Author: "Kui, Lin" / Topic: biology - Searchworks@Jio Institute Digital Library Search Results

129 results on '"Kui, Lin"'

1. Different rates of pollen and seed gene flow cause branch‐length and geographic cytonuclear discordance within Asian butternuts

Author: Bowen Zhang, Xin-Rui Lin, Lin-Lin Xu, Wei-Ning Bai, Rui-Min Yu, Kui Lin, Da-Yong Zhang, Nan Li, and CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.
Subjects: Gene Flow, Nuclear gene, Physiology, Lineage (evolution), whole-genome resequencing, introgression, Introgression, Plant Science, whole‐genome resequencing, Biology, Genome, Gene flow, Coalescent theory, Genome, Chloroplast, Phylogeny, Cell Nucleus, Full Paper, Research, food and beverages, Cline (biology), Full Papers, branch-length discordance, geographic discordance, Evolutionary biology, Seeds, Pollen, Biological dispersal, branch‐length discordance, gene flow
Abstract: Summary Topological cytonuclear discordance is commonly observed in plant phylogenetic and phylogeographic studies, yet few studies have attempted to detect two other forms of cytonuclear discordance (branch length and geographical) and to uncover the causes of the discordance.We used the whole nuclear and chloroplast genome data from 80 individual Asian butternuts to reveal the pattern and processes of cytonuclear discordance.Our findings indicate that the chloroplast genome had substantially deeper divergence (branch‐length discordance) and a steeper cline in the contact zone (geographic discordance) compared with the nuclear genome. After various hypothesis have been tested, the results suggest that incomplete lineage sorting, positive selection and cytonuclear incompatibility are probably insufficient to explain this pattern. However, isolation‐by‐distance analysis and gene flow estimation point to a much higher level of gene flow by pollen compared with by seeds, which may have slowed down lineage divergence and mediated wider contact for nuclear genome compared with the chloroplast genome.Altogether, this study highlights a critical role of sex‐biased dispersal in causing discordance between the nuclear and plastid genome of Asian butternuts. Given its ubiquity among plants, asymmetric gene flow should be given a high priority in future studies of cytonuclear discordance.
Published: 2021
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2. Genomic survey and gene expression analysis of the MYB-related transcription factor superfamily in potato (Solanum tuberosum L.)

Author: Richard V. Espley, Kui Lin-Wang, Yuting Zeng, Yuanming Li, Andrew C. Allan, Yuhui Liu, Junlian Zhang, and Zhen Liu
Subjects: 02 engineering and technology, Biochemistry, 03 medical and health sciences, Gene Expression Regulation, Plant, Structural Biology, Arabidopsis, Gene expression, Gene family, MYB, RNA-Seq, Molecular Biology, Gene, Plant Proteins, Solanum tuberosum, 030304 developmental biology, Synteny, Genetics, 0303 health sciences, biology, fungi, food and beverages, Genomics, General Medicine, 021001 nanoscience & nanotechnology, biology.organism_classification, White (mutation), Multigene Family, 0210 nano-technology, Transcription Factors
Abstract: The MYB transcription factors (TFs) comprise a major TF family in the plant kingdom. Studies increasingly show that MYB-related genes drive physiological functions in plants. However, little is known regarding their regulatory networks and downstream pathways in potato. We conducted a genome-wide analysis of MYB TFs and related proteins in potato (Solanum tuberosum, abbreviated as St), and identified 138 StMYB-related TFs that were phylogenetically classified into three distinct subgroups based on highly conserved gene structures, consensus motifs and protein domain architecture. Segmental duplication events were detected in the StMYB-related gene family by collinearity analysis, which likely contributed to the expansion of this family. Synteny analysis indicated that 41 StMYB-related genes were orthologous to Arabidopsis and 24 to wheat. In addition, RNA-seq analysis identified several tissue-specific and abiotic stress-responsive StMYB-related genes. To determine a potential role of these genes in anthocyanin biosynthesis and drought response, we analyzed the transcriptomes of the white, pigmented, drought-sensitive ('Atlantic') and drought-resistant ('Qingshu No.9') tetraploid potato cultivars from three flowering stages: early, peak (full blooms) and late (foliage falling). The interaction networks of StMYB-related proteins that were differentially expressed between pigmented versus white, as well as the drought-tolerant versus sensitive cultivars were also predicted. Our findings lay the foundation for prospective functional studies of potato StMYB-related TFs.
Published: 2020
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3. Alternative splicing during fruit development among fleshy fruits

Author: Erli Pang, Kui Lin, Xiaomin Yan, Hongtao Song, and Dan Bai
Subjects: Prunus persica, Genetics, Ripe stage, Melon, Research, Alternative splicing, Fruit development, Immature stage, Intron, food and beverages, Ripening, Plants, QH426-470, Biology, Transcriptome, Gene Expression Regulation, Plant, Fruit, Fleshy fruits, DNA microarray, Gene, TP248.13-248.65, Biotechnology
Abstract: Background Alternative splicing (AS) is an important mechanism of posttranscriptional modification and dynamically regulates multiple physiological processes in plants, including fruit ripening. However, little is known about alternative splicing during fruit development in fleshy fruits. Results We studied the alternative splicing at the immature and ripe stages during fruit development in cucumber, melon, papaya and peach. We found that 14.96–17.48% of multiexon genes exhibited alternative splicing. Intron retention was not always the most frequent event, indicating that the alternative splicing pattern during different developmental process differs. Alternative splicing was significantly more prevalent at the ripe stage than at the immature stage in cucumber and melon, while the opposite trend was shown in papaya and peach, implying that developmental stages adopt different alternative splicing strategies for their specific functions. Some genes involved in fruit ripening underwent stage-specific alternative splicing, indicating that alternative splicing regulates fruits ripening. Conserved alternative splicing events did not appear to be stage-specific. Clustering fruit developmental stages across the four species based on alternative splicing profiles resulted in species-specific clustering, suggesting that diversification of alternative splicing contributes to lineage-specific evolution in fleshy fruits. Conclusions We obtained high quality transcriptomes and alternative splicing events during fruit development across the four species. Dynamics and nonconserved alternative splicing were discovered. The candidate stage-specific AS genes involved in fruit ripening will provide valuable insight into the roles of alternative splicing during the developmental processes of fleshy fruits.
Published: 2021
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4. Ab Initio Construction and Evolutionary Analysis of Protein-Coding Gene Families with Partially Homologous Relationships: Closely Related Drosophila Genomes as a Case Study

Author: Hongtao Song, Xia Han, Kui Lin, Jindan Guo, and Erli Pang
Subjects: 0106 biological sciences, Genome, Insect, subgene rearrangement, Biology, 010603 evolutionary biology, 01 natural sciences, Genome, Homology (biology), Evolution, Molecular, 03 medical and health sciences, Phylogenetics, Sequence Homology, Nucleic Acid, evolution, Gene duplication, Genetics, Homologous chromosome, Animals, Drosophila Proteins, Gene family, Gene, Phylogeny, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Protein coding, 0303 health sciences, module architecture, Evolutionary biology, Multigene Family, gene family, Drosophila, partial homology, Research Article
Abstract: How have genes evolved within a well-known genome phylogeny? Many protein-coding genes should have evolved as a whole at the gene level, and some should have evolved partly through fragments at the subgene level. To comprehensively explore such complex homologous relationships and better understand gene family evolution, here, with de novo-identified modules, the subgene units which could consecutively cover proteins within a set of closely related species, we applied a new phylogeny-based approach that considers evolutionary models with partial homology to classify all protein-coding genes in nine Drosophila genomes. Compared with two other popular methods for gene family construction, our approach improved practical gene family classifications with a more reasonable view of homology and provided a much more complete landscape of gene family evolution at the gene and subgene levels. In the case study, we found that most expanded gene families might have evolved mainly through module rearrangements rather than gene duplications and mainly generated single-module genes through partial gene duplication, suggesting that there might be pervasive subgene rearrangement in the evolution of protein-coding gene families. The use of a phylogeny-based approach with partial homology to classify and analyze protein-coding gene families may provide us with a more comprehensive landscape depicting how genes evolve within a well-known genome phylogeny.
Published: 2020
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5. DNA demethylation is involved in the regulation of temperature‐dependent anthocyanin accumulation in peach

Author: Kui Lin-Wang, Changjie Xu, Yun Zhao, Yongchao Zhu, Bo Zhang, Kunsong Chen, Ke Wang, and Andrew C. Allan
Subjects: 0106 biological sciences, 0301 basic medicine, Plant Science, 01 natural sciences, DNA methyltransferase, Anthocyanins, 03 medical and health sciences, chemistry.chemical_compound, Gene Expression Regulation, Plant, Genetics, Gene, Transcription factor, Plant Proteins, Prunus persica, biology, fungi, Temperature, food and beverages, Cell Biology, Methylation, DNA Demethylation, 030104 developmental biology, DNA demethylation, Biochemistry, chemistry, DNA methylation, biology.protein, Demethylase, DNA, 010606 plant biology & botany
Abstract: Anthocyanin biosynthesis is induced by low temperatures in a number of plants. However, in peach (cv Zhonghuashoutao), anthocyanin accumulation was observed in fruit stored at 16°C but not at or below 12°C. Fruit stored at 16°C showed elevated transcript levels of genes encoding anthocyanin biosynthetic enzymes, the transport protein glutathione S-transferase and key transcription factors. Higher transcript levels of PpPAL1/2, PpC4H, Pp4CL4/5/8, PpF3H, PpF3'H, PpDFR1/2/3 and PpANS, as well as transcription factor gene PpbHLH3, were associated with lower methylation levels in the promoter of these genes. The DNA methylation level was further highly correlated with the expression of the DNA methyltransferase genes and DNA demethylase genes. The application of DNA methylation inhibitor 5-azacytidine induced anthocyanin accumulation in peach flesh, further implicating a critical role for DNA demethylation in regulating anthocyanin accumulation in peach flesh. Our data reveal that temperature-dependent DNA demethylation is a key factor to the post-harvest temperature-dependent anthocyanin accumulation in peach flesh.
Published: 2020
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6. Heterobifunctional Molecules Induce Dephosphorylation of Kinases–A Proof of Concept Study

Author: Yue Fu, Wenqiong Wu, Sayumi Yamazoe, Changlei Sun, Liang Zeng, Qi Liu, Wayne J. Fairbrother, Jie Lin, Kui Lin, Jeffrey Tom, and Steven T. Staben
Subjects: Phosphatase, Ligands, Proof of Concept Study, 01 natural sciences, Cell Line, Small Molecule Libraries, Dephosphorylation, 03 medical and health sciences, Ubiquitin, Protein Phosphatase 1, Drug Discovery, Humans, Phosphorylation, Protein kinase B, 030304 developmental biology, 0303 health sciences, biology, Chemistry, Kinase, Drug discovery, Phosphotransferases, Small molecule, 0104 chemical sciences, Cell biology, ErbB Receptors, 010404 medicinal & biomolecular chemistry, biology.protein, Molecular Medicine, Protein Processing, Post-Translational, Proto-Oncogene Proteins c-akt
Abstract: Heterobifunctional molecules have proven powerful tools to induce ligase-dependent ubiquitination of target proteins. We describe here a chemical strategy for controlling a different post-translational modification (PTM): phosphorylation. Heterobifunctional molecules were designed to promote the proximity of a protein phosphatase (PP1) to protein targets. The synthesized molecules induced the PP1-dependent dephosphorylation of AKT and EGFR. To our knowledge, this work represents the first examples of small molecules recruiting non-native partners to induce removal of a PTM.
Published: 2019
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7. PpGST1, an anthocyanin‐related glutathione S‐transferase gene, is essential for fruit coloration in peach

Author: Changjie Xu, Andrew C. Allan, Weiqi Dong, Kui Lin-Wang, Yun Zhao, and Yongchao Zhu
Subjects: 0106 biological sciences, 0301 basic medicine, Mutant, glutathione S‐transferase, Plant Science, 01 natural sciences, peach, Anthocyanins, 03 medical and health sciences, chemistry.chemical_compound, Transcription (biology), Gene Expression Regulation, Plant, Arabidopsis, MYB, Gene, Research Articles, Regulator gene, Glutathione Transferase, Plant Proteins, Prunus persica, promoter, biology, MYB10.1, fungi, food and beverages, biology.organism_classification, carbohydrates (lipids), Complementation, 030104 developmental biology, Biochemistry, chemistry, Anthocyanin, Fruit, transport, Agronomy and Crop Science, 010606 plant biology & botany, Biotechnology, Research Article, Transcription Factors
Abstract: Summary Anthocyanins have crucial biological functions and affect quality of horticultural produce. Anthocyanins accumulate in ripe peach fruit; differential accumulation is observed in deep coloured cultivar ‘Hujingmilu’ and lightly pigmented cultivar ‘Yulu’. The difference was not fully explained by accumulation of total flavonoids and expression of anthocyanin biosynthetic genes. Expression analysis was conducted on a glutathione S‐transferase gene (PpGST1), and it was found that the expression correlated well with anthocyanin accumulation in peach fruit tissues. Functional complementation of the Arabidopsis tt19 mutant indicated that PpGST1 was responsible for transport of anthocyanins but not proanthocyanidins. PpGST1 was localized in nuclei and the tonoplast, including the sites at which anthocyanin vacuolar sequestration occurred. Transient overexpression of PpGST1 together with PpMYB10.1 in tobacco leaves and peach fruit significantly increased anthocyanin accumulation as compared with PpMYB10.1 alone. Furthermore, virus‐induced gene silencing of PpGST1 in a blood‐fleshed peach not only resulted in a reduction in anthocyanin accumulation but also a decline in expression of anthocyanin biosynthetic and regulatory genes. Cis‐element analysis of the PpGST1 promoter revealed the presence of four MYB binding sites (MBSs). Dual‐luciferase assays indicated that PpMYB10.1 bound to the promoter and activated the transcription of PpGST1 by recognizing MBS1, the one closest to the ATG start codon, with this trans‐activation being stronger against the promoter of deep coloured ‘Hujingmilu’ compared with lightly coloured cultivar ‘Yulu’. Altogether, our data provided molecular evidence supporting coordinative regulatory roles of PpGST1 and PpMYB10.1 in anthocyanin accumulation in peach.
Published: 2019

