43 results on '"Xin, Yi"'
Search Results
2. CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation
- Author
-
Shang-Ze Li, Qi-Peng Shu, Hai-Meng Zhou, Yu-Ying Liu, Meng-Qi Fan, Xin-Yi Liang, Lin-Zhi Qi, Ya-Nan He, Xue-Yi Liu, Xue-Hua Du, Xi-Chen Huang, Yu-Zhen Chen, Run-Lei Du, Yue-Xiu Liang, and Xiao-Dong Zhang
- Subjects
Science - Abstract
Abstract Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.
- Published
- 2024
- Full Text
- View/download PDF
3. Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system
- Author
-
Jun-Tao Zhang, Xiao-Yu Liu, Zhuolin Li, Xin-Yang Wei, Xin-Yi Song, Ning Cui, Jirui Zhong, Hongchun Li, and Ning Jia
- Subjects
Science - Abstract
Abstract Silent information regulator 2 (Sir2) proteins typically catalyze NAD+-dependent protein deacetylation. The recently identified bacterial Sir2 domain-containing protein, defense-associated sirtuin 2 (DSR2), recognizes the phage tail tube and depletes NAD+ to abort phage propagation, which is counteracted by the phage-encoded DSR anti-defense 1 (DSAD1), but their molecular mechanisms remain unclear. Here, we determine cryo-EM structures of inactive DSR2 in its apo form, DSR2–DSAD1 and DSR2–DSAD1–NAD+, as well as active DSR2–tube and DSR2–tube–NAD+ complexes. DSR2 forms a tetramer with its C-terminal sensor domains (CTDs) in two distinct conformations: CTDclosed or CTDopen. Monomeric, rather than oligomeric, tail tube proteins preferentially bind to CTDclosed and activate Sir2 for NAD+ hydrolysis. DSAD1 binding to CTDopen allosterically inhibits tube binding and tube-mediated DSR2 activation. Our findings provide mechanistic insight into DSR2 assembly, tube-mediated DSR2 activation, and DSAD1-mediated inhibition and NAD+ substrate catalysis in bacterial DSR2 anti-phage defense systems.
- Published
- 2024
- Full Text
- View/download PDF
4. Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy
- Author
-
Jiefei Han, Yiting Dong, Xiuli Zhu, Alexandre Reuben, Jianjun Zhang, Jiachen Xu, Hua Bai, Jianchun Duan, Rui Wan, Jie Zhao, Jing Bai, Xuefeng Xia, Xin Yi, Chao Cheng, Jie Wang, and Zhijie Wang
- Subjects
Science - Abstract
Abstract Despite the central role of human leukocyte antigen class I (HLA-I) in tumor neoantigen presentation, quantitative determination of presentation capacity remains elusive. Based on a pooled pan-cancer genomic dataset of 885 patients treated with immune checkpoint inhibitors (ICIs), we developed a score integrating the binding affinity of neoantigens to HLA-I, as well as HLA-I allele divergence, termed the HLA tumor-Antigen Presentation Score (HAPS). Patients with a high HAPS were more likely to experience survival benefit following ICI treatment. Analysis of the tumor microenvironment indicated that the antigen presentation pathway was enriched in patients with a high HAPS. Finally, we built a neural network incorporating factors associated with neoantigen production, presentation, and recognition, which exhibited potential for differentiating cancer patients likely to benefit from ICIs. Our findings highlight the clinical utility of evaluating HLA-I tumor antigen presentation capacity and describe how ICI response may depend on HLA-mediated immunity.
- Published
- 2024
- Full Text
- View/download PDF
5. A transcriptome based molecular classification scheme for cholangiocarcinoma and subtype-derived prognostic biomarker
- Author
-
Zhongqi Fan, Xinchen Zou, Guangyi Wang, Yahui Liu, Yanfang Jiang, Haoyan Wang, Ping Zhang, Feng Wei, Xiaohong Du, Meng Wang, Xiaodong Sun, Bai Ji, Xintong Hu, Liguo Chen, Peiwen Zhou, Duo Wang, Jing Bai, Xiao Xiao, Lijiao Zuo, Xuefeng Xia, Xin Yi, and Guoyue Lv
- Subjects
Science - Abstract
Abstract Previous studies on the molecular classification of cholangiocarcinoma (CCA) focused on certain anatomical sites, and disregarded tissue contamination biases in transcriptomic profiles. We aim to provide universal molecular classification scheme and prognostic biomarker of CCAs across anatomical locations. Comprehensive bioinformatics analysis is performed on transcriptomic data from 438 CCA cases across various anatomical locations. After excluding CCA tumors showing normal tissue expression patterns, we identify two universal molecular subtypes across anatomical subtypes, explore the molecular, clinical, and microenvironmental features of each class. Subsequently, a 30-gene classifier and a biomarker (called “CORE-37”) are developed to predict the molecular subtype of CCA and prognosis, respectively. Two subtypes display distinct molecular characteristics and survival outcomes. Key findings are validated in external cohorts regardless of the stage and anatomical location. Our study provides a CCA classification scheme that complements the conventional anatomy-based classification and presents a promising prognostic biomarker for clinical application.
- Published
- 2024
- Full Text
- View/download PDF
6. Ground-state electron transfer in all-polymer donor:acceptor blends enables aqueous processing of water-insoluble conjugated polymers
- Author
-
Tiefeng Liu, Johanna Heimonen, Qilun Zhang, Chi-Yuan Yang, Jun-Da Huang, Han-Yan Wu, Marc-Antoine Stoeckel, Tom P. A. van der Pol, Yuxuan Li, Sang Young Jeong, Adam Marks, Xin-Yi Wang, Yuttapoom Puttisong, Asaminew Y. Shimolo, Xianjie Liu, Silan Zhang, Qifan Li, Matteo Massetti, Weimin M. Chen, Han Young Woo, Jian Pei, Iain McCulloch, Feng Gao, Mats Fahlman, Renee Kroon, and Simone Fabiano
- Subjects
Science - Abstract
Abstract Water-based conductive inks are vital for the sustainable manufacturing and widespread adoption of organic electronic devices. Traditional methods to produce waterborne conductive polymers involve modifying their backbone with hydrophilic side chains or using surfactants to form and stabilize aqueous nanoparticle dispersions. However, these chemical approaches are not always feasible and can lead to poor material/device performance. Here, we demonstrate that ground-state electron transfer (GSET) between donor and acceptor polymers allows the processing of water-insoluble polymers from water. This approach enables macromolecular charge-transfer salts with 10,000× higher electrical conductivities than pristine polymers, low work function, and excellent thermal/solvent stability. These waterborne conductive films have technological implications for realizing high-performance organic solar cells, with efficiency and stability superior to conventional metal oxide electron transport layers, and organic electrochemical neurons with biorealistic firing frequency. Our findings demonstrate that GSET offers a promising avenue to develop water-based conductive inks for various applications in organic electronics.
