Ziqiang Yu1, Jiuping Xu1, Mingfeng Shao1, Jianan Zou1. 1. Department of Urology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei City, Anhui Province 230031, People's Republic of China.
Abstract
BACKGROUND: Germacrone, a natural product isolated from the traditional Chinese medicine Rhizoma Curcuma, has been reported to exhibit antitumor activities in vitro. To further understand the antitumor mechanism of germacrone, we investigated the growth inhibitory effect of germacrone on the human prostate cancer cell lines PC-3 (androgen independent) and 22RV1 (androgen dependent). MATERIALS AND METHODS: Prostate cancer cells were cultured with different concentrations of germacrone, and cell viability was measured by MTT assay. The levels of proteins were measured by Western blotting. Cell apoptosis was assessed by flow cytometry. Images of autophagy-related protein staining were captured by fluorescence microscopy. Autophagic flux was assessed by detecting the LC3B-II level. RESULTS: Our results indicated that germacrone treatment significantly inhibited cell proliferation by inducing apoptosis in a dose-dependent manner, with IC50 values of 259 μM for PC-3 cells and 396.9 μM for 22RV1 cells. Germacrone-treated cells also exhibited induction of autophagy, as evidenced by elevated LC3B-II protein expression levels and punctuate patterns. Additionally, an autophagy inhibitor enhanced the growth inhibitory effect of germacrone. Moreover, the phosphorylation of Akt and mTOR was inhibited in germacrone-treated prostate cancer cells. CONCLUSION: Germacrone induced apoptosis and autophagy in prostate cancer cells by inhibiting the Akt/mTOR signaling pathway. Germacrone treatment also led to the activation of protective autophagy. These findings suggest that germacrone may potentially contribute to the development of a new therapeutic agent for prostate cancer treatment.
BACKGROUND: Germacrone, a natural product isolated from the traditional Chinese medicine Rhizoma Curcuma, has been reported to exhibit antitumor activities in vitro. To further understand the antitumor mechanism of germacrone, we investigated the growth inhibitory effect of germacrone on the human prostate cancer cell lines PC-3 (androgen independent) and 22RV1 (androgen dependent). MATERIALS AND METHODS: Prostate cancer cells were cultured with different concentrations of germacrone, and cell viability was measured by MTT assay. The levels of proteins were measured by Western blotting. Cell apoptosis was assessed by flow cytometry. Images of autophagy-related protein staining were captured by fluorescence microscopy. Autophagic flux was assessed by detecting the LC3B-II level. RESULTS: Our results indicated that germacrone treatment significantly inhibited cell proliferation by inducing apoptosis in a dose-dependent manner, with IC50 values of 259 μM for PC-3 cells and 396.9 μM for 22RV1 cells. Germacrone-treated cells also exhibited induction of autophagy, as evidenced by elevated LC3B-II protein expression levels and punctuate patterns. Additionally, an autophagy inhibitor enhanced the growth inhibitory effect of germacrone. Moreover, the phosphorylation of Akt and mTOR was inhibited in germacrone-treated prostate cancer cells. CONCLUSION: Germacrone induced apoptosis and autophagy in prostate cancer cells by inhibiting the Akt/mTOR signaling pathway. Germacrone treatment also led to the activation of protective autophagy. These findings suggest that germacrone may potentially contribute to the development of a new therapeutic agent for prostate cancer treatment.