8. StMYB44 negatively regulates anthocyanin biosynthesis at high temperatures in tuber flesh of potato

Author: Lihui Zeng, Li Wang, Richard V. Espley, Xiaojing Zhang, Kui Lin-Wang, Zhen Liu, Yuanming Li, Yuhui Liu, Junlian Zhang, Ping Zhou, and Andrew C. Allan
Subjects: 0106 biological sciences, 0301 basic medicine, StMYB44, Physiology, Nicotiana tabacum, Repressor, Plant Science, Reductase, 01 natural sciences, high temperature, Anthocyanins, 03 medical and health sciences, chemistry.chemical_compound, stomatognathic system, Chlorogenic acid, Anthocyanin biosynthesis, Gene Expression Regulation, Plant, Tobacco, MYB, Transcription factor, Plant Proteins, Solanum tuberosum, repressor, Phenylpropanoid, biology, Chemistry, fungi, Temperature, food and beverages, Plants, Genetically Modified, biology.organism_classification, Research Papers, carbohydrates (lipids), Alcohol Oxidoreductases, Plant Tubers, 030104 developmental biology, Crop Molecular Genetics, Biochemistry, Anthocyanin, potato, RNA-seq, 010606 plant biology & botany
Abstract: Temperature-induced reduction of anthocyanin accumulation in potato flesh is caused by down-regulation of the activating anthocyanin regulatory complex mediated by enhanced expression of flesh-specific StMYB44 which results in alteration of phenylpropanoid flux., High temperatures are known to reduce anthocyanin accumulation in a number of diverse plant species. In potato (Solanum tuberosum L.), high temperature significantly reduces tuber anthocyanin pigment content. However, the mechanism of anthocyanin biosynthesis in potato tuber under heat stress remains unknown. Here we show that high temperature causes reduction of anthocyanin biosynthesis in both potato tuber skin and flesh, with white areas forming between the vasculature and periderm. Heat stress reduced the expression of the R2R3 MYB transcription factors (TFs) StAN1 and StbHLH1, members of the transcriptional complex responsible for coordinated regulation of the skin and flesh pigmentation, as well as anthocyanin biosynthetic pathway genes in white regions. However, the core phenylpropanoid pathway, lignin, and chlorogenic acid (CGA) pathway genes were up-regulated in white areas, suggesting that suppression of the anthocyanin branch may result in re-routing phenylpropanoid flux into the CGA or lignin biosynthesis branches. Two R2R3 MYB TFs, StMYB44-1 and StMYB44-2, were highly expressed in white regions under high temperature. In transient assays, StMYB44 represses anthocyanin accumulation in leaves of Nicotiana tabacum and N. benthamiana by directly suppressing the activity of the dihydroflavonol reductase (DFR) promoter. StMYB44-1 showed stronger repressive capacity than StMYB44-2, with both predicted proteins containing the repression-associated EAR motif with some variation. StMYB44-1 conferred repression without a requirement for a basic helix–loop–helix (bHLH) partner, suggesting a different repression mechanism from that of reported anthocyanin repressors. We propose that temperature-induced reduction of anthocyanin accumulation in potato flesh is caused by down-regulation of the activating anthocyanin regulatory complex, by enhancing the expression of flesh-specific StMYB44 and alteration of phenylpropanoid flux.
Published: 2019
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9. Phylogenomics Reveals an Ancient Hybrid Origin of the Persian Walnut

Author: Da-Yong Zhang, Bowen Zhang, Nan Li, Peng-Cheng Yan, Kui Lin, Xin-Hua Jiang, Wei-Ning Bai, Keith E. Woeste, Lin-Lin Xu, and Susanne S. Renner
Subjects: 0106 biological sciences, 0303 health sciences, Nuclear gene, biology, Platycarya, Introgression, Pterocarya stenoptera, biology.organism_classification, 010603 evolutionary biology, 01 natural sciences, Genome, 03 medical and health sciences, Evolutionary biology, Phylogenomics, Genetics, Approximate Bayesian computation, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Juglans
Abstract: Persian walnut (Juglans regia) is cultivated worldwide for its high-quality wood and nuts, but its origin has remained mysterious because in phylogenies it occupies an unresolved position between American black walnuts and Asian butternuts. Equally unclear is the origin of the only American butternut, J. cinerea. We resequenced the whole genome of 80 individuals from 19 of the 22 species of Juglans and assembled the genome of its relatives Pterocarya stenoptera and Platycarya strobilacea. Using phylogenetic-network analysis of single-copy nuclear genes, genome-wide site pattern probabilities, and Approximate Bayesian Computation, we discovered that J. regia (and its landrace J. sigillata) arose as a hybrid between the American and the Asian lineages and that J. cinerea resulted from massive introgression from an immigrating Asian butternut into the genome of an American black walnut. Approximate Bayesian Computation modeling placed the hybrid origin in the late Pliocene, ∼3.45 My, with both parental lineages since having gone extinct in Europe.
Published: 2019
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10. Competition between anthocyanin and kaempferol glycosides biosynthesis affects pollen tube growth and seed set of Malus

Author: Pengmin Li, Zhengcao Xiao, Jinxiao Wang, Weifeng Chen, Yule Wang, Kui Lin-Wang, Fengwang Ma, Rui Zhai, and Richard V. Espley
Subjects: 0106 biological sciences, 0301 basic medicine, Gynoecium, Malus, Cyanidin, Plant physiology, Plant Science, Horticulture, 01 natural sciences, Biochemistry, Article, 03 medical and health sciences, chemistry.chemical_compound, Auxin, Botany, Genetics, Metabolomics, chemistry.chemical_classification, biology, fungi, food and beverages, biology.organism_classification, 030104 developmental biology, chemistry, Anthocyanin, Petal, Pollen tube, Kaempferol, 010606 plant biology & botany, Biotechnology
Abstract: Flavonoids play important roles in regulating plant growth and development. In this study, three kaempferol 3-O-glycosides were identified and mainly accumulated in flowers but not in leaves or fruits ofMalus. InMalus, flower petal color is normally white, but some genotypes have red flowers containing anthocyanin. Anthocyanin biosynthesis appears to be in competition with kaempferol 3-O-glycosides production and controlled by the biosynthetic genes. The white flowerMalusgenotypes had better-developed seeds than the red flower genotypes. In flowers, the overexpression ofMYB10inMalus domesticaenhanced the accumulation of anthocyanin, but decreased that of kaempferol 3-O-glycosides. After pollination the transgenic plants showed slower pollen tube growth and fewer developed seeds. Exogenous application of different flavonoid compounds suggested that kaempferol 3-O-glycosides, especially kaempferol 3-O-rhamnoside, regulated pollen tube growth and seed set rather than cyanidin or quercetin 3-O-glycosides. It was found that kaempferol 3-O-rhamnoside might regulate pollen tube growth through effects on auxin, the Rho of plants (ROP) GTPases, calcium and the phosphoinositides signaling pathway. With the inhibition of auxin transport, the transcription levels of Heat Shock Proteins (HSPs) and ROP GTPases were downregulated while the levels were not changed or even enhanced when blocking calcium signaling, suggesting that HSPs and ROP GTPases were downstream of auxin signaling, but upstream of calcium signaling. In summary, kaempferol glycoside concentrations in pistils correlated with auxin transport, the transcription of HSPs and ROP GTPases, and calcium signaling in pollen tubes, culminating in changes to pollen tube growth and seed set.
Published: 2021

11. Activation of PsMYB10.2 Transcription Causes Anthocyanin Accumulation in Flesh of the Red-Fleshed Mutant of ‘Sanyueli’ (Prunus salicina Lindl.)

Author: Zhi-Zhen Fang, Kui Lin-Wang, Dan-Rong Zhou, Yan-Juan Lin, Cui-Cui Jiang, Shao-Lin Pan, Richard V. Espley, Christelle M. Andre, and Xin-Fu Ye
Subjects: Prunus salicina, anthocyanin biosynthesis, Mutant, Plant Science, Biology, SB1-1110, chemistry.chemical_compound, stomatognathic system, Transcription (biology), PsMYB10.2, Cultivar, plum, Transcription factor, Original Research, Activator (genetics), Flesh, fungi, Plant culture, food and beverages, biology.organism_classification, carbohydrates (lipids), Horticulture, chemistry, Anthocyanin, transcriptome, red-fleshed mutant
Abstract: Plum is one of the most important stone fruits in the world and anthocyanin-rich plums are increasingly popular due to their health-promoting potential. In this study, we investigated the mechanisms of anthocyanin accumulation in the flesh of the red-fleshed mutant of the yellow-fleshed plum ‘Sanyueli’. RNA-Seq and qRT-PCR showed that anthocyanin biosynthetic genes and the transcription factor PsMYB10.2 were upregulated in the flesh of the mutant. Functional testing in tobacco leaves indicated that PsMYB10.2 was an anthocyanin pathway activator and can activate the promoter of the anthocyanin biosynthetic genes PsUFGT and PsGST. The role of PsMYB10.2 in anthocyanin accumulation in the flesh of plum was further confirmed by virus-induced gene silencing. These results provide information for further elucidating the underlying mechanisms of anthocyanin accumulation in the flesh of plum and for the breeding of new red-fleshed plum cultivars.
Published: 2021

12. Differential regulation of triterpene biosynthesis induced by an early failure in cuticle formation in apple

Author: Christelle M. Andre, Kui Lin-Wang, Ria Rebstock, Lindy F. Guo, Sylvain Legay, Blue Plunkett, Cecilia H. Deng, Guido Cipriani, Andrew P. Dare, Richard V. Espley, and Luigi Falginella
Subjects: 0106 biological sciences, 0301 basic medicine, Cuticle, Plant Science, Horticulture, Biology, 01 natural sciences, Biochemistry, Article, 03 medical and health sciences, chemistry.chemical_compound, Triterpene, Transcription (biology), Genetics, MYB, Secondary metabolism, Transcription factor, Lupeol, chemistry.chemical_classification, Abiotic, Metabolic pathway, 030104 developmental biology, chemistry, 010606 plant biology & botany, Biotechnology
Abstract: Waxy apple cuticles predominantly accumulate ursane-type triterpenes, but the profile shifts with the induction of skin russeting towards lupane-type triterpenes. We previously characterised several key enzymes in the ursane-type and lupane-type triterpene pathways, but this switch in triterpene metabolism associated with loss of cuticle integrity is not fully understood. To analyse the relationship between triterpene biosynthesis and russeting, we used microscopy, RNA-sequencing and metabolite profiling during apple fruit development. We compared the skin of three genetically-close clones of ‘Golden Delicious’ (with waxy, partially russeted and fully russeted skin). We identified a unique molecular profile for the russet clone, including low transcript abundance of multiple cuticle-specific metabolic pathways in the early stages of fruit development. Using correlation analyses between gene transcription and metabolite concentration we found MYB transcription factors strongly associated with lupane-type triterpene biosynthesis. We showed how their transcription changed with the onset of cuticle cracking followed by russeting and that one factor, MYB66, was able to bind the promoter of the oxidosqualene cyclase OSC5, to drive the production of lupeol derivatives. These results provide insights into the breakdown of cuticle integrity leading to russet and how this drives MYB-regulated changes to triterpene biosynthesis.
Published: 2021

13. Unraveling a genetic roadmap for improved taste in the domesticated apple

Author: Yaming Cai, Da Gang Hu, Jinsheng Xu, Ting Fang, Baiquan Ma, Quan-Yan Zhang, Yuepeng Han, Xiaoqing Nie, Bo Zhang, Li Li, Jian-Qiang Yu, Weihan Zhang, Andrew C. Allan, Kui Lin-Wang, Gang Chen, Chun Xiang You, Liao Liao, Yi-Ran Ren, Xiao-Fei Wang, Zhangjun Fei, Yu Jin Hao, Cecilia H. Deng, Chu-Kun Wang, Lei Gao, Awais Khan, Richard V. Espley, Jia-Long Yao, Schuyler S. Korban, Collins Ogutu, Beibei Zheng, and Ray Ming
Subjects: 0106 biological sciences, 0301 basic medicine, Taste, Candidate gene, Malus, Malates, Plant Science, Biology, Genes, Plant, 01 natural sciences, Domestication, 03 medical and health sciences, chemistry.chemical_compound, Sugar, Molecular Biology, Gene, Genetic diversity, food and beverages, biology.organism_classification, Biological Evolution, Horticulture, 030104 developmental biology, chemistry, Fruit, Mutation, Sorbitol, 010606 plant biology & botany
Abstract: Although taste is an important aspect of fruit quality, an understanding of its genetic control remains elusive in apple and other fruit crops. In this study, we conducted genomic sequence analysis of 497 Malus accessions and revealed erosion of genetic diversity caused by apple breeding and possible independent domestication events of dessert and cider apples. Signatures of selection for fruit acidity and size, but not for fruit sugar content, were detected during the processes of both domestication and improvement. Furthermore, we found that single mutations in major genes affecting fruit taste, including Ma1, MdTDT, and MdSOT2, dramatically decrease malate, citrate, and sorbitol accumulation, respectively, and correspond to important domestication events. Interestingly, Ma1 was identified to have pleiotropic effects on both organic acid content and sugar:acid ratio, suggesting that it plays a vital role in determining fruit taste. Fruit taste is unlikely to have been negatively affected by linkage drag associated with selection for larger fruit that resulted from the pyramiding of multiple genes with minor effects on fruit size. Collectively, our study provides new insights into the genetic basis of fruit quality and its evolutionary roadmap during apple domestication, pinpointing several candidate genes for genetic manipulation of fruit taste in apple.
Published: 2021

14. The Photomorphogenic Transcription Factor PpHY5 Regulates Anthocyanin Accumulation in Response to UVA and UVB Irradiation