- Published
- 2023
- Full Text
- View/download PDF
7. D-serine reconstitutes synaptic and intrinsic inhibitory control of pyramidal neurons in a neurodevelopmental mouse model for schizophrenia
- Author
-
Xiao-Qin Zhang, Le Xu, Xin-Yi Zhu, Zi-Hang Tang, Yi-Bei Dong, Zhi-Peng Yu, Qing Shang, Zheng-Chun Wang, and Hao-Wei Shen
- Subjects
Science - Abstract
Abstract The hypothesis of N-methyl-D-aspartate receptor (NMDAR) dysfunction for cognitive impairment in schizophrenia constitutes the theoretical basis for the translational application of NMDAR co-agonist D-serine or its analogs. However, the cellular mechanism underlying the therapeutic effect of D-serine remains unclear. In this study, we utilize a mouse neurodevelopmental model for schizophrenia that mimics prenatal pathogenesis and exhibits hypoexcitability of parvalbumin-positive (PV) neurons, as well as PV-preferential NMDAR dysfunction. We find that D-serine restores excitation/inhibition balance by reconstituting both synaptic and intrinsic inhibitory control of cingulate pyramidal neurons through facilitating PV excitability and activating small-conductance Ca2+-activated K+ (SK) channels in pyramidal neurons, respectively. Either amplifying inhibitory drive via directly strengthening PV neuron activity or inhibiting pyramidal excitability via activating SK channels is sufficient to improve cognitive function in this model. These findings unveil a dual mechanism for how D-serine improves cognitive function in this model.
- Published
- 2023
- Full Text
- View/download PDF
8. Identification of errors in draft genome assemblies at single-nucleotide resolution for quality assessment and improvement
- Author
-
Kunpeng Li, Peng Xu, Jinpeng Wang, Xin Yi, and Yuannian Jiao
- Subjects
Science - Abstract
Abstract Assembly of a high-quality genome is important for downstream comparative and functional genomic studies. However, most tools for genome assembly assessment only give qualitative reports, which do not pinpoint assembly errors at specific regions. Here, we develop a new reference-free tool, Clipping information for Revealing Assembly Quality (CRAQ), which maps raw reads back to assembled sequences to identify regional and structural assembly errors based on effective clipped alignment information. Error counts are transformed into corresponding assembly evaluation indexes to reflect the assembly quality at single-nucleotide resolution. Notably, CRAQ distinguishes assembly errors from heterozygous sites or structural differences between haplotypes. This tool can clearly indicate low-quality regions and potential structural error breakpoints; thus, it can identify misjoined regions that should be split for further scaffold building and improvement of the assembly. We have benchmarked CRAQ on multiple genomes assembled using different strategies, and demonstrated the misjoin correction for improving the constructed pseudomolecules.
- Published
- 2023
- Full Text
- View/download PDF
9. Ground-state electron transfer in all-polymer donor:acceptor blends enables aqueous processing of water-insoluble conjugated polymers
- Author
-
Liu, Tiefeng, Heimonen, Johanna, Zhang, Qilun, Yang, Chi-Yuan, Huang, Jun-Da, Wu, Han-Yan, Stoeckel, Marc-Antoine, van der Pol, Tom P. A., Li, Yuxuan, Jeong, Sang Young, Marks, Adam, Wang, Xin-Yi, Puttisong, Yuttapoom, Shimolo, Asaminew Y., Liu, Xianjie, Zhang, Silan, Li, Qifan, Massetti, Matteo, Chen, Weimin M., Woo, Han Young, Pei, Jian, McCulloch, Iain, Gao, Feng, Fahlman, Mats, Kroon, Renee, and Fabiano, Simone
- Published
- 2023
- Full Text
- View/download PDF
10. D-serine reconstitutes synaptic and intrinsic inhibitory control of pyramidal neurons in a neurodevelopmental mouse model for schizophrenia
- Author
-
Zhang, Xiao-Qin, Xu, Le, Zhu, Xin-Yi, Tang, Zi-Hang, Dong, Yi-Bei, Yu, Zhi-Peng, Shang, Qing, Wang, Zheng-Chun, and Shen, Hao-Wei
- Published
- 2023
- Full Text
- View/download PDF
11. Visualizing the multi-level assembly structures of conjugated molecular systems with chain-length dependent behavior
- Author
-
Yang-Yang Zhou, Yu-Chun Xu, Ze-Fan Yao, Jia-Ye Li, Chen-Kai Pan, Yang Lu, Chi-Yuan Yang, Li Ding, Bu-Fan Xiao, Xin-Yi Wang, Yu Shao, Wen-Bin Zhang, Jie-Yu Wang, Huan Wang, and Jian Pei
- Subjects
Science - Abstract
Abstract It remains challenging to understand the structural evolution of conjugated polymers from single chains to solvated aggregates and film microstructures, although it underpins the performance of optoelectrical devices fabricated via the mainstream solution processing method. With several ensemble visual measurements, here we unravel the morphological evolution process of a model system of isoindigo-based conjugated molecules, including the hidden molecular assembly pathways, the mesoscale network formation, and their unorthodox chain dependence. Short chains show rigid chain conformations forming discrete aggregates in solution, which further grow to form a highly ordered film that exhibits poor electrical performance. In contrast, long chains exhibit flexible chain conformations, creating interlinked aggregates networks in solution, which are directly imprinted into films, forming interconnective solid-state microstructure with excellent electrical performance. Visualizing multi-level assembly structures of conjugated molecules provides a deep understanding of the inheritance of assemblies from solution to solid-state, accelerating the optimization of device fabrication.
- Published
- 2023
- Full Text
- View/download PDF
12. Insular cortical circuits as an executive gateway to decipher threat or extinction memory via distinct subcortical pathways
- Author
-
Qi Wang, Jia-Jie Zhu, Lizhao Wang, Yan-Peng Kan, Yan-Mei Liu, Yan-Jiao Wu, Xue Gu, Xin Yi, Ze-Jie Lin, Qin Wang, Jian-Fei Lu, Qin Jiang, Ying Li, Ming-Gang Liu, Nan-Jie Xu, Michael X. Zhu, Lu-Yang Wang, Siyu Zhang, Wei-Guang Li, and Tian-Le Xu
- Subjects
Science - Abstract
Ensembles of fear and extinction memories compete and interact to drive opposing behaviors. Here the authors identified insular cortical circuits as an executive gateway that decipher between fear and extinction memories via distinct subcortical pathways.