Prostate cancer (PCa) has been reported as the most common cancer in men over 50 years old, and it is the second most frequent cause of cancer-related death in males worldwide.1,2 PCa is initially dependent on androgen and is sensitive to androgen deprivation therapy.3 However, tumors become insensitive to androgen deprivation within two years. As a result, PCa can slowly progress to the high-risk aggressive phase.4 Both surgical therapies and chemotherapy treatments may cause serious side effects.5,6 Therefore, the identification and development of novel remedies against prostate cancer are urgently needed. Recent studies have shown that traditional Chinese medicine is efficient in regulating tumor growth with low toxicity.7,8 Thus, finding new anti-prostate cancer agents derived from traditional Chinese medicine has aroused our interest.Rhizoma Curcuma (Ezhu in Chinese) is usually used in traditional Chinese medicine for cancer treatment.9 The underlying mechanisms of Rhizoma Curcuma action in cancer treatment remain elusive and controversial. Germacrone (Figure 1) is a major bioactive constituent extracted from Rhizoma Curcuma.10 Recent studies have determined that germacrone exerts significant anticancer activity. Treatment of human hepatoma cells and breast cancer cells with germacrone results in cell cycle arrest and apoptosis.11,12 Additionally, germacrone inhibits ERα-mediated gene expression at the transcriptional level in breast cancer cells.13 Moreover, germacrone reverses adriamycin resistance in human chronic myelogenous leukemia cells.14 However, the effect of germacrone on prostate cancer cells has never been investigated.
Figure 1
Chemical structure of germacrone.
Chemical structure of germacrone.Autophagy involves providing energy by degrading long-lived proteins and damaged organelles.15 Autophagic cells are characterized by the formation of notable double-membraned vesicles, known as autophagosomes.16 Since autophagy is an important intracellular mechanism in maintaining homeostasis maintenance and growth regulation, this process participates in many physiological processes and human diseases.17 The protective role of autophagy helps cancer cells obtain energy sources for rapid proliferation and to develop resistance against chemotherapy.18,19 Many bioactive compounds from plants have been shown to trigger autophagy in cancer cells. However, there are no reports on the effect of germacrone on autophagy in cancer cells.The present study aimed to investigate the inhibitory effects and molecular mechanisms of germacrone in prostate cancer cells.
Materials and Methods
Materials
Germacrone (purity >98%) was bought from Shanghai YuanYe Biotechnology Co. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) was bought from Bio Basic. Antibody against GAPDH was bought from Merck Millipore (Darmstadt, Germany). Antibodies against LC3B, mTOR, p-mTOR, Akt, and p-Akt were bought from Cell Signaling Technology (Danvers, MA). HRP-conjugated anti-rabbit antibody was bought from Promega (Madison, USA). An enhanced chemiluminescence (ECL) kit was bought from Biological Industries (Kibbutz Beit Haemek, Israel). Chloroquine and 3-methyladenine were purchased from Sigma Aldrich (St. Louis, MO). Goat anti-rabbit IgG H&L was bought from Abcam (Cambridge, United Kingdom).
Cell Culture
Human prostate cancer cells (PC-3 and 22RV1 cells) were obtained from Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (Shanghai, China). The cells were cultured in the RPMI-1640 culture medium, 10% fetal bovine serum containing 100 U/mL penicillin and 10 U/mL streptomycin at 37°C in an atmosphere of 5% CO2.
MTT Assay
The inhibitory effects of germacrone on the viability of human prostate cancer cells were evaluated by MTT assay. The cells (3x103) were seeded into 96-well plates and left to adhere overnight. They were then treated with different concentrations (30–480 μM) of germacrone for 48 h at 37°C. Then, 20 μL of MTT solution (5 mg/mL) was added and incubated at 37°C for 4 h. After the MTT medium was aspirated, 150 μL of DMSO was added to dissolve the insoluble formation product. The absorbance was determined at 490 nm using a spectrometer (Elx800, BioTek, Winooski, VT, USA).
Detection of Apoptosis
Cell apoptosis was assessed using an annexin V-FITC/PI apoptosis kit (Vazyme Biotech Co.). A total of 10,000 cells/well were seeded in 6-well plates and treated with germacrone for 48 h. Then, the cells were harvested and washed twice in cold PBS and resuspended in 100 μL binding buffer. The cell suspension was mixed with 5 μL annexin V-FITC and 5 μL PI staining solution for 10 min in the dark at room temperature. The cells were resuspended in 400 μL binding buffer and were analyzed by flow cytometry (Becton Dickinson FACSCanto II, USA) within 1 h.