Author: Yun Zhao, Ting Min, Miaojin Chen, Hongxun Wang, Changqing Zhu, Rong Jin, Andrew C. Allan, Kui Lin-Wang, and Changjie Xu
Subjects: Chalcone synthase, UVR8, Plant Science, lcsh:Plant culture, anthocyanin, peach, Cryptochrome, Transcription (biology), Arabidopsis, Arabidopsis thaliana, lcsh:SB1-1110, Transcription factor, PpMYB10.1, Original Research, biology, Chemistry, fungi, food and beverages, biology.organism_classification, photoreceptor, Cell biology, UVA, biology.protein, Transcription Factor Gene, UVB, HY5
Abstract: Red coloration contributes to fruit quality and is determined by anthocyanin content in peach (Prunus persica). Our previous study illustrated that anthocyanin accumulation is strongly regulated by light, and the effect of induction differs according to light quality. Here we showed that both ultraviolet-A (UVA) and ultraviolet-B (UVB) irradiation promoted anthocyanin biosynthesis in “Hujingmilu” peach fruit, and a combination of UVA and UVB had additional effects. The expression of anthocyanin biosynthesis and light signaling related genes, including transcription factor genes and light signaling elements, were induced following UV irradiation as early as 6 h post-treatment, earlier than apparent change in coloration which occurred at 72 h. To investigate the molecular mechanisms for UVA- and UVB-induced anthocyanin accumulation, the genes encoding ELONGATED HYPOCOTYL 5 (HY5), CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), Cryptochrome (CRY), and UV RESISTANCE LOCUS 8 (UVR8) in peach were isolated and characterized through functional complementation in corresponding Arabidopsis (Arabidopsis thaliana) mutants. PpHY5 and PpCOP1.1 restored hypocotyl length and anthocyanin content in Arabidopsis mutants under white light; while PpCRY1 and PpUVR8.1 restored AtHY5 expression in Arabidopsis mutants in response to UV irradiation. Arabidopsis PpHY5/hy5 transgenic lines accumulated higher amounts of anthocyanin under UV supplementation (compared with weak white light only), especially when UVA and UVB were applied together. These data indicated that PpHY5, acting as AtHY5 counterpart, was a vital regulator in UVA and UVB signaling pathway. In peach, the expression of PpHY5 was up-regulated by UVA and UVB, and PpHY5 positively regulated both its own transcription by interacting with an E-box in its own promoter, and the transcription of the downstream anthocyanin biosynthetic genes chalcone synthase 1 (PpCHS1), chalcone synthase 2 (PpCHS2), and dihydroflavonol 4-reductase (PpDFR1) as well as the transcription factor gene PpMYB10.1. In summary, functional evidence supports the role of PpHY5 in UVA and UVB light transduction pathway controlling anthocyanin biosynthesis. In peach this is via up-regulation of expression of genes encoding biosynthetic enzymes, as well as the transcription factor PpMYB10.1 and PpHY5 itself.
Published: 2021
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15. The genome of low-chill Chinese plum ‘Sanyueli’ (Prunus salicina Lindl.) provides insights into the regulation of the chilling requirement of flower buds

Author: Zhou Danrong, Ye Xinfu, Jiang Cuicui, Lin Yanjuan, Kui Lin-Wang, He Dai, Richard V. Espley, Fang Zhizhen, and Pan Shaolin
Subjects: Prunus salicina, Horticulture, Prunus, biology, Chilling requirement, Bud, food and beverages, Dormancy, biology.organism_classification, Gene, Genome, Genome size
Abstract: Chinese plum (Prunus salicina Lindl.) is a stone fruit that belongs to the Prunus genus and plays an important role in the global production of plum. In this study, we report the genome sequence of the Chinese plum ‘Sanyueli’, which is known to have a low-chill requirement for flower bud break. The assembled genome size was 308.06 Mb, with a contig N50 of 815.7 kb. A total of 30,159 protein-coding genes were predicted from the genome and 56.4% (173.39 Mb) of the genome was annotated as repetitive sequence. Bud dormancy is influenced by chilling requirement in plum and partly controlled by DORMANCY ASSOCIATED MADS-box (DAM) genes. Six tandemly arrayed PsDAM genes were identified in the assembled genome. Sequence analysis of PsDAM6 in ‘Sanyueli’revealed the presence of large insertions in the intron and exon regions. Transcriptome analysis indicated that the expression of PsDAM6 in the dormant flower buds of ‘Sanyueli’ was significantly lower than that in the dormant flower buds of the high chill requiring ‘Furongli’ plum. In addition, the expression of PsDAM6 was repressed by chilling treatment. The genome sequence of ‘Sanyueli’ plum provides a valuable resource for elucidating the molecular mechanisms responsible for the regulation of chilling requirements, and is also useful for the identification of the genes involved in the control of other important agronomic traits and molecular breeding in plum.
Published: 2020
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16. Green synthesis of multifunctional fluorescent carbon dots from mulberry leaves (Morus alba L.) residues for simultaneous intracellular imaging and drug delivery

Author: Lifeng Han, Caoyuan Zhu, Zhifei Fu, Yingying Shao, Fei Tian, Kui Lin, Yan-xu Chang, Yidan Wang, and Haiyang Yu
Subjects: Fluorescence-lifetime imaging microscopy, Materials science, Bioengineering, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, chemistry.chemical_compound, General Materials Science, biology, General Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, biology.organism_classification, Lycorine, Fluorescence, Atomic and Molecular Physics, and Optics, 0104 chemical sciences, Lycoris radiata, chemistry, Modeling and Simulation, Reagent, Drug delivery, 0210 nano-technology, Drug carrier, Intracellular, Nuclear chemistry
Abstract: Fluorescent carbon dots (CDs) were directly synthesized by hydrothermal treatment of medicinal mulberry leaves (Morus alba L.) residues without the need for any chemical reagent. The CDs were collected successively through filtration, centrifugation, and dialysis from the resultant solution. The as-purified CDs were almost non-cytotoxic and successfully used for the intracellular fluorescence imaging of human hepatocellular carcinoma cells (HepG2). Due to the presence of plentiful surface groups, the CDs were further used as drug carriers for the loading of Lycorine, an anti-cancer alkaloidal extracted from bulbs of Lycoris radiata L. Importantly, the Lycorine-loaded CDs were successfully applied for simultaneous intracellular imaging and drug delivery for the better anti-cancer cell activity. The present work both provides a strategy for the reuse of medicinal herb residues for the preparation of CDs and promotes a potential application of CDs in biomedicine and bioimaging.
Published: 2020
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17. Proteasome activator PA200 maintains stability of histone marks during transcription and aging

Author: Kui Lin, Shuang Ma, Tomoki Chiba, Qian-Qian Zhu, Xia Han, Zi-Yu Luo, Xiao-Bo Qiu, Wei Xie, and Tian-Xia Jiang
Subjects: 0301 basic medicine, Aging, Proteasome Endopeptidase Complex, Transcription, Genetic, DNA damage, medicine.drug_class, Medicine (miscellaneous), Histones, 03 medical and health sciences, Mice, 0302 clinical medicine, Transcription (biology), medicine, Animals, Epigenetics, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), proteasome activator PA200, biology, Chemistry, Activator (genetics), Histone marks, Lysine, Histone deacetylase inhibitor, Nuclear Proteins, Acetylation, Cell biology, Histone Code, 030104 developmental biology, Histone, Proteasome, histone degradation, biology.protein, H3K4me3, transcription, 030217 neurology & neurosurgery, Research Paper
Abstract: The epigenetic inheritance relies on stability of histone marks, but various diseases, including aging-related disorders, are usually associated with alterations of histone marks. Whether and how the proteasome is responsible for maintaining the histone marks during transcription and aging remain unclear. The core histones can be degraded by the atypical proteasome, which contains the proteasome activator PA200, in an acetylation-dependent manner during somatic DNA damage response and spermiogenesis. Methods: By utilizing a substitute of methionine to label proteins metabolically, we analyzed histone degradation genome-wide by sequencing the DNA fragments following pulse-chase assays. The genome-wide RNA-sequencing analysis was performed to analyze transcription and chromatin-immunoprecipitation (ChIP)-sequencing was used for analyses of histone marks. The experimental models included gene-manipulated cells (including both mouse and yeast), mouse liver, and mice. Results: Degradation of H4 or the transcription-coupled histone variant H3.3 could be suppressed by deletion of PA200 or its yeast ortholog Blm10. The histone deacetylase inhibitor accelerated the degradation rates of H3, while the mutations of the putative acetyl-lysine-binding region of PA200 abolished histone degradation in the G1-arrested cells. Deletion of PA200 dramatically altered deposition of the active transcriptional hallmarks (H3K4me3 and H3K56ac) and transcription, especially during cellular aging. Furthermore, deletion of PA200 or Blm10 accelerated cellular aging. Notably, the PA200-deficient mice displayed a range of aging-related deteriorations, including immune malfunction, anxiety-like behavior and shorter lifespan. Conclusion: PA200 promotes the transcription-coupled degradation of the core histones, and plays an important role in maintaining the stability of histone marks during transcription and aging.
Published: 2020

18. Standing genetic variation as the predominant source for adaptation of a songbird

Author: Lu Dong, Yu Cheng Hsu, Kui Lin, Chia Fen Yeh, Shou Hsien Li, Kevin E. Omland, Erli Pang, Ben-Yang Liao, Carol K.L. Yeung, Cheng Te Yao, Yu Ting Lai, Yu Hao, Hui Fen Cao, Wei Liang, Chih-Ming Hung, Bo Wen Zhang, Hsin Yi Hung, and Mingyu Yang
Subjects: 0106 biological sciences, 0301 basic medicine, RNA, Untranslated, population genomics, Evolution, standing variation, Population, Adaptation, Biological, Taiwan, Context (language use), Genomics, adaptation, Environment, Biology, Polymorphism, Single Nucleotide, 010603 evolutionary biology, 01 natural sciences, Songbirds, Population genomics, 03 medical and health sciences, Genetic variation, Animals, Selection, Genetic, education, Genetic diversity, education.field_of_study, Genome, Multidisciplinary, Genetic Variation, Parrotbill, Biological Sciences, biology.organism_classification, Biological Evolution, postglacial expansion, Genetics, Population, 030104 developmental biology, Evolutionary biology, Adaptation
Abstract: Significance It is a tenet of modern biology that species adapt through natural selection to cope with the ever-changing environment. By comparing genetic variants between the island and mainland populations of a passerine, we inferred the related age of genetic variants across its entire genome and suggest that preexisting standing variants played the predominant role in local adaptation. Our findings not only resolve a long-standing fundamental problem in biology regarding the genetic sources of adaptation, but imply that the evolutionary potential of a population is highly associated with its preexisting genetic variation., What kind of genetic variation contributes the most to adaptation is a fundamental question in evolutionary biology. By resequencing genomes of 80 individuals, we inferred the origin of genomic variants associated with a complex adaptive syndrome involving multiple quantitative traits, namely, adaptation between high and low altitudes, in the vinous-throated parrotbill (Sinosuthora webbiana) in Taiwan. By comparing these variants with those in the Asian mainland population, we revealed standing variation in 24 noncoding genomic regions to be the predominant genetic source of adaptation. Parrotbills at both high and low altitudes exhibited signatures of recent selection, suggesting that not only the front but also the trailing edges of postglacial expanding populations could be subjected to environmental stresses. This study verifies and quantifies the importance of standing variation in adaptation in a cohort of genes, illustrating that the evolutionary potential of a population depends significantly on its preexisting genetic diversity. These findings provide important context for understanding adaptation and conservation of species in the Anthropocene.
Published: 2019
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19. Proteasome activator PA200 maintains stability of histone marks during transcription and aging

Author: Zi-Yu Luo, Suren Chen, Xia Han, Tomoki Chiba, Xiao-Bo Qiu, Kui Lin, Shuang Ma, Qian-Qian Zhu, Wei Xie, and Tian-Xia Jiang
Subjects: biology, Chemistry, medicine.drug_class, Histone deacetylase inhibitor, Chromatin, Cell biology, Histone, Proteasome, Acetylation, biology.protein, medicine, Proteasome inhibitor, H3K4me3, Epigenetics, medicine.drug
Abstract: The epigenetic inheritance relies on stability of histone marks, but various diseases, including aging-related diseases, are usually associated with alterations of histone marks. How the stability of histone marks is maintained still remains unclear. The core histones can be degraded by the atypical proteasome, which contains the proteasome activator PA200, in an acetylation-dependent manner during somatic DNA damage response and spermiogenesis. Here we show that PA200 promotes the transcription-coupled degradation of the core histones, and plays an important role in maintaining the stability of histone marks. Degradation of the histone variant H3.3, which is incorporated into chromatin during transcription, was much faster than that of its canonical form H3.1, which is incorporated during DNA replication. This degradation of the core histones could be suppressed by the transcription inhibitor, the proteasome inhibitor or deletion of PA200. The histone deacetylase inhibitor accelerated the degradation rates of H3 in general, especially its variant H3.3, while the mutations of the putative acetyl-lysine-binding region of PA200 abolished histone degradation in the G1-arrested cells, supporting that acetylation is involved in the degradation of the core histones. Deletion of PA200 dramatically altered deposition of the active transcriptional hallmarks (H3K4me3 and H3K56ac) and transcription, especially during cellular aging. Furthermore, deletion of PA200 or its yeast ortholog Blm10 accelerated cellular aging. Notably, the PA200-deficient mice displayed a range of aging-related deteriorations, including immune malfunction, anxiety-like behaviors and shorter lifespan. Thus, the proteasome activator PA200 is critical to the maintenance of the stability of histone marks during transcription and aging.
Published: 2020
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20. Evolutionary patterns of 64 vertebrate genomes (species) revealed by phylogenomics analysis of protein-coding gene families

Author: Kui Lin, Xia Han, and Jia Song
Subjects: biology, Evolutionary biology, biology.animal, Phylogenomics, Gene duplication, Gene family, Vertebrate, Inference, Gene, Genome, Function (biology)
Abstract: BackgroundRecent studies have demonstrated that phylogenomics is an important basis for answering many fundamental evolutionary questions. With more high-quality whole genome sequences published, more efficient phylogenomics analysis workflows are required urgently.ResultsTo this end and in order to capture putative differences among evolutionary histories of gene families and species, we developed a phylogenomics workflow for gene family classification, gene family tree inference, species tree inference and duplication/loss events dating. Our analysis framework is on the basis of two guiding ideas: 1) gene trees tend to be different from species trees but they influence each other in evolution; 2) different gene families have undergone different evolutionary mechanisms. It has been applied to the genomic data from 64 vertebrates and 5 out-group species. And the results showed high accuracy on species tree inference and few false-positives in duplication events dating.ConclusionsBased on the inferred gene duplication and loss event, only 9∼16% gene families have duplication retention after a whole genome duplication (WGD) event. A large part of these families have ohnologs from two or three WGDs. Consistent with the previous study results, the gene function of these families are mainly involved in nervous system and signal transduction related biological processes. Specifically, we found that the gene families with ohnologs from the teleost-specific (TS) WGD are enriched in fat metabolism, this result implyng that the retention of such ohnologs might be associated with the environmental status of high concentration of oxygen during that period.
Published: 2020
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21. CuAS: a database of annotated transcripts generated by alternative splicing in cucumbers