- Published
- 2022
- Full Text
- View/download PDF
13. CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation
- Author
-
Li, Shang-Ze, primary, Shu, Qi-Peng, additional, Zhou, Hai-Meng, additional, Liu, Yu-Ying, additional, Fan, Meng-Qi, additional, Liang, Xin-Yi, additional, Qi, Lin-Zhi, additional, He, Ya-Nan, additional, Liu, Xue-Yi, additional, Du, Xue-Hua, additional, Huang, Xi-Chen, additional, Chen, Yu-Zhen, additional, Du, Run-Lei, additional, Liang, Yue-Xiu, additional, and Zhang, Xiao-Dong, additional
- Published
- 2024
- Full Text
- View/download PDF
14. LNK suppresses interferon signaling in melanoma.
- Author
-
Ding, Ling-Wen, Sun, Qiao-Yang, Edwards, Jarem J, Fernández, Lucia Torres, Ran, Xue-Bin, Zhou, Si-Qin, Scolyer, Richard A, Wilmott, James S, Thompson, John F, Doan, Ngan, Said, Jonathan W, Venkatachalam, Nachiyappan, Xiao, Jin-Fen, Loh, Xin-Yi, Pein, Maren, Xu, Liang, Mullins, David W, Yang, Henry, Lin, De-Chen, and Koeffler, H Phillip
- Subjects
Cell Line ,Tumor ,Animals ,Mice ,Inbred C57BL ,Mice ,Inbred NOD ,Humans ,Mice ,Mice ,SCID ,Melanoma ,Skin Neoplasms ,Intracellular Signaling Peptides and Proteins ,Proteins ,Interferons ,Xenograft Model Antitumor Assays ,Apoptosis ,STAT1 Transcription Factor ,HEK293 Cells ,Cell Cycle Checkpoints ,Membrane Proteins ,Cell Line ,Tumor ,Inbred C57BL ,Inbred NOD ,SCID - Abstract
LNK (SH2B3) is a key negative regulator of JAK-STAT signaling which has been extensively studied in malignant hematopoietic diseases. We found that LNK is significantly elevated in cutaneous melanoma; this elevation is correlated with hyperactive signaling of the RAS-RAF-MEK pathway. Elevated LNK enhances cell growth and survival in adverse conditions. Forced expression of LNK inhibits signaling by interferon-STAT1 and suppresses interferon (IFN) induced cell cycle arrest and cell apoptosis. In contrast, silencing LNK expression by either shRNA or CRISPR-Cas9 potentiates the killing effect of IFN. The IFN-LNK signaling is tightly regulated by a negative feedback mechanism; melanoma cells exposed to IFN upregulate expression of LNK to prevent overactivation of this signaling pathway. Our study reveals an unappreciated function of LNK in melanoma and highlights the critical role of the IFN-STAT1-LNK signaling axis in this potentially devastating disease. LNK may be further explored as a potential therapeutic target for melanoma immunotherapy.
- Published
- 2019
15. Comprehensive and clinically accurate head and neck cancer organs-at-risk delineation on a multi-institutional study
- Author
-
Ye, Xianghua, Guo, Dazhou, Ge, Jia, Yan, Senxiang, Xin, Yi, Song, Yuchen, Yan, Yongheng, Huang, Bing-shen, Hung, Tsung-Min, Zhu, Zhuotun, Peng, Ling, Ren, Yanping, Liu, Rui, Zhang, Gong, Mao, Mengyuan, Chen, Xiaohua, Lu, Zhongjie, Li, Wenxiang, Chen, Yuzhen, Huang, Lingyun, Xiao, Jing, Harrison, Adam P., Lu, Le, Lin, Chien-Yu, Jin, Dakai, and Ho, Tsung-Ying
- Published
- 2022
- Full Text
- View/download PDF
16. Exploring a blue-light-sensing transcription factor to double the peak productivity of oil in Nannochloropsis oceanica
- Author
-
Zhang, Peng, Xin, Yi, He, Yuehui, Tang, Xianfeng, Shen, Chen, Wang, Qintao, Lv, Nana, Li, Yun, Hu, Qiang, and Xu, Jian
- Published
- 2022
- Full Text
- View/download PDF
17. Clinical and genomic features of Chinese lung cancer patients with germline mutations
- Author
-
Wenying Peng, Bin Li, Jin Li, Lianpeng Chang, Jing Bai, Yuting Yi, Rongrong Chen, Yanyan Zhang, Chen Chen, Xingxiang Pu, Meilin Jiang, Jia Li, Rui Zhong, Fang Xu, Bolin Chen, Li Xu, Ning Wang, Jiaojiao Huan, Pingping Dai, Yanfang Guan, Ling Yang, Xuefeng Xia, Xin Yi, Jiayin Wang, Fenglei Yu, and Lin Wu
- Subjects
Science - Abstract
Germline variants that predispose to lung cancer have been mostly studied in Western populations, but data from Chinese patients is lacking. Here the authors analyze lung cancer germline variants in 1794 Chinese patients, finding exclusive variants or with different frequency compared to TCGA data.
- Published
- 2022
- Full Text
- View/download PDF
18. Multi-region exome sequencing reveals the intratumoral heterogeneity of surgically resected small cell lung cancer
- Author
-
Huaqiang Zhou, Yi Hu, Rongzhen Luo, Yuanyuan Zhao, Hui Pan, Liyan Ji, Ting Zhou, Lanjun Zhang, Hao Long, Jianhua Fu, Zhesheng Wen, Siyu Wang, Xin Wang, Peng Lin, Haoxian Yang, Junye Wang, Mengmeng Song, Xin Yi, Ling Yang, Xuefang Xia, Yanfang Guan, Wenfeng Fang, Yunpeng Yang, Shaodong Hong, Yan Huang, Pansong Li, Yaxiong Zhang, and Ningning Zhou
- Subjects
Science - Abstract
Multi-region sequencing of small cell lung cancers (SCLC) can improve our understanding of the disease. Here the authors analyse 120 multi-region samples from 40 SCLC patients with whole exome sequencing and characterise their mutational burden, evolution, heterogeneity, and potential prognostic biomarkers.
- Published
- 2021
- Full Text
- View/download PDF
19. Valence band engineering of GaAsBi for low noise avalanche photodiodes
- Author
-
Yuchen Liu, Xin Yi, Nicholas J. Bailey, Zhize Zhou, Thomas B. O. Rockett, Leh W. Lim, Chee H. Tan, Robert D. Richards, and John P. R. David
- Subjects
Science - Abstract
An avalanche photodiode is an opto-electronic amplifier that uses impact ionization to provide enhanced sensitivity at the expense of excess noise. In this manuscript, the authors demonstrate that a small amount of Bismuth (Bi) in Gallium Arsenide (GaAs) avalanche photodiodes significantly reduces this excess noise.
