostate cancer. Methods: Before undertaking68 Ga-PSMA PET imaging, referring medical specialists completed a questionnaire detailing relevant demographic and clinical data as well as their proposed management plan. A separate follow-up questionnaire was completed after the68 Ga-PSMA PET/CT scan results were available to determine whether the management plan would change. Results: A total of 431 patients with prostate cancer from 4 Australian centers had pre- and post-68 Ga-PSMA management plans completed. Scans were obtained for primary staging of intermediate- and high-risk disease in 25% of patients and for restaging/biochemical recurrence in 75% of patients. Overall,68 Ga-PSMA PET/CT scanning led to a change in planned management in 51% of patients. The impact was greater in the group of patients with biochemical failure after definitive surgery or radiation treatment (62% change in management intent) than in patients undergoing primary staging (21% change). Imaging with68 Ga-PSMA PET/CT revealed unsuspected disease in the prostate bed in 27% of patients, locoregional lymph nodes in 39%, and distant metastatic disease in 16%. Conclusion:68 Ga-PSMA PET/CT scans detect previously unsuspected disease and may influence planned clinical management in a high proportion of patients with prostate cancer. The impact was greater in patients with biochemical recurrence. These results demonstrate the potential clinical value of68 Ga-PSMA PET/CT in management of prostate cancer., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2018
- Full Text
- View/download PDF
48. Lack of liver glycogen causes hepatic insulin resistance and steatosis in mice.
- Author
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Irimia JM, Meyer CM, Segvich DM, Surendran S, DePaoli-Roach AA, Morral N, and Roach PJ
- Subjects
- Acetyl-CoA Carboxylase genetics, Acetyl-CoA Carboxylase metabolism, Active Transport, Cell Nucleus genetics, Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cell Nucleus genetics, Cell Nucleus pathology, Fatty Liver genetics, Fatty Liver pathology, Forkhead Box Protein O1 genetics, Forkhead Box Protein O1 metabolism, Glycogen genetics, Glycogen Synthase Kinase 3 genetics, Glycogen Synthase Kinase 3 metabolism, Hepatocytes pathology, Insulin Receptor Substrate Proteins genetics, Insulin Receptor Substrate Proteins metabolism, Mice, Mice, Knockout, Nuclear Proteins genetics, Nuclear Proteins metabolism, Phosphorylation genetics, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, Sterol Regulatory Element Binding Protein 1 genetics, Sterol Regulatory Element Binding Protein 1 metabolism, Transcription Factors genetics, Transcription Factors metabolism, Cell Nucleus metabolism, Fatty Liver metabolism, Glycogen deficiency, Hepatocytes metabolism, Insulin Resistance, Signal Transduction
- Abstract
Disruption of the Gys2 gene encoding the liver isoform of glycogen synthase generates a mouse strain (LGSKO) that almost completely lacks hepatic glycogen, has impaired glucose disposal, and is pre-disposed to entering the fasted state. This study investigated how the lack of liver glycogen increases fat accumulation and the development of liver insulin resistance. Insulin signaling in LGSKO mice was reduced in liver, but not muscle, suggesting an organ-specific defect. Phosphorylation of components of the hepatic insulin-signaling pathway, namely IRS1, Akt, and GSK3, was decreased in LGSKO mice. Moreover, insulin stimulation of their phosphorylation was significantly suppressed, both temporally and in an insulin dose response. Phosphorylation of the insulin-regulated transcription factor FoxO1 was somewhat reduced and insulin treatment did not elicit normal translocation of FoxO1 out of the nucleus. Fat overaccumulated in LGSKO livers, showing an aberrant distribution in the acinus, an increase not explained by a reduction in hepatic triglyceride export. Rather, when administered orally to fasted mice, glucose was directed toward hepatic lipogenesis as judged by the activity, protein levels, and expression of several fatty acid synthesis genes, namely, acetyl-CoA carboxylase, fatty acid synthase, SREBP1c, chREBP, glucokinase, and pyruvate kinase. Furthermore, using cultured primary hepatocytes, we found that lipogenesis was increased by 40% in LGSKO cells compared with controls. Of note, the hepatic insulin resistance was not associated with increased levels of pro-inflammatory markers. Our results suggest that loss of liver glycogen synthesis diverts glucose toward fat synthesis, correlating with impaired hepatic insulin signaling and glucose disposal., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2017
- Full Text
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49. Prognostic and predictive biomarkers in neuroendocrine tumours.