Author: Quanbao Zhang, Zhonghua Zhang, Erli Pang, Bing Liu, Ying Sun, and Kui Lin
Subjects: 0106 biological sciences, 0301 basic medicine, Gene isoform, Tissue-specific alternative splicing events, Plant Science, Biology, computer.software_genre, Genes, Plant, 01 natural sciences, Transcriptome, Database, 03 medical and health sciences, lcsh:Botany, Databases, Genetic, Gene family, natural sciences, Gene, Isoform-level features, Cucumber, Alternative splicing, Isoform-level function, lcsh:QK1-989, Alternative Splicing, 030104 developmental biology, Proteome, RNA splicing, UniProt, Cucumis sativus, computer, 010606 plant biology & botany
Abstract: Background Alternative splicing (AS) plays a critical regulatory role in modulating transcriptome and proteome diversity. In particular, it increases the functional diversity of proteins. Recent genome-wide analysis of AS using RNA-Seq has revealed that AS is highly pervasive in plants. Furthermore, it has been suggested that most AS events are subject to tissue-specific regulation. Description To reveal the functional characteristics induced by AS and tissue-specific splicing events, a database for exploring these characteristics is needed, especially in plants. To address these goals, we constructed a database of annotated transcripts generated by alternative splicing in cucumbers (CuAS: http://cmb.bnu.edu.cn/alt_iso/index.php) that integrates genomic annotations, isoform-level functions, isoform-level features, and tissue-specific AS events among multiple tissues. CuAS supports a retrieval system that identifies unique IDs (gene ID, isoform ID, UniProt ID, and gene name), chromosomal positions, and gene families, and a browser for visualization of each gene. Conclusion We believe that CuAS could be helpful for revealing the novel functional characteristics induced by AS and tissue-specific AS events in cucumbers. CuAS is freely available at http://cmb.bnu.edu.cn/alt_iso/index.php.
Published: 2020

22. Identification of Genes Involved in Flavonoid Biosynthesis of Chinese Narcissus (Narcissus tazetta L. var. chinensis)

Author: Kui Lin-Wang, Lihui Zeng, Richard V. Espley, Guiqing Wang, Biyun Yang, Andrew C. Allan, Jiacheng Wu, Muhammad Anwar, and Peng Luo
Subjects: 0106 biological sciences, 0301 basic medicine, Flavonoid, Plant Science, Biology, Reductase, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Flavonol synthase, Narcissus tazetta, Molecular Biology, chemistry.chemical_classification, fungi, food and beverages, Leucoanthocyanidin reductase, biology.organism_classification, Narcissus, carbohydrates (lipids), 030104 developmental biology, Flavonoid biosynthesis, Biochemistry, chemistry, Anthocyanin, biology.protein, 010606 plant biology & botany
Abstract: Chinese narcissus (Narcissus tazetta L. var. chinensis Roem.) is a popular flower in Asia. However, flower colors are limited with all cultivars having a white perianth and yellow corona. Previous studies have shown no anthocyanin accumulation in this species. The reason for an absence of anthocyanins remains unknown, with the flavonoid biosynthetic pathway in this flower recently being investigated. In this study, a transcriptomic approach combined with gene expression and biochemical analysis was used to predict and annotate genes in the flavonoid biosynthetic pathway. Results showed that the major flavonoid metabolites are flavonols and proanthocyanidins. Proanthocyanidin biosynthesis is exclusively catechin-based, with the gene encoding leucoanthocyanidin reductase (LAR) being well expressed. We identified 16 unigenes encoding key enzymes involved in flavonoid biosynthesis. Flavonol synthase (FLS) and dihydroflavonol reductase (DFR) appear to play important roles in regulating proanthocyanidin and flavonol levels, while anthocyanidin synthase (ANS) expression is not detected. Our results suggest that the absence of anthocyanins in Chinese narcissus is due to high expression of LAR and FLS, and a lack of ANS expression.
Published: 2018
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23. The comparison of alternative splicing among the multiple tissues in cucumber

Author: Hongtao Song, Erli Pang, Jinglu Hu, Kui Lin, Zhonghua Zhang, Han Hou, and Ying Sun
Subjects: 0106 biological sciences, 0301 basic medicine, DNA damage, Plant Science, Biology, 01 natural sciences, 03 medical and health sciences, Exon, lcsh:Botany, Gene, Actin, Genetics, Cucumber, Tissue-specific, Gene Expression Profiling, Alternative splicing, Intron, lcsh:QK1-989, Cellular component organization, Tissues, 030104 developmental biology, RNA splicing, Cucumis sativus, Transcriptome, 010606 plant biology & botany, Research Article
Abstract: Background Alternative splicing (AS) is an important post-transcriptional process. It has been suggested that most AS events are subject to tissue-specific regulation. However, the global dynamics of AS in different tissues are poorly explored. Results To analyse global changes in AS in multiple tissues, we identified the AS events and constructed a comprehensive catalogue of AS events within each tissue based on the genome-wide RNA-seq reads from ten tissues in cucumber. First, we found that 58% of the multi-exon genes underwent AS. We further obtained 565 genes with significantly more AS events compared with random genes. These genes were found significant enrichment in biological processes related to the regulation of actin filament length. Second, significantly different AS event profiles among ten tissues were found. The tissues with the same origin of development are more likely to have a relatively similar AS profile. Moreover, 7370 genes showed tissue-specific AS events and were highly enriched in biological processes related to the positive regulation of cellular component organization. Root-specificity AS genes were related to the cellular response to DNA damage stimulus. Third, the genes with different intron retention (IR) patterns among the ten tissues showed significant difference in GC percentages of the retained intron, and the number of exons and FPKM of the major transcripts. Conclusions Our study provided a comprehensive view of AS in multiple tissues. We revealed novel insights into the patterns of AS in multiple tissues and the tissue-specific AS in cucumber. Electronic supplementary material The online version of this article (10.1186/s12870-017-1217-x) contains supplementary material, which is available to authorized users.
Published: 2018
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24. Demographically idiosyncratic responses to climate change and rapid Pleistocene diversification of the walnut genusJuglans(Juglandaceae) revealed by whole-genome sequences

Author: Peng-Cheng Yan, Keith E. Woeste, Kui Lin, Da-Yong Zhang, Wei-Ning Bai, and Bowen Zhang
Subjects: 0301 basic medicine, Time Factors, Early Pleistocene, Physiology, Climate Change, Population, Juglans, Plant Science, Coalescent theory, 03 medical and health sciences, Species Specificity, Effective population size, Genus, education, Phylogeny, Coevolution, Population Density, education.field_of_study, Base Sequence, Whole Genome Sequencing, biology, Ecology, Genetic Variation, Juglandaceae, biology.organism_classification, Markov Chains, Populus, 030104 developmental biology, Fraxinus, Genome, Plant
Abstract: Whether species demography and diversification are driven primarily by extrinsic environmental changes such as climatic oscillations in the Quaternary or by intrinsic biological interactions like coevolution between antagonists is a matter of active debate. In fact, their relative importance can be assessed by tracking past population fluctuations over considerable time periods. We applied the pairwise sequentially Markovian coalescent approach on the genomes of 11 temperate Juglans species to estimate trajectories of changes in effective population size (Ne ) and used a Bayesian-coalescent based approach that simultaneously considers multiple genomes (G-PhoCS) to estimate divergence times between lineages. Ne curves of all study species converged 1.0 million yr ago, probably reflecting the time when the walnut genus last shared a common ancestor. This estimate was confirmed by the G-PhoCS estimates of divergence times. But all species did not react similarly to the dramatic climatic oscillations following early Pleistocene cooling, so the timing and amplitude of changes in Ne differed among species and even among conspecific lineages. The population histories of temperate walnut species were not driven by extrinsic environmental changes alone, and a key role was probably played by species-specific factors such as coevolutionary interactions with specialized pathogens.
Published: 2017
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25. Integrated pipeline for inferring the evolutionary history of a gene family embedded in the species tree: a case study on the STIMATE gene family

Author: Kui Lin, Yubin Zhou, Youjun Wang, Sisi Zheng, Nhung T. Nguyen, and Jia Song
Subjects: 0301 basic medicine, Pipeline (computing), Biology, lcsh:Computer applications to medicine. Medical informatics, Biochemistry, Genome, Coalescent theory, Evolution, Molecular, 03 medical and health sciences, Evolutionary history, STIMATE, Structural Biology, Gene Duplication, Gene family, Animals, Humans, Chordate, Molecular Biology, Gene, lcsh:QH301-705.5, Phylogeny, Likelihood Functions, Phylogenetic tree, Models, Genetic, Applied Mathematics, Membrane Proteins, Computer Science Applications, Tree (data structure), 030104 developmental biology, ComputingMethodologies_PATTERNRECOGNITION, lcsh:Biology (General), Evolutionary biology, Multigene Family, lcsh:R858-859.7, ComputingMethodologies_GENERAL, DNA microarray, Algorithms, Research Article
Abstract: Background Because phylogenetic inference is an important basis for answering many evolutionary problems, a large number of algorithms have been developed. Some of these algorithms have been improved by integrating gene evolution models with the expectation of accommodating the hierarchy of evolutionary processes. To the best of our knowledge, however, there still is no single unifying model or algorithm that can take all evolutionary processes into account through a stepwise or simultaneous method. Results On the basis of three existing phylogenetic inference algorithms, we built an integrated pipeline for inferring the evolutionary history of a given gene family; this pipeline can model gene sequence evolution, gene duplication-loss, gene transfer and multispecies coalescent processes. As a case study, we applied this pipeline to the STIMATE (TMEM110) gene family, which has recently been reported to play an important role in store-operated Ca2+ entry (SOCE) mediated by ORAI and STIM proteins. We inferred their phylogenetic trees in 69 sequenced chordate genomes. Conclusions By integrating three tree reconstruction algorithms with diverse evolutionary models, a pipeline for inferring the evolutionary history of a gene family was developed, and its application was demonstrated. Electronic supplementary material The online version of this article (10.1186/s12859-017-1850-2) contains supplementary material, which is available to authorized users.
Published: 2017
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26. The Genome of Medicinal Plant Macleaya cordata Provides New Insights into Benzylisoquinoline Alkaloids Metabolism

Author: Xiubin Liu, Yongshuo Ma, Yuan Zhou, Kui Lin, Peng Huang, Jia-Lu Huang, Dae-Kyun Ro, Linlan Yu, Xingyao Xiong, Wenkai Jiang, Zhonghua Zhang, Zhaoshan Tang, Yi-Song Liu, Qi Tang, Huifen Cao, Xiao-Ya Chen, Yan-Cong Zhang, Zhixing Qing, Jianguo Zeng, Yajie Zheng, Sanwen Huang, Jinbo Zhang, Jinfeng Liu, Yi Shang, Qiong Peng, Yixiu Zhuo, Peng Yang, Pi Cheng, and Zejun Yuan
Subjects: 0301 basic medicine, Genomics, Plant Science, Benzylisoquinolines, Genome, 03 medical and health sciences, chemistry.chemical_compound, Alkaloids, Papaveraceae, Botany, Sanguinarine, Secondary metabolism, Benzylisoquinoline, Molecular Biology, Benzophenanthridines, Macleaya cordata, Plants, Medicinal, biology, Isoquinolines, biology.organism_classification, Metabolic pathway, 030104 developmental biology, chemistry, Isotope Labeling, Genome, Plant
Abstract: The overuse of antibiotics in animal agriculture and medicine has caused a series of potential threats to public health. Macleaya cordata is a medicinal plant species from the Papaveraceae family, providing a safe resource for the manufacture of antimicrobial feed additive for livestock. The active constituents from M. cordata are known to include benzylisoquinoline alkaloids (BIAs) such as sanguinarine (SAN) and chelerythrine (CHE), but their metabolic pathways have yet to be studied in this non-model plant. The active biosynthesis of SAN and CHE in M. cordata was first examined and confirmed by feeding 13 C-labeled tyrosine. To gain further insights, we de novo sequenced the whole genome of M . cordata , the first to be sequenced from the Papaveraceae family. The M. cordata genome covering 378 Mb encodes 22,328 predicted protein-coding genes with 43.5% being transposable elements. As a member of basal eudicot, M. cordata genome lacks the paleohexaploidy event that occurred in almost all eudicots. From the genomics data, a complete set of 16 metabolic genes for SAN and CHE biosynthesis was retrieved, and 14 of their biochemical activities were validated. These genomics and metabolic data show the conserved BIA metabolic pathways in M. cordata and provide the knowledge foundation for future productions of SAN and CHE by crop improvement or microbial pathway reconstruction.
Published: 2017
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27. A simple method for non-denaturing purification of biotin-tagged proteins through competitive elution with free biotin

Author: Audrey Mitchell, Kui Lin, Natasha Funk, Qin Yan, Catherlin Lu, and Hao Xiao
Subjects: Streptavidin, Proteomics, Protein Denaturation, Immunoprecipitation, Biotin, 030204 cardiovascular system & hematology, General Biochemistry, Genetics and Molecular Biology, Antibodies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Affinity chromatography, Carbon-Nitrogen Ligases, Bovine serum albumin, 030304 developmental biology, 0303 health sciences, Chromatography, biology, Elution, Escherichia coli Proteins, Proteins, Serum Albumin, Bovine, Hydrogen-Ion Concentration, Repressor Proteins, chemistry, Biotinylation, biology.protein, Biotechnology, Avidin, Chromatography, Liquid
Abstract: The use of avidin or streptavidin in the purification of biotinylated proteins has been highly restricted due to the harsh and denaturing elution conditions. Here, we use biotinylated bovine serum albumin as a working model to demonstrate a simple and rapid method for biotin-tagged protein purification under non-denaturing conditions. The biotinylated bovine serum albumin is specifically bound to the anti-biotin antibody agarose beads and competitively eluted with free biotin under near-neutral conditions. The optimized elution conditions include using 4 mg/ml biotin (pH 8.5) as the elution buffer and allowing the buffer to incubate with agarose beads for 30 min prior to elution. The elution recovery rate is over 85% without apparent protein denaturation. The method is applicable for both immunoprecipitation and column chromatography.
Published: 2019

28. The involvement of PybZIPa in light-induced anthocyanin accumulation via the activation of PyUFGT through binding to tandem G-boxes in its promoter