- Published
- 2021
- Full Text
- View/download PDF
20. Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection
- Author
-
Zhe Zhao, Huimeng Wang, Mai Shi, Tianyuan Zhu, Troi Pediongco, Xin Yi Lim, Bronwyn S. Meehan, Adam G. Nelson, David P. Fairlie, Jeffrey Y. W. Mak, Sidonia B. G. Eckle, Marcela de Lima Moreira, Carolin Tumpach, Michael Bramhall, Cameron G. Williams, Hyun Jae Lee, Ashraful Haque, Maximilien Evrard, Jamie Rossjohn, James McCluskey, Alexandra J. Corbett, and Zhenjun Chen
- Subjects
Science - Abstract
Mucosal-Associated Invariant T (MAIT) cells are associated with established functions during bacterial infection. Here the authors show inoculation with Francisella tularensis results in induction of MAIT cells associated with prototypic Th1 immunity and confer protection to systemic and local infection.
- Published
- 2021
- Full Text
- View/download PDF
21. Transcriptional signature in microglia associated with Aβ plaque phagocytosis
- Author
-
Alexandra Grubman, Xin Yi Choo, Gabriel Chew, John F. Ouyang, Guizhi Sun, Nathan P. Croft, Fernando J. Rossello, Rebecca Simmons, Sam Buckberry, Dulce Vargas Landin, Jahnvi Pflueger, Teresa H. Vandekolk, Zehra Abay, Yichen Zhou, Xiaodong Liu, Joseph Chen, Michael Larcombe, John M. Haynes, Catriona McLean, Sarah Williams, Siew Yeen Chai, Trevor Wilson, Ryan Lister, Colin W. Pouton, Anthony W. Purcell, Owen J. L. Rackham, Enrico Petretto, and Jose M. Polo
- Subjects
Science - Abstract
Microglia associated with Aβ plaques may have a distinct transcriptional signature compared to those in plaque-free areas of the brain in Alzheimer’s disease (AD) models. Here the authors show that amyloid plaque phagocytosis is associated with a specific microglia transcriptional signature in a mouse model of AD.
- Published
- 2021
- Full Text
- View/download PDF
22. Hyperproduction of 3-hydroxypropionate by Halomonas bluephagenesis
- Author
-
Xiao-Ran Jiang, Xu Yan, Lin-Ping Yu, Xin-Yi Liu, and Guo-Qiang Chen
- Subjects
Science - Abstract
3-Hydroxypropionic acid (3HP) is an important platform chemical. Here, the authors engineer Halomonas bluephagenesis by deleting newly identified degradation pathway and balancing redox state to achieve high level production of 3HP and its copolymer under open and unsterile conditions.
- Published
- 2021
- Full Text
- View/download PDF
23. Hyperproduction of 3-hydroxypropionate by Halomonas bluephagenesis
- Author
-
Jiang, Xiao-Ran, Yan, Xu, Yu, Lin-Ping, Liu, Xin-Yi, and Chen, Guo-Qiang
- Published
- 2021
- Full Text
- View/download PDF
24. Transcriptional signature in microglia associated with Aβ plaque phagocytosis
- Author
-
Grubman, Alexandra, Choo, Xin Yi, Chew, Gabriel, Ouyang, John F., Sun, Guizhi, Croft, Nathan P., Rossello, Fernando J., Simmons, Rebecca, Buckberry, Sam, Landin, Dulce Vargas, Pflueger, Jahnvi, Vandekolk, Teresa H., Abay, Zehra, Zhou, Yichen, Liu, Xiaodong, Chen, Joseph, Larcombe, Michael, Haynes, John M., McLean, Catriona, Williams, Sarah, Chai, Siew Yeen, Wilson, Trevor, Lister, Ryan, Pouton, Colin W., Purcell, Anthony W., Rackham, Owen J. L., Petretto, Enrico, and Polo, Jose M.
- Published
- 2021
- Full Text
- View/download PDF
25. Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection
- Author
-
Zhao, Zhe, Wang, Huimeng, Shi, Mai, Zhu, Tianyuan, Pediongco, Troi, Lim, Xin Yi, Meehan, Bronwyn S., Nelson, Adam G., Fairlie, David P., Mak, Jeffrey Y. W., Eckle, Sidonia B. G., de Lima Moreira, Marcela, Tumpach, Carolin, Bramhall, Michael, Williams, Cameron G., Lee, Hyun Jae, Haque, Ashraful, Evrard, Maximilien, Rossjohn, Jamie, McCluskey, James, Corbett, Alexandra J., and Chen, Zhenjun
- Published
- 2021
- Full Text
- View/download PDF
26. ABCB1 protects bat cells from DNA damage induced by genotoxic compounds
- Author
-
Javier Koh, Yoko Itahana, Ian H. Mendenhall, Dolyce Low, Eunice Xin Yi Soh, Alvin Kunyao Guo, Yok Teng Chionh, Lin-Fa Wang, and Koji Itahana
- Subjects
Science - Abstract
Bats possess an extended lifespan compared to most mammals of their size, and have a low cancer incidence. Here the authors show that several bat species exhibit resistance to genotoxic agents that is in part attributable to high expression of the ABCB1 transporter.
- Published
- 2019
- Full Text
- View/download PDF
27. LNK suppresses interferon signaling in melanoma
- Author
-
Ling-Wen Ding, Qiao-Yang Sun, Jarem J. Edwards, Lucia Torres Fernández, Xue-Bin Ran, Si-Qin Zhou, Richard A. Scolyer, James S. Wilmott, John F. Thompson, Ngan Doan, Jonathan W. Said, Nachiyappan Venkatachalam, Jin-Fen Xiao, Xin-Yi Loh, Maren Pein, Liang Xu, David W. Mullins, Henry Yang, De-Chen Lin, and H. Phillip Koeffler
- Subjects
Science - Abstract
LNK is a tumor suppressor in hematopoietic cancers, but its function in melanoma is unclear. Here, the authors show that the overexpression of LNK in melanomas correlate with hyperactive signaling of the RAS-RAF-MEK pathway and LNK enhances melanoma growth and survival and immune evasion by inhibiting IFN signalling.
