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Multidisciplinary Sciences
Katherine A. Freitas, Julia A. Belk, Elena Sotillo, Patrick J. Quinn, Maria C. Ramello, Meena Malipatlolla, Bence Daniel, Katalin Sandor, Dorota Klysz, Jeremy Bjelajac, Peng Xu, Kylie A. Burdsall, Victor Tieu, Vandon T. Duong, Micah G. Donovan, Evan W. Weber, Howard Y. Chang, Robbie G. Majzner, Joaquin M. Espinosa, Ansuman T. Satpathy, Crystal L. Mackall
Summary: This research identified MED12 and CCNC as key genes controlling T cell function through CRISPR knockout screening. Knockout of MED12 gene enhances antitumor activity, prolongs the effector phenotype of CAR-T and TCR-T cells, and promotes the expansion of non-engineered T cells. The study reveals the importance of Mediator in T cell effector programming and provides a new target to enhance the potency of antitumor T cell responses.
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Medicine, Research & Experimental
Ghaidaa Kashgari, Sanan Venkatesh, Samuel Refuerzo, Brandon Pham, Anita Bayat, Rachel Herndon Klein, Raul Ramos, Albert Paul Ta, Maksim Plikus, Ping H. Wang, Bogi Andersen
Summary: This research uncovers a signaling pathway regulated by GRHL3, FSCN1, and E-cadherin, which is crucial for adhesion between keratinocytes and wound closure.
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Multidisciplinary Sciences
Fengying Wu, Jue Fan, Yayi He, Anwen Xiong, Jia Yu, Yixin Li, Yan Zhang, Wencheng Zhao, Fei Zhou, Wei Li, Jie Zhang, Xiaosheng Zhang, Meng Qiao, Guanghui Gao, Shanhao Chen, Xiaoxia Chen, Xuefei Li, Likun Hou, Chunyan Wu, Chunxia Su, Shengxiang Ren, Margarete Odenthal, Reinhard Buettner, Nan Fang, Caicun Zhou
Summary: This study utilized single-cell RNA sequencing to analyze 42 late-stage NSCLC patients, revealing significant heterogeneity in tumors in terms of cellular composition, chromosomal structure, developmental trajectory, and the identification of rare cell types. The research also highlighted the correlation between tumor heterogeneity and tumor-associated neutrophils.
NATURE COMMUNICATIONS
(2021)
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Cell Biology
Teppei Shibata, Masahito Ikawa, Ryo Sakasai, Yasuhito Ishigaki, Etsuko Kiyokawa, Kuniyoshi Iwabuchi, Dhirendra P. Singh, Hiroshi Sasaki, Eri Kubo
Summary: Tpm1 is important for lens development and homeostasis, as its deficiency can lead to lens abnormalities and potentially cataract formation.
MECHANISMS OF AGEING AND DEVELOPMENT
(2021)
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Cell Biology
Connor Finkbeiner, Isabel Ortuno-Lizaran, Akshayalakshmi Sridhar, Marcus Hooper, Sidnee Petter, Thomas A. Reh
Summary: This study combines single-cell transcriptomic analysis with chromatin sequencing to investigate human fetal retinal development and identify key transcription factors and their cascades. By comparing retinal organoids, differences in signaling pathways and gene regulation are discovered. These findings are crucial for improving retinal organoid technology and advancing regenerative medicine approaches for retinal diseases.
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Cell Biology
Athanasios Papadas, Gauri Deb, Alexander Cicala, Adam Officer, Chelsea Hope, Adam Pagenkopf, Evan Flietner, Zachary T. Morrow, Philip Emmerich, Joshua Wiesner, Garrett Arauz, Varun Bansal, Karla Esbona, Christian M. Capitini, Kristina A. Matkowskyj, Dustin A. Deming, Katerina Politi, Scott I. Abrams, Olivier Harismendy, Fotis Asimakopoulos
Summary: The stroma near the tumor edge plays a crucial role in regulating the abundance and activity of cDC1, which in turn affects the T cell inflammatory response in the tumor microenvironment.
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Biochemistry & Molecular Biology
Soumaya Belhadj, Nina Sofia Hermann, Yu Zhu, Gustav Christensen, Torsten Strasser, Francois Paquet-Durand
Summary: In this study, the researchers successfully detected the activity of calpain in the retina using a specific substrate. They found that calpain-2 activity may occur in the late stage of photoreceptor cell death, and the substrate used was not toxic to photoreceptor cells. These findings support the development of calpain activity detection as a novel in vivo biomarker for RD, which can be combined with non-invasive imaging techniques.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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Cell Biology
Xinxin Chi, Wei Jin, Xue Bai, Xiaohong Zhao, Jing Shao, Jiaqi Li, Qinli Sun, Bing Su, Xiaohu Wang, Xuexian O. Yang, Chen Dong
Summary: The study found that RORα is highly expressed in active UC patients, especially in those non-responsive to anti-TNF treatment. RORα plays a crucial role in promoting IBD development in CD4(+) T cells by regulating T cell infiltration, inhibiting T cell apoptosis, and promoting mTORC1 activation. This indicates that the RORα-mTORC1 axis may be a potential therapeutic target for human patients with IBD.