- Author
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Chan DL, Clarke SJ, Diakos CI, Roach PJ, Bailey DL, Singh S, and Pavlakis N
- Subjects
- Chromogranin A analysis, Epigenesis, Genetic, Humans, Hydroxyindoleacetic Acid urine, Ki-67 Antigen analysis, MicroRNAs analysis, Mutation, Neoplasm Staging, Neuroendocrine Tumors genetics, Neuroendocrine Tumors pathology, Positron-Emission Tomography, Biomarkers, Tumor analysis, Neuroendocrine Tumors diagnosis
- Abstract
Neuroendocrine tumours are extremely heterogeneous malignancies. Despite marked heterogeneity in clinical course and prognosis, few biomarkers exist to help predict prognosis and guide treatment. Many tumour-based biomarkers (Ki-67, mitotic count, genetic/epigenetic changes and microRNAs) exist, but only Ki-67 and mitotic count have strong evidence to support their routine use. Blood-based markers are easily repeatable, but currently established biomarkers (chromogranin A and urinary 5-HIAA) are difficult to measure accurately in practice. Structural imaging is used routinely via the TNM system. Functional imaging such as
68 Ga-based and FDG PET may become valuable biomarkers with their increasing availability, aided by ongoing quantitative research. Multiple nomograms have been proposed to integrate the above factors, but most have not been prospectively validated and are difficult to use in practice. Further research should aim to establish robust new biomarkers and integrate existing ones to help optimise NET treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
50. Novel method for detection of glycogen in cells.
- Author
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Skurat AV, Segvich DM, DePaoli-Roach AA, and Roach PJ
- Subjects
- Animals, Enzyme-Linked Immunosorbent Assay, Glutathione Transferase chemistry, Glycogen chemistry, Glycogen metabolism, Glycogen Storage Disease metabolism, Humans, Lafora Disease metabolism, Lysosomes metabolism, Membrane Proteins chemistry, Mice, Muscle Proteins chemistry, Recombinant Proteins chemistry, Glucose metabolism, Glycogen isolation & purification, Glycogen Storage Disease diagnosis, Lafora Disease diagnosis
- Abstract
Y: Glycogen, a branched polymer of glucose, functions as an energy reserve in many living organisms. Abnormalities in glycogen metabolism, usually excessive accumulation, can be caused genetically, most often through mutation of the enzymes directly involved in synthesis and degradation of the polymer leading to a variety of glycogen storage diseases (GSDs). Microscopic visualization of glycogen deposits in cells and tissues is important for the study of normal glycogen metabolism as well as diagnosis of GSDs. Here, we describe a method for the detection of glycogen using a renewable, recombinant protein which contains the carbohydrate-binding module (CBM) from starch-binding domain containing protein 1 (Stbd1). We generated a fusion protein containing g lutathione S-transferase, a cM c eptitope and the tbd1 BM (GYSC) for use as a glycogen-binding probe, which can be detected with secondary antibodies against glutathione S-transferase or cMyc. By enzyme-linked immunosorbent assay, we demonstrate that GYSC binds glycogen and two other polymers of glucose, amylopectin and amylose. Immunofluorescence staining of cultured cells indicate a GYSC-specific signal that is co-localized with signals obtained with anti-glycogen or anti-glycogen synthase antibodies. GYSC-positive staining inside of lysosomes is observed in individual muscle fibers isolated from mice deficient in lysosomal enzyme acid alpha-glucosidase, a well-characterized model of GSD II (Pompe disease). Co-localized GYSC and glycogen signals are also found in muscle fibers isolated from mice deficient in malin, a model for Lafora disease. These data indicate that GYSC is a novel probe that can be used to study glycogen metabolism under normal and pathological conditions., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)
- Published
- 2017
- Full Text
- View/download PDF
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