- Published
- 2019
- Full Text
- View/download PDF
28. Clonal architectures predict clinical outcome in clear cell renal cell carcinoma
- Author
-
Yi Huang, Jiayin Wang, Peilin Jia, Xiangchun Li, Guangsheng Pei, Changxi Wang, Xiaodong Fang, Zhongming Zhao, Zhiming Cai, Xin Yi, Song Wu, and Baifeng Zhang
- Subjects
Science - Abstract
Clear cell renal cell carcinoma (ccRCC) is a urogenital cancer with a well-defined genetic landscape. Here, the authors analyse the clonal architecture of ccRCC patients from three populations, and find prognostic subtypes linked to immune infiltrates and clonal architecture.
- Published
- 2019
- Full Text
- View/download PDF
29. Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer
- Author
-
Qingzhu Jia, Wei Wu, Yuqi Wang, Peter B. Alexander, Chengdu Sun, Zhihua Gong, Jia-Nan Cheng, Huaibo Sun, Yanfang Guan, Xuefeng Xia, Ling Yang, Xin Yi, Yisong Y. Wan, Haidong Wang, Ji He, P. Andrew Futreal, Qi-Jing Li, and Bo Zhu
- Subjects
Science - Abstract
Intratumoral immunity heterogeneity is poorly characterized. Here the authors apply exome sequencing, transcriptome profiling and T-cell repertoire profiling to multiple loci of non-small-cell lung cancer patients' biopsies and find high spatial immune heterogeneity with local mutational burden correlating with T-cell clonal expansion but not with cytotoxicity.
- Published
- 2018
- Full Text
- View/download PDF
30. Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer
- Author
-
Jingying Nong, Yuhua Gong, Yanfang Guan, Xin Yi, Yuting Yi, Lianpeng Chang, Ling Yang, Jialin Lv, Zhirong Guo, Hongyan Jia, Yuxing Chu, Tao Liu, Ming Chen, Lauren Byers, Emily Roarty, Vincent K. Lam, Vassiliki A. Papadimitrakopoulou, Ignacio Wistuba, John V. Heymach, Bonnie Glisson, Zhongxing Liao, J. Jack Lee, P. Andrew Futreal, Shucai Zhang, Xuefeng Xia, Jianjun Zhang, and Jinghui Wang
- Subjects
Science - Abstract
Small cell lung cancer (SCLC) may evolve under treatment. But tumor tissues are often not available to study evolution of SCLC. Here, the authors utilize circulating tumor DNA to investigate the genomic evolution and subclonal architecture of SCLC during therapy.
- Published
- 2018
- Full Text
- View/download PDF
31. MAIT cells protect against pulmonary Legionella longbeachae infection
- Author
-
Huimeng Wang, Criselle D’Souza, Xin Yi Lim, Lyudmila Kostenko, Troi J. Pediongco, Sidonia B. G. Eckle, Bronwyn S. Meehan, Mai Shi, Nancy Wang, Shihan Li, Ligong Liu, Jeffrey Y. W. Mak, David P. Fairlie, Yoichiro Iwakura, Jennifer M. Gunnersen, Andrew W. Stent, Dale I. Godfrey, Jamie Rossjohn, Glen P. Westall, Lars Kjer-Nielsen, Richard A. Strugnell, James McCluskey, Alexandra J. Corbett, Timothy S. C. Hinks, and Zhenjun Chen
- Subjects
Science - Abstract
Mucosal associated invariant T (MAIT) cells have been implicated in antibacterial responses. Here the authors show MAIT cells confer IFN-γ-mediated protection from lethal infection in a mouse model of Legionella infection, which can be enhanced by synthetic MR1 ligands.
- Published
- 2018
- Full Text
- View/download PDF
32. Visualizing the multi-level assembly structures of conjugated molecular systems with chain-length dependent behavior
- Author
-
Zhou, Yang-Yang, primary, Xu, Yu-Chun, additional, Yao, Ze-Fan, additional, Li, Jia-Ye, additional, Pan, Chen-Kai, additional, Lu, Yang, additional, Yang, Chi-Yuan, additional, Ding, Li, additional, Xiao, Bu-Fan, additional, Wang, Xin-Yi, additional, Shao, Yu, additional, Zhang, Wen-Bin, additional, Wang, Jie-Yu, additional, Wang, Huan, additional, and Pei, Jian, additional
- Published
- 2023
- Full Text
- View/download PDF
33. ABCB1 protects bat cells from DNA damage induced by genotoxic compounds
- Author
-
Koh, Javier, Itahana, Yoko, Mendenhall, Ian H., Low, Dolyce, Soh, Eunice Xin Yi, Guo, Alvin Kunyao, Chionh, Yok Teng, Wang, Lin-Fa, and Itahana, Koji
- Published
- 2019
- Full Text
- View/download PDF
34. Valence band engineering of GaAsBi for low noise avalanche photodiodes
- Author
-
Leh W. Lim, Xin Yi, Chee Hing Tan, Nicholas J. Bailey, John P. R. David, Thomas B. O. Rockett, Robert D. Richards, Zhize Zhou, and Yuchen Liu
- Subjects
Materials science ,Physics::Instrumentation and Detectors ,Science ,General Physics and Astronomy ,Physics::Optics ,Noise (electronics) ,Article ,General Biochemistry, Genetics and Molecular Biology ,Gallium arsenide ,chemistry.chemical_compound ,Condensed Matter::Materials Science ,Signal-to-noise ratio ,Ionization ,Electronic devices ,Diode ,Multidisciplinary ,business.industry ,Astrophysics::Instrumentation and Methods for Astrophysics ,General Chemistry ,Avalanche photodiode ,Impact ionization ,Semiconductor ,chemistry ,Optoelectronics ,business - Abstract
Avalanche Photodiodes (APDs) are key semiconductor components that amplify weak optical signals via the impact ionization process, but this process’ stochastic nature introduces ‘excess’ noise, limiting the useful signal to noise ratio (or sensitivity) that is practically achievable. The APD material’s electron and hole ionization coefficients (α and β respectively) are critical parameters in this regard, with very disparate values of α and β necessary to minimize this excess noise. Here, the analysis of thirteen complementary p-i-n/n-i-p diodes shows that alloying GaAs with ≤ 5.1 % Bi dramatically reduces β while leaving α virtually unchanged—enabling a 2 to 100-fold enhancement of the GaAs α/β ratio while extending the wavelength beyond 1.1 µm. Such a dramatic change in only β is unseen in any other dilute alloy and is attributed to the Bi-induced increase of the spin-orbit splitting energy (∆so). Valence band engineering in this way offers an attractive route to enable low noise semiconductor APDs to be developed., An avalanche photodiode is an opto-electronic amplifier that uses impact ionization to provide enhanced sensitivity at the expense of excess noise. In this manuscript, the authors demonstrate that a small amount of Bismuth (Bi) in Gallium Arsenide (GaAs) avalanche photodiodes significantly reduces this excess noise.