Immunofluorescence Analysis
A total of 10,000 cells were seeded on glass bottom dishes and treated with germacrone for 48 h. Then, the cells were fixed with 4% paraformaldehyde and permeabilized with 0.1% Triton X-100. Cells were incubated with a rabbit anti-LC3B antibody at 4°C overnight. Fluorescent secondary antibody was incubated for 1 h in the dark at room temperature. The nuclei were stained with DAPI. Fluorescence images were captured by using a fluorescence microscope (Olympus TH4-200, Tokyo, Japan).
Western Blotting
Prostate cancer cells were treated with germacrone, 50 μM chloroquine (CQ) or 5 mM 3-methyladeseven (3-MA) was added to the culture medium for the last 6 h. After the cells were collected, the total proteins were extracted with RIPA buffer containing protease and phosphatase inhibitors on ice. The proteins were separated by SDS-PAGE and transferred to PVDF membranes. Then, the membrane was blocked with 5% BSA for 1 h. Subsequently, the PVDF membrane was incubated with primary antibodies overnight at 4°C and then incubated with an HRP-conjugated secondary antibody for 1 h. Protein bands were visualized using an enhanced chemiluminescence (ECL) kit. Images of the protein bands were captured by chemiluminescent detection (LASmini 4000, GE Healthcare).
Statistical Analysis
One-way ANOVA was used between multiple groups. All data are expressed as the mean ± SD. *P < 0.05 and **P < 0.01 were considered statistically significant.
Results
Germacrone Decreased the Viability and Induced the Apoptosis of Prostate Cancer Cells
Germacrone concentrations from 40 to 400 μM exerted significant anticancer activities in different cancer cell lines in previous studies.11–14 Prostate cancer cells were incubated with or without germacrone at doses of 30, 60, 120, 240 and 480 μM for 48 h and were harvested for MTT assay to measure viability. As shown in Figure 2, germacrone significantly inhibited the growth of prostate cancer cells in a dose-dependent manner, with IC50 values of 259 μM for PC-3 cells and 396.9 μM for 22RV1 cells.
Figure 2
Effect of germacrone on the viability of human prostate cancer cells. PC-3 and 22RV1 cells were incubated with various concentrations (30–480 μM) of germacrone for 48 h, after which the MTT assay was used to measure the cell proliferation rate. *P < 0.05, **P < 0.01.
Effect of germacrone on the viability of human prostate cancer cells. PC-3 and 22RV1 cells were incubated with various concentrations (30–480 μM) of germacrone for 48 h, after which the MTT assay was used to measure the cell proliferation rate. *P < 0.05, **P < 0.01.To determine whether germacrone-induced cell death was related to apoptosis, annexin-V and PI double staining was performed to analyze the percentage of apoptotic cells by flow cytometry. The results revealed that after treatment with 240 μM germacrone for 48 h, the proportion of early and late apoptotic cells increased from 7.24% to 47.3% in PC-3 cells and from 5.27% to 47.48% in 22RV1 cells (Figure 3).
Figure 3
The apoptosis effect induced by germacrone alone or by germacrone cotreatment with an autophagy inhibitor. PC-3 and 22RV1 cells were treated with 240 μM germacrone for 48 h, and 50 μM CQ was added to the culture medium for the last 6 h. Cell apoptosis was assessed by flow cytometry with annexin V/PI staining. **P < 0.01.
The apoptosis effect induced by germacrone alone or by germacrone cotreatment with an autophagy inhibitor. PC-3 and 22RV1 cells were treated with 240 μM germacrone for 48 h, and 50 μM CQ was added to the culture medium for the last 6 h. Cell apoptosis was assessed by flow cytometry with annexin V/PI staining. **P < 0.01.