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Biochemistry & Molecular Biology
Yuefang Zhou, Thomas M. Bennett, Thomas W. White, Alan Shiels
Summary: CHMP4B is a core sub-unit of the ESCRT-III machinery involved in remodeling and scission processes of biological membranes. It has been found to associate with connexin 46 (Cx46) and connexin 50 (Cx50), and its membrane localization is dependent on Cx50 in lens fiber cells.
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Chemistry, Applied
Jian Lyu, Per Ertbjerg
Summary: The study investigated the subcellular distribution of calpain-1 and -2 as well as the proteolytic activity of myofibril-bound calpains during 12 days cold storage in pork. The results showed that calpain-1 gradually translocated from sarcoplasm to myofibrils during the initial 6 days of postmortem storage, and both calpain-1 and calpain-2 were found to bind to myofibrils and subsequently degrade structural proteins, including desmin.
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Biochemistry & Molecular Biology
Swantje Liedmann, Xueyan Liu, Clifford S. Guy, Jeremy Chase Crawford, Diego A. Rodriguez, Duygu Kuzuoglu-Ozturk, Ao Guo, Katherine C. Verbist, Jamshid Temirov, Mark J. Chen, Davide Ruggero, Hui Zhang, Paul G. Thomas, Douglas R. Green
Summary: Activated CD8(+) T lymphocytes undergo heterogeneous differentiation, and this study reveals the mechanisms involved in establishing distinct T cell fate trajectories during the first division. The researchers discovered that dynein-dependent vesicular transport polarizes active TORC1 and eIF4F complexes towards the microtubule-organizing center (MTOC) at the proximal pole, leading to polarized translation of c-myc mRNA. Furthermore, the TORC1-eIF4A complex sorts preferentially to the proximal daughter cell upon division, facilitating asymmetric c-Myc synthesis. Disrupting eIF4A activity at first division skews long-term cell fate trajectories to memory-like function. These findings highlight the importance of localized translation and protein sorting in determining T cell fate.
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Plant Sciences
Chengcheng Li, Fan Hu, Hongyu Chen, Jie Zhao
Summary: The study characterized the early embryo and endosperm development in the naa15 mutant compared to the wild type of Arabidopsis, showing abnormal embryo differentiation and incomplete endosperm cellularization. Transcriptome analyses revealed differentially expressed genes (DEGs) involved in lipid metabolic processes, cell wall biogenesis, hormone signaling pathways, and transcriptional regulation. Immunofluorescent assays also showed differences in the features of cell walls, providing important insights into the regulatory mechanisms of endosperm cellularization and embryonic differentiation.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Xin Long, Qiuyun Yang, Jingjing Qian, Huiying Yao, Rui Yan, Xin Cheng, Qiancheng Zhang, Chan Gu, Fei Gao, Hongmei Wang, Lin Zhang, Fan Guo
Summary: Obesity affects female reproduction by disrupting the balance of ovarian follicle cell types. This study reveals that excessive androgen secretion from endocrine theca cells contributes to this imbalance through interactions with granulosa cells. The use of an androgen receptor antagonist can alleviate this imbalance. Additionally, specific markers for evaluating female fertility in obesity were identified.
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Medicine, Research & Experimental
Satomi Ando, Charles M. Perkins, Yamato Sajiki, Chase Chastain, Rajesh M. Valanparambil, Andreas Wieland, William H. Hudson, Masao Hashimoto, Suresh S. Ramalingam, Gordon J. Freeman, Rafi Ahmed, Koichi Araki
Summary: T cell exhaustion is associated with dysfunction and expression of PD-1. mTOR inhibition during the expansion phase enhances T cell response, while inhibition after exhaustion progresses causes immunosuppression with decreased TIM3(+) cells and increased viral load. mTOR signaling is essential for differentiation of stem-like T cells into TIM3(+) cells.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
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Biochemistry & Molecular Biology
Yongjian Yang, Guanxun Li, Yan Zhong, Qian Xu, Bo-Jia Chen, Yu-Te Lin, Robert S. Chapkin, James J. Cai
Summary: In this paper, the authors present GenKI, a virtual knockout tool for gene function prediction using scRNA-seq data. GenKI captures shifting patterns in gene regulation caused by knockout perturbations and provides a robust framework for gene function studies. By adapting a VGAE model, GenKI learns latent representations of genes and interactions between genes from input scRNA-seq data and a derived scGRN. Virtual knockout data is generated by computationally removing edges corresponding to the knockout gene from the scGRN. GenKI accurately approximates perturbation profiles and outperforms existing methods in simulations. It also recapitulates discoveries of real-animal knockout experiments and predicts cell type-specific functions of knockout genes.
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