- Published
- 2021
35. Author Correction: Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer
- Author
-
Jingying Nong, Yuhua Gong, Yanfang Guan, Xin Yi, Yuting Yi, Lianpeng Chang, Ling Yang, Jialin Lv, Zhirong Guo, Hongyan Jia, Yuxing Chu, Tao Liu, Ming Chen, Lauren Byers, Emily Roarty, Vincent K. Lam, Vassiliki A. Papadimitrakopoulou, Ignacio Wistuba, John V. Heymach, Bonnie Glisson, Zhongxing Liao, J. Jack Lee, P. Andrew Futreal, Shucai Zhang, Xuefeng Xia, Jianjun Zhang, and Jinghui Wang
- Subjects
Science - Abstract
The original version of this Article contained an error in Fig. 2, in which the left y-axis labels ‘tDNA’ and ‘ctDNA’ were inadvertently inverted. This has been corrected in the PDF and HTML versions of the Article.
- Published
- 2019
- Full Text
- View/download PDF
36. Clonal architectures predict clinical outcome in clear cell renal cell carcinoma
- Author
-
Jiayin Wang, Peilin Jia, Yi Huang, Xiaodong Fang, Zhongming Zhao, Xiangchun Li, Baifeng Zhang, Xin Yi, Changxi Wang, Song Wu, Zhiming Cai, and Guangsheng Pei
- Subjects
0301 basic medicine ,Somatic cell ,General Physics and Astronomy ,02 engineering and technology ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,Kidney ,T-Lymphocytes, Regulatory ,PBRM1 ,Cohort Studies ,lcsh:Science ,BAP1 ,Mutation ,Multidisciplinary ,Nuclear Proteins ,021001 nanoscience & nanotechnology ,Prognosis ,Kidney Neoplasms ,3. Good health ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,Von Hippel-Lindau Tumor Suppressor Protein ,0210 nano-technology ,DNA Copy Number Variations ,Science ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Evolution, Molecular ,03 medical and health sciences ,Genetic Heterogeneity ,Th2 Cells ,Carcinoma ,medicine ,Humans ,Carcinoma, Renal Cell ,Whole Genome Sequencing ,Genetic heterogeneity ,General Chemistry ,medicine.disease ,Survival Analysis ,Clone Cells ,Clear cell renal cell carcinoma ,030104 developmental biology ,Cancer research ,Th17 Cells ,lcsh:Q ,CD8 ,Transcription Factors - Abstract
The genetic landscape of clear cell renal cell carcinoma (ccRCC) had been investigated extensively but its evolution patterns remained unclear. Here we analyze the clonal architectures of 473 patients from three different populations. We find that the mutational signatures vary substantially across different populations and evolution stages. The evolution patterns of ccRCC have great inter-patient heterogeneities, with del(3p) being regarded as the common earliest event followed by three early departure points: VHL and PBRM1 mutations, del(14q) and other somatic copy number alterations (SCNAs) including amp(7), del(1p) and del(6q). We identify three prognostic subtypes of ccRCC with distinct clonal architectures and immune infiltrates: long-lived patients, enriched with VHL but depleted of BAP1 mutations, have high levels of Th17 and CD8+ T cells while short-lived patients with high burden of SCNAs have high levels of Tregs and Th2 cells, highlighting the importance of evaluating evolution patterns in the clinical management of ccRCC., Clear cell renal cell carcinoma (ccRCC) is a urogenital cancer with a well-defined genetic landscape. Here, the authors analyse the clonal architecture of ccRCC patients from three populations, and find prognostic subtypes linked to immune infiltrates and clonal architecture.
- Published
- 2019
37. Hyperproduction of 3-hydroxypropionate by Halomonas bluephagenesis
- Author
-
Xu Yan, Xin-Yi Liu, Guo-Qiang Chen, Xiao-Ran Jiang, and Lin-Ping Yu
- Subjects
0106 biological sciences ,0301 basic medicine ,Science ,Polyesters ,General Physics and Astronomy ,Aldehyde dehydrogenase ,Hydroxybutyrates ,01 natural sciences ,Redox ,General Biochemistry, Genetics and Molecular Biology ,Article ,Metabolic engineering ,Applied microbiology ,03 medical and health sciences ,Biopolymers ,Bacterial Proteins ,010608 biotechnology ,Lactic Acid ,chemistry.chemical_classification ,Gene Editing ,Halomonas ,Multidisciplinary ,biology ,Strain (chemistry) ,General Chemistry ,Gene Expression Regulation, Bacterial ,biology.organism_classification ,Bioproduction ,Biosynthetic Pathways ,030104 developmental biology ,Enzyme ,chemistry ,Biochemistry ,Metabolic Engineering ,Propylene Glycols ,biology.protein ,Degradation (geology) - Abstract
3-Hydroxypropionic acid (3HP), an important three carbon (C3) chemical, is designated as one of the top platform chemicals with an urgent need for improved industrial production. Halomonas bluephagenesis shows the potential as a chassis for competitive bioproduction of various chemicals due to its ability to grow under an open, unsterile and continuous process. Here, we report the strategy for producing 3HP and its copolymer poly(3-hydroxybutyrate-co-3-hydroxypropionate) (P3HB3HP) by the development of H. bluephagenesis. The transcriptome analysis reveals its 3HP degradation and synthesis pathways involving endogenous synthetic enzymes from 1,3-propanediol. Combing the optimized expression of aldehyde dehydrogenase (AldDHb), an engineered H. bluephagenesis strain of whose 3HP degradation pathway is deleted and that overexpresses alcohol dehydrogenases (AdhP) on its genome under a balanced redox state, is constructed with an enhanced 1.3-propanediol-dependent 3HP biosynthetic pathway to produce 154 g L−1 of 3HP with a yield and productivity of 0.93 g g−1 1,3-propanediol and 2.4 g L−1 h−1, respectively. Moreover, the strain could also accumulate 60% poly(3-hydroxybutyrate-co-32–45% 3-hydroxypropionate) in the dry cell mass, demonstrating to be a suitable chassis for hyperproduction of 3HP and P3HB3HP., 3-Hydroxypropionic acid (3HP) is an important platform chemical. Here, the authors engineer Halomonas bluephagenesis by deleting newly identified degradation pathway and balancing redox state to achieve high level production of 3HP and its copolymer under open and unsterile conditions.