Author: Hainan Liu, Yang-Fan Zhu, Shaoling Zhang, Jun Wu, Yao Gaifang, Kui Lin-Wang, Jun Su, Qun Shu, Andrew C. Allan, and Charles Ampomah-Dwamena
Subjects: PEAR, biology, Structural gene, food and beverages, Promoter, Plant Science, Horticulture, biology.organism_classification, Biochemistry, Cell biology, Transcriptome, chemistry.chemical_compound, chemistry, Arabidopsis, Anthocyanin, Genetics, Transcriptional regulation, Transcription factor, Biotechnology
Abstract: To gain insight into how anthocyanin biosynthesis is controlled by light in fruit, transcriptome and metabolome analyses were performed in the Chinese sand pear cultivar “Mantianhong” (Pyrus pyrifolia) after bagging and bag removal. We investigated transcriptional and metabolic changes and gene-metabolite correlation networks. Correlation tests of anthocyanin content and transcriptional changes revealed that 1,530 transcripts were strongly correlated with 15 anthocyanin derivatives (R2 > 0.9, P-value PybZIPa, that might play an important role during light-induced anthocyanin accumulation. The overexpression of PybZIPa promoted anthocyanin accumulation in pear and strawberry fruit as well as tobacco leaves. Dual luciferase and Y1H assays further verified that PybZIPa directly activated the expression of PyUFGT by binding to tandem G-box motifs in the promoter, which was key to differential anthocyanin accumulation in debagged pear skin, and the number of G-box motifs affected the transcriptional activation of PyUFGT by PybZIPa. The results indicate that the light-induced anthocyanin biosynthesis regulatory mechanism in pear differs from that described in previous reports suggesting that a bZIP family member co-regulates anthocyanin biosynthesis with other transcription factors in apple and Arabidopsis. It was found that, in response to light, PybZIPa promoted anthocyanin biosynthesis by regulating important transcription factors (PyMYB114, PyMYB10, and PyBBX22) as well as structural genes (PyUFGT) via binding to G-boxes within promoters. This activation was amplified by the self-binding of PybZIPa to activate its own promoter. Overall, we demonstrate the utility of a multiomics integrative approach for discovering new functional genes and pathways underlying light-induced anthocyanin biosynthesis.
Published: 2019
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29. PbGA2ox8 induces vascular-related anthocyanin accumulation and contributes to red stripe formation on pear fruit

Author: Kui Lin-Wang, Zhigang Wang, Xieyu Li, Pengmin Li, Zhongying Wu, Chengquan Yang, Lingfei Xu, Qingmei Guan, Fengwang Ma, Jianlong Liu, Richard V. Espley, and Rui Zhai
Subjects: PEAR, food and beverages, Plant Science, Horticulture, Biology, medicine.disease, Vascular bundle, Biochemistry, Article, Gibberellins, Cell biology, Transcriptome, chemistry.chemical_compound, chemistry, Anthocyanin, Gene expression, Genetics, medicine, Gibberellin, Secondary metabolism, Infiltration (medical), Biotechnology
Abstract: Fruit with stripes, which are generally longitudinal, can occur naturally, but the bioprocesses underlying this phenomenon are unclear. Previously, we observed an atypical anthocyanin distribution that caused red-striped fruit on the spontaneous pear bud sport “Red Zaosu” (Pyrus bretschneideri Rehd.). In this study, comparative transcriptome analysis of the sport and wild-type “Zaosu” revealed that this atypical anthocyanin accumulation was tightly correlated with abnormal overexpression of the gene-encoding gibberellin (GA) 2-beta-dioxygenase 8, PbGA2ox8. Consistently, decreased methylation was also observed in the promoter region of PbGA2ox8 from “Red Zaosu” compared with “Zaosu”. Moreover, the GA levels in “Red Zaosu” seedlings were lower than those in “Zaosu” seedlings, and the application of exogenous GA4 reduced abnormal anthocyanin accumulation in “Red Zaosu”. Transient overexpression of PbGA2ox8 reduced the GA4 level and caused anthocyanin accumulation in pear fruit skin. Moreover, the presence of red stripes indicated anthocyanin accumulation in the hypanthial epidermal layer near vascular branches (VBs) in “Red Zaosu”. Transient overexpression of PbGA2ox8 resulting from vacuum infiltration induced anthocyanin accumulation preferentially in calcium-enriched areas near the vascular bundles in pear leaves. We propose a fruit-striping mechanism, in which the abnormal overexpression of PbGA2ox8 in “Red Zaosu” induces the formation of a longitudinal array of anthocyanin stripes near vascular bundles in fruit.
Published: 2019

30. Genome-wide analysis and expression profiles of the StR2R3-MYB transcription factor superfamily in potato (Solanum tuberosum L.)

Author: Shuhao Qin, Zhen Liu, Junlian Zhang, Yuanming Li, Kui Lin-Wang, Yuhui Liu, and Andrew C. Allan
Subjects: animal structures, Genes, myb, Amino Acid Motifs, Arabidopsis, 02 engineering and technology, Biology, Biochemistry, 03 medical and health sciences, Negative selection, Structural Biology, Gene Expression Regulation, Plant, Stress, Physiological, Gene family, MYB, Amino Acid Sequence, Molecular Biology, Gene, Transcription factor, Phylogeny, 030304 developmental biology, Synteny, Segmental duplication, Plant Proteins, Solanum tuberosum, Genetics, 0303 health sciences, Gene Expression Profiling, fungi, food and beverages, General Medicine, 021001 nanoscience & nanotechnology, biology.organism_classification, Droughts, Multigene Family, 0210 nano-technology, Genome, Plant, Transcription Factors
Abstract: MYB transcription factors comprise one of the largest families in plant kingdom, which play a variety of functions in plant developmental processes and defence responses, the R2R3-MYB members are the predominant form found in higher plants. In the present study, a total of 111 StR2R3-MYB transcription factors were identified and further phylogenetically classified into 31 subfamilies, as supported by highly conserved gene structures and motifs. Collinearity analysis showed that the segmental duplication events played a crucial role in the expansion of StR2R3-MYB gene family. Synteny analysis indicated that 37 and 13 StR2R3-MYB genes were orthologous to Arabidopsis and wheat (Triticum aestivum), respectively, and these gene pairs have evolved under strong purifying selection. RNA-seq data from different tissues and abiotic stresses revealed tissue-preferential and abiotic stress-responsive StR2R3-MYB genes. We further analyzed StR2R3-MYB genes might be involved in anthocyanin biosynthesis and drought stress by using RNA-seq data of pigmented tetraploid potato cultivars and drought-sensitive and -tolerant tetraploid potato cultivars under drought stress, respectively. Moreover, EAR motifs were found in 21 StR2R3-MYB proteins and 446 pairs of proteins were predicted to interact with 21 EAR motif-containing StR2R3-MYB proteins by constructing the interaction network with medium confidence (0.4). Additionally, Gene Ontology (GO) analysis of the 21 EAR motif-containing StR2R3-MYB proteins was performed to further investigate their functions. This work will facilitate future biologically functional studies of potato StR2R3-MYB transcription factors and enrich the knowledge of MYB superfamily genes in plant species.
Published: 2019

31. miR‑21 inhibits autophagy and promotes malignant development in the bladder cancer T24 cell line

Author: Hui‑Hui Zhang, Su‑Quan Zhong, Zhong‑Xin Huang, Kui‑Lin Fei, and You‑Han Cao
Subjects: 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Vimentin, Apoptosis, 03 medical and health sciences, 0302 clinical medicine, Cyclin D1, Cell Movement, Cell Line, Tumor, medicine, Autophagy, PTEN, Humans, Epithelial–mesenchymal transition, Cell Proliferation, Bladder cancer, biology, Cell growth, Cell migration, Cell cycle, medicine.disease, MicroRNAs, 030104 developmental biology, Oncology, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, biology.protein, Cancer research
Abstract: MicroRNA‑21 (miR‑21) is reported to exhibit cancer‑promoting activity in various types of cancer. It has been previously demonstrated that miR‑21 is overexpressed in bladder tumor tissue compared with normal mucosa. However, the functional mechanism of miR‑21 in bladder cancer remains largely unknown. Thus, the current study aimed to determine the roles of miR‑21 in autophagy and the malignant development of bladder cancer in T24 cells. Upregulation or downregulation of miR‑21 was achieved following the transfection of miR‑21 mimic or miR‑21 inhibitor. An MTT assay was additionally performed to measure cell growth. Wound healing and transwell invasion assays were used to detect cell migration and invasion. The apoptotic potential and cell cycle were examined via flow cytometry and reverse transcription‑quantitative PCR was performed to evaluate the expression of phosphatase and tensin homolog (PTEN), beclin 1, microtubule‑associated protein l light chain 3B (LC3‑II), cyclin D1, caspase‑3, E‑cadherin, matrix metallopeptidase‑9 (MMP‑9) and vimentin. The results revealed that the proliferation, migration and invasion of T24 cells was greatly increased in the miR‑21 mimic group, while apoptosis was greatly inhibited. Additionally, T24 cells treated with miR‑21 mimic exhibited G1‑phase arrest. In the miR‑21 mimic group, the expression of PTEN, beclin 1, LC3‑II, caspase‑3 and E‑cadherin were decreased, while the expression of cyclin D1, MMP‑9 and vimentin were increased. Opposite effects were observed in the miR‑21 inhibitor group. The data of the current study may indicate that miR‑21 overexpression inhibited autophagy and promoted the proliferation, migration, invasion and epithelial to mesenchymal transition of bladder cancer T24 cells. The results may further elucidate the molecular mechanism of miR‑21 in the development of bladder cancer.
Published: 2019

32. Differential regulation of the anthocyanin profile in purple kiwifruit (Actinidia species)

Author: Kui Lin-Wang, Tianchi Wang, Janine M. Cooney, Yongyan Peng, Andrew C. Allan, and Richard V. Espley
Subjects: 0106 biological sciences, 0301 basic medicine, Chalcone synthase, Actinidia chinensis, Cyanidin, Plant Science, Horticulture, Biology, 01 natural sciences, Biochemistry, Article, 03 medical and health sciences, chemistry.chemical_compound, lcsh:Botany, Genetics, MYB, lcsh:QH301-705.5, Actinidia, fungi, food and beverages, Promoter, biology.organism_classification, lcsh:QK1-989, carbohydrates (lipids), 030104 developmental biology, chemistry, lcsh:Biology (General), Anthocyanin, biology.protein, Delphinidin, 010606 plant biology & botany, Biotechnology
Abstract: Anthocyanins are a group of secondary metabolites that colour fruit and flowers orange, red, purple or blue depending on a number of factors, such as the basic structure, co-pigmentation, metal ion complexation and vacuolar pH. The biosynthesis of anthocyanin is regulated at the transcriptional level by a group of transcription factors, the MYB–bHLH–WD40 (MBW) complex. In this study, the purple colouration in several kiwifruit (Actinidia) species was identified and characterised as red cyanidin-based and blue delphinidin-based anthocyanins. The differential pigmentation in the skin and flesh can be attributed to the differential ratio of cyanidin and delphinidin derivatives accumulated in the total anthocyanin profile. The expression of anthocyanin biosynthetic genes chalcone synthase (CHS), flavonoid 3-O-glucosyltransferase (F3GT), flavonoid 3′-hydroxylase (F3′H) and flavonoid 3′5′-hydroxylase (F3′5′H) is crucial for anthocyanin accumulation. However, the balance of expression of the F3′H and F3′5′H genes appears responsible for the ratio of cyanidin and delphinidin derivatives, while a lack of CHS, F3GT and MYB110 expression is responsible for a lack of total anthocyanins. The transcriptional regulation of the F3′H and F3′5′H promoters by the R2R3 MYB transcription factor MYB110 is markedly different in tobacco transient assays. When kiwifruit MYB10 or MYB110 are over-expressed in Actinidia chinensis both cyanidin-based and delphinidin-based anthocyanins are elevated, but F3′H and F3′5′H genes are not strongly correlated with MYB expression. These results suggest that the core kiwifruit anthocyanin pathway genes are dependent on characterised MYB transcription factors, while other regulatory proteins are more directly responsible for the expression of the F3′H and F3′5′H genes., Anthocyanins: Coloring Kiwifruit The genetic processes that determine the colors in purple kiwifruit have been revealed by researchers in New Zealand. Anthocyanin pigments are not only essential for plant growth and development, but also provide color to make fruit attractive to pollinators and indicate ripeness for the food industry. Andrew Allan and co-workers at the University of Auckland and The New Zealand Institute for Plant and Food Research Limited examined several different kiwifruit species, and found that their color was determined by the ratio of red cyanidin-based to blue delphinidin-based anthocyanins. The team identified four biosynthetic genes that are crucial for accumulating anthocyanins, and showed that two of those genes control the red-to-blue pigment ratio. This new understanding of the anthocyanin profile could allow metabolic engineering of novel fruit colors, possibly with greater health benefits for humans.
Published: 2019

33. Temperature responses of mutation rate and mutational spectrum in an Escherichia coli strain and the correlation with metabolic rate

Author: Bowen Zhang, Bi-Ru Zhu, Kui Lin, Quan-Guo Zhang, Xiao-Lin Chu, and Da-Yong Zhang
Subjects: 0301 basic medicine, Mutation rate, Evolution, Mutation accumulation, Metabolic theory of ecology, Biology, medicine.disease_cause, 03 medical and health sciences, INDEL Mutation, Mutation Rate, Molecular evolution, QH359-425, medicine, Escherichia coli, Evolutionary speed hypothesis, Base Pairing, Ecology, Evolution, Behavior and Systematics, Genetics, Natural selection, Temperature, Mutation Accumulation, 030104 developmental biology, Mutational spectrum, Oxidative DNA damage, Mutation (genetic algorithm), Mutation, Research Article
Abstract: Background Temperature is a major determinant of spontaneous mutation, but the precise mode, and the underlying mechanisms, of the temperature influences remain less clear. Here we used a mutation accumulation approach combined with whole-genome sequencing to investigate the temperature dependence of spontaneous mutation in an Escherichia coli strain. Experiments were performed under aerobic conditions at 25, 28 and 37 °C, three temperatures that were non-stressful for the bacterium but caused significantly different bacterial growth rates. Results Mutation rate did not differ between 25 and 28 °C, but was higher at 37 °C. Detailed analyses of the molecular spectrum of mutations were performed; and a particularly interesting finding is that higher temperature led to a bias of mutation to coding, relative to noncoding, DNA. Furthermore, the temperature response of mutation rate was extremely similar to that of metabolic rate, consistent with an idea that metabolic rate predicts mutation rate. Conclusions Temperature affects mutation rate and the types of mutation supply, both being crucial for the opportunity of natural selection. Our results help understand how temperature drives evolutionary speed of organisms and thus the global patterns of biodiversity. This study also lend support to the metabolic theory of ecology for linking metabolic rate and molecular evolution rate. Electronic supplementary material The online version of this article (10.1186/s12862-018-1252-8) contains supplementary material, which is available to authorized users.
Published: 2018