Germacrone Induced Autophagy in Prostate Cancer Cells
Apoptosis and autophagy are highly interactive. We next examined the effect of germacrone on autophagy. It is well known that LC3-II is regarded as an important marker of autophagy.20 Prostate cancer cells were treated with 120, 240 and 480 μM germacrone for 48 h. As shown in Figure 4A, a marked upregulation of LC3B-II expression was observed in a dose-dependent manner compared with the untreated cells. The diffusely expressed LC3 protein becomes concentrated and presents as puncta in the cytoplasm during the process of autophagy.21 In the present study, a significant increase in LC3B-II puncta formation was found in prostate cancer cells as soon as 48 h after treatment with 240 μM germacrone (Figure 4B).
Figure 4
The effect of germacrone on the levels of LC3B in human prostate cancer cells. (A) PC-3 and 22RV1 cells were treated with 120, 240 and 480 μM germacrone for 48 h. The proteins of LC3B were detected by Western blotting. (B) PC-3 and 22RV1 cells were treated with 240 μM germacrone for 48 h. After staining endogenous LC3 protein and nuclei with anti-LC3 antibody (FITC, green) and DAPI (blue), respectively, images of LC3 distribution were captured under a fluorescence microscope. *P < 0.05, **P < 0.01.
The effect of germacrone on the levels of LC3B in human prostate cancer cells. (A) PC-3 and 22RV1 cells were treated with 120, 240 and 480 μM germacrone for 48 h. The proteins of LC3B were detected by Western blotting. (B) PC-3 and 22RV1 cells were treated with 240 μM germacrone for 48 h. After staining endogenous LC3 protein and nuclei with anti-LC3 antibody (FITC, green) and DAPI (blue), respectively, images of LC3 distribution were captured under a fluorescence microscope. *P < 0.05, **P < 0.01.The accumulation of LC3-II protein is associated either with the increasing generation of autophagosomes or with the blockage of autophagosome and lysosome fusion processes.21 To determine whether germacrone induced autophagic flux, two autophagy inhibitors, 3-MA and CQ, which inhibit early-stage and late-stage autophagy, respectively, were used. As shown in Figure 5, the combination treatment with germacrone and 3-MA exhibited less LC3B-II expression than that of germacrone treatment alone, and the combination treatment with germacrone and CQ resulted in higher LC3B-II expression than that with germacrone or CQ treatment alone, indicating that germacrone induced autophagy in PC-3 and 22RV1 cells.
Figure 5
The effect of autophagy inhibitors on LC3B expression in germacrone-treated human prostate cancer cells. PC-3 and 22RV1 cells were treated with 240 μM germacrone for 48 h, and 50 μM CQ or 5 mM 3-MA was added to the culture medium for the last 6 h. The proteins of LC3B were detected by Western blotting. *P < 0.05, **P < 0.01.
The effect of autophagy inhibitors on LC3B expression in germacrone-treated human prostate cancer cells. PC-3 and 22RV1 cells were treated with 240 μM germacrone for 48 h, and 50 μM CQ or 5 mM 3-MA was added to the culture medium for the last 6 h. The proteins of LC3B were detected by Western blotting. *P < 0.05, **P < 0.01.
The Akt/mTOR Pathway Was Involved in Germacrone-Induced Apoptosis and Autophagy in Prostate Cancer Cells
Akt/mTOR is one of the most important signaling pathways in regulating survival and metabolism and has been proven to play a critical role in the regulation of apoptosis and autophagy.22 Therefore, we speculated that germacrone might induce apoptosis and autophagy in prostate cancer cells via the Akt/mTOR signaling pathway. To verify this hypothesis, we used Western blot analysis to determine whether Akt/mTOR was inhibited in germacrone-treated prostate cancer cells. Prostate cancer cells were treated with 120, 240 and 480 μM germacrone for 48 h, and the levels of p-Akt and p-mTOR decreased in a dose-dependent manner (Figure 6). The results supported that germacrone induced both apoptosis and autophagy by inhibiting the Akt/mTOR pathway in prostate cancer cells.