- Published
- 2020
38. Clinical and genomic features of Chinese lung cancer patients with germline mutations
- Author
-
Wenying Peng, Bin Li, Jin Li, Lianpeng Chang, Jing Bai, Yuting Yi, Rongrong Chen, Yanyan Zhang, Chen Chen, Xingxiang Pu, Meilin Jiang, Jia Li, Rui Zhong, Fang Xu, Bolin Chen, Li Xu, Ning Wang, Jiaojiao Huan, Pingping Dai, Yanfang Guan, Ling Yang, Xuefeng Xia, Xin Yi, Jiayin Wang, Fenglei Yu, and Lin Wu
- Subjects
BRCA2 Protein ,China ,Multidisciplinary ,Lung Neoplasms ,BRCA1 Protein ,General Physics and Astronomy ,Humans ,Genetic Predisposition to Disease ,General Chemistry ,Genomics ,Middle Aged ,General Biochemistry, Genetics and Molecular Biology ,Germ-Line Mutation - Abstract
The germline mutation landscape in Chinese lung cancer patients has not been well defined. In this study, sequencing data of 1,021 cancer genes of 1,794 Chinese lung cancer patients was analyzed. A total of 111 pathogenic or likely pathogenic germline mutations were identified, significantly higher than non-cancer individuals (111/1794 vs. 84/10,588, p BRCA1/2 germline mutations are associated with earlier onset age (median 52.5 vs 60 years-old, p = 0.008). Among 29 cancer disposition genes with germline mutations detected in Chinese cohort and/or TCGA lung cancer cohort, Only 11 from 29 genes are identified in both cohorts and BRCA2 mutations are significantly more common in Chinese cohort (p = 0.015). Chinese patients with germline mutations have different prevalence of somatic KRAS, MET exon 14 skipping and TP53 mutations compared to those without. Our findings suggest potential ethnic and etiologic differences between Western and Asian lung cancer patients.
- Published
- 2019
39. Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer
- Author
-
Xin Yi, Hongyan Jia, Vassiliki A. Papadimitrakopoulou, John V. Heymach, Liu Tao, Zhongxing Liao, Yanfang Guan, Jianjun Zhang, Jialin Lv, Emily Roarty, Shucai Zhang, Zhirong Guo, Yuting Yi, Bonnie S. Glisson, Ling Yang, Yuxing Chu, Ignacio I. Wistuba, Lauren Averett Byers, P. Andrew Futreal, Vincent K. Lam, Yuhua Gong, Jingying Nong, Xuefeng Xia, Lianpeng Chang, J. Jack Lee, Jinghui Wang, and Ming Chen
- Subjects
0301 basic medicine ,DNA repair ,Science ,General Physics and Astronomy ,Genomics ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Deep sequencing ,Article ,03 medical and health sciences ,0302 clinical medicine ,DNA Mutational Analysis ,medicine ,Lung cancer ,lcsh:Science ,Allele frequency ,neoplasms ,Mutation ,Multidisciplinary ,Point mutation ,General Chemistry ,medicine.disease ,humanities ,3. Good health ,respiratory tract diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,lcsh:Q - Abstract
Subclonal architecture and genomic evolution of small-cell lung cancer (SCLC) under treatment has not been well studied primarily due to lack of tumor specimens, particularly longitudinal samples acquired during treatment. SCLC is characterized by early hematogenous spread, which makes circulating cell-free tumor DNA (ctDNA) sequencing a promising modality for genomic profiling. Here, we perform targeted deep sequencing of 430 cancer genes on pre-treatment tumor biopsies, as well as on plasma samples collected prior to and during treatment from 22 SCLC patients. Similar subclonal architecture is observed between pre-treatment ctDNA and paired tumor DNA. Mean variant allele frequency of clonal mutations from pre-treatment ctDNA is associated with progression-free survival and overall survival. Pre- and post-treatment ctDNA mutational analysis demonstrate that mutations of DNA repair and NOTCH signaling pathways are enriched in post-treatment samples. These data suggest that ctDNA sequencing is promising to delineate genomic landscape, subclonal architecture, and genomic evolution of SCLC., Small cell lung cancer (SCLC) may evolve under treatment. But tumor tissues are often not available to study evolution of SCLC. Here, the authors utilize circulating tumor DNA to investigate the genomic evolution and subclonal architecture of SCLC during therapy.
- Published
- 2018
40. ABCB1 protects bat cells from DNA damage induced by genotoxic compounds
- Author
-
Lin-Fa Wang, Koji Itahana, Alvin Kunyao Guo, Yoko Itahana, Dolyce H. W. Low, Eunice Xin Yi Soh, Javier Koh, Ian H. Mendenhall, and Yok Teng Chionh
- Subjects
0301 basic medicine ,Drug ,Programmed cell death ,ATP Binding Cassette Transporter, Subfamily B ,animal structures ,DNA damage ,Science ,media_common.quotation_subject ,General Physics and Astronomy ,ATP-binding cassette transporter ,02 engineering and technology ,Biology ,DNA damage response ,Article ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Cancer prevention ,Mice ,03 medical and health sciences ,Chiroptera ,medicine ,Animals ,Humans ,Doxorubicin ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,lcsh:Science ,media_common ,Multidisciplinary ,Cell Death ,Cancer ,General Chemistry ,021001 nanoscience & nanotechnology ,medicine.disease ,Cell biology ,Transporters ,030104 developmental biology ,Cell culture ,lcsh:Q ,Efflux ,0210 nano-technology ,DNA Damage ,Mutagens ,medicine.drug - Abstract
Bats are unusual mammals, with the ability to fly, and long lifespans. In addition, bats have a low incidence of cancer, but the mechanisms underlying this phenomenon remain elusive. Here we discovered that bat cells are more resistant than human and mouse cells to DNA damage induced by genotoxic drugs. We found that bat cells accumulate less chemical than human and mouse cells, and efficient drug efflux mediated by the ABC transporter ABCB1 underlies this improved response to genotoxic reagents. Inhibition of ABCB1 triggers an accumulation of doxorubicin, DNA damage, and cell death. ABCB1 is expressed at higher levels in several cell lines and tissues derived from bats compared to humans. Furthermore, increased drug efflux and high expression of ABCB1 are conserved across multiple bat species. Our findings suggest that enhanced efflux protects bat cells from DNA damage induced by genotoxic compounds, which may contribute to their low cancer incidence., Bats possess an extended lifespan compared to most mammals of their size, and have a low cancer incidence. Here the authors show that several bat species exhibit resistance to genotoxic agents that is in part attributable to high expression of the ABCB1 transporter.