34. An Updated Functional Annotation of Protein-Coding Genes in the Cucumber Genome

Author: Erli Pang, Jinglu Hu, Hongtao Song, and Kui Lin
Subjects: 0301 basic medicine, Genome evolution, Plant Science, Computational biology, Collinearity, Biology, lcsh:Plant culture, protein-coding gene, Genome, 03 medical and health sciences, Annotation, 030104 developmental biology, Order (biology), gene functional annotation, Identification (biology), lcsh:SB1-1110, orthology, Gene, cucumber, collinear segments, Original Research, Reference genome
Abstract: Background: Although the cucumber reference genome and its annotation were published several years ago, the functional annotation of predicted genes, particularly protein-coding genes, still requires further improvement. In general, accurately determining orthologous relationships between genes allows for better and more robust functional assignments of predicted genes. As one of the most reliable strategies, the determination of collinearity information may facilitate reliable orthology inferences among genes from multiple related genomes. Currently, the identification of collinear segments has mainly been based on conservation of gene order and orientation. Over the course of plant genome evolution, various evolutionary events have disrupted or distorted the order of genes along chromosomes, making it difficult to use those genes as genome-wide markers for plant genome comparisons. Results: Using the localized LASTZ/MULTIZ analysis pipeline, we aligned 15 genomes, including cucumber and other related angiosperm plants, and identified a set of genomic segments that are short in length, stable in structure, uniform in distribution and highly conserved across all 15 plants. Compared with protein-coding genes, these conserved segments were more suitable for use as genomic markers for detecting collinear segments among distantly divergent plants. Guided by this set of identified collinear genomic segments, we inferred 94,486 orthologous protein-coding gene pairs (OPPs) between cucumber and 14 other angiosperm species, which were used as proxies for transferring functional terms to cucumber genes from the annotations of the other 14 genomes. In total, 10,885 protein-coding genes were assigned Gene Ontology (GO) terms which was nearly 1,300 more than results collected in Uniprot-proteomic database. Our results showed that annotation accuracy would been improved compared with other existing approaches. Conclusions: In this study, we provided an alternative resource for the functional annotation of predicted cucumber protein-coding genes, which we expect will be beneficial for the cucumber's biological study, accessible from http://cmb.bnu.edu.cn/functional_annotation. Meanwhile, using the cucumber reference genome as a case study, we presented an efficient strategy for transferring gene functional information from previously well-characterized protein-coding genes in model species to newly sequenced or “non-model” plant species.
Published: 2018
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35. A GENOMICS APPROACH TO UNDERSTANDING FRUIT CHARACTERS

Author: A. White, R.N. Crowhurst, Benjamin A. Warren, Christina G. Fullerton, Alastair Currie, Dwayne J. Jensen, J.M. Burdon, K.B. Marsh, Adam J. Matich, Annette C. Richardson, Cyril Hamiaux, Sean Bulley, Ian C. Hallett, A. Blackmore, Kui Lin-Wang, Hilary S. Ireland, Mirco Montefiori, Kirsten Hoeata, Cyril Brendolise, Helen L. Boldingh, David Chagné, Ross G. Atkinson, Edwige J. F. Souleyre, Robert J. Schaffer, Andrew C. Allan, Denise C. Hunter, C. Edwards, Janine M. Cooney, J.N. McCallum, and A. Nangul
Subjects: Botany, Genomics, Computational biology, Horticulture, Biology
Published: 2015
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36. A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants

Author: Yongyan Peng, Kelvina I. Manako, Jenny Hanley, Judith H. Bowen, Ella R. P. Grierson, Ben Warren, Davide Scaglione, Yifei Liu, Mareike Knäbel, Roger P. Hellens, Marcela Martínez-Sánchez, Jia-Long Yao, Sarah M. Pilkington, Zac Hanley, Sathiyamoorthy Meiyalaghan, K.B. Marsh, Andrew C. Allan, Canhong Cheng, H. Bassett, Joey Cheung, Kui Lin-Wang, Nikolai Macnee, Davin Leif, Dawei Li, Mirco Montefiori, Donald A. Hunter, Zoe A. Erridge, P. M. Datson, Chethi N. Waite, Marcus Davy, Andrew Catanach, Ross G. Atkinson, Marian J. McKenzie, Jibran Tahir, Simona Nardozza, Rongmei Wu, Karine M. David, Hilary S. Ireland, Revel S.M. Drummond, David A. Brummell, Kularajathevan Gunaseelan, Marion Wood, Robert M. Simpson, Charlotte Voogd, Bart J. Janssen, Niels J. Nieuwenhuizen, Lena G. Fraser, Hongwen Huang, Blue Plunkett, Rebecca Kirk, Yen-Yi Wang, Angela Chen, Simon C. Deroles, Mindy Y. Wang, Toshi Foster, Susan Thomson, Sean Bulley, Heather R. Tiffin, Lara Brian, Helge Dzierzon, Huaibi Zhang, Richard V. Espley, Susan E. Gardiner, Francesco Gambi, Kimberley C. Snowden, Lorna Barron, Nihal De Silva, William A. Laing, Elena Hilario, Nadeesha R. Ileperuma, Charles David, Kevin M. Davies, Robert Campin, Mark A McNeilage, Raffaele Testolin, Roy Storey, Edwige J. F. Souleyre, Ross N. Crowhurst, Kerry Robert Templeton, Christina G. Fullerton, Nicola C. Read, Cecilia H. Deng, Peter A. McAtee, Alastair Harris, David Chagné, Robert J. Schaffer, Charles Ampomah-Dwamena, Xiuyin Chen, Zhiwei Luo, Andrew P. Gleave, Sakuntala Karunairetnam, John McCallum, Qiong Zhang, Roneel Prakash, Erika Varkonyi-Gasic, Shayhan Chunkath, Declan J. Lafferty, Amali H. Thrimawithana, and Kathy E. Schwinn
Subjects: 0301 basic medicine, Genotype, lcsh:QH426-470, Gene prediction, lcsh:Biotechnology, Actinidia, Genomics, Computational biology, Biology, Genes, Plant, Genome sequencing, Genome, DNA sequencing, 03 medical and health sciences, lcsh:TP248.13-248.65, Genetics, Gene family, Actinidia chinensis, Gene, Manual annotation, Plant Proteins, Computational gene, Molecular Sequence Annotation, lcsh:Genetics, 030104 developmental biology, Genome, Plant, Biotechnology, Research Article
Abstract: Background Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) ‘Hongyang’ draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. Results A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within ‘Hongyang’ The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned ‘Hort16A’ cDNAs and comparing with the predicted protein models for Red5 and both the original ‘Hongyang’ assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised ‘Hongyang’ annotation, respectively, compared with 90.9% to the Red5 models. Conclusions Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis. Electronic supplementary material The online version of this article (10.1186/s12864-018-4656-3) contains supplementary material, which is available to authorized users.
Published: 2018

37. In the Solanaceae, a hierarchy of bHLHs confer distinct target specificity to the anthocyanin regulatory complex

Author: Kui Lin-Wang, Andrew P. Dare, Andrew C. Allan, Kevin M. Davies, Cyril Brendolise, Mirco Montefiori, and Roger P. Hellens
Subjects: Physiology, transcription factors, Nicotiana tabacum, Actinidia, Transcription factor complex, MYB, Plant Science, Biology, tobacco, Anthocyanins, Transcription (biology), bHLH, Gene Expression Regulation, Plant, Gene expression, Botany, Transcriptional regulation, Basic Helix-Loop-Helix Transcription Factors, Gene, Transcription factor, Solanaceae, Plant Proteins, Genetics, fungi, food and beverages, biology.organism_classification, Plants, Genetically Modified, Biosynthetic Pathways, carbohydrates (lipids), Research Paper, transcriptional control, Transcription Factors
Abstract: Summary Anthocyanin biosynthesis is regulated by a transcription factor complex. Here, it is determined that the potential bHLH partners in this complex function in a hierarchy to control each other and the anthocyanin biosynthesis pathway., The anthocyanin biosynthetic pathway is regulated by a transcription factor complex consisting of an R2R3 MYB, a bHLH, and a WD40. Although R2R3 MYBs belonging to the anthocyanin-activating class have been identified in many plants, and their role well elucidated, the subgroups of bHLH implicated in anthocyanin regulation seem to be more complex. It is not clear whether these potential bHLH partners are biologically interchangeable with redundant functions, or even if heterodimers are involved. In this study, AcMYB110, an R2R3 MYB isolated from kiwifruit (Actinidia sp.) showing a strong activation of the anthocyanin pathway in tobacco (Nicotiana tabacum) was used to examine the function of interacting endogenous bHLH partners. Constitutive expression of AcMYB110 in tobacco leaves revealed different roles for two bHLHs, NtAN1 and NtJAF13. A hierarchical mechanism is shown to control the regulation of transcription factors and consequently of the anthocyanin biosynthetic pathway. Here, a model is proposed for the regulation of the anthocyanin pathway in Solanaceous plants in which AN1 is directly involved in the activation of the biosynthetic genes, whereas JAF13 is involved in the regulation of AN1 transcription.
Published: 2015

38. The distribution pattern of genetic variation in the transcript isoforms of the alternatively spliced protein-coding genes in the human genome

Author: Ting Liu and Kui Lin
Subjects: Gene isoform, Biology, Polymorphism, Single Nucleotide, Genome, Open Reading Frames, Gene Frequency, INDEL Mutation, RNA Isoforms, Databases, Genetic, Humans, Coding region, 1000 Genomes Project, Molecular Biology, Gene, Alleles, Genetic Association Studies, Genetics, Genome, Human, Alternative splicing, Computational Biology, Genetic Variation, Genomics, Alternative Splicing, Human genome, Transcriptome, Biotechnology
Abstract: By enabling the transcription of multiple isoforms from the same gene locus, alternative-splicing mechanisms greatly expand the diversity of the human transcriptome and proteome. Currently, the alternatively spliced transcripts from each protein-coding gene locus in the human genome can be classified as either principal or non-principal isoforms, providing that they differ with respect to cross-species conservation or biological features. By mapping the variants from the 1000 Genomes Project onto the coding region of each isoform, an interesting pattern of the genetic variation distributions of the coding regions for these two types of transcript isoforms was revealed on a whole-genome scale: compared with the principal isoform-specific coding regions, the non-principal isoform-specific coding regions are significantly enriched in amino acid-changing variants, particularly those that have a strong impact on protein function and have higher derived allele frequencies, suggesting that non-principal isoform-specific substitutions are less likely to be related to phenotype changes or disease. The results herein can help us better understand the potential consequences of alternatively spliced products from a population perspective.
Published: 2015
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39. Multiple Copies of a Simple MYB-Binding Site Confers Trans-regulation by Specific Flavonoid-Related R2R3 MYBs in Diverse Species

Author: Andrew C. Allan, Yongyan Peng, Cyril Brendolise, Richard V. Espley, William A. Laing, Sumathi Tomes, Kui Lin-Wang, Supinya Dejnoprat, Tony K. McGhie, and Roger P. Hellens
Subjects: 0106 biological sciences, 0301 basic medicine, MYB, Plant Science, lcsh:Plant culture, Biology, 01 natural sciences, Petunia, anthocyanin, 03 medical and health sciences, Arabidopsis, lcsh:SB1-1110, Binding site, Transcription factor, Gene, transcription factor, Original Research, Genetics, promoter, fungi, food and beverages, Promoter, DNA-binding domain, biology.organism_classification, 030104 developmental biology, flavonoids, 010606 plant biology & botany, biotechnology
Abstract: In apple, the MYB transcription factor MYB10 controls the accumulation of anthocyanins. MYB10 is able to auto-activate its expression by binding its own promoter at a specific motif, the R1 motif. In some apple accessions a natural mutation, termed R6, has more copies of this motif within the MYB10 promoter resulting in stronger auto-activation and elevated anthocyanins. Here we show that other anthocyanin-related MYBs selected from apple, pear, strawberry, petunia, kiwifruit and Arabidopsis are able to activate promoters containing the R6 motif. To examine the specificity of this motif, members of the R2R3 MYB family were screened against a promoter harboring the R6 mutation. Only MYBs from subgroups 5 and 6 activate expression by binding the R6 motif, with these MYBs sharing conserved residues in their R2R3 DNA binding domains. Insertion of the apple R6 motif into orthologous promoters of MYB10 in pear (PcMYB10) and Arabidopsis (AtMY75) elevated anthocyanin levels. Introduction of the R6 motif into the promoter region of an anthocyanin biosynthetic enzyme F3′5′H of kiwifruit imparts regulation by MYB10. This results in elevated levels of delphinidin in both tobacco and kiwifruit. Finally, an R6 motif inserted into the promoter the vitamin C biosynthesis gene GDP-L-Gal phosphorylase increases vitamin C content in a MYB10-dependent manner. This motif therefore provides a tool to re-engineer novel MYB-regulated responses in plants.
Published: 2017