Figure 6
The inhibitory effect of germacrone on the Akt/mTOR signaling pathway. PC-3 and 22RV1 cells were treated with 120, 240 and 480 μM germacrone for 48 h. The mTOR, p-mTOR, Akt, and p-Akt protein levels were detected by Western blotting. *P < 0.05, **P < 0.01.
The inhibitory effect of germacrone on the Akt/mTOR signaling pathway. PC-3 and 22RV1 cells were treated with 120, 240 and 480 μM germacrone for 48 h. The mTOR, p-mTOR, Akt, and p-Akt protein levels were detected by Western blotting. *P < 0.05, **P < 0.01.
The relationships between autophagy and apoptosis are complicated. To clarify the role of germacrone-induced autophagy in the antitumor process, the autophagy inhibitor CQ was used in the following experiments. We found that the addition of CQ enhanced germacrone inhibition of cell proliferation (Figure 7). Furthermore, annexin V/PI double staining showed that CQ promoted germacrone-induced apoptosis in prostate cancer cells (Figure 3). Compared with germacrone treatment alone, germacrone and CQ cotreatment increased the proportion of early and late apoptotic cells from 47.3% to 70.3% in PC-3 cells and from 47.48% to 77.6% in 22RV1 cells. Taken together, the results indicate that autophagy can protect prostate cancer cells from apoptosis in this case.
Figure 7
The inhibitory effect of germacrone on human prostate cancer cells was promoted by an autophagy inhibitor. PC-3 and 22RV1 cells were treated with 240 μM germacrone for 48 h, and 50 μM CQ was added to the culture medium for the last 6 h. Cell viability was detected by MTT assay. *P < 0.05, **P < 0.01.
The inhibitory effect of germacrone on human prostate cancer cells was promoted by an autophagy inhibitor. PC-3 and 22RV1 cells were treated with 240 μM germacrone for 48 h, and 50 μM CQ was added to the culture medium for the last 6 h. Cell viability was detected by MTT assay. *P < 0.05, **P < 0.01.
Discussion
Natural herbal products are significant sources for the development of novel chemotherapeutics and have been used traditionally in various countries. Numerous studies indicate that these herbs have the ability to suppress tumor progression by regulating the proliferation, invasion or apoptosis of cancer cells.23 Germacrone, found in Rhizoma Curcuma essential oils, has been previously demonstrated to be a promising therapeutic agent against several types of cancer cells.11–14 However, the anticancer activities of germacrone against prostate cancer cells are not explicit.In this study, we demonstrated that germacrone markedly inhibited the proliferation of prostate cancer cells. Apoptosis, also called programmed cell death, plays a vital role in suppressing the growth of cancer cells. Amplified apoptosis leads to damage or death of cells and tissues. Therefore, the induction of apoptosis has been recognized as an efficient strategy for cancer treatment.24 Our data indicated that the percentages of early and late apoptotic cells were markedly increased following treatment with germacrone. In accordance with our findings, other researchers have reported that germacrone inhibits the growth of cancer cells through the induction of apoptosis.11,12Autophagy is an essential intracellular degradation mechanism to promote survival under stress conditions of starvation or growth factor withdrawal. Autophagy generates autophagosomes in the cytosol and can be estimated by detecting the expression of LC3-II.20 Our results showed that germacrone markedly elevated LC3B-II levels in a dose-dependent manner. Based on these results, the autophagy inhibitors 3-MA and CQ were used to check whether germacrone induced autophagy. As a result, germacrone-induced LC3B-II expression in prostate cancer cells was decreased by the addition of the early-stage autophagy inhibitor 3-MA and increased by the addition of the late-stage autophagy inhibitor CQ. These results demonstrated that germacrone induced autophagy in prostate cancer cells. Autophagosomes observed by electron microscopy are the morphological hallmark of autophagy, and the lack of electron microscopy data is one of the limitations of this study.Apoptosis and autophagy can be induced by the same stimulus, but there is complex crosstalk between them. Autophagy has the ability to inhibit, delay or promote apoptosis.25–27 In