- Published
- 2019
41. Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer
- Author
-
Bo Zhu, Qingzhu Jia, Peter B. Alexander, Wei Wu, Wang Yuqi, Jia Nan Cheng, P. Andrew Futreal, Xuefeng Xia, Chengdu Sun, Zhihua Gong, Yisong Y. Wan, Ji He, Qi-Jing Li, Xin Yi, Huaibo Sun, Yanfang Guan, Ling Yang, and Haidong Wang
- Subjects
0301 basic medicine ,Lung Neoplasms ,Science ,Biopsy ,T-Lymphocytes ,DNA Mutational Analysis ,General Physics and Astronomy ,Biology ,medicine.disease_cause ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immune system ,Antigen ,Antigens, Neoplasm ,Carcinoma, Non-Small-Cell Lung ,Exome Sequencing ,Tumor Microenvironment ,medicine ,Humans ,Lung cancer ,Lung ,Exome sequencing ,Mutation ,Multidisciplinary ,medicine.diagnostic_test ,Gene Expression Profiling ,General Chemistry ,medicine.disease ,3. Good health ,Gene expression profiling ,030104 developmental biology ,Cancer research - Abstract
Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses of 15 patients with non-small cell lung cancer (NSCLC). This revealed that the immune microenvironment has high spatial heterogeneity such that intratumoral regional variation is as large as inter-personal variation. While the local total mutational burden (TMB) is associated with local T-cell clonal expansion, local anti-tumor cytotoxicity does not directly correlate with neoantigen abundance. Together, these findings caution against that immunological signatures can be predicted solely from TMB or microenvironmental analysis from a single locus biopsy., Intratumoral immunity heterogeneity is poorly characterized. Here the authors apply exome sequencing, transcriptome profiling and T-cell repertoire profiling to multiple loci of non-small-cell lung cancer patients' biopsies and find high spatial immune heterogeneity with local mutational burden correlating with T-cell clonal expansion but not with cytotoxicity.
- Published
- 2018
42. MAIT cells protect against pulmonary Legionella longbeachae infection
- Author
-
Wang, Huimeng, D’Souza, Criselle, Lim, Xin Yi, Kostenko, Lyudmila, Pediongco, Troi J., Eckle, Sidonia B. G., Meehan, Bronwyn S., Shi, Mai, Wang, Nancy, Li, Shihan, Liu, Ligong, Mak, Jeffrey Y. W., Fairlie, David P., Iwakura, Yoichiro, Gunnersen, Jennifer M., Stent, Andrew W., Godfrey, Dale I., Rossjohn, Jamie, Westall, Glen P., Kjer-Nielsen, Lars, Strugnell, Richard A., McCluskey, James, Corbett, Alexandra J., Hinks, Timothy S. C., and Chen, Zhenjun
- Subjects
CD4-Positive T-Lymphocytes ,Male ,Legionellosis ,Perforin ,Science ,Interleukin-17 ,Article ,Mucosal-Associated Invariant T Cells ,DNA-Binding Proteins ,Mice ,Legionella longbeachae ,Animals ,Humans ,lcsh:Q ,lcsh:Science ,Lung - Abstract
Mucosal associated invariant T (MAIT) cells recognise conserved microbial metabolites from riboflavin synthesis. Striking evolutionary conservation and pulmonary abundance implicate them in antibacterial host defence, yet their functions in protection against clinically important pathogens are unknown. Here we show that mouse Legionella longbeachae infection induces MR1-dependent MAIT cell activation and rapid pulmonary accumulation of MAIT cells associated with immune protection detectable in immunocompetent host animals. MAIT cell protection is more evident in mice lacking CD4+ cells, and adoptive transfer of MAIT cells rescues immunodeficient Rag2−/−γC−/− mice from lethal Legionella infection. Protection is dependent on MR1, IFN-γ and GM-CSF, but not IL-17A, TNF or perforin, and enhanced protection is detected earlier after infection of mice antigen-primed to boost MAIT cell numbers before infection. Our findings define a function for MAIT cells in protection against a major human pathogen and indicate a potential role for vaccination to enhance MAIT cell immunity., Mucosal associated invariant T (MAIT) cells have been implicated in antibacterial responses. Here the authors show MAIT cells confer IFN-γ-mediated protection from lethal infection in a mouse model of Legionella infection, which can be enhanced by synthetic MR1 ligands.
- Published
- 2018
43. Author Correction: Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer
- Author
-
Jinghui Wang, Bonnie S. Glisson, Xin Yi, Vassiliki A. Papadimitrakopoulou, Yuxing Chu, Yanfang Guan, Emily Roarty, John V. Heymach, Ignacio I. Wistuba, Lauren Averett Byers, J. Jack Lee, Jingying Nong, Ling Yang, Zhirong Guo, Ming Chen, Liu Tao, Hongyan Jia, Yuting Yi, Vincent K. Lam, P. Andrew Futreal, Jialin Lv, Yuhua Gong, Lianpeng Chang, Zhongxing Liao, Jianjun Zhang, Xuefeng Xia, and Shucai Zhang
- Subjects
Adult ,Male ,0301 basic medicine ,DNA, Complementary ,Lung Neoplasms ,DNA Repair ,Biopsy ,Science ,DNA Mutational Analysis ,General Physics and Astronomy ,02 engineering and technology ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Circulating Tumor DNA ,Evolution, Molecular ,03 medical and health sciences ,Gene Frequency ,Humans ,Point Mutation ,lcsh:Science ,Author Correction ,Aged ,Multidisciplinary ,High-Throughput Nucleotide Sequencing ,DNA, Neoplasm ,Genomics ,General Chemistry ,Middle Aged ,021001 nanoscience & nanotechnology ,Small Cell Lung Carcinoma ,030104 developmental biology ,Circulating tumor DNA ,Mutation ,Cancer research ,lcsh:Q ,Female ,Non small cell ,0210 nano-technology ,Signal Transduction - Abstract
Subclonal architecture and genomic evolution of small-cell lung cancer (SCLC) under treatment has not been well studied primarily due to lack of tumor specimens, particularly longitudinal samples acquired during treatment. SCLC is characterized by early hematogenous spread, which makes circulating cell-free tumor DNA (ctDNA) sequencing a promising modality for genomic profiling. Here, we perform targeted deep sequencing of 430 cancer genes on pre-treatment tumor biopsies, as well as on plasma samples collected prior to and during treatment from 22 SCLC patients. Similar subclonal architecture is observed between pre-treatment ctDNA and paired tumor DNA. Mean variant allele frequency of clonal mutations from pre-treatment ctDNA is associated with progression-free survival and overall survival. Pre- and post-treatment ctDNA mutational analysis demonstrate that mutations of DNA repair and NOTCH signaling pathways are enriched in post-treatment samples. These data suggest that ctDNA sequencing is promising to delineate genomic landscape, subclonal architecture, and genomic evolution of SCLC.
- Published
- 2019
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.