40. Differential Sensitivity of Fruit Pigmentation to Ultraviolet Light between Two Peach Cultivars

Author: Ke Wang, Kunsong Chen, Andrew C. Allan, Yun Zhao, Bo Zhang, Kui Lin-Wang, Weiqi Dong, and Changjie Xu
Subjects: 0106 biological sciences, 0301 basic medicine, Plant Science, lcsh:Plant culture, Biology, 01 natural sciences, Hypocotyl, peach, Transcriptome, 03 medical and health sciences, Prunus, chemistry.chemical_compound, transcription factors, Botany, Ultraviolet light, lcsh:SB1-1110, MYB, Gene, Original Research, glutathione S-transferase, fungi, food and beverages, anthocyanins, 030104 developmental biology, chemistry, Biochemistry, Anthocyanin, Darkness, light, 010606 plant biology & botany
Abstract: Anthocyanins provide nutritional benefits and are responsible for red coloration in many fruits. Light affects anthocyanin biosynthesis in peach (Prunus persica). However, some cultivars show differential sensitivity to light. In the present study, ‘Hujingmilu (HJ),’ a naturally deeply colored cultivar, and ‘Yulu (YL),’ showing low pigmentation, were used to study the mechanism underlying UV-light-induced anthocyanin biosynthesis. Both UVA and UVB induced fruit pigmentation of ‘HJ,’ but ‘YL’ was only sensitive to UVB. Transcriptomic analyses showed over 5000 genes were differentially expressed by pairwise comparisons of RNA libraries isolated from tissue of each cultivar treated with darkness, UVA and UVB. Twenty-three genes related to anthocyanin biosynthesis were identified from the transcriptome data, which were coordinately up-regulated during accumulation of anthocyanins, and down-regulated in the dark. Altered expression of several light receptors, as well as CONSTITUTIVE PHOTOMORPHOGENIC10 (COP10) and ELONGATED HYPOCOTYL 5 homolog (HYH), and a specific anthocyanin transporter glutathione S-transferase (GST), in ‘YL’ fruit appears to be responsible for the insensitivity to UVA of this cultivar. Expression profiles of several transcription factors of the families MYB, bHLH, bZIP and NAC were highly correlated with those of the anthocyanin biosynthesis genes. The study provides a valuable overview of the underlying molecular mechanisms of UV-light induced anthocyanin response using peach cultivars with differing light sensitivities.
Published: 2017
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41. REGULATION OF ANTHOCYANIN BIOSYNTHESIS IN STRAWBERRY (FRAGARIA SP.) BY OVER-EXPRESSION OF A KEY TRANSCRIPTION FACTOR

Author: Tony K. McGhie, Richard Espley, Roger P. Hellens, Yuhui Liu, Sakuntala Karunairetnam, Andrew C. Allan, and Kui Lin-Wang
Subjects: Structural gene, Horticulture, Biology, biology.organism_classification, Fragaria, Genetically modified organism, chemistry.chemical_compound, Biochemistry, Biosynthesis, chemistry, Anthocyanin biosynthesis, Over expression, Arabidopsis thaliana, Transcription factor
Published: 2014
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42. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Author: 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. Silverman, Jan Simak, Thomas Simmet, Anna Katharina Simon, Hans Uwe Simon, Cristiano Simone, Matias Simons, 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 Sivridis, 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. Sparks, Peter G. Speck, Stephen A. Spector, Claudia D. Spies, Wolfdieter Springer, Daret St Clair, Alessandra Stacchiotti, Bart Staels, Michael T. Stang, Daniel T. Starczynowski, Petro Starokadomskyy, Clemens Steegborn, John W. Steele, Leonidas Stefanis, Joan Steffan, Christine M. Stellrecht, Harald Stenmark, Tomasz M. Stepkowski, Stęphan T. Stern, Craig Stevens, Brent R. Stockwell, Veronika Stoka, Zuzana Storchova, Björn Stork, Vassilis Stratoulias, Dimitrios J. Stravopodis, 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 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. Titorenko, Lilach Toker, Stefano Toldo, Sharon A. Tooze, Ivan Topisirovic, Maria Lyngaas Torgersen, Liliana Torosantucci, Alicia Torriglia, Maria Rosaria Torrisi, Cathy Tournier, Roberto Towns, Vladimir Trajkovic, Leonardo H. Travassos, Gemma Triola, Durga Nand Tripathi, Daniela Trisciuoglio, Rodrigo Troncoso, Ioannis P. Trougakos, 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 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., Brito, G., Brodin, B., Brookes, P., Brown, E., Brown, K., Broxmeyer, H., Bruhat, A., Brum, P., Brumell, J., Brunetti-Pierri, N., Bryson-Richardson, R., Buch, S., Buchan, A., Budak, H., Bulavin, D., Bultman, S., Bultynck, G., Bumbasirevic, V., Burelle, Y., Burke, R., Burmeister, M., Bütikofer, P., Caberlotto, L., Cadwell, K., Cahova, M., Cai, D., Cai, J., Cai, Q., Calatayud, S., Camougrand, N., Campanella, M., Campbell, G., Campbell, M., Campello, S., Candau, R., Caniggia, I., Cantoni, L., Cao, L., Caplan, A., Caraglia, M., Cardinali, C., Cardoso, S., Carew, J., Carleton, L., Carlin, C., Carloni, S., Carlsson, S., Carmona-Gutierrez, D., Carneiro, L., 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, A., Ceña, V., Cenci, S., Cerella, C., Cervia, D., Cetrullo, S., Chaachouay, H., Chae, H., Chagin, A., Chai, C., Chakrabarti, G., Chamilos, G., Chan, E., Chan, M., Chandra, D., Chandra, P., Chang, C., Chang, R., Chang, T., Chatham, J., Chatterjee, S., Chauhan, S., Che, Y., Cheetham, M., Cheluvappa, R., Chen, C., Chen, G., Chen, H., Chen, J., Chen, M., Chen, P., Chen, Q., Chen, S., Chen, W., Chen, X., Chen, Y., Chen, Z., Cheng, A., Cheng, C., Cheng, H., Cheong, H., Cherry, S., Chesney, J., Cheung, C., Chevet, E., Chi, H., Chi, S., Chiacchiera, F., Chiang, H., Chiarelli, R., Chiariello, M., Chieppa, M., Chin, L., Chiong, M., Chiu, G., Cho, D., Cho, S., Cho, W., Cho, Y., Choi, A., Choi, E., Choi, J., Choi, M., Choi, S., Chou, T., Chouaib, S., Choubey, D., Choubey, V., Chow, K., Chowdhury, K., Chu, C., Chuang, T., Chun, T., Chung, H., Chung, T., Chung, Y., Chwae, Y., Cianfanelli, V., Ciarcia, R., Ciechomska, I., Ciriolo, M., Cirone, M., Claerhout, S., Clague, M., Clària, J., Clarke, P., Clarke, R., Clementi, E., Cleyrat, C., Cnop, M., Coccia, E., Cocco, T., Codogno, P., Coers, J., Cohen, E., Colecchia, D., Coletto, L., Coll, N., Colucci-Guyon, E., Comincini, S., Condello, M., Cook, K., Coombs, G., Cooper, C., Cooper, J., Coppens, I., Corasaniti, M., Corazzari, M., Corbalan, R., Corcelle-Termeau, E., Cordero, M., Corral-Ramos, C., Corti, O., Cossarizza, A., Costelli, P., Costes, S., Cotman, S., Coto-Montes, A., Cottet, S., Couve, E., Covey, L., Cowart, L., Cox, J., Coxon, F., Coyne, C., Cragg, M., Craven, R., Crepaldi, T., Crespo, J., Criollo, A., Crippa, V., Cruz, M., Cuervo, A., Cuezva, J., Cui, T., Cutillas, P., Czaja, M., Czyzyk-Krzeska, M., Dagda, R., Dahmen, U., Dai, C., Dai, W., Dai, Y., Dalby, K., Dalla Valle, L., Dalmasso, G., D'Amelio, M., Damme, M., Darfeuille-Michaud, A., Dargemont, C., Darley-Usmar, V., Dasarathy, S., Dasgupta, B., Dash, S., Dass, C., Davey, H., Davids, L., Dávila, D., Davis, R., Dawson, T., Dawson, V., Daza, P., de Belleroche, J., de Figueiredo, P., de Figueiredo, R., de la Fuente, J., De Martino, L., De Matteis, A., De Meyer, G., De Milito, A., De Santi, M., de Souza, W., De Tata, V., De Zio, D., Debnath, J., Dechant, R., Decuypere, J., Deegan, S., Dehay, B., Del Bello, B., Del Re, D., Delage-Mourroux, R., Delbridge, L., Deldicque, L., Delorme-Axford, E., Deng, Y., Dengjel, J., Denizot, M., Dent, P., Der, C., Deretic, V., Derrien, B., Deutsch, E., Devarenne, T., Devenish, R., 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, M., Diaz-Nido, J., Dickey, C., Dickson, R., Diederich, M., Digard, P., Dikic, I., Dinesh-Kumar, S., Ding, C., Ding, W., Ding, Z., Dini, L., Distler, J., Diwan, A., Djavaheri-Mergny, M., Dmytruk, K., Dobson, R., Doetsch, V., Dokladny, K., Dokudovskaya, S., Donadelli, M., Dong, X., Dong, Z., Donohue, T., Doran, K., D'Orazi, G., Dorn, G., Dosenko, V., Dridi, S., Drucker, L., Du, J., Du, L., du Toit, A., Dua, P., Duan, L., Duann, P., Dubey, V., Duchen, M., Duchosal, M., Duez, H., Dugail, I., Dumit, V., Duncan, M., Dunlop, E., Dunn, W., Dupont, N., Dupuis, L., Durán, R., Durcan, T., Duvezin-Caubet, S., Duvvuri, U., Eapen, V., Ebrahimi-Fakhari, D., Echard, A., Eckhart, L., Edelstein, C., Edinger, A., Eichinger, L., Eisenberg, T., Eisenberg-Lerner, A., Eissa, N., El-Deiry, W., El-Khoury, V., Elazar, Z., Eldar-Finkelman, H., Elliott, C., Emanuele, E., Emmenegger, U., Engedal, N., Engelbrecht, A., Engelender, S., Enserink, J., Erdmann, R., Erenpreisa, J., Eri, R., Eriksen, J., Erman, A., Escalante, R., Eskelinen, E., Espert, L., Esteban-Martínez, L., Evans, T., Fabri, M., Fabrias, G., Fabrizi, C., Facchiano, A., Færgeman, N., Faggioni, A., Fairlie, W., Fan, C., Fan, D., Fan, J., Fang, S., Fanto, M., Fanzani, A., Farkas, T., Faure, M., Favier, F., Fearnhead, H., Federici, M., Fei, E., Felizardo, T., Feng, H., Feng, Y., Ferguson, T., Fernández, Á., Fernandez-Barrena, M., Fernandez-Checa, J., Fernández-López, A., Fernandez-Zapico, M., Feron, O., Ferraro, E., Ferreira-Halder, C., Fesus, L., Feuer, R., Fiesel, F., Filippi-Chiela, E., Filomeni, G., Fimia, G., Fingert, J., Finkbeiner, S., Finkel, T., Fiorito, F., Fisher, P., Flajolet, M., Flamigni, F., Florey, O., Florio, S., Floto, R., Folini, M., Follo, C., Fon, E., Fornai, F., Fortunato, F., Fraldi, A., Franco, R., Francois, A., François, A., Frankel, L., Fraser, I., Frey, N., Freyssenet, D., Frezza, C., Friedman, S., Frigo, D., Fu, D., Fuentes, J., 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, M., Galliciotti, G., Galluzzi, L., Galy, V., Gammoh, N., Gandy, S., Ganesan, A., Ganesan, S., Ganley, I., Gannagé, M., Gao, F., Gao, J., García Nannig, L., García Véscovi, E., Garcia-Macía, M., Garcia-Ruiz, C., Garg, A., Garg, P., Gargini, R., Gassen, N., Gatica, D., Gatti, E., Gavard, J., Gavathiotis, E., Ge, L., Ge, P., Ge, S., Gean, P., Gelmetti, V., Genazzani, A., Geng, J., Genschik, P., Gerner, L., Gestwicki, J., Gewirtz, D., Ghavami, S., Ghigo, E., Ghosh, D., Giammarioli, A., Giampieri, F., Giampietri, C., Giatromanolaki, A., Gibbings, D., Gibellini, L., Gibson, S., Ginet, V., Giordano, A., Giorgini, F., Giovannetti, E., Girardin, S., Gispert, S., Giuliano, S., Gladson, C., Glavic, A., Gleave, M., Godefroy, N., Gogal, R., Gokulan, K., Goldman, G., Goletti, D., Goligorsky, M., Gomes, A., Gomes, L., Gomez, H., Gomez-Manzano, C., Gómez-Sánchez, R., Gonçalves, D., Goncu, E., Gong, Q., Gongora, C., Gonzalez, C., Gonzalez-Alegre, P., Gonzalez-Cabo, P., González-Polo, R., Goping, I., Gorbea, C., Gorbunov, N., Goring, D., Gorman, A., Gorski, S., Goruppi, S., Goto-Yamada, S., Gotor, C., Gottlieb, R., Gozes, I., Gozuacik, D., Graba, Y., Graef, M., Granato, G., Grant, G., Grant, S., Gravina, G., Green, D., Greenhough, A., Greenwood, M., Grimaldi, B., Gros, F., Grose, C., Groulx, J., Gruber, F., Grumati, P., Grune, T., Guan, J., Guan, K., Guerra, B., Guillen, C., Gulshan, K., Gunst, J., Guo, C., Guo, L., Guo, M., Guo, 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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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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, 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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, 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 Coer, Ezra EW Cohen, David Colecchia, Luisa Coletto, Núria S Coll, Emma Colucci-Guyon, Sergio Comincini, Maria Condello, Katherine L Cook, Graham H Coomb, Cynthia D Cooper, J Mark Cooper, Isabelle Coppen, Maria Tiziana Corasaniti, Marco Corazzari, Ramon Corbalan, Elisabeth Corcelle-Termeau, Mario D Cordero, Cristina Corral-Ramo, Olga Corti, Andrea Cossarizza, Paola Costelli, Safia Coste, Susan L Cotman, Ana Coto-Monte, 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 Cutilla, 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, 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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
Subjects: [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.
Published: 2016
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43. Sequencing Angiosperm Plastid Genomes Made Easy: A Complete Set of Universal Primers and a Case Study on the Phylogeny of Saxifragales