the process of our study, we found that apoptosis was significantly increased with the inhibition of autophagy by CQ. Compared with germacrone treatment alone, the combination treatment with CQ and germacrone resulted in decreased viability and increased apoptosis in prostate cancer cells. We hypothesized that germacrone induced apoptosis and autophagy simultaneously, whereas autophagy decreased prostate cancer cell susceptibility to germacrone-induced apoptosis. Autophagy functions as a cytoprotective factor in response to germacrone-induced apoptosis.Increasing evidence indicates that autophagy and apoptosis share many common regulatory molecules. The Akt/mTOR pathway, a well-known major regulatory signaling pathway in modulating cell proliferation, metabolism and survival, is very frequently dysregulated in the pathogenesis of human cancers.28 Therefore, targeting the Akt/mTOR pathway is an attractive strategy for cancer prevention and treatment. Inhibition of the Akt/mTOR signaling pathway, which causes cell death, is associated with apoptosis and autophagy.29 Our data showed that germacrone inhibited the phosphorylation of both Akt and mTOR. The inhibitory effects of germacrone on prostate cancer cells may be correlated with the decrease in the phosphorylation of Akt and mTOR. These findings indicated that germacrone induced apoptosis and autophagy in prostate cancer cells by inhibiting the Akt/mTOR signaling pathway.Taken together, this study demonstrated that germacrone inhibited the proliferation of human prostate cancer cells by inducing apoptosis. Germacrone treatment also led to the activation of protective autophagy. Inhibition of autophagy significantly enhanced the apoptosis-inducing ability. More importantly, the Akt/mTOR signaling pathway was inhibited by germacrone, suggesting that germacrone may serve as a promising active antitumor drug by direct regulation of the Akt/mTOR pathway in prostate cancer cells. Due to the complicated metabolism of germacrone in vivo, further research will be necessary to explore its molecular mechanisms and to evaluate its anticancer activities in animal experiments. In addition, germacrone, as an Akt/mTOR inhibitor, needs to be exploited in combination with targeted therapies to improve prostate cancer clinical outcomes.
Authors: Qianhui Dou; Hai-Ning Chen; Kui Wang; Kefei Yuan; Yunlong Lei; Kai Li; Jiang Lan; Yan Chen; Zhao Huang; Na Xie; Lu Zhang; Rong Xiang; Edouard C Nice; Yuquan Wei; Canhua Huang Journal: Cancer Res Date: 2016-06-14 Impact factor: 12.701
Authors: 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; 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; 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; Marie-Agnès 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; Silvia Cetrullo; 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; Kelly S Doran; Gabriella D'Orazi; Gerald W Dorn; 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; 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; Flavio Flamigni; 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; 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; 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 J R 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; Ju-Hyun 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; Min Li; Qiang Li; Rui Li; Sheng Li; Wei 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; Alberto M Martelli; 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; Anna Rita Migliaccio; 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; 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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; 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; 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Authors: Milad Ashrafizadeh; Mahshid Deldar Abad Paskeh; Sepideh Mirzaei; Mohammad Hossein Gholami; Ali Zarrabi; Farid Hashemi; Kiavash Hushmandi; Mehrdad Hashemi; Noushin Nabavi; Francesco Crea; Jun Ren; Daniel J Klionsky; Alan Prem Kumar; Yuzhuo Wang Journal: J Exp Clin Cancer Res Date: 2022-03-22
Authors: Igor A Schepetkin; Gulmira Özek; Temel Özek; Liliya N Kirpotina; Andrei I Khlebnikov; Mark T Quinn Journal: Molecules Date: 2021-06-15 Impact factor: 4.411
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