Author: Shiliang Zhou, Chao Xu, Wenpan Dong, Tao Cheng, and Kui Lin
Subjects: Genome, Plastid, Biology, Genome, law.invention, Evolution, Molecular, Magnoliopsida, Phylogenetics, law, universal primers, plastid genome, Genetics, Plastids, Saxifragales, Phylogeny, Ecology, Evolution, Behavior and Systematics, Polymerase chain reaction, DNA Primers, Base Sequence, Phylogenetic tree, fungi, High-Throughput Nucleotide Sequencing, food and beverages, biology.organism_classification, Chloroplast, Evolutionary biology, GenBank, Molecular phylogenetics, Research Article
Abstract: Plastid genomes are an invaluable resource for plant biological studies. However, the number of completely sequenced plant plastid genomes is still small compared with the vast number of species. To provide an alternative generalized approach, we designed a set of 138 pairs of universal primers for amplifying (termed "short-range PCR") and sequencing the entire genomes of the angiosperm plastid genomes. The universality of the primers was tested by using species from the basal to asterid angiosperms. The polymerase chain reaction (PCR) success rate was higher than 96%. We sequenced the complete chloroplast genome of Liquidambar formosana as an example using this method and compared it to the genomes independently determined by long-range PCR (from 6.3 kb to 13.3 kb) and next-generation sequencing methods. The three genomes showed that they were completely identical. To test the phylogenetic efficiency of this method, we amplified and sequenced 18 chloroplast regions of 19 Saxifragales and Saxifragales-related taxa, as a case study, to reconstruct the phylogeny of all families of the order. Phylograms based on a combination of our data, together with those from GenBank, clearly indicate three family groups and three single families within the order. This set of universal primers is expected to accelerate the accumulation of angiosperm plastid genomes and to make faster mass data collection of plastid genomes for molecular systematics.
Published: 2013
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44. Targeting Activated Akt with GDC-0068, a Novel Selective Akt Inhibitor That Is Efficacious in Multiple Tumor Models

Author: Nicholas J. Skelton, Hartmut Koeppen, Heidi Savage, Jeffrey Wallin, Tyler Risom, Jason Oeh, Bianca M. Liederer, Lori Friedman, Kui Lin, Stefan D. Gross, Michael Degtyarev, Robert Kassees, Rebecca Hong, Marcia Belvin, Zhengyu Guan, Deepak Sampath, Michelle Nannini, Leslie Lee, Elizabeth Punnoose, Brian Lee, and Jie Lin
Subjects: Male, Cancer Research, Antineoplastic Agents, Apoptosis, Pharmacology, Biology, Ipatasertib, Piperazines, Mice, In vivo, Cell Line, Tumor, Neoplasms, medicine, Animals, Humans, PTEN, Protein Kinase Inhibitors, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, Cancer, medicine.disease, Xenograft Model Antitumor Assays, Enzyme Activation, Disease Models, Animal, Pyrimidines, Oncology, Cell culture, biology.protein, Phosphorylation, Female, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract: Purpose: We describe the preclinical pharmacology and antitumor activity of GDC-0068, a novel highly selective ATP-competitive pan-Akt inhibitor currently in clinical trials for the treatment of human cancers. Experimental Design: The effect of GDC-0068 on Akt signaling was characterized using specific biomarkers of the Akt pathway, and response to GDC-0068 was evaluated in human cancer cell lines and xenograft models with various genetic backgrounds, either as a single agent or in combination with chemotherapeutic agents. Results: GDC-0068 blocked Akt signaling both in cultured human cancer cell lines and in tumor xenograft models as evidenced by dose-dependent decrease in phosphorylation of downstream targets. Inhibition of Akt activity by GDC-0068 resulted in blockade of cell-cycle progression and reduced viability of cancer cell lines. Markers of Akt activation, including high-basal phospho-Akt levels, PTEN loss, and PIK3CA kinase domain mutations, correlate with sensitivity to GDC-0068. Isogenic PTEN knockout also sensitized MCF10A cells to GDC-0068. In multiple tumor xenograft models, oral administration of GDC-0068 resulted in antitumor activity ranging from tumor growth delay to regression. Consistent with the role of Akt in a survival pathway, GDC-0068 also enhanced antitumor activity of classic chemotherapeutic agents. Conclusions: GDC-0068 is a highly selective, orally bioavailable Akt kinase inhibitor that shows pharmacodynamic inhibition of Akt signaling and robust antitumor activity in human cancer cells in vitro and in vivo. Our preclinical data provide a strong mechanistic rationale to evaluate GDC-0068 in cancers with activated Akt signaling. Clin Cancer Res; 19(7); 1760–72. ©2012 AACR.
Published: 2013
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45. A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors

Author: Jin Zhu, Teresa Macarulla, Premal Patel, Juan Manuel Sanchís-García, Susana Roselló, Luna Musib, Wai Y. Chan, José Baselga, Rafael Morales-Barrera, Yibing Yan, Sandra Sanabria Bohorquez, Raymond D. Meng, Desamparados Roda, Nageshwar Budha, Josep Tabernero, Mafalda Oliveira, Jose Alejandro Perez-Fidalgo, Andrés Cervantes, Kui Lin, Michelle Nannini, and Cristina Saura
Subjects: Adult, Male, 0301 basic medicine, Proto-Oncogene Proteins c-akt, Administration, Oral, Pharmacology, Ipatasertib, Drug Administration Schedule, Piperazines, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Neoplasms, Humans, PTEN, Medicine, Protein Kinase Inhibitors, Protein kinase B, PI3K/AKT/mTOR pathway, Aged, biology, business.industry, Middle Aged, Xenograft Model Antitumor Assays, Small molecule, Pyrimidines, 030104 developmental biology, Oncology, Cell culture, 030220 oncology & carcinogenesis, Pharmacodynamics, biology.protein, Female, business
Abstract: Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers, but targeting AKT has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of AKT. Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of AKT that preferentially targets active phosphorylated AKT (pAKT) and is potent in cell lines with evidence of AKT activation. In this phase I study, ipatasertib was well tolerated; most adverse events were gastrointestinal and grade 1–2 in severity. The exposures of ipatasertib ≥200 mg daily in patients correlated with preclinical TGI90, and pharmacodynamic studies confirmed that multiple targets (i.e., PRAS40, GSK3β, and mTOR) were inhibited in paired on-treatment biopsies. Preliminary antitumor activity was observed; 16 of 52 patients (30%), with diverse solid tumors and who progressed on prior therapies, had radiographic stable disease, and many of their tumors had activation of AKT. Significance: Potent inhibition of AKT signaling with ipatasertib was associated with a tolerable safety profile and meaningful disease control in a subgroup of patients. Targeting pAKT with an ATP-competitive inhibitor provides a greater therapeutic window than allosteric inhibitors. Further investigation with ipatasertib is ongoing in phase II studies. Cancer Discov; 7(1); 102–13. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 1
Published: 2017

46. Structural and computational studies of the maleate isomerase fromPseudomonas putidaS16 reveal a breathing motion wrapping the substrate inside

Author: Hongzhi Tang, Ping Xu, Kunlong Shen, Duoduo Chen, Yi-Lei Zhao, Geng Wu, Kui Lin, Yang Lv, and Zhenyi Zhang
Subjects: Maleate isomerase, biology, Stereochemistry, Pseudomonas, Wild type, Active site, Substrate (chemistry), Isomerase, biology.organism_classification, Microbiology, Pseudomonas putida, Protein structure, Biochemistry, biology.protein, Molecular Biology
Abstract: Summary Nicotine is an environmental toxicant in tobacco waste, imposing a serious hazard for human health. Some bacteria including Pseudomonas spp. strains are able to metabolize nicotine to non-toxic compounds. The pyrrolidine pathway of nicotine degradation in Pseudomonas putida S16 has recently been revealed. The maleate isomerase (Pp-Iso) catalyses the last step in nicotine degradation of P. putida S16, the cis-trans isomerization of maleate to fumarate. In this study, we determined the crystal structures of both wild type isomerase by itself and its C200A point mutant in complex with its substrate maleate, to resolutions of 2.95 A and 2.10 A respectively. Our structures reveal that Asn17 and Asn169 play critical roles in recognizing the maleate by site-directed mutants' analysis. Surprisingly, our structure shows that the maleate is completely wrapped inside the isomerase. Examination of the structure prompted us to hypothesize that the β2-α2 loop and the β6-α7 loop have a breathing motion that regulates substrate/solvent entry and product departure. Our results of molecular dynamics simulation and enzymatic activity assay are fully consistent with this hypothesis. The isomerase probably uses this breathing motion to prevent the solvent from entering the active site and prohibit unproductive side reactions from happening.
Published: 2013
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47. Differential variation patterns between hubs and bottlenecks in human protein-protein interaction networks

Author: Kui Lin, Yu Hao, Ying Sun, and Erli Pang
Subjects: 0301 basic medicine, Physics::Physics and Society, Systems biology, Variation (game tree), Computational biology, Biology, Protein protein interaction network, Evolution, Molecular, 03 medical and health sciences, Protein Domains, Interaction network, Protein Interaction Mapping, Humans, natural sciences, Protein Interaction Maps, Ecology, Evolution, Behavior and Systematics, Bottlenecks, Variation rate, Ecology, Genome, Human, Quantitative Biology::Molecular Networks, A protein, food and beverages, Genetic Variation, Proteins, Differential (mechanical device), Computer Science::Social and Information Networks, social sciences, Protein interaction network, 030104 developmental biology, Hubs, Protein Interaction Networks, Biological structure, population characteristics, Research Article
Abstract: Background The identification, description and understanding of protein-protein networks are important in cell biology and medicine, especially for the study of system biology where the focus concerns the interaction of biomolecules. Hubs and bottlenecks refer to the important proteins of a protein interaction network. Until now, very little attention has been paid to differentiate these two protein groups. Results By integrating human protein-protein interaction networks and human genome-wide variations across populations, we described the differences between hubs and bottlenecks in this study. Our findings showed that similar to interspecies, hubs and bottlenecks changed significantly more slowly than non-hubs and non-bottlenecks. To distinguish hubs from bottlenecks, we extracted their special members: hub-non-bottlenecks and non-hub-bottlenecks. The differences between these two groups represent what is between hubs and bottlenecks. We found that the variation rate of hubs was significantly lower than that of bottlenecks. In addition, we verified that stronger constraint is exerted on hubs than on bottlenecks. We further observed fewer non-synonymous sites on the domains of hubs than on those of bottlenecks and different molecular functions between them. Conclusions Based on these results, we conclude that in recent human history, different variation patterns exist in hubs and bottlenecks in protein interaction networks. By revealing the difference between hubs and bottlenecks, our results might provide further insights in the relationship between evolution and biological structure. Electronic supplementary material The online version of this article (doi:10.1186/s12862-016-0840-8) contains supplementary material, which is available to authorized users.
Published: 2016

48. Hierarchical Map of Orthologous Genomic Regions Reconstructed from Two Closely Related Genomes: Cucumber Case Study

Author: Huifen Cao, Erli Pang, and Kui Lin
Subjects: 0106 biological sciences, 0301 basic medicine, lcsh:QH426-470, Genomics, Plant Science, Computational biology, lcsh:Plant culture, Subspecies, Biology, 01 natural sciences, Genome, 03 medical and health sciences, Botany, Genetics, lcsh:SB1-1110, Chromosome Mapping, Phenotype, lcsh:Genetics, 030104 developmental biology, Identification (biology), Cucumis sativus, Agronomy and Crop Science, Genome, Plant, 010606 plant biology & botany
Abstract: Accurate identification of orthologous genomic regions (OGRs) between two closely related genomes is crucial for the reliable detection of genomic changes, which range from small-scale changes (e.g., single nucleotide or small nucleotides) to large-scale structural changes. Although diverse OGRs inferred at different levels have been successfully applied to address various biological questions, a limited number of studies have simultaneously integrated OGRs from different levels. Here, we report on a new approach to construct a hierarchical map of OGRs. Using different types of genomic markers, this approach was applied to two very closely related cucumber genomes [ L. var. and L. var. (Royle) Alef.]. We identified two different levels of OGRs using Mugsy (denoted as dnaOGRs) and i-ADHoRe (denoted as proOGRs). Using information regarding the anchored chromosomes of the two genomes, a third level of OGRs (denoted chrOGRs) could be built at the chromosomal level. Together, these OGRs could be organized into a hierarchical map that represented the parent–child relationships (chrOGR:proOGRs:dnaOGRs) between the two genomes. For this case study, the map consisted of seven chrOGRs, 540 proOGRs, and 22,321 dnaOGRs. Based on this map, we designed different methods to detect both small-scale and large-scale genomic changes. Surprisingly, many genomic changes were detected at each OGR level despite the very short divergence time between the two subspecies. Together, our results show that a hierarchical map of OGRs and their related genomic changes are useful resources for elucidating the diversity and evolution of cucumber genomes and phenotypes.
Published: 2016
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49. PHYSIOLOGICAL, MOLECULAR AND GENETIC CONTROL OF APPLE SKIN COLOURATION UNDER HOT TEMPERATURE ENVIRONMENTS

Author: M. Troggio, David Chagné, A. White, Satish Kumar, Lidia Lozano, Joan Bonany, Andrew C. Allan, J.W. Palmer, Diego Micheletti, Kui Lin-Wang, Richard K. Volz, and I. Iglesias
Subjects: Botany, Horticulture, Biology, Hot Temperature
Published: 2012
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50. Demographic trade-offs determine species abundance and diversity

Author: Fangliang He, Da-Yong Zhang, Boyu Zhang, Kui Lin, Xin-Hua Jiang, Stephen P. Hubbell, Yi Tao, and Annette Ostling
Subjects: Coexistence theory, Metacommunity, Ecology, Biodiversity, Species diversity, Plant Science, Biology, Econometrics, Per capita, Neutral theory of molecular evolution, Relative species abundance, Ecology, Evolution, Behavior and Systematics, Diversity (business)
Abstract: Aims Much recent theory has focused on the role of neutral processes in assembling communities, but the basic assumption that all species are demographically identical has found little empirical support. Here, we show that the framework of the current neutral theory can easily be generalized to incorporate species differences so long as fitness equivalence among individuals is maintained through trade-offs between birth and death. Methods Our theory development is based on a careful reformulation of the Moran model of metacommunity dynamics in terms of a non-linear one-step stochastic process,which is describedbyamaster equation. Important Findings We demonstrate how fitness equalization through demographic trade-offs can generate significant macroecological diversity patterns,leadingtoaverydifferentinterpretation oftherelationbetween Fisher’s a and Hubbell’s fundamental biodiversity number. Our model shows that equal fitness (not equal demographics) significantly promotes species diversity through strong selective sieving of community membership against high-mortality species, resulting in a positive association between species abundance and per capita death rate. An important implication of demographic trade-off is that it can partly explain the excessively high speciation rates predicted by the neutral theory of the stronger symmetry. Fitness equalization through demographic trade-offs generalizes neutral theory by considering heterospecific demographic difference, thus representing a significant step toward integrating the neutral and niche paradigms of biodiversity.
Published: 2012
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